Increased segregation of brain networks in focal epilepsy: An fMRI graph theory finding.

PubMed

Pedersen, Mangor; Omidvarnia, Amir H; Walz, Jennifer M; Jackson, Graeme D

2015-01-01

Focal epilepsy is conceived of as activating local areas of the brain as well as engaging regional brain networks. Graph theory represents a powerful quantitative framework for investigation of brain networks. Here we investigate whether functional network changes are present in extratemporal focal epilepsy. Task-free functional magnetic resonance imaging data from 15 subjects with extratemporal epilepsy and 26 age and gender matched healthy controls were used for analysis. Local network properties were calculated using local efficiency, clustering coefficient and modularity metrics. Global network properties were assessed with global efficiency and betweenness centrality metrics. Cost-efficiency of the networks at both local and global levels was evaluated by estimating the physical distance between functionally connected nodes, in addition to the overall numbers of connections in the network. Clustering coefficient, local efficiency and modularity were significantly higher in individuals with focal epilepsy than healthy control subjects, while global efficiency and betweenness centrality were not significantly different between the two groups. Local network properties were also highly efficient, at low cost, in focal epilepsy subjects compared to healthy controls. Our results show that functional networks in focal epilepsy are altered in a way that the nodes of the network are more isolated. We postulate that network regularity, or segregation of the nodes of the networks, may be an adaptation that inhibits the conversion of the interictal state to seizures. It remains possible that this may be part of the epileptogenic process or an effect of medications.

Increased segregation of brain networks in focal epilepsy: An fMRI graph theory finding

PubMed Central

Pedersen, Mangor; Omidvarnia, Amir H.; Walz, Jennifer M.; Jackson, Graeme D.

2015-01-01

Focal epilepsy is conceived of as activating local areas of the brain as well as engaging regional brain networks. Graph theory represents a powerful quantitative framework for investigation of brain networks. Here we investigate whether functional network changes are present in extratemporal focal epilepsy. Task-free functional magnetic resonance imaging data from 15 subjects with extratemporal epilepsy and 26 age and gender matched healthy controls were used for analysis. Local network properties were calculated using local efficiency, clustering coefficient and modularity metrics. Global network properties were assessed with global efficiency and betweenness centrality metrics. Cost-efficiency of the networks at both local and global levels was evaluated by estimating the physical distance between functionally connected nodes, in addition to the overall numbers of connections in the network. Clustering coefficient, local efficiency and modularity were significantly higher in individuals with focal epilepsy than healthy control subjects, while global efficiency and betweenness centrality were not significantly different between the two groups. Local network properties were also highly efficient, at low cost, in focal epilepsy subjects compared to healthy controls. Our results show that functional networks in focal epilepsy are altered in a way that the nodes of the network are more isolated. We postulate that network regularity, or segregation of the nodes of the networks, may be an adaptation that inhibits the conversion of the interictal state to seizures. It remains possible that this may be part of the epileptogenic process or an effect of medications. PMID:26110111

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 American Society for Therapeutic Radiology and Oncology (ASTRO) evidence-based review of the role of radiosurgery for brain metastases

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

Mehta, Minesh P.; Tsao, May N.; Whelan, Timothy J.

2005-09-01

Purpose: To systematically review the evidence for the use of stereotactic radiosurgery in adult patients with brain metastases. Methods: Key clinical questions to be addressed in this evidence-based review were identified. Outcomes considered were overall survival, quality of life or symptom control, brain tumor control or response and toxicity. MEDLINE (1990-2004 June Week 2), CANCERLIT (1990-2003), CINAHL (1990-2004 June Week 2), EMBASE (1990-2004 Week 25), and the Cochrane library (2004 issue 2) databases were searched using OVID. In addition, the Physician Data Query clinical trials database, the proceedings of the American Society of Clinical Oncology (ASCO) (1997-2004), ASTRO (1997-2004), andmore » the European Society of Therapeutic Radiology and Oncology (ESTRO) (1997-2003) were searched. Data from the literature search were reviewed and tabulated. This process included an assessment of the level of evidence. Results: For patients with newly diagnosed brain metastases, managed with whole-brain radiotherapy alone vs. whole-brain radiotherapy and radiosurgery boost, there were three randomized controlled trials, zero prospective studies, and seven retrospective series (which satisfied inclusion criteria). For patients with up to three (<4 cm) newly diagnosed brain metastases (and in one study up to four brain metastases), radiosurgery boost with whole-brain radiotherapy significantly improves local brain control rates as compared with whole-brain radiotherapy alone (Level I-III evidence). In one large randomized trial, survival benefit with whole-brain radiotherapy was observed in patients with single brain metastasis. In this trial, an overall increased ability to taper down on steroid dose and an improvement in Karnofsky performance status was seen in patients who were treated with radiosurgery boost as compared with patients treated with whole-brain radiotherapy alone. However, Level I evidence regarding overall quality of life outcomes using a validated instrument has not been reported. All randomized trials showed improved local control with the addition of radiosurgery to whole-brain radiotherapy. For patients with multiple brain metastases, there is no overall survival benefit with the use of radiosurgery boost to whole-brain radiotherapy (Level I-III evidence). Radiosurgery boost is associated with a small risk of early or late toxicity. In patients treated with radiosurgery alone (withholding whole-brain radiotherapy) as initial treatment, there were 2 randomized trials, 2 prospective cohort studies, and 16 retrospective series. There is Level I to Level III evidence that the use of radiosurgery alone does not alter survival as compared to the use of whole-brain radiotherapy. However, there is Level I to Level III evidence that omission of whole-brain radiotherapy results in poorer intracranial disease control, both local and distant (defined as remaining brain, outside the radiosurgery field). Quality of life outcomes have not been adequately reported. Radiosurgery is associated with a small risk of early or late toxicity. Radiosurgery as salvage for patients with brain metastases was reported in zero randomized trials, one prospective study, and seven retrospective series. Conclusions: Based on Level I-III evidence, for selected patients with small (up to 4 cm) brain metastases (up to three in number and four in one randomized trial), the addition of radiosurgery boost to whole-brain radiotherapy improves brain control as compared with whole-brain radiotherapy alone. In patients with a single brain metastasis, radiosurgery boost with whole-brain radiotherapy improves survival. There is a small risk of toxicity associated with radiosurgery boost as compared with whole-brain radiotherapy alone. In selected patients treated with radiosurgery alone for newly diagnosed brain metastases, overall survival is not altered. However, local and distant brain control is significantly poorer with omission of upfront whole-brain radiotherapy (Level I-III evidence). Whether neurocognition or quality of life outcomes are different between initial radiosurgery alone vs. whole-brain radiotherapy (with or without radiosurgery boost) is unknown, because this has not been adequately tested. There was no statistically significant difference in overall toxicity between those treated with radiosurgery alone vs. whole-brain radiotherapy and radiosurgery boost based on an interim report from one randomized study. There is insufficient evidence as to the clinical benefit/risks radiosurgery used in the setting of recurrent or progressive brain metastases, although radiographic responses are well-documented.« less

Disruptions of brain structural network in end-stage renal disease patients with long-term hemodialysis and normal-appearing brain tissues.

PubMed

Chou, Ming-Chung; Ko, Chih-Hung; Chang, Jer-Ming; Hsieh, Tsyh-Jyi

2018-05-04

End-stage renal disease (ESRD) patients on hemodialysis were demonstrated to exhibit silent and invisible white-matter alterations which would likely lead to disruptions of brain structural networks. Therefore, the purpose of this study was to investigate the disruptions of brain structural network in ESRD patients. Thiry-three ESRD patients with normal-appearing brain tissues and 29 age- and gender-matched healthy controls were enrolled in this study and underwent both cognitive ability screening instrument (CASI) assessment and diffusion tensor imaging (DTI) acquisition. Brain structural connectivity network was constructed using probabilistic tractography with automatic anatomical labeling template. Graph-theory analysis was performed to detect the alterations of node-strength, node-degree, node-local efficiency, and node-clustering coefficient in ESRD patients. Correlational analysis was performed to understand the relationship between network measures, CASI score, and dialysis duration. Structural connectivity, node-strength, node-degree, and node-local efficiency were significantly decreased, whereas node-clustering coefficient was significantly increased in ESRD patients as compared with healthy controls. The disrupted local structural networks were generally associated with common neurological complications of ESRD patients, but the correlational analysis did not reveal significant correlation between network measures, CASI score, and dialysis duration. Graph-theory analysis was helpful to investigate disruptions of brain structural network in ESRD patients with normal-appearing brain tissues. Copyright © 2018. Published by Elsevier Masson SAS.

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-01-01

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

A Bayesian network meta-analysis of whole brain radiotherapy and stereotactic radiotherapy for brain metastasis.

PubMed

Yuan, Xi; Liu, Wen-Jie; Li, Bing; Shen, Ze-Tian; Shen, Jun-Shu; Zhu, Xi-Xu

2017-08-01

This study was conducted to compare the effects of whole brain radiotherapy (WBRT) and stereotactic radiotherapy (SRS) in treatment of brain metastasis.A systematical retrieval in PubMed and Embase databases was performed for relative literatures on the effects of WBRT and SRS in treatment of brain metastasis. A Bayesian network meta-analysis was performed by using the ADDIS software. The effect sizes included odds ratio (OR) and 95% confidence interval (CI). A random effects model was used for the pooled analysis for all the outcome measures, including 1-year distant control rate, 1-year local control rate, 1-year survival rate, and complication. The consistency was tested by using node-splitting analysis and inconsistency standard deviation. The convergence was estimated according to the Brooks-Gelman-Rubin method.A total of 12 literatures were included in this meta-analysis. WBRT + SRS showed higher 1-year distant control rate than SRS. WBRT + SRS was better for the 1-year local control rate than WBRT. SRS and WBRT + SRS had higher 1-year survival rate than the WBRT. In addition, there was no difference in complication among the three therapies.Comprehensively, WBRT + SRS might be the choice of treatment for brain metastasis.

Is the Internet gaming-addicted brain close to be in a pathological state?

PubMed

Park, Chang-Hyun; Chun, Ji-Won; Cho, Huyn; Jung, Young-Chul; Choi, Jihye; Kim, Dai Jin

2017-01-01

Internet gaming addiction (IGA) is becoming a common and widespread mental health concern. Although IGA induces a variety of negative psychosocial consequences, it is yet ambiguous whether the brain addicted to Internet gaming is considered to be in a pathological state. We investigated IGA-induced abnormalities of the brain specifically from the network perspective and qualitatively assessed whether the Internet gaming-addicted brain is in a state similar to the pathological brain. Topological properties of brain functional networks were examined by applying a graph-theoretical approach to analyzing functional magnetic resonance imaging data acquired during a resting state in 19 IGA adolescents and 20 age-matched healthy controls. We compared functional distance-based measures, global and local efficiency of resting state brain functional networks between the two groups to assess how the IGA subjects' brain was topologically altered from the controls' brain. The IGA subjects had severer impulsiveness and their brain functional networks showed higher global efficiency and lower local efficiency relative to the controls. These topological differences suggest that IGA induced brain functional networks to shift toward the random topological architecture, as exhibited in other pathological states. Furthermore, for the IGA subjects, the topological alterations were specifically attributable to interregional connections incident on the frontal region, and the degree of impulsiveness was associated with the topological alterations over the frontolimbic connections. The current findings lend support to the proposition that the Internet gaming-addicted brain could be in the state similar to pathological states in terms of topological characteristics of brain functional networks. © 2015 Society for the Study of Addiction.

Analyzing the dynamics of brain circuits with temperature: design and implementation of a miniature thermoelectric device.

PubMed

Aronov, Dmitriy; Fee, Michale S

2011-04-15

Traditional lesion or inactivation methods are useful for determining if a given brain area is involved in the generation of a behavior, but not for determining if circuit dynamics in that area control the timing of the behavior. In contrast, localized mild cooling or heating of a brain area alters the speed of neuronal and circuit dynamics and can reveal the role of that area in the control of timing. It has been shown that miniaturized solid-state heat pumps based on the Peltier effect can be useful for analyzing brain dynamics in small freely behaving animals (Long and Fee, 2008). Here we present a theoretical analysis of these devices and a procedure for optimizing their design. We describe the construction and implementation of one device for cooling surface brain areas, such as cortex, and another device for cooling deep brain regions. We also present measurements of the magnitude and localization of the brain temperature changes produced by these two devices. Copyright © 2011 Elsevier B.V. All rights reserved.

The Effects of Long-term Abacus Training on Topological Properties of Brain Functional Networks.

PubMed

Weng, Jian; Xie, Ye; Wang, Chunjie; Chen, Feiyan

2017-08-18

Previous studies in the field of abacus-based mental calculation (AMC) training have shown that this training has the potential to enhance a wide variety of cognitive abilities. It can also generate specific changes in brain structure and function. However, there is lack of studies investigating the impact of AMC training on the characteristics of brain networks. In this study, utilizing graph-based network analysis, we compared topological properties of brain functional networks between an AMC group and a matched control group. Relative to the control group, the AMC group exhibited higher nodal degrees in bilateral calcarine sulcus and increased local efficiency in bilateral superior occipital gyrus and right cuneus. The AMC group also showed higher nodal local efficiency in right fusiform gyrus, which was associated with better math ability. However, no relationship was significant in the control group. These findings provide evidence that long-term AMC training may improve information processing efficiency in visual-spatial related regions, which extend our understanding of training plasticity at the brain network level.

Assessment of Blood-Brain Barrier Permeability by Dynamic Contrast-Enhanced MRI in Transient Middle Cerebral Artery Occlusion Model after Localized Brain Cooling in Rats.

PubMed

Kim, Eun Soo; Lee, Seung-Koo; Kwon, Mi Jung; Lee, Phil Hye; Ju, Young-Su; Yoon, Dae Young; Kim, Hye Jeong; Lee, Kwan Seop

2016-01-01

The purpose of this study was to evaluate the effects of localized brain cooling on blood-brain barrier (BBB) permeability following transient middle cerebral artery occlusion (tMCAO) in rats, by using dynamic contrast-enhanced (DCE)-MRI. Thirty rats were divided into 3 groups of 10 rats each: control group, localized cold-saline (20℃) infusion group, and localized warm-saline (37℃) infusion group. The left middle cerebral artery (MCA) was occluded for 1 hour in anesthetized rats, followed by 3 hours of reperfusion. In the localized saline infusion group, 6 mL of cold or warm saline was infused through the hollow filament for 10 minutes after MCA occlusion. DCE-MRI investigations were performed after 3 hours and 24 hours of reperfusion. Pharmacokinetic parameters of the extended Tofts-Kety model were calculated for each DCE-MRI. In addition, rotarod testing was performed before tMCAO, and on days 1-9 after tMCAO. Myeloperoxidase (MPO) immunohisto-chemistry was performed to identify infiltrating neutrophils associated with the inflammatory response in the rat brain. Permeability parameters showed no statistical significance between cold and warm saline infusion groups after 3-hour reperfusion 0.09 ± 0.01 min(-1) vs. 0.07 ± 0.02 min(-1), p = 0.661 for K(trans); 0.30 ± 0.05 min(-1) vs. 0.37 ± 0.11 min(-1), p = 0.394 for kep, respectively. Behavioral testing revealed no significant difference among the three groups. However, the percentage of MPO-positive cells in the cold-saline group was significantly lower than those in the control and warm-saline groups (p < 0.05). Localized brain cooling (20℃) does not confer a benefit to inhibit the increase in BBB permeability that follows transient cerebral ischemia and reperfusion in an animal model, as compared with localized warm-saline (37℃) infusion group.

Assessment of Blood-Brain Barrier Permeability by Dynamic Contrast-Enhanced MRI in Transient Middle Cerebral Artery Occlusion Model after Localized Brain Cooling in Rats

PubMed Central

Kim, Eun Soo; Kwon, Mi Jung; Lee, Phil Hye; Ju, Young-Su; Yoon, Dae Young; Kim, Hye Jeong; Lee, Kwan Seop

2016-01-01

Objective The purpose of this study was to evaluate the effects of localized brain cooling on blood-brain barrier (BBB) permeability following transient middle cerebral artery occlusion (tMCAO) in rats, by using dynamic contrast-enhanced (DCE)-MRI. Materials and Methods Thirty rats were divided into 3 groups of 10 rats each: control group, localized cold-saline (20℃) infusion group, and localized warm-saline (37℃) infusion group. The left middle cerebral artery (MCA) was occluded for 1 hour in anesthetized rats, followed by 3 hours of reperfusion. In the localized saline infusion group, 6 mL of cold or warm saline was infused through the hollow filament for 10 minutes after MCA occlusion. DCE-MRI investigations were performed after 3 hours and 24 hours of reperfusion. Pharmacokinetic parameters of the extended Tofts-Kety model were calculated for each DCE-MRI. In addition, rotarod testing was performed before tMCAO, and on days 1-9 after tMCAO. Myeloperoxidase (MPO) immunohisto-chemistry was performed to identify infiltrating neutrophils associated with the inflammatory response in the rat brain. Results Permeability parameters showed no statistical significance between cold and warm saline infusion groups after 3-hour reperfusion 0.09 ± 0.01 min-1 vs. 0.07 ± 0.02 min-1, p = 0.661 for Ktrans; 0.30 ± 0.05 min-1 vs. 0.37 ± 0.11 min-1, p = 0.394 for kep, respectively. Behavioral testing revealed no significant difference among the three groups. However, the percentage of MPO-positive cells in the cold-saline group was significantly lower than those in the control and warm-saline groups (p < 0.05). Conclusion Localized brain cooling (20℃) does not confer a benefit to inhibit the increase in BBB permeability that follows transient cerebral ischemia and reperfusion in an animal model, as compared with localized warm-saline (37℃) infusion group. PMID:27587960

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

PubMed

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

2012-08-01

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

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

PubMed

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

2015-01-01

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

Cognitive performance in mid-stage Parkinson's disease: functional connectivity under chronic antiparkinson treatment.

PubMed

Vancea, Roxana; Simonyan, Kristina; Petracca, Maria; Brys, Miroslaw; Di Rocco, Alessandro; Ghilardi, Maria Felice; Inglese, Matilde

2017-09-23

Cognitive impairment in Parkinson's disease (PD) is related to the reorganization of brain topology. Although drug challenge studies have proven how levodopa treatment can modulate functional connectivity in brain circuits, the role of chronic dopaminergic therapy on cognitive status and functional connectivity has never been investigated. We sought to characterize brain functional topology in mid-stage PD patients under chronic antiparkinson treatment and explore the presence of correlation between reorganization of brain architecture and specific cognitive deficits. We explored networks topology and functional connectivity in 16 patients with PD and 16 matched controls through a graph theoretical analysis of resting state-functional MRI data, and evaluated the relationships between network metrics and cognitive performance. PD patients showed a preserved small-world network topology but a lower clustering coefficient in comparison with healthy controls. Locally, PD patients showed lower degree of connectivity and local efficiency in many hubs corresponding to functionally relevant areas. Four disconnected subnetworks were also identified in regions responsible for executive control, sensory-motor control and planning, motor coordination and visual elaboration. Executive functions and information processing speed were directly correlated with degree of connectivity and local efficiency in frontal, parietal and occipital areas. While functional reorganization appears in both motor and cognitive areas, the clinical expression of network imbalance seems to be partially compensated by the chronic levodopa treatment with regards to the motor but not to the cognitive performance. In a context of reduced network segregation, the presence of higher local efficiency in hubs regions correlates with a better cognitive performance.

Levodopa modulates small-world architecture of functional brain networks in Parkinson's disease.

PubMed

Berman, Brian D; Smucny, Jason; Wylie, Korey P; Shelton, Erika; Kronberg, Eugene; Leehey, Maureen; Tregellas, Jason R

2016-11-01

PD is associated with disrupted connectivity to a large number of distributed brain regions. How the disease alters the functional topological organization of the brain, however, remains poorly understood. Furthermore, how levodopa modulates network topology in PD is largely unknown. The objective of this study was to use resting-state functional MRI and graph theory to determine how small-world architecture is altered in PD and affected by levodopa administration. Twenty-one PD patients and 20 controls underwent functional MRI scanning. PD patients were scanned off medication and 1 hour after 200 mg levodopa. Imaging data were analyzed using 226 nodes comprising 10 intrinsic brain networks. Correlation matrices were generated for each subject and converted into cost-thresholded, binarized adjacency matrices. Cost-integrated whole-brain global and local efficiencies were compared across groups and tested for relationships with disease duration and severity. Data from 2 patients and 4 controls were excluded because of excess motion. Patients off medication showed no significant changes in global efficiency and overall local efficiency, but in a subnetwork analysis did show increased local efficiency in executive (P = 0.006) and salience (P = 0.018) networks. Levodopa significantly decreased local efficiency (P = 0.039) in patients except within the subcortical network, in which it significantly increased local efficiency (P = 0.007). Levodopa modulates global and local efficiency measures of small-world topology in PD, suggesting that degeneration of nigrostriatal neurons in PD may be associated with a large-scale network reorganization and that levodopa tends to normalize the disrupted network topology in PD. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Therapeutic Effect of Gamma Knife Radiosurgery for Multiple Brain Metastases

PubMed Central

Lee, Chul-Kyu; Lee, Sang Ryul; Cho, Jin Mo; Yang, Kyung Ah

2011-01-01

Objective The aim of this study is to evaluate the therapeutic effects of gamma knife radiosurgery (GKRS) in patients with multiple brain metastases and to investigate prognostic factors related to treatment outcome. Methods We retrospectively reviewed clinico-radiological and dosimetric data of 36 patients with 4-14 brain metastases who underwent GKRS for 264 lesions between August 2008 and April 2011. The most common primary tumor site was the lung (n=22), followed by breast (n=7). At GKRS, the median Karnofsky performance scale score was 90 and the mean tumor volume was 1.2 cc (0.002-12.6). The mean prescription dose of 17.8 Gy was delivered to the mean 61.1% isodose line. Among 264 metastases, 175 lesions were assessed for treatment response by at least one imaging follow-up. Results The overall median survival after GKRS was 9.1±1.7 months. Among various factors, primary tumor control was a significant prognostic factor (11.1±1.3 months vs. 3.3±2.4 months, p=0.031). The calculated local tumor control rate at 6 and 9 months after GKRS were 87.9% and 84.2%, respectively. Paddick's conformity index (>0.75) was significantly related to local tumor control. The actuarial peritumoral edema reduction rate was 22.4% at 6 months. Conclusion According to our results, GKRS can provide beneficial effect for the patients with multiple (4 or more) brain metastases, when systemic cancer is controlled. And, careful dosimetry is essential for local tumor control. Therefore, GKRS can be considered as one of the treatment modalities for multiple brain metastase. PMID:22102945

Control of brain development and homeostasis by local and systemic insulin signalling.

PubMed

Liu, J; Spéder, P; Brand, A H

2014-09-01

Insulin and insulin-like growth factors (IGFs) are important regulators of growth and metabolism. In both vertebrates and invertebrates, insulin/IGFs are made available to various organs, including the brain, through two routes: the circulating systemic insulin/IGFs act on distant organs via endocrine signalling, whereas insulin/IGF ligands released by local tissues act in a paracrine or autocrine fashion. Although the mechanisms governing the secretion and action of systemic insulin/IGF have been the focus of extensive investigation, the significance of locally derived insulin/IGF has only more recently come to the fore. Local insulin/IGF signalling is particularly important for the development and homeostasis of the central nervous system, which is insulated from the systemic environment by the blood-brain barrier. Local insulin/IGF signalling from glial cells, the blood-brain barrier and the cerebrospinal fluid has emerged as a potent regulator of neurogenesis. This review will address the main sources of local insulin/IGF and how they affect neurogenesis during development. In addition, we describe how local insulin/IGF signalling couples neural stem cell proliferation with systemic energy state in Drosophila and in mammals. © 2014 John Wiley & Sons Ltd.

Spatio-temporal neural stem cell behavior that leads to both perfect and imperfect structural brain regeneration in adult newts.

PubMed

Urata, Yuko; Yamashita, Wataru; Inoue, Takeshi; Agata, Kiyokazu

2018-06-14

Adult newts can regenerate large parts of their brain from adult neural stem cells (NSCs), but how adult NSCs reorganize brain structures during regeneration remains unclear. In development, elaborate brain structures are produced under broadly coordinated regulations of embryonic NSCs in the neural tube, whereas brain regeneration entails exquisite control of the reestablishment of certain brain parts, suggesting a yet-unknown mechanism directs NSCs upon partial brain excision. Here we report that upon one-quarter excision of the adult newt ( Pleurodeles waltl ) mesencephalon, active participation of local NSCs around specific brain subregions' boundaries leads to some imperfect and some perfect brain regeneration along an individual's rostrocaudal axis. Regeneration phenotypes depend on how the wound closing occurs using local NSCs, and perfect regeneration replicates development-like processes but takes more than one year. Our findings indicate that newt brain regeneration is supported by modularity of boundary-domain NSCs with self-organizing ability in neighboring fields. © 2018. Published by The Company of Biologists Ltd.

Gamma Knife Radiosurgery for the Treatment of Cystic Cerebral Metastases

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

Ebinu, Julius O.; Lwu, Shelly; Monsalves, Eric

Purpose: To assess the role of Gamma Knife radiosurgery (GKRS) in the treatment of nonsurgical cystic brain metastasis, and to determine predictors of response to GKRS. Methods: We reviewed a prospectively maintained database of brain metastases patients treated at our institution between 2006 and 2010. All lesions with a cystic component were identified, and volumetric analysis was done to measure percentage of cystic volume on day of treatment and consecutive follow-up MRI scans. Clinical, radiologic, and dosimetry parameters were reviewed to establish the overall response of cystic metastases to GKRS as well as identify potential predictive factors of response. Results:more » A total of 111 lesions in 73 patients were analyzed; 57% of lesions received prior whole-brain radiation therapy (WBRT). Lung carcinoma was the primary cancer in 51% of patients, 10% breast, 10% colorectal, 4% melanoma, and 26% other. Fifty-seven percent of the patients were recursive partitioning analysis class 1, the remainder class 2. Mean target volume was 3.3 mL (range, 0.1-23 mL). Median prescription dose was 21 Gy (range, 15-24 Gy). Local control rates were 91%, 63%, and 37% at 6, 12, and 18 months, respectively. Local control was improved in lung primary and worse in patients with prior WBRT (univariate). Only lung primary predicted local control in multivariate analysis, whereas age and tumor volume did not. Lesions with a large cystic component did not show a poorer response compared with those with a small cystic component. Conclusions: This study supports the use of GKRS in the management of nonsurgical cystic metastases, despite a traditionally perceived poorer response. Our local control rates are comparable to a matched cohort of noncystic brain metastases, and therefore the presence of a large cystic component should not deter the use of GKRS. Predictors of response included tumor subtype. Prior WBRT decreased effectiveness of SRS for local control rates.« less

Stereotactic radiosurgery of brain metastases.

PubMed

Specht, Hanno M; Combs, Stephanie E

2016-09-01

Brain metastases are a common problem in solid malignancies and still represent a major cause of morbidity and mortality. With the ongoing improvement in systemic therapies, the expectations on the efficacy of brain metastases directed treatment options are growing. As local therapies against brain metastases continue to evolve, treatment patterns have shifted from a palliative "one-treatment-fits-all" towards an individualized, patient adapted approach. In this article we review the evidence for stereotactic radiation treatment based on the current literature. Stereotactic radiosurgery (SRS) as a local high precision approach for the primary treatment of asymptomatic brain metastases has gained wide acceptance. It leads to lasting tumor control with only minor side effects compared to whole brain radiotherapy, since there is only little dose delivered to the healthy brain. The same holds true for hypofractionated stereotactic radiotherapy (HFSRT) for large metastases or for lesions close to organs at risk (e.g. the brainstem). New treatment indications such as neoadjuvant SRS followed by surgical resection or postoperative local therapy to the resection cavity show promising data and are also highlighted in this manuscript. With the evolution of local treatment options, optimal patient selection becomes more and more crucial. This article aims to aid decision making by outlining prognostic factors, treatment techniques and indications and common dose prescriptions.

Increased resting-state brain entropy in Alzheimer's disease.

PubMed

Xue, Shao-Wei; Guo, Yonghu

2018-03-07

Entropy analysis of resting-state functional MRI (R-fMRI) is a novel approach to characterize brain temporal dynamics and facilitates the identification of abnormal brain activity caused by several disease conditions. However, Alzheimer's disease (AD)-related brain entropy mapping based on R-fMRI has not been assessed. Here, we measured the sample entropy and voxel-wise connectivity of the network degree centrality (DC) of the intrinsic brain activity acquired by R-fMRI in 26 patients with AD and 26 healthy controls. Compared with the controls, AD patients showed increased entropy in the middle temporal gyrus and the precentral gyrus and also showed decreased DC in the precuneus. Moreover, the magnitude of the negative correlation between local brain activity (entropy) and network connectivity (DC) was increased in AD patients in comparison with healthy controls. These findings provide new evidence on AD-related brain entropy alterations.

Graph analysis of functional brain networks for cognitive control of action in traumatic brain injury.

PubMed

Caeyenberghs, Karen; Leemans, Alexander; Heitger, Marcus H; Leunissen, Inge; Dhollander, Thijs; Sunaert, Stefan; Dupont, Patrick; Swinnen, Stephan P

2012-04-01

Patients with traumatic brain injury show clear impairments in behavioural flexibility and inhibition that often persist beyond the time of injury, affecting independent living and psychosocial functioning. Functional magnetic resonance imaging studies have shown that patients with traumatic brain injury typically show increased and more broadly dispersed frontal and parietal activity during performance of cognitive control tasks. We constructed binary and weighted functional networks and calculated their topological properties using a graph theoretical approach. Twenty-three adults with traumatic brain injury and 26 age-matched controls were instructed to switch between coordination modes while making spatially and temporally coupled circular motions with joysticks during event-related functional magnetic resonance imaging. Results demonstrated that switching performance was significantly lower in patients with traumatic brain injury compared with control subjects. Furthermore, although brain networks of both groups exhibited economical small-world topology, altered functional connectivity was demonstrated in patients with traumatic brain injury. In particular, compared with controls, patients with traumatic brain injury showed increased connectivity degree and strength, and higher values of local efficiency, suggesting adaptive mechanisms in this group. Finally, the degree of increased connectivity was significantly correlated with poorer switching task performance and more severe brain injury. We conclude that analysing the functional brain network connectivity provides new insights into understanding cognitive control changes following brain injury.

Modeling Brain Dynamics in Brain Tumor Patients Using the Virtual Brain.

PubMed

Aerts, Hannelore; Schirner, Michael; Jeurissen, Ben; Van Roost, Dirk; Achten, Eric; Ritter, Petra; Marinazzo, Daniele

2018-01-01

Presurgical planning for brain tumor resection aims at delineating eloquent tissue in the vicinity of the lesion to spare during surgery. To this end, noninvasive neuroimaging techniques such as functional MRI and diffusion-weighted imaging fiber tracking are currently employed. However, taking into account this information is often still insufficient, as the complex nonlinear dynamics of the brain impede straightforward prediction of functional outcome after surgical intervention. Large-scale brain network modeling carries the potential to bridge this gap by integrating neuroimaging data with biophysically based models to predict collective brain dynamics. As a first step in this direction, an appropriate computational model has to be selected, after which suitable model parameter values have to be determined. To this end, we simulated large-scale brain dynamics in 25 human brain tumor patients and 11 human control participants using The Virtual Brain, an open-source neuroinformatics platform. Local and global model parameters of the Reduced Wong-Wang model were individually optimized and compared between brain tumor patients and control subjects. In addition, the relationship between model parameters and structural network topology and cognitive performance was assessed. Results showed (1) significantly improved prediction accuracy of individual functional connectivity when using individually optimized model parameters; (2) local model parameters that can differentiate between regions directly affected by a tumor, regions distant from a tumor, and regions in a healthy brain; and (3) interesting associations between individually optimized model parameters and structural network topology and cognitive performance.

Metabolic Brain Network Analysis of Hypothyroidism Symptom Based on [18F]FDG-PET of Rats.

PubMed

Wan, Hongkai; Tan, Ziyu; Zheng, Qiang; Yu, Jing

2018-03-12

Recent researches have demonstrated the value of using 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) positron emission tomography (PET) imaging to reveal the hypothyroidism-related damages in local brain regions. However, the influence of hypothyroidism on the entire brain network is barely studied. This study focuses on the application of graph theory on analyzing functional brain networks of the hypothyroidism symptom. For both the hypothyroidism and the control groups of Wistar rats, the functional brain networks were constructed by thresholding the glucose metabolism correlation matrices of 58 brain regions. The network topological properties (including the small-world properties and the nodal centralities) were calculated and compared between the two groups. We found that the rat brains, like human brains, have typical properties of the small-world network in both the hypothyroidism and the control groups. However, the hypothyroidism group demonstrated lower global efficiency and decreased local cliquishness of the brain network, indicating hypothyroidism-related impairment to the brain network. The hypothyroidism group also has decreased nodal centrality in the left posterior hippocampus, the right hypothalamus, pituitary, pons, and medulla. This observation accorded with the hypothyroidism-related functional disorder of hypothalamus-pituitary-thyroid (HPT) feedback regulation mechanism. Our research quantitatively confirms that hypothyroidism hampers brain cognitive function by causing impairment to the brain network of glucose metabolism. This study reveals the feasibility and validity of applying graph theory method to preclinical [ 18 F]FDG-PET images and facilitates future study on human subjects.

Brain region and epilepsy-associated differences in inflammatory mediator levels in medically refractory mesial temporal lobe epilepsy.

PubMed

Strauss, Kenneth I; Elisevich, Kost V

2016-10-13

Epilepsy patients have distinct immune/inflammatory cell profiles and inflammatory mediator levels in the blood. Although the neural origin of inflammatory cells and mediators has been implied, few studies have measured these inflammatory components in the human brain itself. This study examines the brain levels of chemokines (8), cytokines (14), and vascular injury mediators (3) suspected of being altered in epilepsy. Soluble protein extracts of fresh frozen resected hippocampus, entorhinal cortex, and temporal cortex from 58 medically refractory mesial temporal lobe epilepsy subjects and 4 nonepileptic neurosurgical subjects were assayed for 25 inflammation-related mediators using ultrasensitive low-density arrays. Brain mediator levels were compared between regions and between epileptic and nonepileptic cases, showing a number of regional and possible epilepsy-associated differences. Eotaxin, interferon-γ, interleukin (IL)-2, IL-4, IL-12 p70, IL-17A, tumor necrosis factor-α, and intercellular adhesion molecule (ICAM)-1 levels were highest in the hippocampus, the presumptive site of epileptogenesis. Surprisingly, IL-1β and IL-1α were lowest in the hippocampus, compared to cortical regions. In the temporal cortex, IL-1β, IL-8, and MIP-1α levels were highest, compared to the entorhinal cortex and the hippocampus. The most pronounced epilepsy-associated differences were decreased levels of eotaxin, IL-1β, C-reactive protein, and vascular cell adhesion molecule (VCAM)-1 and increased IL-12 p70 levels. Caution must be used in interpreting these results, however, because nonepileptic subjects were emergent neurosurgical cases, not a control group. Correlation analyses of each mediator in each brain region yielded valuable insights into the regulation of these mediator levels in the brain. Over 70 % of the associations identified were between different mediators in a single brain region, providing support for local control of mediator levels. Correlations of different mediators in different brain regions suggested more distributed control mechanisms, particularly in the hippocampus. Interestingly, only four mediators showed robust correlations between the brain regions, yet levels in three of these were significantly different between regions, indicating both global and local controls for these mediators. Both brain region-specific and epilepsy-associated changes in inflammation-related mediators were detected. Correlations in mediator levels within and between brain regions indicated local and global regulation, respectively. The hippocampus showed the majority of interregional associations, suggesting a focus of inflammatory control between these regions.

Discrimination surfaces with application to region-specific brain asymmetry analysis.

PubMed

Martos, Gabriel; de Carvalho, Miguel

2018-05-20

Discrimination surfaces are here introduced as a diagnostic tool for localizing brain regions where discrimination between diseased and nondiseased participants is higher. To estimate discrimination surfaces, we introduce a Mann-Whitney type of statistic for random fields and present large-sample results characterizing its asymptotic behavior. Simulation results demonstrate that our estimator accurately recovers the true surface and corresponding interval of maximal discrimination. The empirical analysis suggests that in the anterior region of the brain, schizophrenic patients tend to present lower local asymmetry scores in comparison with participants in the control group. Copyright © 2018 John Wiley & Sons, Ltd.

Delivery of local therapeutics to the brain: working toward advancing treatment for malignant gliomas

PubMed Central

Chaichana, Kaisorn L; Pinheiro, Leon; Brem, Henry

2015-01-01

Malignant gliomas, including glioblastoma and anaplastic astrocytomas, are characterized by their propensity to invade surrounding brain parenchyma, making curative resection difficult. These tumors typically recur within two centimeters of the resection cavity even after gross total removal. As a result, there has been an emphasis on developing therapeutics aimed at achieving local disease control. In this review, we will summarize the current developments in the delivery of local therapeutics, namely direct injection, convection-enhanced delivery and implantation of drug-loaded polymers, as well as the application of these therapeutics in future methods including microchip drug delivery and local gene therapy. PMID:25853310

Delivery of local therapeutics to the brain: working toward advancing treatment for malignant gliomas.

PubMed

Chaichana, Kaisorn L; Pinheiro, Leon; Brem, Henry

2015-03-01

Malignant gliomas, including glioblastoma and anaplastic astrocytomas, are characterized by their propensity to invade surrounding brain parenchyma, making curative resection difficult. These tumors typically recur within two centimeters of the resection cavity even after gross total removal. As a result, there has been an emphasis on developing therapeutics aimed at achieving local disease control. In this review, we will summarize the current developments in the delivery of local therapeutics, namely direct injection, convection-enhanced delivery and implantation of drug-loaded polymers, as well as the application of these therapeutics in future methods including microchip drug delivery and local gene therapy.

Increased densities of monocarboxylate transport protein MCT1 after chronic administration of nicotine in rat brain.

PubMed

Canis, Martin; Mack, Brigitte; Gires, Olivier; Maurer, Martin H; Kuschinsky, Wolfgang; Duembgen, Lutz; Duelli, Roman

2009-08-01

Chronic administration of nicotine is followed by a general stimulation of brain metabolism that results in a distinct increase of glucose transport protein densities for Glut1 and Glu3, and local cerebral glucose utilization (LCGU). This increase of LCGU might be paralleled by an enhanced production of lactate. Therefore, the question arose as to whether chronic nicotine infusion is accompanied by increased local densities of monocarboxylate transporter MCT1 in the brain. Secondly, we inquired whether LCGU might be correlated with local densities of MCT1 during normal conditions and after chronic nicotine infusion. Nicotine was given subcutaneously for 1 week by osmotic mini-pumps and local densities of MCT1 were measured by immunoautoradiographic methods in cryosections of rat brains. MCT1 density was significantly increased in 21 of 32 brain structures investigated (median increase 15.0+/-3.6%). Immunohistochemical stainings of these substructures revealed an over-expression of MCT1 within endothelial cells and astrocytes of treated animals. A comparison of 23 MCT1 densities with LCGU measured in the same structures in a previous study revealed a partial correlation between both parameters under control conditions and after chronic nicotine infusion. 10 out of 23 brain areas, which showed a significant increase of MCT1 density due to chronic nicotine infusion, also showed a significant increase of LCGU. In summary, our data show that chronic nicotine infusion induces a moderate increase of local and global density of MCT1 in defined brain structures. However, in terms of brain topologies and substructures this phenomenon did partially match with increased LCGU. It is concluded that MCT1 transporters were upregulated during chronic nicotine infusion at the level of brain substructures and, at least partially, independently of LCGU.

Aberrant Global and Regional Topological Organization of the Fractional Anisotropy-weighted Brain Structural Networks in Major Depressive Disorder

PubMed Central

Chen, Jian-Huai; Yao, Zhi-Jian; Qin, Jiao-Long; Yan, Rui; Hua, Ling-Ling; Lu, Qing

2016-01-01

Background: Most previous neuroimaging studies have focused on the structural and functional abnormalities of local brain regions in major depressive disorder (MDD). Moreover, the exactly topological organization of networks underlying MDD remains unclear. This study examined the aberrant global and regional topological patterns of the brain white matter networks in MDD patients. Methods: The diffusion tensor imaging data were obtained from 27 patients with MDD and 40 healthy controls. The brain fractional anisotropy-weighted structural networks were constructed, and the global network and regional nodal metrics of the networks were explored by the complex network theory. Results: Compared with the healthy controls, the brain structural network of MDD patients showed an intact small-world topology, but significantly abnormal global network topological organization and regional nodal characteristic of the network in MDD were found. Our findings also indicated that the brain structural networks in MDD patients become a less strongly integrated network with a reduced central role of some key brain regions. Conclusions: All these resulted in a less optimal topological organization of networks underlying MDD patients, including an impaired capability of local information processing, reduced centrality of some brain regions and limited capacity to integrate information across different regions. Thus, these global network and regional node-level aberrations might contribute to understanding the pathogenesis of MDD from the view of the brain network. PMID:26960371

Annexin A1 Complex Mediates Oxytocin Vesicle Transport

PubMed Central

Makani, Vishruti; Sultana, Rukhsana; Sie, Khin Sander; Orjiako, Doris; Tatangelo, Marco; Dowling, Abigail; Cai, Jian; Pierce, William; Butterfield, D. Allan; Hill, Jennifer; Park, Joshua

2013-01-01

Oxytocin is a major neuropeptide that modulates the brain functions involved in social behavior and interaction. Despite of the importance of oxytocin for neural control of social behavior, little is known about the molecular mechanism(s) by which oxytocin secretion in the brain is regulated. Pro-oxytocin is synthesized in the cell bodies of hypothalamic neurons in the supraoptic and paraventricular nuclei and processed to a 9-amino-acid mature form during post-Golgi transport to the secretion sites at the axon terminals and somatodendritic regions. Oxytocin secreted from the somatodendritic regions diffuses throughout the hypothalamus and its neighboring brain regions. Some oxytocin-positive axons innervate and secrete oxytocin to the brain regions distal to the hypothalamus. Brain oxytocin binds to its receptors in the brain regions involved in social behavior. Oxytocin is also secreted from the axon terminal at the posterior pituitary gland into the blood circulation. We have discovered a new molecular complex consisting of annexin A1 (ANXA1), A-kinase anchor protein 150 (AKAP150), and microtubule motor, that controls the distribution of oxytocin vesicles between the axon and the cell body in a protein kinase A (PKA)- and protein kinase C (PKC)-sensitive manner. ANXA1 showed significant co-localization with oxytocin vesicles. Activation of PKA enhanced the association of kinesin-2 with ANXA1, thus increasing the axon-localization of oxytocin vesicles. Conversely, activation of PKC decreased the binding of kinesin-2 to ANXA1, thus attenuating the axon-localization of oxytocin vesicles. Our study suggests that ANXA1 complex coordinates the actions of PKA and PKC to control the distribution of oxytocin vesicles between the axon and the cell body. PMID:24118254

Reduced integration and improved segregation of functional brain networks in Alzheimer’s disease

NASA Astrophysics Data System (ADS)

Kabbara, A.; Eid, H.; El Falou, W.; Khalil, M.; Wendling, F.; Hassan, M.

2018-04-01

Objective. Emerging evidence shows that cognitive deficits in Alzheimer’s disease (AD) are associated with disruptions in brain functional connectivity. Thus, the identification of alterations in AD functional networks has become a topic of increasing interest. However, to what extent AD induces disruption of the balance of local and global information processing in the human brain remains elusive. The main objective of this study is to explore the dynamic topological changes of AD networks in terms of brain network segregation and integration. Approach. We used electroencephalography (EEG) data recorded from 20 participants (10 AD patients and 10 healthy controls) during resting state. Functional brain networks were reconstructed using EEG source connectivity computed in different frequency bands. Graph theoretical analyses were performed assess differences between both groups. Main results. Results revealed that AD networks, compared to networks of age-matched healthy controls, are characterized by lower global information processing (integration) and higher local information processing (segregation). Results showed also significant correlation between the alterations in the AD patients’ functional brain networks and their cognitive scores. Significance. These findings may contribute to the development of EEG network-based test that could strengthen results obtained from currently-used neurophysiological tests in neurodegenerative diseases.

Reduced integration and improved segregation of functional brain networks in Alzheimer's disease.

PubMed

Kabbara, A; Eid, H; El Falou, W; Khalil, M; Wendling, F; Hassan, M

2018-04-01

Emerging evidence shows that cognitive deficits in Alzheimer's disease (AD) are associated with disruptions in brain functional connectivity. Thus, the identification of alterations in AD functional networks has become a topic of increasing interest. However, to what extent AD induces disruption of the balance of local and global information processing in the human brain remains elusive. The main objective of this study is to explore the dynamic topological changes of AD networks in terms of brain network segregation and integration. We used electroencephalography (EEG) data recorded from 20 participants (10 AD patients and 10 healthy controls) during resting state. Functional brain networks were reconstructed using EEG source connectivity computed in different frequency bands. Graph theoretical analyses were performed assess differences between both groups. Results revealed that AD networks, compared to networks of age-matched healthy controls, are characterized by lower global information processing (integration) and higher local information processing (segregation). Results showed also significant correlation between the alterations in the AD patients' functional brain networks and their cognitive scores. These findings may contribute to the development of EEG network-based test that could strengthen results obtained from currently-used neurophysiological tests in neurodegenerative diseases.

Classification and localization of early-stage Alzheimer's disease in magnetic resonance images using a patch-based classifier ensemble.

PubMed

Simões, Rita; van Cappellen van Walsum, Anne-Marie; Slump, Cornelis H

2014-09-01

Classification methods have been proposed to detect Alzheimer’s disease (AD) using magnetic resonance images. Most rely on features such as the shape/volume of brain structures that need to be defined a priori. In this work, we propose a method that does not require either the segmentation of specific brain regions or the nonlinear alignment to a template. Besides classification, we also analyze which brain regions are discriminative between a group of normal controls and a group of AD patients. We perform 3D texture analysis using Local Binary Patterns computed at local image patches in the whole brain, combined in a classifier ensemble.We evaluate our method in a publicly available database including very mild-to-mild AD subjects and healthy elderly controls. For the subject cohort including only mild AD subjects, the best results are obtained using a combination of large (30×30×30 and 40×40×40 voxels) patches. A spatial analysis on the best performing patches shows that these are located in the medial-temporal lobe and in the periventricular regions. When very mild AD subjects are included in the dataset, the small (10×10×10 voxels) patches perform best, with the most discriminative ones being located near the left hippocampus. We show that our method is able not only to perform accurate classification, but also to localize dis-criminative brain regions, which are in accordance with the medical literature. This is achieved without the need to segment-specific brain structures and without performing nonlinear registration to a template, indicating that the method may be suitable for a clinical implementation that can help to diagnose AD at an earlier stage.

Theranostic 3-Dimensional nano brain-implant for prolonged and localized treatment of recurrent glioma

NASA Astrophysics Data System (ADS)

Ramachandran, Ranjith; Junnuthula, Vijayabhaskar Reddy; Gowd, G. Siddaramana; Ashokan, Anusha; Thomas, John; Peethambaran, Reshmi; Thomas, Anoop; Unni, Ayalur Kodakara Kochugovindan; Panikar, Dilip; Nair, Shantikumar V.; Koyakutty, Manzoor

2017-03-01

Localized and controlled delivery of chemotherapeutics directly in brain-tumor for prolonged periods may radically improve the prognosis of recurrent glioblastoma. Here, we report a unique method of nanofiber by fiber controlled delivery of anti-cancer drug, Temozolomide, in orthotopic brain-tumor for one month using flexible polymeric nano-implant. A library of drug loaded (20 wt%) electrospun nanofiber of PLGA-PLA-PCL blends with distinct in vivo brain-release kinetics (hours to months) were numerically selected and a single nano-implant was formed by co-electrospinning of nano-fiber such that different set of fibres releases the drug for a specific periods from days to months by fiber-by-fiber switching. Orthotopic rat glioma implanted wafers showed constant drug release (116.6 μg/day) with negligible leakage into the peripheral blood (<100 ng) rendering ~1000 fold differential drug dosage in tumor versus peripheral blood. Most importantly, implant with one month release profile resulted in long-term (>4 month) survival of 85.7% animals whereas 07 day releasing implant showed tumor recurrence in 54.6% animals, rendering a median survival of only 74 days. In effect, we show that highly controlled drug delivery is possible for prolonged periods in orthotopic brain-tumor using combinatorial nanofibre libraries of bulk-eroding polymers, thereby controlling glioma recurrence.

Aberrant topological organization of the functional brain network associated with prior overt hepatic encephalopathy in cirrhotic patients.

PubMed

Chen, Hua-Jun; Chen, Qiu-Feng; Yang, Zhe-Ting; Shi, Hai-Bin

2018-05-30

A higher risk of cognitive impairments has been found after an overt hepatic encephalopathy (OHE) episode in cirrhotic patients. We investigated the effect of prior OHE episodes on the topological organization of the functional brain network and its association with the relevant cognitive impairments. Resting-state functional MRI data were acquired from 41 cirrhotic patients (19 with prior OHE (Prior-OHE) and 22 without (Non-Prior-OHE)) and 21 healthy controls (HC). A Psychometric Hepatic Encephalopathy Score (PHES) assessed cognition. The whole-brain functional network was constructed by thresholding functional correlation matrices of 90 brain regions (derived from the Automated Anatomic Labeling atlas). The topological properties of the brain network, including small-worldness, network efficiency, and nodal efficiency, were examined using graph theory-based analysis. Globally, the Prior-OHE group had a significantly decreased clustering coefficient and local efficiency, compared with the controls. Locally, the nodal efficiency in the bilateral medial superior frontal gyrus and the right postcentral gyrus decreased in the Prior-OHE group, while the nodal efficiency in the bilateral anterior cingulate/paracingulate gyri and right superior parietal gyrus increased in the Prior-OHE group. The alterations of global and regional network parameters progressed from Non-Prior-OHE to Prior-OHE and the clustering coefficient and local efficiency values were significantly correlated with PHES results. In conclusion, cirrhosis leads to the reduction of brain functional network efficiency, which could be aggravated by a prior OHE episode. Aberrant topological organization of the functional brain network may contribute to a higher risk of cognitive impairments in Prior-OHE patients.

Dipole source localization of event-related brain activity indicative of an early visual selective attention deficit in ADHD children.

PubMed

Jonkman, L M; Kenemans, J L; Kemner, C; Verbaten, M N; van Engeland, H

2004-07-01

This study was aimed at investigating whether attention-deficit hyperactivity disorder (ADHD) children suffer from specific early selective attention deficits in the visual modality with the aid of event-related brain potentials (ERPs). Furthermore, brain source localization was applied to identify brain areas underlying possible deficits in selective visual processing in ADHD children. A two-channel visual color selection task was administered to 18 ADHD and 18 control subjects in the age range of 7-13 years and ERP activity was derived from 30 electrodes. ADHD children exhibited lower perceptual sensitivity scores resulting in poorer target selection. The ERP data suggested an early selective-attention deficit as manifested in smaller frontal positive activity (frontal selection positivity; FSP) in ADHD children around 200 ms whereas later occipital and fronto-central negative activity (OSN and N2b; 200-400 ms latency) appeared to be unaffected. Source localization explained the FSP by posterior-medial equivalent dipoles in control subjects, which may reflect the contribution of numerous surrounding areas. ADHD children have problems with selective visual processing that might be caused by a specific early filtering deficit (absent FSP) occurring around 200 ms. The neural sources underlying these problems have to be further identified. Source localization also suggested abnormalities in the 200-400 ms time range, pertaining to the distribution of attention-modulated activity in lateral frontal areas.

Postoperative Stereotactic Radiosurgery Without Whole-Brain Radiation Therapy for Brain Metastases: Potential Role of Preoperative Tumor Size

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

Hartford, Alan C., E-mail: Alan.C.Hartford@Hitchcock.org; Paravati, Anthony J.; Spire, William J.

2013-03-01

Purpose: Radiation therapy following resection of a brain metastasis increases the probability of disease control at the surgical site. We analyzed our experience with postoperative stereotactic radiosurgery (SRS) as an alternative to whole-brain radiotherapy (WBRT), with an emphasis on identifying factors that might predict intracranial disease control and overall survival (OS). Methods and Materials: We retrospectively reviewed all patients through December 2008, who, after surgical resection, underwent SRS to the tumor bed, deferring WBRT. Multiple factors were analyzed for time to intracranial recurrence (ICR), whether local recurrence (LR) at the surgical bed or “distant” recurrence (DR) in the brain, formore » time to WBRT, and for OS. Results: A total of 49 lesions in 47 patients were treated with postoperative SRS. With median follow-up of 9.3 months (range, 1.1-61.4 months), local control rates at the resection cavity were 85.5% at 1 year and 66.9% at 2 years. OS rates at 1 and 2 years were 52.5% and 31.7%, respectively. On univariate analysis (preoperative) tumors larger than 3.0 cm exhibited a significantly shorter time to LR. At a cutoff of 2.0 cm, larger tumors resulted in significantly shorter times not only for LR but also for DR, ICR, and salvage WBRT. While multivariate Cox regressions showed preoperative size to be significant for times to DR, ICR, and WBRT, in similar multivariate analysis for OS, only the graded prognostic assessment proved to be significant. However, the number of intracranial metastases at presentation was not significantly associated with OS nor with other outcome variables. Conclusions: Larger tumor size was associated with shorter time to recurrence and with shorter time to salvage WBRT; however, larger tumors were not associated with decrements in OS, suggesting successful salvage. SRS to the tumor bed without WBRT is an effective treatment for resected brain metastases, achieving local control particularly for tumors up to 3.0 cm diameter.« less

Outcome Evaluation of HER2 Breast Cancer Patients with Limited Brain Metastasis.

PubMed

Pessina, Federico; Navarria, Pierina; Cozzi, Luca; Franceschini, Davide; Tomatis, Stefano; Clerici, Elena; Ascolese, Anna Maria; DE Rose, Fiorenza; Bello, Lorenzo; Masci, Giovanna; Santoro, Armando; Scorsetti, Marta

2017-12-01

To appraise the outcome of limited brain metastasis (BMs) from HER2 breast cancer. The study cohort included sixty-six patients Treatments consisted of surgery followed by radiotherapy (RT), or radiosurgery (SRS/HSRS) or whole brain radiotherapy (WBRT). Surgery followed by RT was performed in 25.8% of patients, SRS/HSRS alone in 48.5%, and WBRT alone in 25.7%. The median follow-up time was 23.4 months and 32.5 months for alive patients. Local recurrence occurred in 16 (24.2%) patients. The median, 1-, 2-, 3-year local control were (median not reached=nr), 87.5%, 71.2%, and 63.0%. The median 1-, 2-, 3-year overall survival were 30.7 months (95%CI: 18.9-42.6 months), 78.5%, 57.4%, 43.3%. Karnofsky Performance Scale (KPS), number of BMs, local treatment performed, the presence of extracranial (EC) metastases at the time of BMs diagnosis, and the administration of trastuzumab affected survival. HER2BC patients with good performance status, controlled EC disease and single BM had better outcome. In this long-term survivor patients, local BMs treatment can affect survival. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Altered local spontaneous activity in frontal lobe epilepsy: a resting-state functional magnetic resonance imaging study.

PubMed

Dong, Li; Li, Hechun; He, Zhongqiong; Jiang, Sisi; Klugah-Brown, Benjamin; Chen, Lin; Wang, Pu; Tan, Song; Luo, Cheng; Yao, Dezhong

2016-11-01

The purpose of this study was to investigate the local spatiotemporal consistency of spontaneous brain activity in patients with frontal lobe epilepsy (FLE). Eyes closed resting-state functional magnetic resonance imaging (fMRI) data were collected from 19 FLE patients and 19 age- and gender-matched healthy controls. A novel measure, named FOur-dimensional (spatiotemporal) Consistency of local neural Activities (FOCA) was used to assess the spatiotemporal consistency of local spontaneous activity (emphasizing both local temporal homogeneity and regional stability of brain activity states). Then, two-sample t test was performed to detect the FOCA differences between two groups. Partial correlations between the FOCA values and durations of epilepsy were further analyzed. Compared with controls, FLE patients demonstrated increased FOCA in distant brain regions including the frontal and parietal cortices, as well as the basal ganglia. The decreased FOCA was located in the temporal cortex, posterior default model regions, and cerebellum. In addition, the FOCA measure was linked to the duration of epilepsy in basal ganglia. Our study suggested that alterations of local spontaneous activity in frontoparietal cortex and basal ganglia was associated with the pathophysiology of FLE; and the abnormality in frontal and default model regions might account for the potential cognitive impairment in FLE. We also presumed that the FOCA measure had potential to provide important insights into understanding epilepsy such as FLE.

Clinical outcomes of patients treated with a second course of stereotactic radiosurgery for locally or regionally recurrent brain metastases after prior stereotactic radiosurgery.

PubMed

Kim, Daniel H; Schultheiss, Timothy E; Radany, Eric H; Badie, Behnam; Pezner, Richard D

2013-10-01

Patients with metastatic disease are living longer and may be confronted with locally or regionally recurrent brain metastases (BM) after prior stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT). This study analyzes outcomes in patients without prior whole brain radiotherapy (WBRT) who were treated with a second course of SRS/FSRT for locally or regionally recurrent BM. We identified 32 patients at our institution who were treated with a second course of SRS/FSRT after initial SRS/FSRT for newly diagnosed BM. We report clinical outcomes including local control, survival, and toxicities. Control rates and survival were calculated using Kaplan-Meier analysis and the multivariate proportional hazards model. The Kaplan-Meier estimate of local control at 6 months was 77 % for targets treated by a second course of SRS/FSRT with 11/71 (15 %) targets experiencing local failure. Multivariate analysis shows that upon re-treatment, local recurrences were more likely to fail than regional recurrences (OR 8.8, p = 0.02). Median survival for all patients from first SRS/FSRT was 14.6 months (5.3-72.2 months) and 7.9 months (0.7-61.1 months) from second SRS/FSRT. Thirty-eight percent of patients ultimately received WBRT as salvage therapy after the second SRS/FSRT. Seventy-one percent of patients died without active neurologic symptoms. The present study demonstrates that the majority of patients who progress after SRS/FSRT for newly diagnosed BM are candidates for salvage SRS/FSRT. By reserving WBRT for later salvage, we believe that a significant proportion of patients can avoid WBRT all together, thus putting fewer patients at risk for neurocognitive toxicity.

Postoperative stereotactic radiosurgery for resected brain metastases: A comparison of outcomes for large resection cavities.

PubMed

Zhong, Jim; Ferris, Matthew J; Switchenko, Jeffrey; Press, Robert H; Buchwald, Zachary; Olson, Jeffrey J; Eaton, Bree R; Curran, Walter J; Shu, Hui-Kuo G; Crocker, Ian R; Patel, Kirtesh R

Although historical trials have established the role of surgical resection followed by whole brain irradiation (WBRT) for brain metastases, WBRT has recently been shown to cause significant neurocognitive decline. Many practitioners have employed postoperative stereotactic radiosurgery (SRS) to tumor resection cavities to increase local control without causing significant neurocognitive sequelae. However, studies analyzing outcomes of large brain metastases treated with resection and postoperative SRS are lacking. Here we compare outcomes in patients with large brain metastases >4 cm to those with smaller metastases ≤4 cm treated with surgical resection followed by SRS to the resection cavity. Consecutive patients with brain metastases treated at our institution with surgical resection and postoperative SRS were retrospectively reviewed. Patients were stratified into ≤4 cm and >4 cm cohorts based on preoperative maximal tumor dimension. Cumulative incidence of local failure, radiation necrosis, and death were analyzed for the 2 cohorts using a competing-risk model, defined as the time from SRS treatment date to the measured event, death, or last follow-up. A total of 117 consecutive cases were identified. Of these patients, 90 (77%) had preoperative tumors ≤4 cm, and 27 (23%) >4 cm in greatest dimension. The only significant baseline difference between the 2 groups was a higher proportion of patients who underwent gross total resection in the ≤4 cm compared with the >4 cm cohort, 76% versus 48%, respectively (P <.01). The 1-year rates of local failure, radiation necrosis, and overall survival for the ≤4 cm and >4 cm cohorts were 12.3% and 16.0%, 26.9% and 28.4%, and 80.6% and 67.6%, respectively (all P >.05). The rates of local failure and radiation necrosis were not statistically different on multivariable analysis based on tumor size. Brain metastases >4 cm in largest dimension managed by resection and radiosurgery to the tumor cavity have promising local control rates without a significant increase in radiation necrosis on our retrospective review. Copyright © 2017 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Functional connectivity changes detected with magnetoencephalography after mild traumatic brain injury

PubMed Central

Dimitriadis, Stavros I.; Zouridakis, George; Rezaie, Roozbeh; Babajani-Feremi, Abbas; Papanicolaou, Andrew C.

2015-01-01

Mild traumatic brain injury (mTBI) may affect normal cognition and behavior by disrupting the functional connectivity networks that mediate efficient communication among brain regions. In this study, we analyzed brain connectivity profiles from resting state Magnetoencephalographic (MEG) recordings obtained from 31 mTBI patients and 55 normal controls. We used phase-locking value estimates to compute functional connectivity graphs to quantify frequency-specific couplings between sensors at various frequency bands. Overall, normal controls showed a dense network of strong local connections and a limited number of long-range connections that accounted for approximately 20% of all connections, whereas mTBI patients showed networks characterized by weak local connections and strong long-range connections that accounted for more than 60% of all connections. Comparison of the two distinct general patterns at different frequencies using a tensor representation for the connectivity graphs and tensor subspace analysis for optimal feature extraction showed that mTBI patients could be separated from normal controls with 100% classification accuracy in the alpha band. These encouraging findings support the hypothesis that MEG-based functional connectivity patterns may be used as biomarkers that can provide more accurate diagnoses, help guide treatment, and monitor effectiveness of intervention in mTBI. PMID:26640764

Changes in brain-behavior relationships following a 3-month pilot cognitive intervention program for adults with traumatic brain injury.

PubMed

Porter, S; Torres, I J; Panenka, W; Rajwani, Z; Fawcett, D; Hyder, A; Virji-Babul, N

2017-08-01

Facilitating functional recovery following brain injury is a key goal of neurorehabilitation. Direct, objective measures of changes in the brain are critical to understanding how and when meaningful changes occur, however, assessing neuroplasticity using brain based results remains a significant challenge. Little is known about the underlying changes in functional brain networks that correlate with cognitive outcomes in traumatic brain injury (TBI). The purpose of this pilot study was to assess the feasibility of an intensive three month cognitive intervention program in individuals with chronic TBI and to evaluate the effects of this intervention on brain-behavioral relationships. We used tools from graph theory to evaluate changes in global and local brain network features prior to and following cognitive intervention. Network metrics were calculated from resting state electroencephalographic (EEG) recordings from 10 adult participants with mild to severe brain injury and 11 age and gender matched healthy controls. Local graph metrics showed hyper-connectivity in the right inferior frontal gyrus and hypo-connectivity in the left inferior frontal gyrus in the TBI group at baseline in comparison with the control group. Following the intervention, there was a statistically significant increase in the composite cognitive score in the TBI participants and a statistically significant decrease in functional connectivity in the right inferior frontal gyrus. In addition, there was evidence of changes in the brain-behavior relationships following intervention. The results from this pilot study provide preliminary evidence for functional network reorganization that parallels cognitive improvements after cognitive rehabilitation in individuals with chronic TBI.

Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es): An American Society for Radiation Oncology evidence-based guideline

PubMed Central

Tsao, May N.; Rades, Dirk; Wirth, Andrew; Lo, Simon S.; Danielson, Brita L.; Gaspar, Laurie E.; Sperduto, Paul W.; Vogelbaum, Michael A.; Radawski, Jeffrey D.; Wang, Jian Z.; Gillin, Michael T.; Mohideen, Najeeb; Hahn, Carol A.; Chang, Eric L.

2012-01-01

Purpose To systematically review the evidence for the radiotherapeutic and surgical management of patients newly diagnosed with intraparenchymal brain metastases. Methods and Materials Key clinical questions to be addressed in this evidence-based Guideline were identified. Fully published randomized controlled trials dealing with the management of newly diagnosed intraparenchymal brain metastases were searched systematically and reviewed. The U.S. Preventative Services Task Force levels of evidence were used to classify various options of management. Results The choice of management in patients with newly diagnosed single or multiple brain metastases depends on estimated prognosis and the aims of treatment (survival, local treated lesion control, distant brain control, neurocognitive preservation). Single brain metastasis and good prognosis (expected survival 3 months or more): For a single brain metastasis larger than 3 to 4 cm and amenable to safe complete resection, whole brain radiotherapy (WBRT) and surgery (level 1) should be considered. Another alternative is surgery and radiosurgery/radiation boost to the resection cavity (level 3). For single metastasis less than 3 to 4 cm, radiosurgery alone or WBRT and radiosurgery or WBRT and surgery (all based on level 1 evidence) should be considered. Another alternative is surgery and radiosurgery or radiation boost to the resection cavity (level 3). For single brain metastasis (less than 3 to 4 cm) that is not resectable or incompletely resected, WBRT and radiosurgery, or radiosurgery alone should be considered (level 1). For nonresectable single brain metastasis (larger than 3 to 4 cm), WBRT should be considered (level 3). Multiple brain metastases and good prognosis (expected survival 3 months or more): For selected patients with multiple brain metastases (all less than 3 to 4 cm), radiosurgery alone, WBRT and radiosurgery, or WBRT alone should be considered, based on level 1 evidence. Safe resection of a brain metastasis or metastases causing significant mass effect and postoperative WBRT may also be considered (level 3). Patients with poor prognosis (expected survival less than 3 months): Patients with either single or multiple brain metastases with poor prognosis should be considered for palliative care with or without WBRT (level 3). It should be recognized, however, that there are limitations in the ability of physicians to accurately predict patient survival. Prognostic systems such as recursive partitioning analysis, and diagnosis-specific graded prognostic assessment may be helpful. Conclusions Radiotherapeutic intervention (WBRT or radiosurgery) is associated with improved brain control. In selected patients with single brain metastasis, radiosurgery or surgery has been found to improve survival and locally treated metastasis control (compared with WBRT alone). PMID:25925626

Age-related functional brain changes in young children.

PubMed

Long, Xiangyu; Benischek, Alina; Dewey, Deborah; Lebel, Catherine

2017-07-15

Brain function and structure change significantly during the toddler and preschool years. However, most studies focus on older or younger children, so the specific nature of these changes is unclear. In the present study, we analyzed 77 functional magnetic resonance imaging datasets from 44 children aged 2-6 years. We extracted measures of both local (amplitude of low frequency fluctuation and regional homogeneity) and global (eigenvector centrality mapping) activity and connectivity, and examined their relationships with age using robust linear correlation analysis and strict control for head motion. Brain areas within the default mode network and the frontoparietal network, such as the middle frontal gyrus, the inferior parietal lobule and the posterior cingulate cortex, showed increases in local and global functional features with age. Several brain areas such as the superior parietal lobule and superior temporal gyrus presented opposite development trajectories of local and global functional features, suggesting a shifting connectivity framework in early childhood. This development of functional connectivity in early childhood likely underlies major advances in cognitive abilities, including language and development of theory of mind. These findings provide important insight into the development patterns of brain function during the preschool years, and lay the foundation for future studies of altered brain development in young children with brain disorders or injury. Copyright © 2017 Elsevier Inc. All rights reserved.

A comparison between surgical resection in combination with WBRT or hypofractionated stereotactic irradiation in the treatment of solitary brain metastases.

PubMed

Lindvall, Peter; Bergström, Per; Löfroth, Per-Olov; Tommy Bergenheim, A

2009-09-01

The standard treatment of solitary brain metastases previously has been tumour resection in combination with whole-brain radiation therapy (WBRT). Stereotactic radiotherapy has emerged as a non-invasive treatment option especially for small brain metastases. We now report our results on resection + WBRT or hypofractionated stereotactic irradiation (HCSRT) in the treatment of solitary brain metastases. Between 1993 and 2004 patients with metastatic cancer and solitary brain metastases were selected for surgical resection + WBRT or HCSRT alone at the Umeå University Hospital. Fifty-nine patients were treated with surgical resection + WBRT (34 male, 25 female, mean age 63.3 years). Forty-seven patients were treated with HCSRT alone (15 male, 32 female, mean age 64.9 years). In patients followed radiologically, 28% treated with resection + WBRT showed a local recurrence after a median time of 8.0 months, whereas there was a lack of local control in 16% in the HCSRT group after a median time of 3.0 months. There was a significantly longer survival time for patients treated with resection + WBRT (median 7.9, mean 12.9 months) compared to HCSRT (median 5.0, mean 7.6 months). Even in patients with a tumour volume <10 cc, there was a significantly longer survival in favour of resection + WBRT (median 8.4, mean 17.4 months) compared to HCSRT (median 5.0, mean 7.9 months). This retrospective and non-randomised study indicates that surgical resection in combination with WBRT may be an option even for small brain metastases suitable for treatment with HCSRT. Since survival and local control following resection + WBRT was at least as favourable as compared to HCSRT alone, tumour location and expected neurological outcome may be the strongest aspect when selecting treatment modality.

On the Application of Quantitative EEG for Characterizing Autistic Brain: A Systematic Review

PubMed Central

Billeci, Lucia; Sicca, Federico; Maharatna, Koushik; Apicella, Fabio; Narzisi, Antonio; Campatelli, Giulia; Calderoni, Sara; Pioggia, Giovanni; Muratori, Filippo

2013-01-01

Autism-Spectrum Disorders (ASD) are thought to be associated with abnormalities in neural connectivity at both the global and local levels. Quantitative electroencephalography (QEEG) is a non-invasive technique that allows a highly precise measurement of brain function and connectivity. This review encompasses the key findings of QEEG application in subjects with ASD, in order to assess the relevance of this approach in characterizing brain function and clustering phenotypes. QEEG studies evaluating both the spontaneous brain activity and brain signals under controlled experimental stimuli were examined. Despite conflicting results, literature analysis suggests that QEEG features are sensitive to modification in neuronal regulation dysfunction which characterize autistic brain. QEEG may therefore help in detecting regions of altered brain function and connectivity abnormalities, in linking behavior with brain activity, and subgrouping affected individuals within the wide heterogeneity of ASD. The use of advanced techniques for the increase of the specificity and of spatial localization could allow finding distinctive patterns of QEEG abnormalities in ASD subjects, paving the way for the development of tailored intervention strategies. PMID:23935579

Multi-frequency localization of aberrant brain activity in autism spectrum disorder.

PubMed

Xiang, Jing; Korostenskaja, Milena; Molloy, Cynthia; deGrauw, Xinyao; Leiken, Kimberly; Gilman, Carley; Meinzen-Derr, Jareen; Fujiwara, Hisako; Rose, Douglas F; Mitchell, Terry; Murray, Donna S

2016-01-01

The abnormality of intrinsic brain activity in autism spectrum disorders (ASDs) is still inconclusive. Contradictory results have been found pointing towards hyper-activity or hypo-activity in various brain regions. The present research aims to investigate the spatial and spectral signatures of aberrant brain activity in an unprecedented frequency range of 1-2884 Hz at source levels in ASD using newly developed methods. Seven ASD subjects and age- and gender-matched controls were studied using a high-sampling rate magnetoencephalography (MEG) system. Brain activity in delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), low gamma (30-55 Hz), high gamma (65-90 Hz), ripples (90-200 Hz), high-frequency oscillations (HFOs, 200-1000 Hz), and very high-frequency oscillations (VHFOs, 1000-2884 Hz) was volumetrically localized and measured using wavelet and beamforming. In comparison to controls, ASD subjects had significantly higher odds of alpha activity (8-12 Hz) in the sensorimotor cortex (mu rhythm), and generally high-frequency activity (90-2884 Hz) in the frontal cortex. The source power of HFOs (200-1000 Hz) in the frontal cortex in ASD was significantly elevated as compared with controls. The results suggest that ASD has significantly altered intrinsic brain activity in both low- and high-frequency ranges. Increased intrinsic high-frequency activity in the frontal cortex may play a key role in ASD. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Correlation between standardized assessment of concussion scores and small-world brain network in mild traumatic brain injury.

PubMed

Yan, Yan; Song, Jian; Xu, Guozheng; Yao, Shun; Cao, Chenglong; Li, Chang; Peng, Guibao; Du, Hao

2017-10-01

This study investigated the characteristics of the small-world brain network architecture of patients with mild traumatic brain injury (MTBI), and a correlation between brain functional connectivity network properties in the resting-state fMRI and Standardized Assessment of Concussion (SAC) parameters. The neurological conditions of 22 MTBI patients and 17 normal control individuals were evaluated according to the SAC. Resting-state fMRI was performed in all subjects 3 and 7days after injury respectively. After preprocessing the fMRI data, cortex functional regions were marked using AAL90 and Dosenbach160 templates. The small-world network parameters and areas under the integral curves were computed in the range of sparsity from 0.01 to 0.5. Independent-sample t-tests were used to compare these parameters between the MTBI and control group. Significantly different parameters were investigated for correlations with SAC scores; those that correlated were chosen for further curve fitting. The clustering coefficient, the communication efficiency across in local networks, and the strength of connectivity were all higher in MTBI patients relative to control individuals. Parameters in 160 brain regions of the MTBI group significantly correlated with total SAC score and score for attention; the network parameters may be a quadratic function of attention scores of SAC and a cubic function of SAC scores. MTBI patients were characterized by elevated communication efficiency across global brain regions, and in local networks, and strength of mean connectivity. These features may be associated with brain function compensation. The network parameters significantly correlated with SAC total and attention scores. Copyright © 2017 Elsevier Ltd. All rights reserved.

Volumetric and Voxel-Based Morphometry Findings in Autism Subjects With and Without Macrocephaly

PubMed Central

Bigler, Erin D.; Abildskov, Tracy J.; Petrie, Jo Ann; Johnson, Michael; Lange, Nicholas; Chipman, Jonathan; Lu, Jeffrey; McMahon, William; Lainhart, Janet E.

2015-01-01

This study sought to replicate Herbert et al. (2003a), which found increased overall white matter (WM) volume in subjects with autism, even after controlling for head size differences. To avoid the possibility that greater WM volume in autism is merely an epiphenomena of macrocephaly over-representation associated with the disorder, the current study included control subjects with benign macrocephaly. The control group also included subjects with a reading disability to insure cognitive heterogeneity. WM volume in autism was significantly larger, even when controlling for brain volume, rate of macrocephaly, and other demographic variables. Autism and controls differed little on whole-brain WM voxel-based morphometry (VBM) analyses suggesting that the overall increase in WM volume was non-localized. Autism subjects exhibited a differential pattern of IQ relationships with brain volumetry findings from controls. Current theories of brain overgrowth and their importance in the development of autism are discussed in the context of these findings. PMID:20446133

[Intelligence and creativity changes induced by pathological growth of space-occupying cerebral lesion].

PubMed

Perfil'ev, A M; Razumnikova, O M; Stupak, V V

2013-01-01

Creativity and intelligence changes depending on tumor localization in frontal or parietal cortex before surgical procedure in 24 patients in comparison with control group are studied. Brain damage-induced intelligence impairment and a decrease of fluency, flexibility of figural divergent thinking, and originality of verbal one without specificity of tumor localization were found. Intelligence decrease was more presented while performing of figural tasks and least of all in verbal ones. The left prefrontal brain damage induced a decrease of all components of intelligence and a trend to a decrease of verbal creativity and figural fluency. The right parietal brain lesion was more associated with a decline of divergent thinking originality.

Social reinforcement can regulate localized brain activity.

PubMed

Mathiak, Krystyna A; Koush, Yury; Dyck, Miriam; Gaber, Tilman J; Alawi, Eliza; Zepf, Florian D; Zvyagintsev, Mikhail; Mathiak, Klaus

2010-11-01

Social learning is essential for adaptive behavior in humans. Neurofeedback based on functional magnetic resonance imaging (fMRI) trains control over localized brain activity. It can disentangle learning processes at the neural level and thus investigate the mechanisms of operant conditioning with explicit social reinforcers. In a pilot study, a computer-generated face provided a positive feedback (smiling) when activity in the anterior cingulate cortex (ACC) increased and gradually returned to a neutral expression when the activity dropped. One female volunteer without previous experience in fMRI underwent training based on a social reinforcer. Directly before and after the neurofeedback runs, neural responses to a cognitive interference task (Simon task) were recorded. We observed a significant increase in activity within ACC during the neurofeedback blocks, correspondent with the a-priori defined anatomical region of interest. In the course of the neurofeedback training, the subject learned to regulate ACC activity and could maintain the control even without direct feedback. Moreover, ACC was activated significantly stronger during Simon task after the neurofeedback training when compared to before. Localized brain activity can be controlled by social reward. The increased ACC activity transferred to a cognitive task with the potential to reduce cognitive interference. Systematic studies are required to explore long-term effects on social behavior and clinical applications.

Physiological self-regulation of regional brain activity using real-time functional magnetic resonance imaging (fMRI): methodology and exemplary data.

PubMed

Weiskopf, Nikolaus; Veit, Ralf; Erb, Michael; Mathiak, Klaus; Grodd, Wolfgang; Goebel, Rainer; Birbaumer, Niels

2003-07-01

A brain-computer interface (BCI) based on real-time functional magnetic resonance imaging (fMRI) is presented which allows human subjects to observe and control changes of their own blood oxygen level-dependent (BOLD) response. This BCI performs data preprocessing (including linear trend removal, 3D motion correction) and statistical analysis on-line. Local BOLD signals are continuously fed back to the subject in the magnetic resonance scanner with a delay of less than 2 s from image acquisition. The mean signal of a region of interest is plotted as a time-series superimposed on color-coded stripes which indicate the task, i.e., to increase or decrease the BOLD signal. We exemplify the presented BCI with one volunteer intending to control the signal of the rostral-ventral and dorsal part of the anterior cingulate cortex (ACC). The subject achieved significant changes of local BOLD responses as revealed by region of interest analysis and statistical parametric maps. The percent signal change increased across fMRI-feedback sessions suggesting a learning effect with training. This methodology of fMRI-feedback can assess voluntary control of circumscribed brain areas. As a further extension, behavioral effects of local self-regulation become accessible as a new field of research.

Presurgical localization and spatial shift of resting state networks in patients with brain metastases.

PubMed

Ding, Ju-Rong; Zhu, Fangmei; Hua, Bo; Xiong, Xingzhong; Wen, Yuqiao; Ding, Zhongxiang; Thompson, Paul M

2018-04-02

Brain metastases are the most prevalent cerebral tumors. Resting state networks (RSNs) are involved in multiple perceptual and cognitive functions. Therefore, precisely localizing multiple RSNs may be extremely valuable before surgical resection of metastases, to minimize neurocognitive impairments. Here we aimed to investigate the reliability of independent component analysis (ICA) for localizing multiple RSNs from resting-state functional MRI (rs-fMRI) data in individual patients, and further evaluate lesion-related spatial shifts of the RSNs. Twelve patients with brain metastases and 14 healthy controls were recruited. Using an improved automatic component identification method, we successfully identified seven common RSNs, including: the default mode network (DMN), executive control network (ECN), dorsal attention network (DAN), language network (LN), sensorimotor network (SMN), auditory network (AN) and visual network (VN), in both individual patients and controls. Moreover, the RSNs in the patients showed a visible spatial shift compared to those in the controls, and the spatial shift of some regions was related to the tumor location, which may reflect a complicated functional mechanism - functional disruptions and reorganizations - caused by metastases. Besides, higher cognitive networks (DMN, ECN, DAN and LN) showed significantly larger spatial shifts than perceptual networks (SMN, AN and VN), supporting a functional dichotomy between the two network groups even in pathologic alterations associated with metastases. Overall, our findings provide evidence that ICA is a promising approach for presurgical localization of multiple RSNs from rs-fMRI data in individual patients. More attention should be paid to the spatial shifts of the RSNs before surgical resection.

HFSRT of the resection cavity in patients with brain metastases.

PubMed

Specht, Hanno M; Kessel, Kerstin A; Oechsner, Markus; Meyer, Bernhard; Zimmer, Claus; Combs, Stephanie E

2016-06-01

Aim of this single center, retrospective study was to assess the efficacy and safety of linear accelerator-based hypofractionated stereotactic radiotherapy (HFSRT) to the resection cavity of brain metastases after surgical resection. Local control (LC), locoregional control (LRC = new brain metastases outside of the treatment volume), overall survival (OS) as well as acute and late toxicity were evaluated. 46 patients with large (> 3 cm) or symptomatic brain metastases were treated with HFSRT. Median resection cavity volume was 14.16 cm(3) (range 1.44-38.68 cm(3)) and median planning target volume (PTV) was 26.19 cm(3) (range 3.45-63.97 cm(3)). Patients were treated with 35 Gy in 7 fractions prescribed to the 95-100 % isodose line in a stereotactic treatment setup. LC and LRC were assessed by follow-up magnetic resonance imaging. The 1-year LC rate was 88 % and LRC was 48 %; 57% of all patients showed cranial progression after HFSRT (4% local, 44% locoregional, 9% local and locoregional). The median follow-up was 19 months; median OS for the whole cohort was 25 months. Tumor histology and recursive partitioning analysis score were significant predictors for OS. HFSRT was tolerated well without any severe acute side effects > grade 2 according to CTCAE criteria. HFSRT after surgical resection of brain metastases was tolerated well without any severe acute side effects and led to excellent LC and a favorable OS. Since more than half of the patients showed cranial progression after local irradiation of the resection cavity, close patient follow-up is warranted. A prospective evaluation in clinical trials is currently being performed.

Local Kernel for Brains Classification in Schizophrenia

NASA Astrophysics Data System (ADS)

Castellani, U.; Rossato, E.; Murino, V.; Bellani, M.; Rambaldelli, G.; Tansella, M.; Brambilla, P.

In this paper a novel framework for brain classification is proposed in the context of mental health research. A learning by example method is introduced by combining local measurements with non linear Support Vector Machine. Instead of considering a voxel-by-voxel comparison between patients and controls, we focus on landmark points which are characterized by local region descriptors, namely Scale Invariance Feature Transform (SIFT). Then, matching is obtained by introducing the local kernel for which the samples are represented by unordered set of features. Moreover, a new weighting approach is proposed to take into account the discriminative relevance of the detected groups of features. Experiments have been performed including a set of 54 patients with schizophrenia and 54 normal controls on which region of interest (ROI) have been manually traced by experts. Preliminary results on Dorso-lateral PreFrontal Cortex (DLPFC) region are promising since up to 75% of successful classification rate has been obtained with this technique and the performance has improved up to 85% when the subjects have been stratified by sex.

Brain antibodies in the cortex and blood of people with schizophrenia and controls

PubMed Central

Glass, L J; Sinclair, D; Boerrigter, D; Naude, K; Fung, S J; Brown, D; Catts, V S; Tooney, P; O'Donnell, M; Lenroot, R; Galletly, C; Liu, D; Weickert, T W; Shannon Weickert, C

2017-01-01

The immune system is implicated in the pathogenesis of schizophrenia, with elevated proinflammatory cytokine mRNAs found in the brains of ~40% of individuals with the disorder. However, it is not clear if antibodies (specifically immunoglobulin-γ (IgG)) can be found in the brain of people with schizophrenia and if their abundance relates to brain inflammatory cytokine mRNA levels. Therefore, we investigated the localization and abundance of IgG in the frontal cortex of people with schizophrenia and controls, and the impact of proinflammatory cytokine status on IgG abundance in these groups. Brain IgGs were detected surrounding blood vessels in the human and non-human primate frontal cortex by immunohistochemistry. IgG levels did not differ significantly between schizophrenia cases and controls, or between schizophrenia cases in ‘high’ and ‘low’ proinflammatory cytokine subgroups. Consistent with the existence of IgG in the parenchyma of human brain, mRNA and protein of the IgG transporter (FcGRT) were present in the brain, and did not differ according to diagnosis or inflammatory status. Finally, brain-reactive antibody presence and abundance was investigated in the blood of living people. The plasma of living schizophrenia patients and healthy controls contained antibodies that displayed positive binding to Rhesus macaque cerebellar tissue, and the abundance of these antibodies was significantly lower in patients than controls. These findings suggest that antibodies in the brain and brain-reactive antibodies in the blood are present under normal circumstances. PMID:28786974

Brain antibodies in the cortex and blood of people with schizophrenia and controls.

PubMed

Glass, L J; Sinclair, D; Boerrigter, D; Naude, K; Fung, S J; Brown, D; Catts, V S; Tooney, P; O'Donnell, M; Lenroot, R; Galletly, C; Liu, D; Weickert, T W; Shannon Weickert, C

2017-08-08

The immune system is implicated in the pathogenesis of schizophrenia, with elevated proinflammatory cytokine mRNAs found in the brains of ~40% of individuals with the disorder. However, it is not clear if antibodies (specifically immunoglobulin-γ (IgG)) can be found in the brain of people with schizophrenia and if their abundance relates to brain inflammatory cytokine mRNA levels. Therefore, we investigated the localization and abundance of IgG in the frontal cortex of people with schizophrenia and controls, and the impact of proinflammatory cytokine status on IgG abundance in these groups. Brain IgGs were detected surrounding blood vessels in the human and non-human primate frontal cortex by immunohistochemistry. IgG levels did not differ significantly between schizophrenia cases and controls, or between schizophrenia cases in 'high' and 'low' proinflammatory cytokine subgroups. Consistent with the existence of IgG in the parenchyma of human brain, mRNA and protein of the IgG transporter (FcGRT) were present in the brain, and did not differ according to diagnosis or inflammatory status. Finally, brain-reactive antibody presence and abundance was investigated in the blood of living people. The plasma of living schizophrenia patients and healthy controls contained antibodies that displayed positive binding to Rhesus macaque cerebellar tissue, and the abundance of these antibodies was significantly lower in patients than controls. These findings suggest that antibodies in the brain and brain-reactive antibodies in the blood are present under normal circumstances.

Spatial Brain Control Interface using Optical and Electrophysiological Measures

DTIC Science & Technology

2013-08-27

appropriate for implementing a reliable brain-computer interface ( BCI ). The LSVM method 1. REPORT DATE (DD-MM-YYYY) 4. TITLE AND SUBTITLE 27-08-2013 13...Machine (LSVM) was the most appropriate for implementing a reliable brain-computer interface ( BCI ). The LSVM method was applied to the imaging data...local field potentials proved to be fast and strongly tuned for the spatial parameters of the task. Thus, a reliable BCI that can predict upcoming

Stereotactic Radiosurgery of the Postoperative Resection Cavity for Brain Metastases: Prospective Evaluation of Target Margin on Tumor Control

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

Choi, Clara Y.H.; Chang, Steven D.; Gibbs, Iris C.

2012-10-01

Purpose: Given the neurocognitive toxicity associated with whole-brain irradiation (WBRT), approaches to defer or avoid WBRT after surgical resection of brain metastases are desirable. Our initial experience with stereotactic radiosurgery (SRS) targeting the resection cavity showed promising results. We examined the outcomes of postoperative resection cavity SRS to determine the effect of adding a 2-mm margin around the resection cavity on local failure (LF) and toxicity. Patients and Methods: We retrospectively evaluated 120 cavities in 112 patients treated from 1998-2009. Factors associated with LF and distant brain failure (DF) were analyzed using competing risks analysis, with death as a competingmore » risk. The overall survival (OS) rate was calculated by the Kaplan-Meier product-limit method; variables associated with OS were evaluated using the Cox proportional hazards and log rank tests. Results: The 12-month cumulative incidence rates of LF and DF, with death as a competing risk, were 9.5% and 54%, respectively. On univariate analysis, expansion of the cavity with a 2-mm margin was associated with decreased LF; the 12-month cumulative incidence rates of LF with and without margin were 3% and 16%, respectively (P=.042). The 12-month toxicity rates with and without margin were 3% and 8%, respectively (P=.27). On multivariate analysis, melanoma histology (P=.038) and number of brain metastases (P=.0097) were associated with higher DF. The median OS time was 17 months (range, 2-114 months), with a 12-month OS rate of 62%. Overall, WBRT was avoided in 72% of the patients. Conclusion: Adjuvant SRS targeting the resection cavity of brain metastases results in excellent local control and allows WBRT to be avoided in a majority of patients. A 2-mm margin around the resection cavity improved local control without increasing toxicity compared with our prior technique with no margin.« less

Relative Differences in Resting-State Brain Connectivity Associated with Long Term Intensive Lifestyle Intervention

PubMed Central

Casanova, Ramon; Hayasaka, Satoru; Saldana, Santiago; Bryan, Nick R.; Demos, Kathryn E.; Desiderio, Lisa; Erickson, Kirk I.; Espeland, Mark A.; Nasrallah, Ilya M.; Wadden, Thomas; Laurienti, Paul J.

2016-01-01

A number of studies have reported that type 2 diabetes mellitus (T2DM) is associated with alterations in resting-state activity and connectivity in the brain. There is also evidence that interventions involving physical activity and weight loss may affect brain functional connectivity. In this study, we examined the effects of nearly 10 years of an intensive lifestyle intervention (ILI), designed to induce and sustain weight loss through lower caloric intake and increased physical activity, on resting-state networks in adults with T2DM. We performed a cross-sectional comparison of global and local characteristics from functional brain networks between individuals who had been randomly assigned to ILI or a control condition of health education and support. Upon examining brain networks from 312 participants (average age: 68.8 for ILI and 67.9 for controls), we found that ILI participants (N=160) had attenuated local efficiency at the network-level compared with controls (N=152). Although there was no group difference in the network-level global efficiency, we found that, among ILI participants, nodal global efficiency was elevated in left fusiform gyrus, right middle frontal gyrus, and pars opercularis of right inferior frontal gyrus. These effects were age-dependent, with more pronounced effects for older participants. Overall these results indicate that the individuals assigned to the ILI had brain networks with less regional and more global connectivity, particularly involving frontal lobes. Such patterns would support greater distributed information processing. Future studies are needed to determine if these differences are associated with age-related compensatory function in the ILI group or worse pathology in the control group. PMID:27685338

Hypofractionated radiosurgery for intact or resected brain metastases: defining the optimal dose and fractionation.

PubMed

Eaton, Bree R; Gebhardt, Brian; Prabhu, Roshan; Shu, Hui-Kuo; Curran, Walter J; Crocker, Ian

2013-06-07

Hypofractionated Radiosurgery (HR) is a therapeutic option for delivering partial brain radiotherapy (RT) to large brain metastases or resection cavities otherwise not amenable to single fraction radiosurgery (SRS). The use, safety and efficacy of HR for brain metastases is not well characterized and the optimal RT dose-fractionation schedule is undefined. Forty-two patients treated with HR in 3-5 fractions for 20 (48%) intact and 22 (52%) resected brain metastases with a median maximum dimension of 3.9 cm (0.8-6.4 cm) between May 2008 and August 2011 were reviewed. Twenty-two patients (52%) had received prior radiation therapy. Local (LC), intracranial progression free survival (PFS) and overall survival (OS) are reported and analyzed for relationship to multiple RT variables through Cox-regression analysis. The most common dose-fractionation schedules were 21 Gy in 3 fractions (67%), 24 Gy in 4 fractions (14%) and 30 Gy in 5 fractions (12%). After a median follow-up time of 15 months (range 2-41), local failure occurred in 13 patients (29%) and was a first site of failure in 6 patients (14%). Kaplan-Meier estimates of 1 year LC, intracranial PFS, and OS are: 61% (95% CI 0.53 - 0.70), 55% (95% CI 0.47 - 0.63), and 73% (95% CI 0.65 - 0.79), respectively. Local tumor control was negatively associated with PTV volume (p = 0.007) and was a significant predictor of OS (HR 0.57, 95% CI 0.33 - 0.98, p = 0.04). Symptomatic radiation necrosis occurred in 3 patients (7%). HR is well tolerated in both new and recurrent, previously irradiated intact or resected brain metastases. Local control is negatively associated with PTV volume and a significant predictor of overall survival, suggesting a need for dose escalation when using HR for large intracranial lesions.

What has fMRI told us about the Development of Cognitive Control through Adolescence?

PubMed Central

Luna, Beatriz; Padmanabhan, Aarthi; O’Hearn, Kirsten

2009-01-01

Cognitive control, the ability to voluntarily guide our behavior, continues to improve throughout adolescence. Below we review the literature on age-related changes in brain function related to response inhibition and working memory, which support cognitive control. Findings from studies using functional magnetic imaging (fMRI) indicate that processing errors, sustaining a cognitive control state, and reaching adult levels of precision, persist through adolescence. Developmental changes in patterns of brain function suggest that core regions of the circuitry underlying cognitive control are on-line early in development. However, age-related changes in localized processes across the brain and in establishing long range connections that support top-down modulation of behavior may support more effective neural processing for optimal mature executive function. While great progress has been made in understanding the age-related changes in brain processes underlying cognitive development, there are still important challenges in developmental neuroimaging methods and the interpretation of data that need to be addressed. PMID:19765880

Unsupervised MRI segmentation of brain tissues using a local linear model and level set.

PubMed

Rivest-Hénault, David; Cheriet, Mohamed

2011-02-01

Real-world magnetic resonance imaging of the brain is affected by intensity nonuniformity (INU) phenomena which makes it difficult to fully automate the segmentation process. This difficult task is accomplished in this work by using a new method with two original features: (1) each brain tissue class is locally modeled using a local linear region representative, which allows us to account for the INU in an implicit way and to more accurately position the region's boundaries; and (2) the region models are embedded in the level set framework, so that the spatial coherence of the segmentation can be controlled in a natural way. Our new method has been tested on the ground-truthed Internet Brain Segmentation Repository (IBSR) database and gave promising results, with Tanimoto indexes ranging from 0.61 to 0.79 for the classification of the white matter and from 0.72 to 0.84 for the gray matter. To our knowledge, this is the first time a region-based level set model has been used to perform the segmentation of real-world MRI brain scans with convincing results. Copyright © 2011 Elsevier Inc. All rights reserved.

Regional homogeneity of the resting-state brain activity correlates with individual intelligence.

PubMed

Wang, Leiqiong; Song, Ming; Jiang, Tianzi; Zhang, Yunting; Yu, Chunshui

2011-01-25

Resting-state functional magnetic resonance imaging has confirmed that the strengths of the long distance functional connectivity between different brain areas are correlated with individual differences in intelligence. However, the association between the local connectivity within a specific brain region and intelligence during rest remains largely unknown. The aim of this study is to investigate the relationship between local connectivity and intelligence. Fifty-nine right-handed healthy adults participated in the study. The regional homogeneity (ReHo) was used to assess the strength of local connectivity. The associations between ReHo and full-scale intelligence quotient (FSIQ) scores were studied in a voxel-wise manner using partial correlation analysis controlling for age and sex. We found that the FSIQ scores were positively correlated with the ReHo values of the bilateral inferior parietal lobules, middle frontal, parahippocampal and inferior temporal gyri, the right thalamus, superior frontal and fusiform gyri, and the left superior parietal lobule. The main findings are consistent with the parieto-frontal integration theory (P-FIT) of intelligence, supporting the view that general intelligence involves multiple brain regions throughout the brain. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Protein kinase C restricts transport of carnitine by amino acid transporter ATB(0,+) apically localized in the blood-brain barrier.

PubMed

Michalec, Katarzyna; Mysiorek, Caroline; Kuntz, Mélanie; Bérézowski, Vincent; Szczepankiewicz, Andrzej A; Wilczyński, Grzegorz M; Cecchelli, Roméo; Nałęcz, Katarzyna A

2014-07-15

Carnitine (3-hydroxy-4-trimethylammoniobutyrate) is necessary for transfer of fatty acids through the inner mitochondrial membrane. Carnitine, not synthesized in the brain, is delivered there through the strongly polarized blood-brain barrier (BBB). Expression and presence of two carnitine transporters - organic cation/carnitine transporter (OCTN2) and amino acid transporter B(0,+) (ATB(0,+)) have been demonstrated previously in an in vitro model of the BBB. Due to potential protein kinase C (PKC) phosphorylation sites within ATB(0,+) sequence, the present study verified effects of this kinase on transporter function and localization in the BBB. ATB(0,+) can be regulated by estrogen receptor α and up-regulated in vitro, therefore its presence in vivo was verified with the transmission electron microscopy. The analyses of brain slices demonstrated ATB(0,+) luminal localization in brain capillaries, confirmed by biotinylation experiments in an in vitro model of the BBB. Brain capillary endothelial cells were shown to control carnitine gradient. ATB(0,+) was phosphorylated by PKC, what correlated with inhibition of carnitine transport. PKC activation did not change the amount of ATB(0,+) present in the apical membrane of brain endothelial cells, but resulted in transporter exclusion from raft microdomains. ATB(0,+) inactivation by a lateral movement in plasma membrane after transporter phosphorylation has been postulated. Copyright © 2014 Elsevier Inc. All rights reserved.

[Peroperative risks in cerebral aneurysm surgery].

PubMed

Mustaki, J P; Bissonnette, B; Archer, D; Boulard, G; Ravussin, P

1996-01-01

The perioperative complications associated with cerebral aneurysm surgery require a specific anaesthetic management. Four major perioperative accidents are discussed in this review. The anaesthetic and surgical management in case of rebleeding subsequent to the re-rupture of the aneurysm is mainly prophylactic. It includes haemodynamic stability assurance, maintenance of mean arterial pressure (MAP) between 80-90 mmHg during stimulation of the patient such as endotracheal intubation, application of the skull-pin head-holder, incision, and craniotomy. The aneurysmal transmural pressure should be adequately maintained by avoiding an aggressive decrease of intracranial pressure. Once the skull is open, the brain must be kept slack in order to decrease pressure under the retractors and avoid the risks of stretching and tearing of the adjacent vessels. If, despite these precautions, the aneurysm ruptures again. MAP should be decreased to 60 mmHg and the brain rendered more slack, in order to allow direct clipping of the aneurysm, or temporary clipping of the adjacent vessels. The optimal agents in this situation are isoflurane (which decreases CMRO2), intravenous anaesthetic agents (inspite their negative inotropic effect, they may potentially protect the brain) and sodium nitroprusside. Vasospasm occurs usually between the 3rd and the 7th day after subarachnoid haemorrhage. It may be seen peroperatively. The optimal treatment, as well as prophylaxis, is moderate controlled hypertension (MAP > 100 mmHg), associated with hypervolaemia and haemodilution, the so-called triple H therapy, with strict control of the filling pressures. Other beneficial therapies are calcium antagonists (nimodipine and nicardipine), the removal of the blood accumulated around the brain and in the cisternae, and possibly local administration of papaverine. Abrupt MAP increases are controlled in order to maintain adequate aneurysmal transmural pressure. Beta-blockers, local anaesthetics administered locally or intravenously, a carefully titrated level of anaesthesia, a maintained volaemia play a protective role. Cerebral oedema is sometimes already present at the opening of the skull or may arise later, due to a high pressure under the retractors, to the surgical manipulations of the brain or to brain ischaemia subsequent to temporary clipping. Its treatment is aggressive, with intravenous agents, mannitol, deep hypocapnia and/or lumbar drainage. Prophylaxis, according to the "brain homeostasis concept", is the preferred method to avoid these four peroperative accidents. It includes normal blood volume, normoglycaemia, moderate hypocapnia, normotension, soft manipulation of the brain and optimal brain relaxation.

Salvage Radiosurgery for Brain Metastases: Prognostic Factors to Consider in Patient Selection

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

Kurtz, Goldie; Zadeh, Gelareh; Gingras-Hill, Geneviève

2014-01-01

Purpose: Stereotactic radiosurgery (SRS) is offered to patients for recurrent brain metastases after prior brain radiation therapy (RT), but few studies have evaluated the efficacy of salvage SRS or factors to consider in selecting patients for this treatment. This study reports overall survival (OS), intracranial progression-free survival (PFS), and local control (LC) after salvage SRS, and factors associated with outcomes. Methods and Materials: This is a retrospective review of patients treated from 2009 to 2011 with salvage SRS after prior brain RT for brain metastases. Survival from salvage SRS and from initial brain metastases diagnosis (IBMD) was calculated. Univariate andmore » multivariable (MVA) analyses included age, performance status, recursive partitioning analysis (RPA) class, extracranial disease control, and time from initial RT to salvage SRS. Results: There were 106 patients included in the analysis with a median age of 56.9 years (range 32.5-82 years). A median of 2 metastases were treated per patient (range, 1-12) with a median dose of 21 Gy (range, 12-24) prescribed to the 50% isodose. With a median follow-up of 10.5 months (range, 0.1-68.2), LC was 82.8%, 60.1%, and 46.8% at 6 months, 1 year, and 3 years, respectively. Median PFS was 6.2 months (95% confidence interval [CI] = 4.9-7.6). Median OS was 11.7 months (95% CI = 8.1-13) from salvage SRS, and 22.1 months from IBMD (95% CI = 18.4-26.8). On MVA, age (P=.01; hazard ratio [HR] = 1.04; 95% CI = 1.01-1.07), extracranial disease control (P=.004; HR = 0.46; 95% CI = 0.27-0.78), and interval from initial RT to salvage SRS of at least 265 days (P=.001; HR = 2.46; 95% CI = 1.47-4.09) were predictive of OS. Conclusions: This study demonstrates that patients can have durable local control and survival after salvage SRS for recurrent brain metastases. In particular, younger patients with controlled extracranial disease and a durable response to initial brain RT are likely to benefit from salvage SRS.« less

Brain Oscillatory Correlates of Altered Executive Functioning in Positive and Negative Symptomatic Schizophrenia Patients and Healthy Controls.

PubMed

Berger, Barbara; Minarik, Tamas; Griesmayr, Birgit; Stelzig-Schoeler, Renate; Aichhorn, Wolfgang; Sauseng, Paul

2016-01-01

Working Memory and executive functioning deficits are core characteristics of patients suffering from schizophrenia. Electrophysiological research indicates that altered patterns of neural oscillatory mechanisms underpinning executive functioning are associated with the psychiatric disorder. Such brain oscillatory changes have been found in local amplitude differences at gamma and theta frequencies in task-specific cortical areas. Moreover, interregional interactions are also disrupted as signified by decreased phase coherence of fronto-posterior theta activity in schizophrenia patients. However, schizophrenia is not a one-dimensional psychiatric disorder but has various forms and expressions. A common distinction is between positive and negative symptomatology but most patients have both negative and positive symptoms to some extent. Here, we examined three groups-healthy controls, predominantly negative, and predominantly positive symptomatic schizophrenia patients-when performing a working memory task with increasing cognitive demand and increasing need for executive control. We analyzed brain oscillatory activity in the three groups separately and investigated how predominant symptomatology might explain differences in brain oscillatory patterns. Our results indicate that differences in task specific fronto-posterior network activity (i.e., executive control network) expressed by interregional phase synchronization are able to account for working memory dysfunctions between groups. Local changes in the theta and gamma frequency range also show differences between patients and healthy controls, and more importantly, between the two patient groups. We conclude that differences in oscillatory brain activation patterns related to executive processing can be an indicator for positive and negative symptomatology in schizophrenia. Furthermore, changes in cognitive and especially executive functioning in patients are expressed by alterations in a task-specific fronto-posterior connectivity even in the absence of behavioral impairment.

Correlations between ventricular enlargement and gray and white matter volumes of cortex, thalamus, striatum, and internal capsule in schizophrenia.

PubMed

Horga, Guillermo; Bernacer, Javier; Dusi, Nicola; Entis, Jonathan; Chu, Kingwai; Hazlett, Erin A; Haznedar, M Mehmet; Kemether, Eileen; Byne, William; Buchsbaum, Monte S

2011-10-01

Ventricular enlargement is one of the most consistent abnormal structural brain findings in schizophrenia and has been used to infer brain shrinkage. However, whether ventricular enlargement is related to local overlying cortex and/or adjacent subcortical structures or whether it is related to brain volume change globally has not been assessed. We systematically assessed interrelations of ventricular volumes with gray and white matter volumes of 40 Brodmann areas (BAs), the thalamus and its medial dorsal nucleus and pulvinar, the internal capsule, caudate and putamen. We acquired structural MRI ( patients with schizophrenia (n = 64) and healthy controls (n = 56)) and diffusion tensor fractional anisotropy (FA) (untreated schizophrenia n = 19, controls n = 32). Volumes were assessed by manual tracing of central structures and a semi-automated parcellation of BAs. Patients with schizophrenia had increased ventricular size associated with decreased cortical gray matter volumes widely across the brain; a similar but less pronounced pattern was seen in normal controls; local correlations (e.g. temporal horn with temporal lobe volume) were not appreciably higher than non-local correlations (e.g. temporal horn with prefrontal volume). White matter regions adjacent to the ventricles similarly did not reveal strong regional relationships. FA and center of mass of the anterior limb of the internal capsule also appeared differentially influenced by ventricular volume but findings were similarly not regional. Taken together, these findings indicate that ventricular enlargement is globally interrelated with gray matter volume diminution but not directly correlated with volume loss in the immediately adjacent caudate, putamen, or internal capsule.

Electromagnetic Evidence of Altered Visual Processing in Autism

ERIC Educational Resources Information Center

Neumann, Nicola; Dubischar-Krivec, Anna M.; Poustka, Fritz; Birbaumer, Niels; Bolte, Sven; Braun, Christoph

2011-01-01

Individuals with autism spectrum disorder (ASD) demonstrate intact or superior local processing of visual-spatial tasks. We investigated the hypothesis that in a disembedding task, autistic individuals exhibit a more local processing style than controls, which is reflected by altered electromagnetic brain activity in response to embedded stimuli…

A novel fMRI paradigm suggests that pedaling-related brain activation is altered after stroke

PubMed Central

Promjunyakul, Nutta-on; Schmit, Brian D.; Schindler-Ivens, Sheila M.

2015-01-01

The purpose of this study was to examine the feasibility of using functional magnetic resonance imaging (fMRI) to measure pedaling-related brain activation in individuals with stroke and age-matched controls. We also sought to identify stroke-related changes in brain activation associated with pedaling. Fourteen stroke and 12 control subjects were asked to pedal a custom, MRI-compatible device during fMRI. Subjects also performed lower limb tapping to localize brain regions involved in lower limb movement. All stroke and control subjects were able to pedal while positioned for fMRI. Two control subjects were withdrawn due to claustrophobia, and one control data set was excluded from analysis due to an incidental finding. In the stroke group, one subject was unable to enter the gantry due to excess adiposity, and one stroke data set was excluded from analysis due to excessive head motion. Consequently, 81% of subjects (12/14 stroke, 9/12 control) completed all procedures and provided valid pedaling-related fMRI data. In these subjects, head motion was ≤3 mm. In both groups, brain activation localized to the medial aspect of M1, S1, and Brodmann’s area 6 (BA6) and to the cerebellum (vermis, lobules IV, V, VIII). The location of brain activation was consistent with leg areas. Pedaling-related brain activation was apparent on both sides of the brain, with values for laterality index (LI) of –0.06 (0.20) in the stroke cortex, 0.05 (±0.06) in the control cortex, 0.29 (0.33) in the stroke cerebellum, and 0.04 (0.15) in the control cerebellum. In the stroke group, activation in the cerebellum – but not cortex – was significantly lateralized toward the damaged side of the brain (p = 0.01). The volume of pedaling-related brain activation was smaller in stroke as compared to control subjects. Differences reached statistical significance when all active regions were examined together [p = 0.03; 27,694 (9,608) μL stroke; 37,819 (9,169) μL control]. When individual regions were examined separately, reduced brain activation volume reached statistical significance in BA6 [p = 0.04; 4,350 (2,347) μL stroke; 6,938 (3,134) μL control] and cerebellum [p = 0.001; 4,591 (1,757) μL stroke; 8,381 (2,835) μL control]. Regardless of whether activated regions were examined together or separately, there were no significant between-group differences in brain activation intensity [p = 0.17; 1.30 (0.25)% stroke; 1.16 (0.20)% control]. Reduced volume in the stroke group was not observed during lower limb tapping and could not be fully attributed to differences in head motion or movement rate. There was a tendency for pedaling-related brain activation volume to increase with increasing work performed by the paretic limb during pedaling (p = 0.08, r = 0.525). Hence, the results of this study provide two original and important contributions. First, we demonstrated that pedaling can be used with fMRI to examine brain activation associated with lower limb movement in people with stroke. Unlike previous lower limb movements examined with fMRI, pedaling involves continuous, reciprocal, multijoint movement of both limbs. In this respect, pedaling has many characteristics of functional lower limb movements, such as walking. Thus, the importance of our contribution lies in the establishment of a novel paradigm that can be used to understand how the brain adapts to stroke to produce functional lower limb movements. Second, preliminary observations suggest that brain activation volume is reduced during pedaling post-stroke. Reduced brain activation volume may be due to anatomic, physiology, and/or behavioral differences between groups, but methodological issues cannot be excluded. Importantly, brain action volume post-stroke was both task-dependent and mutable, which suggests that it could be modified through rehabilitation. Future work will explore these possibilities. PMID:26089789

Altered gray matter organization in children and adolescents with ADHD: a structural covariance connectome study

PubMed Central

Griffiths, K R; Grieve, S M; Kohn, M R; Clarke, S; Williams, L M; Korgaonkar, M S

2016-01-01

Although multiple studies have reported structural deficits in multiple brain regions in attention-deficit hyperactivity disorder (ADHD), we do not yet know if these deficits reflect a more systematic disruption to the anatomical organization of large-scale brain networks. Here we used a graph theoretical approach to quantify anatomical organization in children and adolescents with ADHD. We generated anatomical networks based on covariance of gray matter volumes from 92 regions across the brain in children and adolescents with ADHD (n=34) and age- and sex-matched healthy controls (n=28). Using graph theory, we computed metrics that characterize both the global organization of anatomical networks (interconnectivity (clustering), integration (path length) and balance of global integration and localized segregation (small-worldness)) and their local nodal measures (participation (degree) and interaction (betweenness) within a network). Relative to Controls, ADHD participants exhibited altered global organization reflected in more clustering or network segregation. Locally, nodal degree and betweenness were increased in the subcortical amygdalae in ADHD, but reduced in cortical nodes in the anterior cingulate, posterior cingulate, mid temporal pole and rolandic operculum. In ADHD, anatomical networks were disrupted and reflected an emphasis on subcortical local connections centered around the amygdala, at the expense of cortical organization. Brains of children and adolescents with ADHD may be anatomically configured to respond impulsively to the automatic significance of stimulus input without having the neural organization to regulate and inhibit these responses. These findings provide a novel addition to our current understanding of the ADHD connectome. PMID:27824356

Brain Mechanisms of Attentional Control.

ERIC Educational Resources Information Center

Wilke, Thomas

Lack of attentional control--inability to concentrate--has often made the difference between successful and unsuccessful performance on the part of athletes. Attention is controlled neurologically by a very complex interaction of a large portion of the cerebrum and is not localized to any one structure. The mechanism involves a memory retrieval…

Current and emerging treatments for brain metastases.

PubMed

Lin, Jenny; Jandial, Rahul; Nesbit, Amanda; Badie, Behnam; Chen, Mike

2015-04-01

Brain metastasis in patients with cancer can be indicative of multisystem spread or lead to neurological demise if not locally controlled, and is associated with poor survival and high morbidity. Compared with metastasis to other areas of the body, brain metastasis possesses a unique biology that confers high resistance to systemic therapies. This phenomenon has been historically attributed to the inability of chemotherapeutic agents to pass through the blood-brain barrier. Recent studies challenge this premise, revealing other potentially targetable mechanism(s). Therapies that exploit recent advances in the understanding of brain metastasis are still in early stages of development. Encouragingly, and discovered by happenstance, some molecularly targeted drugs already appear to have efficacy against certain tumors and accompanying cerebral edema. In the meantime, conventional treatment modalities such as surgery and radiation have iteratively reached new levels of refinement. However, these achievements are somewhat muted by the emergence of magnetic resonance (MR)-guided laser interstitial thermal therapy, a minimally invasive neuroablative technique. On the horizon, MR-guided focused ultrasound surgery is similarly intriguing. Even in the absence of further advances, local control is frequently achieved with state-of-the-art therapies. Dramatic improvements will likely require sophisticated approaches that account for the particular effects of the microenvironment of the central nervous system on metastasis.

Reduced hemispheric asymmetry of brain anatomical networks in attention deficit hyperactivity disorder.

PubMed

Li, Dandan; Li, Ting; Niu, Yan; Xiang, Jie; Cao, Rui; Liu, Bo; Zhang, Hui; Wang, Bin

2018-05-11

Despite many studies reporting a variety of alterations in brain networks in patients with attention deficit hyperactivity disorder (ADHD), alterations in hemispheric anatomical networks are still unclear. In this study, we investigated topology alterations in hemispheric white matter in patients with ADHD and the relationship between these alterations and clinical features of the illness. Weighted hemispheric brain anatomical networks were first constructed for each of 40 right-handed patients with ADHD and 53 matched normal controls. Then, graph theoretical approaches were utilized to compute hemispheric topological properties. The small-world property was preserved in the hemispheric network. Furthermore, a significant group-by-hemisphere interaction was revealed in global efficiency, local efficiency and characteristic path length, attributed to the significantly reduced hemispheric asymmetry of global and local integration in patients with ADHD compared with normal controls. Specifically, reduced asymmetric regional efficiency was found in three regions. Finally, we found that the abnormal asymmetry of hemispheric brain anatomical network topology and regional efficiency were both associated with clinical features (the Adult ADHD Self-Report Scale and Wechsler Adult Intelligence Scale) in patients. Our findings provide new insights into the lateralized nature of hemispheric dysconnectivity and highlight the potential for using brain network measures of hemispheric asymmetry as neural biomarkers for ADHD and its clinical features.

Network analysis of functional brain connectivity in borderline personality disorder using resting-state fMRI

PubMed Central

Xu, Tingting; Cullen, Kathryn R.; Mueller, Bryon; Schreiner, Mindy W.; Lim, Kelvin O.; Schulz, S. Charles; Parhi, Keshab K.

2016-01-01

Borderline personality disorder (BPD) is associated with symptoms such as affect dysregulation, impaired sense of self, and self-harm behaviors. Neuroimaging research on BPD has revealed structural and functional abnormalities in specific brain regions and connections. However, little is known about the topological organizations of brain networks in BPD. We collected resting-state functional magnetic resonance imaging (fMRI) data from 20 patients with BPD and 10 healthy controls, and constructed frequency-specific functional brain networks by correlating wavelet-filtered fMRI signals from 82 cortical and subcortical regions. We employed graph-theory based complex network analysis to investigate the topological properties of the brain networks, and employed network-based statistic to identify functional dysconnections in patients. In the 0.03–0.06 Hz frequency band, compared to controls, patients with BPD showed significantly larger measures of global network topology, including the size of largest connected graph component, clustering coefficient, small-worldness, and local efficiency, indicating increased local cliquishness of the functional brain network. Compared to controls, patients showed lower nodal centrality at several hub nodes but greater centrality at several non-hub nodes in the network. Furthermore, an interconnected subnetwork in 0.03–0.06 Hz frequency band was identified that showed significantly lower connectivity in patients. The links in the subnetwork were mainly long-distance connections between regions located at different lobes; and the mean connectivity of this subnetwork was negatively correlated with the increased global topology measures. Lastly, the key network measures showed high correlations with several clinical symptom scores, and classified BPD patients against healthy controls with high accuracy based on linear discriminant analysis. The abnormal topological properties and connectivity found in this study may add new knowledge to the current understanding of functional brain networks in BPD. However, due to limitation of small sample sizes, the results of the current study should be viewed as exploratory and need to be validated on large samples in future works. PMID:26977400

Network analysis of functional brain connectivity in borderline personality disorder using resting-state fMRI.

PubMed

Xu, Tingting; Cullen, Kathryn R; Mueller, Bryon; Schreiner, Mindy W; Lim, Kelvin O; Schulz, S Charles; Parhi, Keshab K

2016-01-01

Borderline personality disorder (BPD) is associated with symptoms such as affect dysregulation, impaired sense of self, and self-harm behaviors. Neuroimaging research on BPD has revealed structural and functional abnormalities in specific brain regions and connections. However, little is known about the topological organizations of brain networks in BPD. We collected resting-state functional magnetic resonance imaging (fMRI) data from 20 patients with BPD and 10 healthy controls, and constructed frequency-specific functional brain networks by correlating wavelet-filtered fMRI signals from 82 cortical and subcortical regions. We employed graph-theory based complex network analysis to investigate the topological properties of the brain networks, and employed network-based statistic to identify functional dysconnections in patients. In the 0.03-0.06 Hz frequency band, compared to controls, patients with BPD showed significantly larger measures of global network topology, including the size of largest connected graph component, clustering coefficient, small-worldness, and local efficiency, indicating increased local cliquishness of the functional brain network. Compared to controls, patients showed lower nodal centrality at several hub nodes but greater centrality at several non-hub nodes in the network. Furthermore, an interconnected subnetwork in 0.03-0.06 Hz frequency band was identified that showed significantly lower connectivity in patients. The links in the subnetwork were mainly long-distance connections between regions located at different lobes; and the mean connectivity of this subnetwork was negatively correlated with the increased global topology measures. Lastly, the key network measures showed high correlations with several clinical symptom scores, and classified BPD patients against healthy controls with high accuracy based on linear discriminant analysis. The abnormal topological properties and connectivity found in this study may add new knowledge to the current understanding of functional brain networks in BPD. However, due to limitation of small sample sizes, the results of the current study should be viewed as exploratory and need to be validated on large samples in future works.

Targeted gene delivery in the cricket brain, using in vivo electroporation.

PubMed

Matsumoto, Chihiro Sato; Shidara, Hisashi; Matsuda, Koji; Nakamura, Taro; Mito, Taro; Matsumoto, Yukihisa; Oka, Kotaro; Ogawa, Hiroto

2013-12-01

The cricket (Gryllus bimaculatus) is a hemimetabolous insect that is emerging as a model organism for the study of neural and molecular mechanisms of behavioral traits. However, research strategies have been limited by a lack of genetic manipulation techniques that target the nervous system of the cricket. The development of a new method for efficient gene delivery into cricket brains, using in vivo electroporation, is described here. Plasmid DNA, which contained an enhanced green fluorescent protein (eGFP) gene, under the control of a G. bimaculatus actin (Gb'-act) promoter, was injected into adult cricket brains. Injection was followed by electroporation at a sufficient voltage. Expression of eGFP was observed within the brain tissue. Localized gene expression, targeted to specific regions of the brain, was also achieved using a combination of local DNA injection and fine arrangement of the electroporation electrodes. Further studies using this technique will lead to a better understanding of the neural and molecular mechanisms that underlie cricket behaviors. Copyright © 2013 Elsevier Ltd. All rights reserved.

Three-dimensional macroporous nanoelectronic networks as minimally invasive brain probes

NASA Astrophysics Data System (ADS)

Xie, Chong; Liu, Jia; Fu, Tian-Ming; Dai, Xiaochuan; Zhou, Wei; Lieber, Charles M.

2015-12-01

Direct electrical recording and stimulation of neural activity using micro-fabricated silicon and metal micro-wire probes have contributed extensively to basic neuroscience and therapeutic applications; however, the dimensional and mechanical mismatch of these probes with the brain tissue limits their stability in chronic implants and decreases the neuron-device contact. Here, we demonstrate the realization of a three-dimensional macroporous nanoelectronic brain probe that combines ultra-flexibility and subcellular feature sizes to overcome these limitations. Built-in strains controlling the local geometry of the macroporous devices are designed to optimize the neuron/probe interface and to promote integration with the brain tissue while introducing minimal mechanical perturbation. The ultra-flexible probes were implanted frozen into rodent brains and used to record multiplexed local field potentials and single-unit action potentials from the somatosensory cortex. Significantly, histology analysis revealed filling-in of neural tissue through the macroporous network and attractive neuron-probe interactions, consistent with long-term biocompatibility of the device.

Control channels in the brain and their influence on brain executive functions

NASA Astrophysics Data System (ADS)

Meng, Qinglei; Choa, Fow-Sen; Hong, Elliot; Wang, Zhiguang; Islam, Mohammad

2014-05-01

In a computer network there are distinct data channels and control channels where massive amount of visual information are transported through data channels but the information streams are routed and controlled by intelligent algorithm through "control channels". Recent studies on cognition and consciousness have shown that the brain control channels are closely related to the brainwave beta (14-40 Hz) and alpha (7-13 Hz) oscillations. The high-beta wave is used by brain to synchronize local neural activities and the alpha oscillation is for desynchronization. When two sensory inputs are simultaneously presented to a person, the high-beta is used to select one of the inputs and the alpha is used to deselect the other so that only one input will get the attention. In this work we demonstrated that we can scan a person's brain using binaural beats technique and identify the individual's preferred control channels. The identified control channels can then be used to influence the subject's brain executive functions. In the experiment, an EEG measurement system was used to record and identify a subject's control channels. After these channels were identified, the subject was asked to do Stroop tests. Binaural beats was again used to produce these control-channel frequencies on the subject's brain when we recorded the completion time of each test. We found that the high-beta signal indeed speeded up the subject's executive function performance and reduced the time to complete incongruent tests, while the alpha signal didn't seem to be able to slow down the executive function performance.

Connectivity-based neurofeedback: Dynamic causal modeling for real-time fMRI☆

PubMed Central

Koush, Yury; Rosa, Maria Joao; Robineau, Fabien; Heinen, Klaartje; W. Rieger, Sebastian; Weiskopf, Nikolaus; Vuilleumier, Patrik; Van De Ville, Dimitri; Scharnowski, Frank

2013-01-01

Neurofeedback based on real-time fMRI is an emerging technique that can be used to train voluntary control of brain activity. Such brain training has been shown to lead to behavioral effects that are specific to the functional role of the targeted brain area. However, real-time fMRI-based neurofeedback so far was limited to mainly training localized brain activity within a region of interest. Here, we overcome this limitation by presenting near real-time dynamic causal modeling in order to provide feedback information based on connectivity between brain areas rather than activity within a single brain area. Using a visual–spatial attention paradigm, we show that participants can voluntarily control a feedback signal that is based on the Bayesian model comparison between two predefined model alternatives, i.e. the connectivity between left visual cortex and left parietal cortex vs. the connectivity between right visual cortex and right parietal cortex. Our new approach thus allows for training voluntary control over specific functional brain networks. Because most mental functions and most neurological disorders are associated with network activity rather than with activity in a single brain region, this novel approach is an important methodological innovation in order to more directly target functionally relevant brain networks. PMID:23668967

Tissue Localization of Glycosphingolipid Accumulation in a Gaucher Disease Mouse Brain by LC-ESI-MS/MS and High-Resolution MALDI Imaging Mass Spectrometry.

PubMed

Jones, E Ellen; Zhang, Wujuan; Zhao, Xueheng; Quiason, Cristine; Dale, Stephanie; Shahidi-Latham, Sheerin; Grabowski, Gregory A; Setchell, Kenneth D R; Drake, Richard R; Sun, Ying

2017-12-01

To better understand regional brain glycosphingolipid (GSL) accumulation in Gaucher disease (GD) and its relationship to neuropathology, a feasibility study using mass spectrometry and immunohistochemistry was conducted using brains derived from a GD mouse model (4L/PS/NA) homozygous for a mutant GCase (V394L [4L]) and expressing a prosaposin hypomorphic (PS-NA) transgene. Whole brains from GD and control animals were collected using one hemisphere for MALDI FTICR IMS analysis and the other for quantitation by LC-ESI-MS/MS. MALDI IMS detected several HexCers across the brains. Comparison with the brain hematoxylin and eosin (H&E) revealed differential signal distributions in the midbrain, brain stem, and CB of the GD brain versus the control. Quantitation of serial brain sections with LC-ESI-MS/MS supported the imaging results, finding the overall HexCer levels in the 4L/PS-NA brains to be four times higher than the control. LC-ESI-MS/MS also confirmed that the elevated hexosyl isomers were glucosylceramides rather than galactosylceramides. MALDI imaging also detected differential analyte distributions of lactosylceramide species and gangliosides in the 4L/PS-NA brain, which was validated by LC-ESI-MS/MS. Immunohistochemistry revealed regional inflammation, altered autophagy, and defective protein degradation correlating with regions of GSL accumulation, suggesting that specific GSLs may have distinct neuropathological effects.

Cerebral atrophy in elderly with subjective memory complaints.

PubMed

Palm, Walter M; Ferrarini, Luca; van der Flier, Wiesje M; Westendorp, Rudi G J; Bollen, Eduard L E M; Middelkoop, Huub A M; Milles, Julien R; van der Grond, Jeroen; van Buchem, Mark A

2013-08-01

To evaluate ventricular shape differences along the complete surface of the lateral and third ventricles of persons with subjective memory complaints (MC). We included 28 controls and 21 persons with MC. FLAIR, T2, and PD-weighted brain MRI scans were acquired at 1.5 Tesla, followed by semi-automated segmentation of the lateral and third ventricles, and local shape difference analysis based on growing and adaptive meshes. Ventricular meshes were used to highlight local areas with significant differences between controls and persons with MC, determined by permutation tests with a predefined threshold (P = 0.01). Compared with control subjects, relevant differences were found in the shape of the ventricular surface adjacent to the thalamus and corona radiata in persons with MC. Before correction for multiple comparisons, relevant differences were also found in the shape of the ventricular surface adjacent to the corpus callosum, hippocampus, and amydala. Our findings suggest the presence of localized structural brain differences in patients with subjective memory complaints in the thalamus and the corona radiata. Copyright © 2013 Wiley Periodicals, Inc.

T-cell brain infiltration and immature antigen-presenting cells in transgenic models of Alzheimer's disease-like cerebral amyloidosis.

PubMed

Ferretti, M T; Merlini, M; Späni, C; Gericke, C; Schweizer, N; Enzmann, G; Engelhardt, B; Kulic, L; Suter, T; Nitsch, R M

2016-05-01

Cerebral beta-amyloidosis, one of the pathological hallmarks of Alzheimer's disease (AD), elicits a well-characterised, microglia-mediated local innate immune response. In contrast, it is not clear whether cells of the adaptive immune system, in particular T-cells, react to cerebral amyloidosis in AD. Even though parenchymal T-cells have been described in post-mortem brains of AD patients, it is not known whether infiltrating T-cells are specifically recruited to the extracellular deposits of beta-amyloid, and whether they are locally activated into proliferating, effector cells upon interaction with antigen-presenting cells (APCs). To address these issues we have analysed by confocal microscopy and flow-cytometry the localisation and activation status of both T-cells and APCs in transgenic (tg) mice models of AD-like cerebral amyloidosis. Increased numbers of infiltrating T-cells were found in amyloid-burdened brain regions of tg mice, with concomitant up-regulation of endothelial adhesion molecules ICAM-1 and VCAM-1, compared to non-tg littermates. The infiltrating T-cells in tg brains did not co-localise with amyloid plaques, produced less interferon-gamma than those in controls and did not proliferate locally. Bona-fide dendritic cells were virtually absent from the brain parenchyma of both non-tg and tg mice, and APCs from tg brains showed an immature phenotype, with accumulation of MHC-II in intracellular compartments. These results indicate that cerebral amyloidosis promotes T-cell infiltration but interferes with local antigen presentation and T-cell activation. The inability of the brain immune surveillance to orchestrate a protective immune response to amyloid-beta peptide might contribute to the accumulation of amyloid in the progression of the disease. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Simultaneous Control of Error Rates in fMRI Data Analysis

PubMed Central

Kang, Hakmook; Blume, Jeffrey; Ombao, Hernando; Badre, David

2015-01-01

The key idea of statistical hypothesis testing is to fix, and thereby control, the Type I error (false positive) rate across samples of any size. Multiple comparisons inflate the global (family-wise) Type I error rate and the traditional solution to maintaining control of the error rate is to increase the local (comparison-wise) Type II error (false negative) rates. However, in the analysis of human brain imaging data, the number of comparisons is so large that this solution breaks down: the local Type II error rate ends up being so large that scientifically meaningful analysis is precluded. Here we propose a novel solution to this problem: allow the Type I error rate to converge to zero along with the Type II error rate. It works because when the Type I error rate per comparison is very small, the accumulation (or global) Type I error rate is also small. This solution is achieved by employing the Likelihood paradigm, which uses likelihood ratios to measure the strength of evidence on a voxel-by-voxel basis. In this paper, we provide theoretical and empirical justification for a likelihood approach to the analysis of human brain imaging data. In addition, we present extensive simulations that show the likelihood approach is viable, leading to ‘cleaner’ looking brain maps and operationally superiority (lower average error rate). Finally, we include a case study on cognitive control related activation in the prefrontal cortex of the human brain. PMID:26272730

Effects of early focal brain injury on memory for visuospatial patterns: selective deficits of global-local processing.

PubMed

Stiles, Joan; Stern, Catherine; Appelbaum, Mark; Nass, Ruth; Trauner, Doris; Hesselink, John

2008-01-01

Selective deficits in visuospatial processing are present early in development among children with perinatal focal brain lesions (PL). Children with right hemisphere PL (RPL) are impaired in configural processing, while children with left hemisphere PL (LPL) are impaired in featural processing. Deficits associated with LPL are less pervasive than those observed with RPL, but this difference may reflect the structure of the tasks used for assessment. Many of the tasks used to date may place greater demands on configural processing, thus highlighting this deficit in the RPL group. This study employed a task designed to place comparable demands on configural and featural processing, providing the opportunity to obtain within-task evidence of differential deficit. Sixty-two 5- to 14-year-old children (19 RPL, 19 LPL, and 24 matched controls) reproduced from memory a series of hierarchical forms (large forms composed of small forms). Global- and local-level reproduction accuracy was scored. Controls were equally accurate on global- and local-level reproduction. Children with RPL were selectively impaired on global accuracy, and children with LPL on local accuracy, thus documenting a double dissociation in global-local processing.

Disrupted Brain Functional Organization in Epilepsy Revealed by Graph Theory Analysis.

PubMed

Song, Jie; Nair, Veena A; Gaggl, Wolfgang; Prabhakaran, Vivek

2015-06-01

The human brain is a complex and dynamic system that can be modeled as a large-scale brain network to better understand the reorganizational changes secondary to epilepsy. In this study, we developed a brain functional network model using graph theory methods applied to resting-state fMRI data acquired from a group of epilepsy patients and age- and gender-matched healthy controls. A brain functional network model was constructed based on resting-state functional connectivity. A minimum spanning tree combined with proportional thresholding approach was used to obtain sparse connectivity matrices for each subject, which formed the basis of brain networks. We examined the brain reorganizational changes in epilepsy thoroughly at the level of the whole brain, the functional network, and individual brain regions. At the whole-brain level, local efficiency was significantly decreased in epilepsy patients compared with the healthy controls. However, global efficiency was significantly increased in epilepsy due to increased number of functional connections between networks (although weakly connected). At the functional network level, there were significant proportions of newly formed connections between the default mode network and other networks and between the subcortical network and other networks. There was a significant proportion of decreasing connections between the cingulo-opercular task control network and other networks. Individual brain regions from different functional networks, however, showed a distinct pattern of reorganizational changes in epilepsy. These findings suggest that epilepsy alters brain efficiency in a consistent pattern at the whole-brain level, yet alters brain functional networks and individual brain regions differently.

Brain shaving: adaptive detection for brain PET data

NASA Astrophysics Data System (ADS)

Grecchi, Elisabetta; Doyle, Orla M.; Bertoldo, Alessandra; Pavese, Nicola; Turkheimer, Federico E.

2014-05-01

The intricacy of brain biology is such that the variation of imaging end-points in health and disease exhibits an unpredictable range of spatial distributions from the extremely localized to the very diffuse. This represents a challenge for the two standard approaches to analysis, the mass univariate and the multivariate that exhibit either strong specificity but not as good sensitivity (the former) or poor specificity and comparatively better sensitivity (the latter). In this work, we develop an analytical methodology for positron emission tomography that operates an extraction (‘shaving’) of coherent patterns of signal variation while maintaining control of the type I error. The methodology operates two rotations on the image data, one local using the wavelet transform and one global using the singular value decomposition. The control of specificity is obtained by using the gap statistic that selects, within each eigenvector, a subset of significantly coherent elements. Face-validity of the algorithm is demonstrated using a paradigmatic data-set with two radiotracers, [11C]-raclopride and [11C]-(R)-PK11195, measured on the same Huntington's disease patients, a disorder with a genetic based diagnosis. The algorithm is able to detect the two well-known separate but connected processes of dopamine neuronal loss (localized in the basal ganglia) and neuroinflammation (diffusive around the whole brain). These processes are at the two extremes of the distributional envelope, one being very sparse and the latter being perfectly Gaussian and they are not adequately detected by the univariate and the multivariate approaches.

Classification of MR brain images by combination of multi-CNNs for AD diagnosis

NASA Astrophysics Data System (ADS)

Cheng, Danni; Liu, Manhua; Fu, Jianliang; Wang, Yaping

2017-07-01

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder with progressive impairment of memory and cognitive functions. Its early diagnosis is crucial for development of future treatment. Magnetic resonance images (MRI) play important role to help understand the brain anatomical changes related to AD. Conventional methods extract the hand-crafted features such as gray matter volumes and cortical thickness and train a classifier to distinguish AD from other groups. Different from these methods, this paper proposes to construct multiple deep 3D convolutional neural networks (3D-CNNs) to learn the various features from local brain images which are combined to make the final classification for AD diagnosis. First, a number of local image patches are extracted from the whole brain image and a 3D-CNN is built upon each local patch to transform the local image into more compact high-level features. Then, the upper convolution and fully connected layers are fine-tuned to combine the multiple 3D-CNNs for image classification. The proposed method can automatically learn the generic features from imaging data for classification. Our method is evaluated using T1-weighted structural MR brain images on 428 subjects including 199 AD patients and 229 normal controls (NC) from Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Experimental results show that the proposed method achieves an accuracy of 87.15% and an AUC (area under the ROC curve) of 92.26% for AD classification, demonstrating the promising classification performances.

Identification of elevated urea as a severe, ubiquitous metabolic defect in the brain of patients with Huntington's disease.

PubMed

Patassini, Stefano; Begley, Paul; Reid, Suzanne J; Xu, Jingshu; Church, Stephanie J; Curtis, Maurice; Dragunow, Mike; Waldvogel, Henry J; Unwin, Richard D; Snell, Russell G; Faull, Richard L M; Cooper, Garth J S

Huntington's disease (HD) is a neurodegenerative disorder wherein the aetiological defect is a mutation in the Huntington's gene (HTT), which alters the structure of the huntingtin protein through the lengthening of a polyglutamine tract and initiates a cascade that ultimately leads to dementia and premature death. However, neurodegeneration typically manifests in HD only in middle age, and processes linking the causative mutation to brain disease are poorly understood. Here, our objective was to elucidate further the processes that cause neurodegeneration in HD, by measuring levels of metabolites in brain regions known to undergo varying degrees of damage. We applied gas-chromatography/mass spectrometry-based metabolomics in a case-control study of eleven brain regions in short post-mortem-delay human tissue from nine well-characterized HD patients and nine controls. Unexpectedly, a single major abnormality was evident in all eleven brain regions studied across the forebrain, midbrain and hindbrain, namely marked elevation of urea, a metabolite formed in the urea cycle by arginase-mediated cleavage of arginine. Urea cycle activity localizes primarily in the liver, where it functions to incorporate protein-derived amine-nitrogen into urea for recycling or urinary excretion. It also occurs in other cell-types, but systemic over-production of urea is not known in HD. These findings are consistent with impaired local urea regulation in brain, by up-regulation of synthesis and/or defective clearance. We hypothesize that defective brain urea metabolism could play a substantive role in the pathogenesis of neurodegeneration, perhaps via defects in osmoregulation or nitrogen metabolism. Brain urea metabolism is therefore a target for generating novel monitoring/imaging strategies and/or therapeutic interventions aimed at ameliorating the impact of HD in patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Mapping the Regional Influence of Genetics on Brain Structure Variability - A Tensor-Based Morphometry Study

PubMed Central

Brun, Caroline; Leporé, Natasha; Pennec, Xavier; Lee, Agatha D.; Barysheva, Marina; Madsen, Sarah K.; Avedissian, Christina; Chou, Yi-Yu; de Zubicaray, Greig I.; McMahon, Katie; Wright, Margaret; Toga, Arthur W.; Thompson, Paul M.

2010-01-01

Genetic and environmental factors influence brain structure and function profoundly The search for heritable anatomical features and their influencing genes would be accelerated with detailed 3D maps showing the degree to which brain morphometry is genetically determined. As part of an MRI study that will scan 1150 twins, we applied Tensor-Based Morphometry to compute morphometric differences in 23 pairs of identical twins and 23 pairs of same-sex fraternal twins (mean age: 23.8 ± 1.8 SD years). All 92 twins’ 3D brain MRI scans were nonlinearly registered to a common space using a Riemannian fluid-based warping approach to compute volumetric differences across subjects. A multi-template method was used to improve volume quantification. Vector fields driving each subject’s anatomy onto the common template were analyzed to create maps of local volumetric excesses and deficits relative to the standard template. Using a new structural equation modeling method, we computed the voxelwise proportion of variance in volumes attributable to additive (A) or dominant (D) genetic factors versus shared environmental (C) or unique environmental factors (E). The method was also applied to various anatomical regions of interest (ROIs). As hypothesized, the overall volumes of the brain, basal ganglia, thalamus, and each lobe were under strong genetic control; local white matter volumes were mostly controlled by common environment. After adjusting for individual differences in overall brain scale, genetic influences were still relatively high in the corpus callosum and in early-maturing brain regions such as the occipital lobes, while environmental influences were greater in frontal brain regions which have a more protracted maturational time-course. PMID:19446645

Dynamic mapping of brain and cognitive control of virtual gameplay (study by functional magnetic resonance imaging).

PubMed

Rezakova, M V; Mazhirina, K G; Pokrovskiy, M A; Savelov, A A; Savelova, O A; Shtark, M B

2013-04-01

Using functional magnetic resonance imaging technique, we performed online brain mapping of gamers, practiced to voluntary (cognitively) control their heart rate, the parameter that operated a competitive virtual gameplay in the adaptive feedback loop. With the default start picture, the regions of interest during the formation of optimal cognitive strategy were as follows: Brodmann areas 19, 37, 39 and 40, i.e. cerebellar structures (vermis, amygdala, pyramids, clivus). "Localization" concept of the contribution of the cerebellum to cognitive processes is discussed.

Scan-stratified case-control sampling for modeling blood-brain barrier integrity in multiple sclerosis.

PubMed

Pomann, Gina-Maria; Sweeney, Elizabeth M; Reich, Daniel S; Staicu, Ana-Maria; Shinohara, Russell T

2015-09-10

Multiple sclerosis (MS) is an immune-mediated neurological disease that causes morbidity and disability. In patients with MS, the accumulation of lesions in the white matter of the brain is associated with disease progression and worse clinical outcomes. Breakdown of the blood-brain barrier in newer lesions is indicative of more active disease-related processes and is a primary outcome considered in clinical trials of treatments for MS. Such abnormalities in active MS lesions are evaluated in vivo using contrast-enhanced structural MRI, during which patients receive an intravenous infusion of a costly magnetic contrast agent. In some instances, the contrast agents can have toxic effects. Recently, local image regression techniques have been shown to have modest performance for assessing the integrity of the blood-brain barrier based on imaging without contrast agents. These models have centered on the problem of cross-sectional classification in which patients are imaged at a single study visit and pre-contrast images are used to predict post-contrast imaging. In this paper, we extend these methods to incorporate historical imaging information, and we find the proposed model to exhibit improved performance. We further develop scan-stratified case-control sampling techniques that reduce the computational burden of local image regression models, while respecting the low proportion of the brain that exhibits abnormal vascular permeability. Copyright © 2015 John Wiley & Sons, Ltd.

Graph theoretical analysis reveals disrupted topological properties of whole brain functional networks in temporal lobe epilepsy.

PubMed

Wang, Junjing; Qiu, Shijun; Xu, Yong; Liu, Zhenyin; Wen, Xue; Hu, Xiangshu; Zhang, Ruibin; Li, Meng; Wang, Wensheng; Huang, Ruiwang

2014-09-01

Temporal lobe epilepsy (TLE) is one of the most common forms of drug-resistant epilepsy. Previous studies have indicated that the TLE-related impairments existed in extensive local functional networks. However, little is known about the alterations in the topological properties of whole brain functional networks. In this study, we acquired resting-state BOLD-fMRI (rsfMRI) data from 26 TLE patients and 25 healthy controls, constructed their whole brain functional networks, compared the differences in topological parameters between the TLE patients and the controls, and analyzed the correlation between the altered topological properties and the epilepsy duration. The TLE patients showed significant increases in clustering coefficient and characteristic path length, but significant decrease in global efficiency compared to the controls. We also found altered nodal parameters in several regions in the TLE patients, such as the bilateral angular gyri, left middle temporal gyrus, right hippocampus, triangular part of left inferior frontal gyrus, left inferior parietal but supramarginal and angular gyri, and left parahippocampus gyrus. Further correlation analysis showed that the local efficiency of the TLE patients correlated positively with the epilepsy duration. Our results indicated the disrupted topological properties of whole brain functional networks in TLE patients. Our findings indicated the TLE-related impairments in the whole brain functional networks, which may help us to understand the clinical symptoms of TLE patients and offer a clue for the diagnosis and treatment of the TLE patients. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Toward more versatile and intuitive cortical brain-machine interfaces.

PubMed

Andersen, Richard A; Kellis, Spencer; Klaes, Christian; Aflalo, Tyson

2014-09-22

Brain-machine interfaces have great potential for the development of neuroprosthetic applications to assist patients suffering from brain injury or neurodegenerative disease. One type of brain-machine interface is a cortical motor prosthetic, which is used to assist paralyzed subjects. Motor prosthetics to date have typically used the motor cortex as a source of neural signals for controlling external devices. The review will focus on several new topics in the arena of cortical prosthetics. These include using: recordings from cortical areas outside motor cortex; local field potentials as a source of recorded signals; somatosensory feedback for more dexterous control of robotics; and new decoding methods that work in concert to form an ecology of decode algorithms. These new advances promise to greatly accelerate the applicability and ease of operation of motor prosthetics. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Aberrant topological properties of whole-brain functional network in chronic right-sided sensorineural hearing loss: a resting-state functional MRI study].

PubMed

Zhang, Lingling; Liu, Bin; Xu, Yangwen; Yang, Ming; Feng, Yuan; Huang, Yaqing; Huan, Zhichun; Hou, Zhaorui

2015-02-03

To investigate the topological properties of the functional brain network in unilateral sensorineural hearing loss patients. In this study, we acquired resting-state BOLD- fMRI data from 19 right-sided SNHL patients and 31 healthy controls with normal hearing and constructed their whole brain functional networks. Two-sample two-tailed t-tests were performed to investigate group differences in topological parameters between the USNHL patients and the controls. Partial correlation analysis was conducted to determine the relationships between the network metrics and USNHL-related variables. Both USNHL patients and controls exhibited small-word architecture in their brain functional networks within the range 0. 1 - 0. 2 of sparsity. Compared to the controls, USNHL patients showed significant increase in characteristic path length and normalized characteristic path length, but significant decrease in global efficiency. Clustering coefficient, local efficiency and normalized clustering coefficient demonstrated no significant difference. Furthermore, USNHL patients exhibited no significant association between the altered network metrics and the duration of USNHL or the severity of hearing loss. Our results indicated the altered topological properties of whole brain functional networks in USNHL patients, which may help us to understand pathophysiologic mechanism of USNHL patients.

Differential Brain Development with Low and High IQ in Attention-Deficit/Hyperactivity Disorder

PubMed Central

de Zeeuw, Patrick; Schnack, Hugo G.; van Belle, Janna; Weusten, Juliette; van Dijk, Sarai; Langen, Marieke; Brouwer, Rachel M.; van Engeland, Herman; Durston, Sarah

2012-01-01

Attention-Deficit/Hyperactivity Disorder (ADHD) and intelligence (IQ) are both heritable phenotypes. Overlapping genetic effects have been suggested to influence both, with neuroimaging work suggesting similar overlap in terms of morphometric properties of the brain. Together, this evidence suggests that the brain changes characteristic of ADHD may vary as a function of IQ. This study investigated this hypothesis in a sample of 108 children with ADHD and 106 typically developing controls, who participated in a cross-sectional anatomical MRI study. A subgroup of 64 children also participated in a diffusion tensor imaging scan. Brain volumes, local cortical thickness and average cerebral white matter microstructure were analyzed in relation to diagnostic group and IQ. Dimensional analyses investigated possible group differences in the relationship between anatomical measures and IQ. Second, the groups were split into above and below median IQ subgroups to investigate possible differences in the trajectories of cortical development. Dimensionally, cerebral gray matter volume and cerebral white matter microstructure were positively associated with IQ for controls, but not for ADHD. In the analyses of the below and above median IQ subgroups, we found no differences from controls in cerebral gray matter volume in ADHD with below-median IQ, but a delay of cortical development in a number of regions, including prefrontal areas. Conversely, in ADHD with above-median IQ, there were significant reductions from controls in cerebral gray matter volume, but no local differences in the trajectories of cortical development. In conclusion, the basic relationship between IQ and neuroanatomy appears to be altered in ADHD. Our results suggest that there may be multiple brain phenotypes associated with ADHD, where ADHD combined with above median IQ is characterized by small, more global reductions in brain volume that are stable over development, whereas ADHD with below median IQ is associated more with a delay of cortical development. PMID:22536435

EEG functional connectivity, axon delays and white matter disease.

PubMed

Nunez, Paul L; Srinivasan, Ramesh; Fields, R Douglas

2015-01-01

Both structural and functional brain connectivities are closely linked to white matter disease. We discuss several such links of potential interest to neurologists, neurosurgeons, radiologists, and non-clinical neuroscientists. Treatment of brains as genuine complex systems suggests major emphasis on the multi-scale nature of brain connectivity and dynamic behavior. Cross-scale interactions of local, regional, and global networks are apparently responsible for much of EEG's oscillatory behaviors. Finite axon propagation speed, often assumed to be infinite in local network models, is central to our conceptual framework. Myelin controls axon speed, and the synchrony of impulse traffic between distant cortical regions appears to be critical for optimal mental performance and learning. Several experiments suggest that axon conduction speed is plastic, thereby altering the regional and global white matter connections that facilitate binding of remote local networks. Combined EEG and high resolution EEG can provide distinct multi-scale estimates of functional connectivity in both healthy and diseased brains with measures like frequency and phase spectra, covariance, and coherence. White matter disease may profoundly disrupt normal EEG coherence patterns, but currently these kinds of studies are rare in scientific labs and essentially missing from clinical environments. Copyright © 2014 International Federation of Clinical Neurophysiology. All rights reserved.

Changes in intrinsic local connectivity after reading intervention in children with autism.

PubMed

Maximo, Jose O; Murdaugh, Donna L; O'Kelley, Sarah; Kana, Rajesh K

2017-12-01

Most of the existing behavioral and cognitive intervention programs in autism spectrum disorders (ASD) have not been tested at the neurobiological level, thus falling short of finding quantifiable neurobiological changes underlying behavioral improvement. The current study takes a translational neuroimaging approach to test the impact of a structured visual imagery-based reading intervention on improving reading comprehension and assessing its underlying local neural circuitry. Behavioral and resting state functional MRI (rs-fMRI) data were collected from children with ASD who were randomly assigned to an Experimental group (ASD-EXP; n=14) and a Wait-list control group (ASD-WLC; n=14). Participants went through an established reading intervention training program (Visualizing and Verbalizing for language comprehension and thinking or V/V; 4-h per day, 10-weeks, 200h of face-to-face instruction). Local functional connectivity was examined using a connection density approach from graph theory focusing on brain areas considered part of the Reading Network. The main results are as follows: (I) the ASD-EXP group showed significant improvement, compared to the ASD-WLC group, in their reading comprehension ability evidenced from change in comprehension scores; (II) the ASD-EXP group showed increased local brain connectivity in Reading Network regions compared to the ASD-WLC group post-intervention; (III) intervention-related changes in local brain connectivity were observed in the ASD-EXP from pre to post-intervention; and (IV) improvement in language comprehension significantly predicted changes in local connectivity. The findings of this study provide novel insights into brain plasticity in children with developmental disorders using targeted intervention programs. Published by Elsevier Inc.

Spikes, Local Field Potentials, and Electrocorticogram Characterization during Motor Learning in Rats for Brain Machine Interface Tasks.

PubMed

Marzullo, T C; Dudley, J R; Miller, C R; Trejo, L; Kipke, D R

2005-01-01

Brain machine interface development typically falls into two arenas, invasive extracellular recording and non-invasive electroencephalogram recording methods. The relationship between action potentials and field potentials is not well understood, and investigation of interrelationships may improve design of neuroprosthetic control systems. Rats were trained on a motor learning task whereby they had to insert their noses into an aperture while simultaneously pressing down on levers with their forepaws; spikes, local field potentials (LFPs), and electrocorticograms (ECoGs) over the motor cortex were recorded and characterized. Preliminary results suggest that the LFP activity in lower cortical layers oscillates with the ECoG.

Cortical thickness and surface area correlates with cognitive dysfunction among first-episode psychosis patients.

PubMed

Haring, L; Müürsepp, A; Mõttus, R; Ilves, P; Koch, K; Uppin, K; Tarnovskaja, J; Maron, E; Zharkovsky, A; Vasar, E; Vasar, V

2016-07-01

In studies using magnetic resonance imaging (MRI), some have reported specific brain structure-function relationships among first-episode psychosis (FEP) patients, but findings are inconsistent. We aimed to localize the brain regions where cortical thickness (CTh) and surface area (cortical area; CA) relate to neurocognition, by performing an MRI on participants and measuring their neurocognitive performance using the Cambridge Neuropsychological Test Automated Battery (CANTAB), in order to investigate any significant differences between FEP patients and control subjects (CS). Exploration of potential correlations between specific cognitive functions and brain structure was performed using CANTAB computer-based neurocognitive testing and a vertex-by-vertex whole-brain MRI analysis of 63 FEP patients and 30 CS. Significant correlations were found between cortical parameters in the frontal, temporal, cingular and occipital brain regions and performance in set-shifting, working memory manipulation, strategy usage and sustained attention tests. These correlations were significantly dissimilar between FEP patients and CS. Significant correlations between CTh and CA with neurocognitive performance were localized in brain areas known to be involved in cognition. The results also suggested a disrupted structure-function relationship in FEP patients compared with CS.

Imaging of glutathione localization in brain with technetium-99M meso-hexamethyl propyleneamine oxime

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

Sasaki, T.; Toyama, H.; Oda, K.

1995-05-01

Previous studies have shown decreasing [Tc-99m] meso-HM-PAO uptake in accordance with glutathione (GSH) content in diethyl, maleate (DEM) treated mice brain. In order to elucidate the retention mechanism of [Tc-99m] HM-PAO in brain and to visualize the regional localization of GSH in the brain with [Tc-99m] meso-HM-PAO, the relationship between the tissue GSH content and uptake of [Tc-99m] meso-HM-PAO was studied in rats and rabbits. Increasing pre-load of DEM (550 mg/kg body weight), an agent to reduce GSH content by glutathione transferase, led to a decrease in GSH (control 1.972{plus_minus}0.017 vs DEM 1.138{plus_minus}0.106 mM) and uptake of [Tc-99m] meso-HM-PAO tomore » half of the control in the rat brain (control 0.281{plus_minus}0.024 vs DEM 0.153 {plus_minus} 0.009 % dose/g). On the other hand, the DEM did not decrease GSH or the uptake of [Tc-99m] meso-HM-PAO in the rabbit brain, in which glutathione transferase activity is very low. These results were also demonstrated by images with pin-hole collimated gamma camera. The uptake of [Tc-99m] meso showed variations in the regional distribution, but the d,l-isomer was uniform. [Tc-99m] meso-HM-PAO uptake was well correlated with GSH content in mice brain regions (r=0.800, p<0.02), whereas [Tc-99m]d,l-HM-PAO was not (r=0.017, p>0.5). Both [Tc-99m] mesa HM-PAO uptake and GSH content were especially high at cerebellum (Uptake: 2.598{plus_minus}0.256 % dose/g. GSH: 2.372{plus_minus}0.107 mM) as compared to other areas (Uptake;cerebral cortex 1.797{plus_minus}0.100 brain stem 1.607 {plus_minus}0.112 % dose/g. GSH: cerebral cortex 1.635{plus_minus}0.142 brain stem 1.478{plus_minus}0.141 mM).« less

Local Brain Activity Differences Between Herpes Zoster and Postherpetic Neuralgia Patients: A Resting-State Functional MRI Study.

PubMed

Cao, Song; Li, Ying; Deng, Wenwen; Qin, Bangyong; Zhang, Yi; Xie, Peng; Yuan, Jie; Yu, Buwei; Yu, Tian

2017-07-01

Herpes zoster (HZ) can develop into postherpetic neuralgia (PHN), both of which are painful diseases. PHN patients suffer chronic pain and emotional disorders. Previous studies showed that the PHN brain displayed abnormal activity and structural change, but the difference in brain activity between HZ and PHN is still not known. To identify regional brain activity changes in HZ and PHN brains with resting-state functional magnetic resonance imaging (rs-fMRI) technique, and to observe the differences between HZ and PHN patients. Observational study. University hospital. Regional homogeneity (ReHo) and fractional aptitude of low-frequency fluctuation (fALFF) methods were employed to analysis resting-state brain activity. Seventy-three age and gender matched patients (50 HZ, 23 PHN) and 55 healthy controls were enrolled. ReHo and fALFF changes were analyzed to detect the functional abnormality in HZ and PHN brains. Compared with healthy controls, HZ and PHN patients exhibited abnormal ReHo and fALFF values in classic pain-related brain regions (such as the frontal lobe, thalamus, insular, and cerebellum) as well as the brainstem, limbic lobe, and temporal lobe. When HZ developed to PHN, the activity in the vast area of the cerebellum significantly increased while that of some regions in the occipital lobe, temporal lobe, parietal lobe, and limbic lobe showed an apparent decrease. (a) Relatively short pain duration (mean 12.2 months) and small sample size (n = 23) for PHN group. (b) Comparisons at different time points (with paired t-tests) for each patient may minimize individual differences. HZ and PHN induced local brain activity changed in the pain matrix, brainstem, and limbic system. HZ chronification induced functional change in the cerebellum, occipital lobe, temporal lobe, parietal lobe, and limbic lobe. These brain activity changes may be correlated with HZ-PHN transition. Herpes zoster, postherpetic neuralgia, resting-state fMRI (rs-fMRI), regional homogeneity (ReHo), fractional aptitude of low-frequency fluctuation (fALFF).

Forever Young(er): potential age-defying effects of long-term meditation on gray matter atrophy

PubMed Central

Luders, Eileen; Cherbuin, Nicolas; Kurth, Florian

2015-01-01

While overall life expectancy has been increasing, the human brain still begins deteriorating after the first two decades of life and continues degrading further with increasing age. Thus, techniques that diminish the negative impact of aging on the brain are desirable. Existing research, although scarce, suggests meditation to be an attractive candidate in the quest for an accessible and inexpensive, efficacious remedy. Here, we examined the link between age and cerebral gray matter re-analyzing a large sample (n = 100) of long-term meditators and control subjects aged between 24 and 77 years. When correlating global and local gray matter with age, we detected negative correlations within both controls and meditators, suggesting a decline over time. However, the slopes of the regression lines were steeper and the correlation coefficients were stronger in controls than in meditators. Moreover, the age-affected brain regions were much more extended in controls than in meditators, with significant group-by-age interactions in numerous clusters throughout the brain. Altogether, these findings seem to suggest less age-related gray matter atrophy in long-term meditation practitioners. PMID:25653628

Stereotactic Radiosurgery for Patients With Brain Metastases From Small Cell Lung Cancer

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

Wegner, Rodney E.; Olson, Adam C.; Kondziolka, Douglas

2011-11-01

Background: Patients with small-cell lung cancer have a high likelihood of developing brain metastases. Many of these patients will have prophylactic cranial irradiation (PCI) or eventually undergo whole brain radiation therapy (WBRT). Despite these treatments, a large number of these patients will have progression of their intracranial disease and require additional local therapy. Stereotactic radiosurgery (SRS) is an important treatment option for such patients. Methods: We retrospectively reviewed the charts of 44 patients with brain metastases from small-cell lung cancer treated with gamma knife SRS. Multivariate analysis was used to determine significant prognostic factors influencing survival. Results: The median follow-upmore » from SRS in this patient population was 9 months (1-49 months). The median overall survival (OS) was 9 months after SRS. Karnofsky performance status (KPS) and combined treatment involving WBRT and SRS within 4 weeks were the two factors identified as being significant predictors of increased OS (p = 0.033 and 0.040, respectively). When comparing all patients, patients treated with a combined approach had a median OS of 14 months compared to 6 months if SRS was delivered alone. We also compared the OS times from the first definitive radiation: WBRT, WBRT and SRS if combined therapy was used, and SRS if the patient never received WBRT. The median survival for those groups was 12, 14, and 13 months, respectively, p = 0.19. Seventy percent of patients had follow-up magnetic resonance imaging available for review. Actuarial local control at 6 months and 12 months was 90% and 86%, respectively. Only 1 patient (2.2%) had symptomatic intracranial swelling related to treatment, which responded to a short course of steroids. New brain metastases outside of the treated area developed in 61% of patients at a median time of 7 months; 81% of these patients had received previous WBRT. Conclusions: Stereotactic radiosurgery for small-cell lung carcinoma brain metastases provided safe and effective local tumor control in the majority of patients.« less

[Study on Abnormal Topological Properties of Structural Brain Networks of Patients with Depression Comorbid with Anxiety].

PubMed

Wu, Xiuyong; Wu, Xiaoming; Peng, Hongjun; Ning, Yuping; Wu, Kai

2016-06-01

This paper is aimed to analyze the topological properties of structural brain networks in depressive patients with and without anxiety and to explore the neuropath logical mechanisms of depression comorbid with anxiety.Diffusion tensor imaging and deterministic tractography were applied to map the white matter structural networks.We collected 20 depressive patients with anxiety(DPA),18 depressive patients without anxiety(DP),and 28 normal controls(NC)as comparative groups.The global and nodal properties of the structural brain networks in the three groups were analyzed with graph theoretical methods.The result showed that1 the structural brain networks in three groups showed small-world properties and highly connected global hubs predominately from association cortices;2DP group showed lower local efficiency and global efficiency compared to NC group,whereas DPA group showed higher local efficiency and global efficiency compared to NC group;3significant differences of network properties(clustering coefficient,characteristic path lengths,local efficiency,global efficiency)were found between DPA and DP groups;4DP group showed significant changes of nodal efficiency in the brain areas primarily in the temporal lobe and bilateral frontal gyrus,compared to DPA and NC groups.The analysis indicated that the DP and DPA groups showed nodal properties of the structural brain networks,compared to NC group.Moreover,the two diseased groups indicated an opposite trend in the network properties.The results of this study may provide a new imaging index for clinical diagnosis for depression comorbid with anxiety.

Cortical and subcortical atrophy in Alzheimer disease: parallel atrophy of thalamus and hippocampus.

PubMed

Štěpán-Buksakowska, Irena; Szabó, Nikoletta; Hořínek, Daniel; Tóth, Eszter; Hort, Jakub; Warner, Joshua; Charvát, František; Vécsei, László; Roček, Miloslav; Kincses, Zsigmond T

2014-01-01

Brain atrophy is a key imaging hallmark of Alzheimer disease (AD). In this study, we carried out an integrative evaluation of AD-related atrophy. Twelve patients with AD and 13 healthy controls were enrolled. We conducted a cross-sectional analysis of total brain tissue volumes with SIENAX. Localized gray matter atrophy was identified with optimized voxel-wise morphometry (FSL-VBM), and subcortical atrophy was evaluated by active shape model implemented in FMRIB's Integrated Registration Segmentation Toolkit. SIENAX analysis demonstrated total brain atrophy in AD patients; voxel-based morphometry analysis showed atrophy in the bilateral mediotemporal regions and in the posterior brain regions. In addition, regarding the diminished volumes of thalami and hippocampi in AD patients, subsequent vertex analysis of the segmented structures indicated shrinkage of the bilateral anterior thalami and the left medial hippocampus. Interestingly, the volume of the thalami and hippocampi were highly correlated with the volume of the thalami and amygdalae on both sides in AD patients, but not in healthy controls. This complex structural information proved useful in the detailed interpretation of AD-related neurodegenerative process, as the multilevel approach showed both global and local atrophy on cortical and subcortical levels. Most importantly, our results raise the possibility that subcortical structure atrophy is not independent in AD patients.

Spatially Nonlinear Interdependence of Alpha-Oscillatory Neural Networks under Chan Meditation

PubMed Central

Chang, Chih-Hao

2013-01-01

This paper reports the results of our investigation of the effects of Chan meditation on brain electrophysiological behaviors from the viewpoint of spatially nonlinear interdependence among regional neural networks. Particular emphasis is laid on the alpha-dominated EEG (electroencephalograph). Continuous-time wavelet transform was adopted to detect the epochs containing substantial alpha activities. Nonlinear interdependence quantified by similarity index S(X∣Y), the influence of source signal Y on sink signal X, was applied to the nonlinear dynamical model in phase space reconstructed from multichannel EEG. Experimental group involved ten experienced Chan-Meditation practitioners, while control group included ten healthy subjects within the same age range, yet, without any meditation experience. Nonlinear interdependence among various cortical regions was explored for five local neural-network regions, frontal, posterior, right-temporal, left-temporal, and central regions. In the experimental group, the inter-regional interaction was evaluated for the brain dynamics under three different stages, at rest (stage R, pre-meditation background recording), in Chan meditation (stage M), and the unique Chakra-focusing practice (stage C). Experimental group exhibits stronger interactions among various local neural networks at stages M and C compared with those at stage R. The intergroup comparison demonstrates that Chan-meditation brain possesses better cortical inter-regional interactions than the resting brain of control group. PMID:24489583

Development of quantitative analysis method for stereotactic brain image: assessment of reduced accumulation in extent and severity using anatomical segmentation.

PubMed

Mizumura, Sunao; Kumita, Shin-ichiro; Cho, Keiichi; Ishihara, Makiko; Nakajo, Hidenobu; Toba, Masahiro; Kumazaki, Tatsuo

2003-06-01

Through visual assessment by three-dimensional (3D) brain image analysis methods using stereotactic brain coordinates system, such as three-dimensional stereotactic surface projections and statistical parametric mapping, it is difficult to quantitatively assess anatomical information and the range of extent of an abnormal region. In this study, we devised a method to quantitatively assess local abnormal findings by segmenting a brain map according to anatomical structure. Through quantitative local abnormality assessment using this method, we studied the characteristics of distribution of reduced blood flow in cases with dementia of the Alzheimer type (DAT). Using twenty-five cases with DAT (mean age, 68.9 years old), all of whom were diagnosed as probable Alzheimer's disease based on NINCDS-ADRDA, we collected I-123 iodoamphetamine SPECT data. A 3D brain map using the 3D-SSP program was compared with the data of 20 cases in the control group, who age-matched the subject cases. To study local abnormalities on the 3D images, we divided the whole brain into 24 segments based on anatomical classification. We assessed the extent of an abnormal region in each segment (rate of the coordinates with a Z-value that exceeds the threshold value, in all coordinates within a segment), and severity (average Z-value of the coordinates with a Z-value that exceeds the threshold value). This method clarified orientation and expansion of reduced accumulation, through classifying stereotactic brain coordinates according to the anatomical structure. This method was considered useful for quantitatively grasping distribution abnormalities in the brain and changes in abnormality distribution.

Focused Ultrasound-Induced Blood–Brain Barrier Opening to Enhance Temozolomide Delivery for Glioblastoma Treatment: A Preclinical Study

PubMed Central

Wei, Kuo-Chen; Chu, Po-Chun; Wang, Hay-Yan Jack; Huang, Chiung-Yin; Chen, Pin-Yuan; Tsai, Hong-Chieh; Lu, Yu-Jen; Lee, Pei-Yun; Tseng, I-Chou; Feng, Li-Ying; Hsu, Peng-Wei; Yen, Tzu-Chen; Liu, Hao-Li

2013-01-01

The purpose of this study is to assess the preclinical therapeutic efficacy of magnetic resonance imaging (MRI)-monitored focused ultrasound (FUS)-induced blood-brain barrier (BBB) disruption to enhance Temozolomide (TMZ) delivery for improving Glioblastoma Multiforme (GBM) treatment. MRI-monitored FUS with microbubbles was used to transcranially disrupt the BBB in brains of Fisher rats implanted with 9L glioma cells. FUS-BBB opening was spectrophotometrically determined by leakage of dyes into the brain, and TMZ was quantitated in cerebrospinal fluid (CSF) and plasma by LC-MS\\MS. The effects of treatment on tumor progression (by MRI), animal survival and brain tissue histology were investigated. Results demonstrated that FUS-BBB opening increased the local accumulation of dyes in brain parenchyma by 3.8-/2.1-fold in normal/tumor tissues. Compared to TMZ alone, combined FUS treatment increased the TMZ CSF/plasma ratio from 22.7% to 38.6%, reduced the 7-day tumor progression ratio from 24.03 to 5.06, and extended the median survival from 20 to 23 days. In conclusion, this study provided preclinical evidence that FUS BBB-opening increased the local concentration of TMZ to improve the control of tumor progression and animal survival, suggesting its clinical potential for improving current brain tumor treatment. PMID:23527068

Distribution of polymer nanoparticles by convection-enhanced delivery to brain tumors.

PubMed

Saucier-Sawyer, Jennifer K; Seo, Young-Eun; Gaudin, Alice; Quijano, Elias; Song, Eric; Sawyer, Andrew J; Deng, Yang; Huttner, Anita; Saltzman, W Mark

2016-06-28

Glioblastoma multiforme (GBM) is a fatal brain tumor characterized by infiltration beyond the margins of the main tumor mass and local recurrence after surgery. The blood-brain barrier (BBB) poses the most significant hurdle to brain tumor treatment. Convection-enhanced delivery (CED) allows for local administration of agents, overcoming the restrictions of the BBB. Recently, polymer nanoparticles have been demonstrated to penetrate readily through the healthy brain when delivered by CED, and size has been shown to be a critical factor for nanoparticle penetration. Because these brain-penetrating nanoparticles (BPNPs) have high potential for treatment of intracranial tumors since they offer the potential for cell targeting and controlled drug release after administration, here we investigated the intratumoral CED infusions of PLGA BPNPs in animals bearing either U87 or RG2 intracranial tumors. We demonstrate that the overall volume of distribution of these BPNPs was similar to that observed in healthy brains; however, the presence of tumors resulted in asymmetric and heterogeneous distribution patterns, with substantial leakage into the peritumoral tissue. Together, our results suggest that CED of BPNPs should be optimized by accounting for tumor geometry, in terms of location, size and presence of necrotic regions, to determine the ideal infusion site and parameters for individual tumors. Copyright © 2016 Elsevier B.V. All rights reserved.

Intensity-Modulated Radiotherapy for Sinonasal Tumors: Ghent University Hospital Update

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

Madani, Indira; Bonte, Katrien; Vakaet, Luc

2009-02-01

Purpose: To report the long-term outcome of intensity-modulated radiotherapy (IMRT) for sinonasal tumors. Methods and Materials: Between July 1998 and November 2006, 84 patients with sinonasal tumors were treated with IMRT to a median dose of 70 Gy in 35 fractions. Of the 84 patients, 73 had a primary tumor and 11 had local recurrence. The tumor histologic type was adenocarcinoma in 54, squamous cell carcinoma in 17, esthesioneuroblastoma in 9, and adenoid cystic carcinoma in 4. The tumors were located in the ethmoid sinus in 47, maxillary sinus in 19, nasal cavity in 16, and multiple sites in 2.more » Postoperative IMRT was performed in 75 patients and 9 patients received primary IMRT. Results: The median follow-up of living patients was 40 months (range, 8-106). The 5-year local control, overall survival, disease-specific survival, disease-free survival, and freedom from distant metastasis rate was 70.7%, 58.5%, 67%, 59.3%, and 82.2%, respectively. No difference was found in local control and survival between patients with primary or recurrent tumors. On multivariate analysis, invasion of the cribriform plate was significantly associated with lower local control (p = 0.0001) and overall survival (p = 0.0001). Local and distant recurrence was detected in 19 and 10 patients, respectively. Radiation-induced blindness was not observed. One patient developed Grade 3 radiation-induced retinopathy and neovascular glaucoma. Nonocular late radiation-induced toxicity comprised complete lacrimal duct stenosis in 1 patient and brain necrosis in 3 patients. Osteoradionecrosis of the maxilla and brain necrosis were detected in 1 of the 5 reirradiated patients. Conclusion: IMRT for sinonasal tumors provides low rates of radiation-induced toxicity without blindness with high local control and survival. IMRT could be considered as the treatment of choi0008.« less

Decoding gripping force based on local field potentials recorded from subthalamic nucleus in humans

PubMed Central

Tan, Huiling; Pogosyan, Alek; Ashkan, Keyoumars; Green, Alexander L; Aziz, Tipu; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Brown, Peter

2016-01-01

The basal ganglia are known to be involved in the planning, execution and control of gripping force and movement vigour. Here we aim to define the nature of the basal ganglia control signal for force and to decode gripping force based on local field potential (LFP) activities recorded from the subthalamic nucleus (STN) in patients with deep brain stimulation (DBS) electrodes. We found that STN LFP activities in the gamma (55–90 Hz) and beta (13–30m Hz) bands were most informative about gripping force, and that a first order dynamic linear model with these STN LFP features as inputs can be used to decode the temporal profile of gripping force. Our results enhance the understanding of how the basal ganglia control gripping force, and also suggest that deep brain LFPs could potentially be used to decode movement parameters related to force and movement vigour for the development of advanced human-machine interfaces. DOI: http://dx.doi.org/10.7554/eLife.19089.001 PMID:27855780

The Role of Surgery, Radiosurgery and Whole Brain Radiation Therapy in the Management of Patients with Metastatic Brain Tumors

PubMed Central

Ellis, Thomas L.; Neal, Matthew T.; Chan, Michael D.

2012-01-01

Brain tumors constitute the most common intracranial tumor. Management of brain metastases has become increasingly complex as patients with brain metastases are living longer and more treatment options develop. The goal of this paper is to review the role of stereotactic radiosurgery (SRS), whole brain radiation therapy (WBRT), and surgery, in isolation and in combination, in the contemporary treatment of brain metastases. Surgery and SRS both offer management options that may help to optimize therapy in selected patients. WBRT is another option but can lead to late toxicity and suboptimal local control in longer term survivors. Improved prognostic indices will be critical for selecting the best therapies. Further prospective trials are necessary to continue to elucidate factors that will help triage patients to the proper brain-directed therapy for their cancer. PMID:22312545

Up-regulation of microtubule-associated protein 2 accompanying the filial imprinting of domestic chicks (Gallus gallus domesticus).

PubMed

Yamaguchi, Shinji; Fujii-Taira, Ikuko; Murakami, Akio; Hirose, Naoki; Aoki, Naoya; Izawa, Ei-Ichi; Fujimoto, Yasuyuki; Takano, Tatsuya; Matsushima, Toshiya; Homma, Koichi J

2008-06-15

Using cDNA microarrays, we have identified elsewhere the genes of microtubule-associated proteins as a group up-regulated in newly hatched chick brains after filial imprinting training. Here we show by in situ hybridization that the mRNA for the microtubule-associated protein 2 (MAP2) gene was enriched in the mesopallium and the hippocampus in the trained chick brain. The regionally specific enrichments of MAP2 mRNA were not observed in the brain of dark-reared or light-exposed chick as controls, implying an association between the degree of expression and the strength of the learned preference. In agreement with the gene expression, MAP2 protein was accumulated in the mesopallium of the trained chick brain, but not in the brains of the controls. The accumulation of MAP2 was found in the cytosol of neurons and co-localized with beta-tubulin, suggesting a change in microtubule assembly. Our results suggest a postnatal reorganization of cytoskeleton following filial imprinting.

Converging evidence for abnormalities of the prefrontal cortex and evaluation of midsagittal structures in pediatric PTSD: an MRI study

PubMed Central

Carrion, Victor G.; Weems, Carl F.; Watson, Christa; Eliez, Stephan; Menon, Vinod; Reiss, Allan L.

2009-01-01

Objective Volumetric imaging research has shown abnormal brain morphology in posttraumatic stress disorder (PTSD) when compared to controls. We present results on a study of brain morphology in the prefrontal cortex (PFC) and midline structures, via indices of gray matter volume and density, in pediatric PTSD. We hypothesized that both methods would demonstrate aberrant morphology in the PFC. Further, we hypothesized aberrant brainstem anatomy and reduced corpus collosum volume in children with PTSD. Methods Twenty-four children (aged 7-14) with history of interpersonal trauma and 24 age, and gender matched controls underwent structural magnetic resonance imaging. Images of the PFC and midline brain structures were first analyzed using volumetric image analysis. The PFC data were then compared with whole-brain voxel-based techniques using statistical parametric mapping (SPM). Results The PTSD group showed significant increased gray matter volume in the right and left inferior and superior quadrants of the prefrontal cortex and smaller gray matter volume in pons, and posterior vermis areas by volumetric image analysis. The voxel-byvoxel group comparisons demonstrated increased gray matter density mostly localized to ventral PFC as compared to the control group. Conclusions Abnormal frontal lobe morphology, as revealed by separate-complementary image analysis methods, and reduced pons and posterior vermis areas are associated with pediatric PTSD. Voxel-based morphometry may help to corroborate and further localize data obtained by volume of interest methods in PTSD. PMID:19349151

Altered structural connectivity of pain-related brain network in burning mouth syndrome-investigation by graph analysis of probabilistic tractography.

PubMed

Wada, Akihiko; Shizukuishi, Takashi; Kikuta, Junko; Yamada, Haruyasu; Watanabe, Yusuke; Imamura, Yoshiki; Shinozaki, Takahiro; Dezawa, Ko; Haradome, Hiroki; Abe, Osamu

2017-05-01

Burning mouth syndrome (BMS) is a chronic intraoral pain syndrome featuring idiopathic oral pain and burning discomfort despite clinically normal oral mucosa. The etiology of chronic pain syndrome is unclear, but preliminary neuroimaging research has suggested the alteration of volume, metabolism, blood flow, and diffusion at multiple brain regions. According to the neuromatrix theory of Melzack, pain sense is generated in the brain by the network of multiple pain-related brain regions. Therefore, the alteration of pain-related network is also assumed as an etiology of chronic pain. In this study, we investigated the brain network of BMS brain by using probabilistic tractography and graph analysis. Fourteen BMS patients and 14 age-matched healthy controls underwent 1.5T MRI. Structural connectivity was calculated in 83 anatomically defined regions with probabilistic tractography of 60-axis diffusion tensor imaging and 3D T1-weighted imaging. Graph theory network analysis was used to evaluate the brain network at local and global connectivity. In BMS brain, a significant difference of local brain connectivity was recognized at the bilateral rostral anterior cingulate cortex, right medial orbitofrontal cortex, and left pars orbitalis which belong to the medial pain system; however, no significant difference was recognized at the lateral system including the somatic sensory cortex. A strengthened connection of the anterior cingulate cortex and medial prefrontal cortex with the basal ganglia, thalamus, and brain stem was revealed. Structural brain network analysis revealed the alteration of the medial system of the pain-related brain network in chronic pain syndrome.

Whole-brain functional hypoconnectivity as an endophenotype of autism in adolescents

PubMed Central

Moseley, R.L.; Ypma, R.J.F.; Holt, R.J.; Floris, D.; Chura, L.R.; Spencer, M.D.; Baron-Cohen, S.; Suckling, J.; Bullmore, E.; Rubinov, M.

2015-01-01

Endophenotypes are heritable and quantifiable markers that may assist in the identification of the complex genetic underpinnings of psychiatric conditions. Here we examined global hypoconnectivity as an endophenotype of autism spectrum conditions (ASCs). We studied well-matched groups of adolescent males with autism, genetically-related siblings of individuals with autism, and typically-developing control participants. We parcellated the brain into 258 regions and used complex-network analysis to detect a robust hypoconnectivity endophenotype in our participant group. We observed that whole-brain functional connectivity was highest in controls, intermediate in siblings, and lowest in ASC, in task and rest conditions. We identified additional, local endophenotype effects in specific networks including the visual processing and default mode networks. Our analyses are the first to show that whole-brain functional hypoconnectivity is an endophenotype of autism in adolescence, and may thus underlie the heritable similarities seen in adolescents with ASC and their relatives. PMID:26413477

Local cerebral hypothermia induced by selective infusion of cold lactated ringer's: a feasibility study in rhesus monkeys.

PubMed

Wang, Bincheng; Wu, Di; Dornbos Iii, David; Shi, Jingfei; Ma, Yanhui; Zhang, Mo; Liu, Yumei; Chen, Jian; Ding, Yuchuan; Luo, Yinghao; Ji, Xunming

2016-06-01

Hypothermia has shown promise as a neuroprotective strategy for stroke. The use of whole body hypothermia has limited clinical utility due to many severe side effects. Selective brain cooling, or local brain hypothermia, has been previously proposed as an alternative treatment strategy. This study investigated the safety, feasibility, and efficacy of selective brain hypothermia induced by local infusion of ice-cold lactated Ringer's solution in rhesus monkeys. Eight male rhesus monkeys were used in this study. Brain temperature in the territory supplied by middle cerebral artery (MCA) was reduced by infusing 100 mL of ice-cold (0 °C) lactated Ringer's solution over 20 min via a micro-catheter placed in the proximal MCA (n = 4). Vital signs and the temperature of the brain and rectum were monitored before and after infusion. Transcranial Doppler, Magnetic resonance imaging (MRI), and digital subtraction angiography (DSA) were used to evaluate cerebral blood flow, cerebrovascular reactivity (CVR), cerebral edema, and vasospasm. Another cohort of rhesus monkeys (n = 4) were used as systemic cooling controls. Oxygen saturation, blood pressure, heart rate, and hematologic analysis of the two groups remained within the normal range after infusion. Mild cerebral hypothermia (<35 °C) was achieved in 10 min (0.3 °C/min) and was maintained for 20 min in local cortex and striatum following local infusion. The average lowest cerebral temperature in the locally cooled animals was 33.9 ± 0.3 °C in the striatum following 20-min infusion. This was not observed in animals cooled by systemic infusion. The decreases in the rectal temperature for local and systemic infusion were 0.5 ± 0.2 °C and 0.5 ± 0.3 °C, respectively. Selective brain cooling did not cause any cerebral edema as determined by MRI or vasospasm in the perfused vessel based on DSA. Selective cerebral hypothermia did not significantly alter CVR. Local infusion of ice-cold lactated Ringer's solution via micro-catheter is a safe and effective method for selective cerebral hypothermia. This cooling method could potentially be developed as a new treatment in acute ischemic stroke.

Localized Down-regulation of P-glycoprotein by Focused Ultrasound and Microbubbles induced Blood-Brain Barrier Disruption in Rat Brain

NASA Astrophysics Data System (ADS)

Cho, Hongseok; Lee, Hwa-Youn; Han, Mun; Choi, Jong-Ryul; Ahn, Sanghyun; Lee, Taekwan; Chang, Yongmin; Park, Juyoung

2016-08-01

Multi-drug resistant efflux transporters found in Blood-Brain Barrier (BBB) acts as a functional barrier, by pumping out most of the drugs into the blood. Previous studies showed focused ultrasound (FUS) induced microbubble oscillation can disrupt the BBB by loosening the tight junctions in the brain endothelial cells; however, no study was performed to investigate its impact on the functional barrier of the BBB. In this study, the BBB in rat brains were disrupted using the MRI guided FUS and microbubbles. The immunofluorescence study evaluated the expression of the P-glycoprotein (P-gp), the most dominant multi-drug resistant protein found in the BBB. Intensity of the P-gp expression at the BBB disruption (BBBD) regions was significantly reduced (63.2 ± 18.4%) compared to the control area. The magnitude of the BBBD and the level of the P-gp down-regulation were significantly correlated. Both the immunofluorescence and histologic analysis at the BBBD regions revealed no apparent damage in the brain endothelial cells. The results demonstrate that the FUS and microbubbles can induce a localized down-regulation of P-gp expression in rat brain. The study suggests a clinically translation of this method to treat neural diseases through targeted delivery of the wide ranges of brain disorder related drugs.

Association of Perivascular Localization of Aquaporin-4 With Cognition and Alzheimer Disease in Aging Brains.

PubMed

Zeppenfeld, Douglas M; Simon, Matthew; Haswell, J Douglas; D'Abreo, Daryl; Murchison, Charles; Quinn, Joseph F; Grafe, Marjorie R; Woltjer, Randall L; Kaye, Jeffrey; Iliff, Jeffrey J

2017-01-01

Cognitive impairment and dementia, including Alzheimer disease (AD), are common within the aging population, yet the factors that render the aging brain vulnerable to these processes are unknown. Perivascular localization of aquaporin-4 (AQP4) facilitates the clearance of interstitial solutes, including amyloid-β, through the brainwide network of perivascular pathways termed the glymphatic system, which may be compromised in the aging brain. To determine whether alterations in AQP4 expression or loss of perivascular AQP4 localization are features of the aging human brain and to define their association with AD pathology. Expression of AQP4 was analyzed in postmortem frontal cortex of cognitively healthy and histopathologically confirmed individuals with AD by Western blot or immunofluorescence for AQP4, amyloid-β 1-42, and glial fibrillary acidic protein. Postmortem tissue and clinical data were provided by the Oregon Health and Science University Layton Aging and Alzheimer Disease Center and Oregon Brain Bank. Postmortem tissue from 79 individuals was evaluated, including cognitively intact "young" individuals aged younger than 60 years (range, 33-57 years), cognitively intact "aged" individuals aged older than 60 years (range, 61-96 years) with no known neurological disease, and individuals older than 60 years (range, 61-105 years) of age with a clinical history of AD confirmed by histopathological evaluation. Forty-eight patient samples (10 young, 20 aged, and 18 with AD) underwent histological analysis. Sixty patient samples underwent Western blot analysis (15 young, 24 aged, and 21 with AD). Expression of AQP4 protein, AQP4 immunoreactivity, and perivascular AQP4 localization in the frontal cortex were evaluated. Expression of AQP4 was associated with advancing age among all individuals (R2 = 0.17; P = .003). Perivascular AQP4 localization was significantly associated with AD status independent of age (OR, 11.7 per 10% increase in localization; z = -2.89; P = .004) and was preserved among eldest individuals older than 85 years of age who remained cognitively intact. When controlling for age, loss of perivascular AQP4 localization was associated with increased amyloid-β burden (R2 = 0.15; P = .003) and increasing Braak stage (R2 = 0.14; P = .006). In this study, altered AQP4 expression was associated with aging brains. Loss of perivascular AQP4 localization may be a factor that renders the aging brain vulnerable to the misaggregation of proteins, such as amyloid-β, in neurodegenerative conditions such as AD.

Localized N20 Component of Somatosensory Evoked Magnetic Fields in Frontoparietal Brain Tumor Patients Using Noise-Normalized Approaches.

PubMed

Elaina, Nor Safira; Malik, Aamir Saeed; Shams, Wafaa Khazaal; Badruddin, Nasreen; Abdullah, Jafri Malin; Reza, Mohammad Faruque

2018-06-01

To localize sensorimotor cortical activation in 10 patients with frontoparietal tumors using quantitative magnetoencephalography (MEG) with noise-normalized approaches. Somatosensory evoked magnetic fields (SEFs) were elicited in 10 patients with somatosensory tumors and in 10 control participants using electrical stimulation of the median nerve via the right and left wrists. We localized the N20m component of the SEFs using dynamic statistical parametric mapping (dSPM) and standardized low-resolution brain electromagnetic tomography (sLORETA) combined with 3D magnetic resonance imaging (MRI). The obtained coordinates were compared between groups. Finally, we statistically evaluated the N20m parameters across hemispheres using non-parametric statistical tests. The N20m sources were accurately localized to Brodmann area 3b in all members of the control group and in seven of the patients; however, the sources were shifted in three patients relative to locations outside the primary somatosensory cortex (SI). Compared with the affected (tumor) hemispheres in the patient group, N20m amplitudes and the strengths of the current sources were significantly lower in the unaffected hemispheres and in both hemispheres of the control group. These results were consistent for both dSPM and sLORETA approaches. Tumors in the sensorimotor cortex lead to cortical functional reorganization and an increase in N20m amplitude and current-source strengths. Noise-normalized approaches for MEG analysis that are integrated with MRI show accurate and reliable localization of sensorimotor function.

CONTROL OF SLEEP AND WAKEFULNESS

PubMed Central

Brown, Ritchie E.; Basheer, Radhika; McKenna, James T.; Strecker, Robert E.; McCarley, Robert W.

2013-01-01

This review summarizes the brain mechanisms controlling sleep and wakefulness. Wakefulness promoting systems cause low-voltage, fast activity in the electroencephalogram (EEG). Multiple interacting neurotransmitter systems in the brain stem, hypothalamus, and basal forebrain converge onto common effector systems in the thalamus and cortex. Sleep results from the inhibition of wake-promoting systems by homeostatic sleep factors such as adenosine and nitric oxide and GABAergic neurons in the preoptic area of the hypothalamus, resulting in large-amplitude, slow EEG oscillations. Local, activity-dependent factors modulate the amplitude and frequency of cortical slow oscillations. Non-rapid-eye-movement (NREM) sleep results in conservation of brain energy and facilitates memory consolidation through the modulation of synaptic weights. Rapid-eye-movement (REM) sleep results from the interaction of brain stem cholinergic, aminergic, and GABAergic neurons which control the activity of glutamatergic reticular formation neurons leading to REM sleep phenomena such as muscle atonia, REMs, dreaming, and cortical activation. Strong activation of limbic regions during REM sleep suggests a role in regulation of emotion. Genetic studies suggest that brain mechanisms controlling waking and NREM sleep are strongly conserved throughout evolution, underscoring their enormous importance for brain function. Sleep disruption interferes with the normal restorative functions of NREM and REM sleep, resulting in disruptions of breathing and cardiovascular function, changes in emotional reactivity, and cognitive impairments in attention, memory, and decision making. PMID:22811426

Long-Term Survival in a Patient with Multiple Brain Metastases from Small-Cell Lung Cancer Treated with Gamma Knife Radiosurgery on Four Occasions: A Case Report

PubMed Central

Elaimy, Ameer L.; Thumma, Sudheer R.; Lamm, Andrew F.; Mackay, Alexander R.; Lamoreaux, Wayne T.; Fairbanks, Robert K.; Demakas, John J.; Cooke, Barton S.; Lee, Christopher M.

2012-01-01

Brain metastases are the most common cancerous neoplasm in the brain. The treatment of these lesions is challenging and often includes a multimodality management approach with whole-brain radiation therapy, stereotactic radiosurgery, and neurosurgery options. Although advances in biomedical imaging technologies and the treatment of extracranial cancer have led to the overall increase in the survival of brain metastases patients, the finding that select patients survive several years remains puzzling. For this reason, we present the case of a 70-year-old patient who was diagnosed with multiple brain metastases from small-cell lung cancer five years ago and is currently alive following treatment with chemotherapy for the primary cancer and whole-brain radiation therapy and Gamma Knife radiosurgery on four separate occasions for the neurological cancer. Since the diagnosis of brain metastases five years ago, the patient's primary cancer has remained controlled. Furthermore, multiple repeat GKRS procedures provided this patient with high levels of local tumor control, which in combination with a stable primary cancer led to an extended period of survival and a highly functional life. Further analysis and clinical research will be valuable in assessing the durability of multiple GKRS for brain metastases patients who experience long-term survival. PMID:23091748

[Neurofeedback for the treatment of chronic tinnitus : Review and future perspectives].

PubMed

Kleinjung, T; Thüring, C; Güntensperger, D; Neff, P; Meyer, M

2018-03-01

Neurofeedback is a noninvasive neuromodulation technique employing real-time display of brain activity in terms of electroencephalography (EEG) signals to teach self-regulation of distinct patterns of brain activity or influence brain activity in a targeted manner. The benefit of this approach for control of symptoms in attention deficit disorders, hyperactivity, depression, and migraine has been proven. Studies in recent years have also repeatedly shown this treatment to improve tinnitus symptoms, although it has not become established as routine therapy. The primary focus of this review is the rational of EEG neurofeedback for tinnitus treatment and the currently available data from published studies. Furthermore, alternative neurofeedback protocols using real-time functional magnetic resonance imaging (fMRI) measurements for tinnitus control are considered. Finally, this article highlights how modern EEG analysis (source localization, connectivity) and the improving understanding of tinnitus pathology can contribute to development of more focused neurofeedback protocols for more sustainable control of tinnitus.

Local brain herniation after partial membranectomy for organized chronic subdural hematoma in an adult patient: case report and review of the literature.

PubMed

Kusano, Yoshikazu; Horiuchi, Tetsuyoshi; Seguchi, Tatsuya; Kakizawa, Yukinari; Tanaka, Yuichiro; Hongo, Kazuhiro

2010-01-01

Local brain herniation after removal of chronic subdural haematoma is extremely rare, especially in adult patients. This study reports a case of local brain herniation after partial membranectomy for organized chronic subdural haematoma. A 77-year-old man presented with dysarthria and dysphasia caused by local brain herniation of the right frontal lobe through a defect of the inner membrane. The herniated brain was detected by magnetic resonance (MR) imaging. The patient underwent a craniotomy to release the herniated and strangulated brain, which were consistent with the MR imaging findings. The patient recovered fully within 1 month after surgery. To date, five cases of brain herniation through the internal subdural membrane have been reported as complications of chronic subdural haematomas. All but one case occurred in the paediatric population. Urgent surgery should be performed, even if an adult patient suffers from local brain herniation, for preservation of brain function. This is the sixth reported case of brain herniation through a defect of the inner membrane and the second reported case in the adult population.

Risk Factors for Preoperative Seizures and Loss of Seizure Control in Patients Undergoing Surgery for Metastatic Brain Tumors.

PubMed

Wu, Adela; Weingart, Jon D; Gallia, Gary L; Lim, Michael; Brem, Henry; Bettegowda, Chetan; Chaichana, Kaisorn L

2017-08-01

Metastatic brain tumors are the most common brain tumors in adults. Patients with metastatic brain tumors have poor prognoses with median survival of 6-12 months. Seizures are a major presenting symptom and cause of morbidity and mortality. In this article, risk factors for the onset of preoperative seizures and postoperative seizure control are examined. Adult patients who underwent resection of one or more brain metastases at a single institution between 1998 and 2011 were reviewed retrospectively. Of 565 patients, 114 (20.2%) patients presented with seizures. Factors independently associated with preoperative seizures were preoperative headaches (P = 0.044), cognitive deficits (P = 0.031), more than 2 intracranial metastatic tumors (P = 0.013), temporal lobe location (P = 0.031), occipital lobe location (P = 0.010), and bone involvement by tumor (P = 0.029). Factors independently associated with loss of seizure control after surgical resection were preoperative seizures (P = 0.001), temporal lobe location (P = 0.037), lack of postoperative chemotherapy (P = 0.010), subtotal resection of tumor (P = 0.022), and local recurrence (P = 0.027). At last follow-up, the majority of patients (93.8%) were seizure-free. Thirty patients (5.30%) in total had loss of seizure control, and only 8 patients (1.41%) who did not have preoperative seizures presented with new-onset seizures after surgical resection of their metastases. The brain is a common site for metastases from numerous primary cancers, such as breast and lung. The identification of factors associated with onset of preoperative seizures as well as seizure control postoperatively could aid management strategies for patients with metastatic brain tumors. Patients with preoperative seizures who underwent resection tended to have good seizure control after surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

A low power flash-FPGA based brain implant micro-system of PID control.

PubMed

Lijuan Xia; Fattah, Nabeel; Soltan, Ahmed; Jackson, Andrew; Chester, Graeme; Degenaar, Patrick

2017-07-01

In this paper, we demonstrate that a low power flash FPGA based micro-system can provide a low power programmable interface for closed-loop brain implant inter- faces. The proposed micro-system receives recording local field potential (LFP) signals from an implanted probe, performs closed-loop control using a first order control system, then converts the signal into an optogenetic control stimulus pattern. Stimulus can be implemented through optoelectronic probes. The long term target is for both fundamental neuroscience applications and for clinical use in treating epilepsy. Utilizing our device, closed-loop processing consumes only 14nJ of power per PID cycle compared to 1.52μJ per cycle for a micro-controller implementation. Compared to an application specific digital integrated circuit, flash FPGA's are inherently programmable.

Implementation of a Peltier-based cooling device for localized deep cortical deactivation during in vivo object recognition testing

NASA Astrophysics Data System (ADS)

Marra, Kyle; Graham, Brett; Carouso, Samantha; Cox, David

2012-02-01

While the application of local cortical cooling has recently become a focus of neurological research, extended localized deactivation deep within brain structures is still unexplored. Using a wirelessly controlled thermoelectric (Peltier) device and water-based heat sink, we have achieved inactivating temperatures (<20 C) at greater depths (>8 mm) than previously reported. After implanting the device into Long Evans rats' basolateral amygdala (BLA), an inhibitory brain center that controls anxiety and fear, we ran an open field test during which anxiety-driven behavioral tendencies were observed to decrease during cooling, thus confirming the device's effect on behavior. Our device will next be implanted in the rats' temporal association cortex (TeA) and recordings from our signal-tracing multichannel microelectrodes will measure and compare activated and deactivated neuronal activity so as to isolate and study the TeA signals responsible for object recognition. Having already achieved a top performing computational face-recognition system, the lab will utilize this TeA activity data to generalize its computational efforts of face recognition to achieve general object recognition.

Category representations in the brain are both discretely localized and widely distributed.

PubMed

Shehzad, Zarrar; McCarthy, Gregory

2018-06-01

Whether category information is discretely localized or represented widely in the brain remains a contentious issue. Initial functional MRI studies supported the localizationist perspective that category information is represented in discrete brain regions. More recent fMRI studies using machine learning pattern classification techniques provide evidence for widespread distributed representations. However, these latter studies have not typically accounted for shared information. Here, we find strong support for distributed representations when brain regions are considered separately. However, localized representations are revealed by using analytical methods that separate unique from shared information among brain regions. The distributed nature of shared information and the localized nature of unique information suggest that brain connectivity may encourage spreading of information but category-specific computations are carried out in distinct domain-specific regions. NEW & NOTEWORTHY Whether visual category information is localized in unique domain-specific brain regions or distributed in many domain-general brain regions is hotly contested. We resolve this debate by using multivariate analyses to parse functional MRI signals from different brain regions into unique and shared variance. Our findings support elements of both models and show information is initially localized and then shared among other regions leading to distributed representations being observed.

The association of antipsychotic medication and lithium with brain measures in patients with bipolar disorder.

PubMed

Abramovic, Lucija; Boks, Marco P M; Vreeker, Annabel; Bouter, Diandra C; Kruiper, Caitlyn; Verkooijen, Sanne; van Bergen, Annet H; Ophoff, Roel A; Kahn, René S; van Haren, Neeltje E M

2016-11-01

There is evidence that brain structure is abnormal in patients with bipolar disorder. Lithium intake appears to ׳normalise׳ global and local brain volumes, but effects of antipsychotic medication on brain volume or cortical thickness are less clear. Here, we aim to disentangle disease-specific brain deviations from those induced by antipsychotic medication and lithium intake using a large homogeneous sample of patients with bipolar disorder type I. Magnetic resonance imaging brain scans were obtained from 266 patients and 171 control subjects. Subcortical volumes and global and focal cortical measures (volume, thickness, and surface area) were compared between patients and controls. In patients, the association between lithium and antipsychotic medication intake and global, subcortical and cortical measures was investigated. Patients showed significantly larger lateral and third ventricles, smaller total brain, caudate nucleus, and pallidum volumes and thinner cortex in some small clusters in frontal, parietal and cingulate regions as compared with controls. Lithium-free patients had significantly smaller total brain, thalamus, putamen, pallidum, hippocampus and accumbens volumes compared to patients on lithium. In patients, use of antipsychotic medication was related to larger third ventricle and smaller hippocampus and supramarginal cortex volume. Patients with bipolar disorder show abnormalities in total brain, subcortical, and ventricle volume, particularly in the nucleus caudate and pallidum. Abnormalities in cortical thickness were scattered and clusters were relatively small. Lithium-free patients showed more pronounced abnormalities as compared with those on lithium. The associations between antipsychotic medication and brain volume are subtle and less pronounced than those of lithium. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Choline availability during embryonic development alters the localization of calretinin in developing and aging mouse hippocampus.

PubMed

Albright, Craig D; Siwek, Donald F; Craciunescu, Corneliu N; Mar, Mei-Heng; Kowall, Neil W; Williams, Christina L; Zeisel, Steven H

2003-04-01

Choline availability in the diet during pregnancy alters fetal brain biochemistry with resulting behavioral changes that persist throughout the lifetime of the offspring. In the present study, the effects of dietary choline on the onset of GABAergic neuronal differentiation in developing fetal brain, as demarcated by the expression of calcium binding protein calretinin, are described. In these studies, timed-pregnant mice were fed choline supplemented, control or choline deficient AIN-76 diet from day 12-17 of pregnancy and the brains of their fetuses were studied on day 17 of gestation. In the primordial dentate gyrus, we found that pups from choline deficient-dams had more calretinin protein (330% increase), and pups from choline supplemented-dams had less calretinin protein (70% decrease), than did pups from control-dams. Importantly, decreased calretinin protein was still detectable in hippocampus in aged, 24-month-old mice, born of choline supplemented-dams and maintained since birth on a control diet. Thus, alterations in the level of calretinin protein in fetal brain hippocampus could underlie the known, life long effects of maternal dietary choline availability on brain development and behavior.

Mobile phone use and brain tumors in children and adolescents: a multicenter case-control study.

PubMed

Aydin, Denis; Feychting, Maria; Schüz, Joachim; Tynes, Tore; Andersen, Tina Veje; Schmidt, Lisbeth Samsø; Poulsen, Aslak Harbo; Johansen, Christoffer; Prochazka, Michaela; Lannering, Birgitta; Klæboe, Lars; Eggen, Tone; Jenni, Daniela; Grotzer, Michael; Von der Weid, Nicolas; Kuehni, Claudia E; Röösli, Martin

2011-08-17

It has been hypothesized that children and adolescents might be more vulnerable to possible health effects from mobile phone exposure than adults. We investigated whether mobile phone use is associated with brain tumor risk among children and adolescents. CEFALO is a multicenter case-control study conducted in Denmark, Sweden, Norway, and Switzerland that includes all children and adolescents aged 7-19 years who were diagnosed with a brain tumor between 2004 and 2008. We conducted interviews, in person, with 352 case patients (participation rate: 83%) and 646 control subjects (participation rate: 71%) and their parents. Control subjects were randomly selected from population registries and matched by age, sex, and geographical region. We asked about mobile phone use and included mobile phone operator records when available. Odds ratios (ORs) for brain tumor risk and 95% confidence intervals (CIs) were calculated using conditional logistic regression models. Regular users of mobile phones were not statistically significantly more likely to have been diagnosed with brain tumors compared with nonusers (OR = 1.36; 95% CI = 0.92 to 2.02). Children who started to use mobile phones at least 5 years ago were not at increased risk compared with those who had never regularly used mobile phones (OR = 1.26, 95% CI = 0.70 to 2.28). In a subset of study participants for whom operator recorded data were available, brain tumor risk was related to the time elapsed since the mobile phone subscription was started but not to amount of use. No increased risk of brain tumors was observed for brain areas receiving the highest amount of exposure. The absence of an exposure-response relationship either in terms of the amount of mobile phone use or by localization of the brain tumor argues against a causal association.

Toward more versatile and intuitive cortical brain machine interfaces

PubMed Central

Andersen, Richard A.; Kellis, Spencer; Klaes, Christian; Aflalo, Tyson

2015-01-01

Brain machine interfaces have great potential in neuroprosthetic applications to assist patients with brain injury and neurodegenerative diseases. One type of BMI is a cortical motor prosthetic which is used to assist paralyzed subjects. Motor prosthetics to date have typically used the motor cortex as a source of neural signals for controlling external devices. The review will focus on several new topics in the arena of cortical prosthetics. These include using 1) recordings from cortical areas outside motor cortex; 2) local field potentials (LFPs) as a source of recorded signals; 3) somatosensory feedback for more dexterous control of robotics; and 4) new decoding methods that work in concert to form an ecology of decode algorithms. These new advances hold promise in greatly accelerating the applicability and ease of operation of motor prosthetics. PMID:25247368

Effect of x-radiation to brain on cerebral glucose utilization in the rat.

PubMed

D'Aquino, S; Cicciarello, R; D'Avella, D; Mesiti, M; Albiero, F; Princi, P; Gagliardi, M E; Russi, E; D'Aquino, A

1990-01-01

We assessed, by means of the [14C]-2-deoxy-D-glucose autoradiography method, the effect of whole-brain x-radiation on local cerebral glucose utilization in the rat brain. Animals were exposed to conventional fractionation (200 +/- cGy/day given 5 days a week) to a total dose of 4000 cGy. Metabolic experiments were made 2 weeks after completion of the radiation exposure. In comparison with control and sham-irradiated animals, cerebral metabolic activity was diffusely decreased following irradiation. Statistically significant decreases in metabolic activity were observed in 13 of 27 brain regions studied. In general, brain areas with the highest basal metabolic rates showed the greatest percentage drop of glucose utilization. Post-irradiation metabolic alterations possibly provide an explanation for the syndrome of early delayed deterioration observed in humans after whole-brain radiotherapy.

Rab proteins in the brain and corpus allatum of Bombyx mori.

PubMed

Uno, Tomohide; Furutani, Masayuki; Watanabe, Chihiro; Sakamoto, Katsuhiko; Uno, Yuichi; Kanamaru, Kengo; Yamagata, Hiroshi; Mizoguchi, Akira; Takeda, Makio

2016-07-01

In eukaryotic cells, Rab guanosine triphosphate-ases serve as key regulators of membrane-trafficking events, such as exocytosis and endocytosis. Rab3, Rab6, and Rab27 control the regulatory secretory pathway of neuropeptides and neurotransmitters. The cDNAs of Rab3, Rab6, and Rab27 from B. mori were inserted into a plasmid, transformed into Escherichia coli, and then subsequently purified. We then produced antibodies against Rab3, Rab6, and Rab27 of Bombyx mori in rabbits and rats for use in western immunoblotting and immunohistochemistry. Western immunoblotting of brain tissue revealed a single band at approximately 26 kDa. Immunohistochemistry results revealed that Rab3, Rab6, and Rab27 expression was restricted to neurons in the pars intercerebralis and dorsolateral protocerebrum of the brain. Rab3 and Rab6 co-localized with bombyxin, an insect neuropeptide. However, there was no Rab that co-localized with prothoracicotropic hormone. The corpus allatum secretes neuropeptides synthesized in the brain into the hemolymph. Results showed that Rab3 and Rab6 co-localized with bombyxin in the corpus allatum. These findings suggest that Rab3 and Rab6 are involved in neurosecretion in B. mori. This study is the first to report a possible relationship between Rab and neurosecretion in the insect corpus allatum.

Interactome of two diverse RNA granules links mRNA localization to translational repression in neurons.

PubMed

Fritzsche, Renate; Karra, Daniela; Bennett, Keiryn L; Ang, Foong Yee; Heraud-Farlow, Jacki E; Tolino, Marco; Doyle, Michael; Bauer, Karl E; Thomas, Sabine; Planyavsky, Melanie; Arn, Eric; Bakosova, Anetta; Jungwirth, Kerstin; Hörmann, Alexandra; Palfi, Zsofia; Sandholzer, Julia; Schwarz, Martina; Macchi, Paolo; Colinge, Jacques; Superti-Furga, Giulio; Kiebler, Michael A

2013-12-26

Transport of RNAs to dendrites occurs in neuronal RNA granules, which allows local synthesis of specific proteins at active synapses on demand, thereby contributing to learning and memory. To gain insight into the machinery controlling dendritic mRNA localization and translation, we established a stringent protocol to biochemically purify RNA granules from rat brain. Here, we identified a specific set of interactors for two RNA-binding proteins that are known components of neuronal RNA granules, Barentsz and Staufen2. First, neuronal RNA granules are much more heterogeneous than previously anticipated, sharing only a third of the identified proteins. Second, dendritically localized mRNAs, e.g., Arc and CaMKIIα, associate selectively with distinct RNA granules. Third, our work identifies a series of factors with known roles in RNA localization, translational control, and RNA quality control that are likely to keep localized transcripts in a translationally repressed state, often in distinct types of RNPs. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Using the virtual brain to reveal the role of oscillations and plasticity in shaping brain's dynamical landscape.

PubMed

Roy, Dipanjan; Sigala, Rodrigo; Breakspear, Michael; McIntosh, Anthony Randal; Jirsa, Viktor K; Deco, Gustavo; Ritter, Petra

2014-12-01

Spontaneous brain activity, that is, activity in the absence of controlled stimulus input or an explicit active task, is topologically organized in multiple functional networks (FNs) maintaining a high degree of coherence. These "resting state networks" are constrained by the underlying anatomical connectivity between brain areas. They are also influenced by the history of task-related activation. The precise rules that link plastic changes and ongoing dynamics of resting-state functional connectivity (rs-FC) remain unclear. Using the framework of the open source neuroinformatics platform "The Virtual Brain," we identify potential computational mechanisms that alter the dynamical landscape, leading to reconfigurations of FNs. Using a spiking neuron model, we first demonstrate that network activity in the absence of plasticity is characterized by irregular oscillations between low-amplitude asynchronous states and high-amplitude synchronous states. We then demonstrate the capability of spike-timing-dependent plasticity (STDP) combined with intrinsic alpha (8-12 Hz) oscillations to efficiently influence learning. Further, we show how alpha-state-dependent STDP alters the local area dynamics from an irregular to a highly periodic alpha-like state. This is an important finding, as the cortical input from the thalamus is at the rate of alpha. We demonstrate how resulting rhythmic cortical output in this frequency range acts as a neuronal tuner and, hence, leads to synchronization or de-synchronization between brain areas. Finally, we demonstrate that locally restricted structural connectivity changes influence local as well as global dynamics and lead to altered rs-FC.

Targeted delivery of growth factors in ischemic stroke animal models.

PubMed

Rhim, Taiyoun; Lee, Minhyung

2016-01-01

Ischemic stroke is caused by reduced blood supply and leads to loss of brain function. The reduced oxygen and nutrient supply stimulates various physiological responses, including induction of growth factors. Growth factors prevent neuronal cell death, promote neovascularization, and induce cell growth. However, the concentration of growth factors is not sufficient to recover brain function after the ischemic damage, suggesting that delivery of growth factors into the ischemic brain may be a useful treatment for ischemic stroke. In this review, various approaches for the delivery of growth factors to ischemic brain tissue are discussed, including local and targeting delivery systems. To develop growth factor therapy for ischemic stroke, important considerations should be taken into account. First, growth factors may have possible side effects. Thus, concentration of growth factors should be restricted to the ischemic tissues by local administration or targeted delivery. Second, the duration of growth factor therapy should be optimized. Growth factor proteins may be degraded too fast to have a high enough therapeutic effect. Therefore, delivery systems for controlled release or gene delivery may be useful. Third, the delivery systems to the brain should be optimized according to the delivery route.

Variation in orbitofrontal cortex volume: relation to sex, emotion regulation and affect.

PubMed

Welborn, B Locke; Papademetris, Xenophon; Reis, Deidre L; Rajeevan, Nallakkandi; Bloise, Suzanne M; Gray, Jeremy R

2009-12-01

Sex differences in brain structure have been examined extensively but are not completely understood, especially in relation to possible functional correlates. Our two aims in this study were to investigate sex differences in brain structure, and to investigate a possible relation between orbitofrontal cortex subregions and affective individual differences. We used tensor-based morphometry to estimate local brain volume from MPRAGE images in 117 healthy right-handed adults (58 female), age 18-40 years. We entered estimates of local brain volume as the dependent variable in a GLM, controlling for age, intelligence and whole-brain volume. Men had larger left planum temporale. Women had larger ventromedial prefrontal cortex (vmPFC), right lateral orbitofrontal (rlOFC), cerebellum, and bilateral basal ganglia and nearby white matter. vmPFC but not rlOFC volume covaried with self-reported emotion regulation strategies (reappraisal, suppression), expressivity of positive emotions (but not of negative), strength of emotional impulses, and cognitive but not somatic anxiety. vmPFC volume statistically mediated sex differences in emotion suppression. The results confirm prior reports of sex differences in orbitofrontal cortex structure, and are the first to show that normal variation in vmPFC volume is systematically related to emotion regulation and affective individual differences.

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

PubMed

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

2017-07-04

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

Localized delivery of low-density lipoprotein docosahexaenoic acid nanoparticles to the rat brain using focused ultrasound.

PubMed

Mulik, Rohit S; Bing, Chenchen; Ladouceur-Wodzak, Michelle; Munaweera, Imalka; Chopra, Rajiv; Corbin, Ian R

2016-03-01

Focused ultrasound exposures in the presence of microbubbles can achieve transient, non-invasive, and localized blood-brain barrier (BBB) opening, offering a method for targeted delivery of therapeutic agents into the brain. Low-density lipoprotein (LDL) nanoparticles reconstituted with docosahexaenoic acid (DHA) could have significant therapeutic value in the brain, since DHA is known to be neuroprotective. BBB opening was achieved using pulsed ultrasound exposures in a localized brain region in normal rats, after which LDL nanoparticles containing the fluorescent probe DiR (1,1'-Dioctadecyl-3,3,3',3'-Tetramethylindotricarbocyanine Iodide) or DHA were administered intravenously. Fluorescent imaging of brain tissue from rats administered LDL-DiR demonstrated strong localization of fluorescence signal in the exposed hemisphere. LDL-DHA administration produced 2 × more DHA in the exposed region of the brain, with a corresponding increase in Resolvin D1 levels, indicating DHA was incorporated into cells and metabolized. Histological evaluation did not indicate any evidence of increased tissue damage in exposed brain regions compared to normal brain. This work demonstrates that localized delivery of DHA to the brain is possible using systemically-administered LDL nanoparticles combined with pulsed focused ultrasound exposures in the brain. This technology could be used in regions of acute brain injury or as a means to target infiltrating tumor cells in the brain. Copyright © 2016 Elsevier Ltd. All rights reserved.

Localized Delivery of Low-Density Lipoprotein Docosahexaenoic Acid Nanoparticles to the Rat Brain using Focused Ultrasound

PubMed Central

Mulik, Rohit S.; Bing, Chenchen; Ladouceur-Wodzak, Michelle; Munaweera, Imalka; Chopra, Rajiv; Corbin, Ian R.

2016-01-01

Focused ultrasound exposures in the presence of microbubbles can achieve transient, non-invasive, and localized blood-brain barrier (BBB) opening, offering a method for targeted delivery of therapeutic agents into the brain. Low-density lipoprotein (LDL) nanoparticles reconstituted with docosahexaenoic acid (DHA) could have significant therapeutic value in the brain, since DHA is known to be neuroprotective. BBB opening was achieved using pulsed ultrasound exposures in a localized brain region in normal rats, after which LDL nanoparticles containing the fluorescent probe DiR (1,1′-Dioctadecyl-3,3,3′,3′-Tetramethylindotricarbocyanine Iodide) or DHA were administered intravenously. Fluorescent imaging of brain tissue from rats administered LDL-DiR demonstrated strong localization of fluorescence signal in the exposed hemisphere. LDL-DHA administration produced 2× more DHA in the exposed region of the brain, with a corresponding increase in Resolvin D1 levels, indicating DHA was incorporated into cells and metabolized. Histological evaluation did not indicate any evidence of increased tissue damage in exposed brain regions compared to normal brain. This work demonstrates that localized delivery of DHA to the brain is possible using systemically-administered LDL nanoparticles combined with pulsed focused ultrasound exposures in the brain. This technology could be used in regions of acute brain injury or as a means to target infiltrating tumor cells in the brain. PMID:26790145

Preoperative Vs Postoperative Radiosurgery For Resected Brain Metastases: A Review.

PubMed

Prabhu, Roshan S; Patel, Kirtesh R; Press, Robert H; Soltys, Scott G; Brown, Paul D; Mehta, Minesh P; Asher, Anthony L; Burri, Stuart H

2018-05-16

Patients who undergo surgical resection of brain metastases are at significant risk of cavity local recurrence without additional radiation therapy. Postoperative stereotactic radiosurgery (SRS) is a method of focal treatment to the cavity to maximize local control while minimizing the risk of neurocognitive detriment associated with whole brain radiation therapy. Recently published randomized trials have demonstrated the benefit of postoperative SRS in terms of cavity tumor control and preserving neurocognition. However, there are several potential drawbacks with postoperative SRS including a possible increase in symptomatic radiation necrosis because of the need for cavity margin expansion due to target delineation uncertainty, the variable postoperative clinical course and potential delay in administering postoperative SRS, and the theoretical risk of tumor spillage into cerebrospinal fluid at the time of surgery. Preoperative SRS is an alternative paradigm wherein SRS is delivered prior to surgical resection, which may effectively address some of these potential drawbacks. The goal of this review is to examine the rationale, technique, outcomes, evidence, and future directions for the use of SRS as an adjunct to surgical resection. This can be delivered as either preoperative or postoperative SRS with potential advantages and disadvantages to both approaches that will be discussed.

F18 EF5 PET/CT Imaging in Patients with Brain Metastases from Breast Cancer

DTIC Science & Technology

2012-07-01

been demonstrated to improve local control and survival in select patients after WBRT . At present we do not have any method of determining a priori...relapse after WBRT would represent a significant step forward in the management of patients with brain metastases from breast cancer. We propose to...use a noninvasive imaging method to detect residual tumor hypoxia in patients receiving WBRT . Body: Task 1. To estimate the degree of hypoxia

Morphometry Based on Effective and Accurate Correspondences of Localized Patterns (MEACOLP)

PubMed Central

Wang, Hu; Ren, Yanshuang; Bai, Lijun; Zhang, Wensheng; Tian, Jie

2012-01-01

Local features in volumetric images have been used to identify correspondences of localized anatomical structures for brain morphometry. However, the correspondences are often sparse thus ineffective in reflecting the underlying structures, making it unreliable to evaluate specific morphological differences. This paper presents a morphometry method (MEACOLP) based on correspondences with improved effectiveness and accuracy. A novel two-level scale-invariant feature transform is used to enhance the detection repeatability of local features and to recall the correspondences that might be missed in previous studies. Template patterns whose correspondences could be commonly identified in each group are constructed to serve as the basis for morphometric analysis. A matching algorithm is developed to reduce the identification errors by comparing neighboring local features and rejecting unreliable matches. The two-sample t-test is finally adopted to analyze specific properties of the template patterns. Experiments are performed on the public OASIS database to clinically analyze brain images of Alzheimer's disease (AD) and normal controls (NC). MEACOLP automatically identifies known morphological differences between AD and NC brains, and characterizes the differences well as the scaling and translation of underlying structures. Most of the significant differences are identified in only a single hemisphere, indicating that AD-related structures are characterized by strong anatomical asymmetry. In addition, classification trials to differentiate AD subjects from NC confirm that the morphological differences are reliably related to the groups of interest. PMID:22540000

Current Dosing Paradigm for Stereotactic Radiosurgery Alone After Surgical Resection of Brain Metastases Needs to Be Optimized for Improved Local Control

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

Prabhu, Roshan; Shu, Hui-Kuo; Winship Cancer Institute, Emory University, Atlanta, GA

2012-05-01

Purpose: To describe the use of radiosurgery (RS) alone to the resection cavity after resection of brain metastases as an alternative to adjuvant whole-brain radiotherapy (WBRT). Methods and Materials: Sixty-two patients with 64 cavities were treated with linear accelerator-based RS alone to the resection cavity after surgical removal of brain metastases between March 2007 and August 2010. Fifty-two patients (81%) had a gross total resection. Median cavity volume was 8.5 cm{sup 3}. Forty-four patients (71%) had a single metastasis. Median marginal and maximum doses were 18 Gy and 20.4 Gy, respectively. Sixty-one cavities (95%) had gross tumor volume to planningmore » target volume expansion of {>=}1 mm. Results: Six-month and 1-year actuarial local recurrence rates were 14% and 22%, respectively, with a median follow-up period of 9.7 months. Six-month and 1-year actuarial distant brain recurrence, total intracranial recurrence, and freedom from WBRT rates were 31% and 51%, 41% and 63%, and 91% and 74%, respectively. The symptomatic cavity radiation necrosis rate was 8%, with 2 patients (3%) undergoing surgery. Of the 11 local failures, 8 were in-field, 1 was marginal, and 2 were both (defined as in-field if {>=}90% of recurrence within the prescription isodose and marginal if {>=}90% outside of the prescription isodose). Conclusions: The high rate of in-field cavity failure suggests that geographic misses with highly conformal RS are not a major contributor to local recurrence. The current dosing regimen derived from Radiation Therapy Oncology Group protocol 90-05 should be optimized in this patient population before any direct comparison with WBRT.« less

Optimal dose and volume for postoperative radiotherapy in brain oligometastases from lung cancer: a retrospective study.

PubMed

Chung, Seung Yeun; Chang, Jong Hee; Kim, Hye Ryun; Cho, Byoung Chul; Lee, Chang Geol; Suh, Chang-Ok

2017-06-01

To evaluate intracranial control after surgical resection according to the adjuvant treatment received in order to assess the optimal radiotherapy (RT) dose and volume. Between 2003 and 2015, a total of 53 patients with brain oligometastases from non-small cell lung cancer (NSCLC) underwent metastasectomy. The patients were divided into three groups according to the adjuvant treatment received: whole brain radiotherapy (WBRT) ± boost (WBRT ± boost group, n = 26), local RT/Gamma Knife surgery (local RT group, n = 14), and the observation group (n = 13). The most commonly used dose schedule was WBRT (25 Gy in 10 fractions, equivalent dose in 2 Gy fractions [EQD2] 26.04 Gy) with tumor bed boost (15 Gy in 5 fractions, EQD2 16.25 Gy). The WBRT ± boost group showed the lowest 1-year intracranial recurrence rate of 30.4%, followed by the local RT and observation groups, at 66.7%, and 76.9%, respectively (p = 0.006). In the WBRT ± boost group, there was no significant increase in the 1-year new site recurrence rate of patients receiving a lower dose of WBRT (EQD2) <27 Gy compared to that in patients receiving a higher WBRT dose (p = 0.553). The 1-year initial tumor site recurrence rate was lower in patients receiving tumor bed dose (EQD2) of ≥42.3 Gy compared to those receiving <42.3 Gy, although the difference was not significant (p = 0.347). Adding WBRT after resection of brain oligometastases from NSCLC seems to enhance intracranial control. Furthermore, combining lower-dose WBRT with a tumor bed boost may be an attractive option.

Optimal dose and volume for postoperative radiotherapy in brain oligometastases from lung cancer: a retrospective study

PubMed Central

Chung, Seung Yeun; Chang, Jong Hee; Kim, Hye Ryun; Cho, Byoung Chul; Lee, Chang Geol; Suh, Chang-Ok

2017-01-01

Purpose To evaluate intracranial control after surgical resection according to the adjuvant treatment received in order to assess the optimal radiotherapy (RT) dose and volume. Materials and Methods Between 2003 and 2015, a total of 53 patients with brain oligometastases from non-small cell lung cancer (NSCLC) underwent metastasectomy. The patients were divided into three groups according to the adjuvant treatment received: whole brain radiotherapy (WBRT) ± boost (WBRT ± boost group, n = 26), local RT/Gamma Knife surgery (local RT group, n = 14), and the observation group (n = 13). The most commonly used dose schedule was WBRT (25 Gy in 10 fractions, equivalent dose in 2 Gy fractions [EQD2] 26.04 Gy) with tumor bed boost (15 Gy in 5 fractions, EQD2 16.25 Gy). Results The WBRT ± boost group showed the lowest 1-year intracranial recurrence rate of 30.4%, followed by the local RT and observation groups, at 66.7%, and 76.9%, respectively (p = 0.006). In the WBRT ± boost group, there was no significant increase in the 1-year new site recurrence rate of patients receiving a lower dose of WBRT (EQD2) <27 Gy compared to that in patients receiving a higher WBRT dose (p = 0.553). The 1-year initial tumor site recurrence rate was lower in patients receiving tumor bed dose (EQD2) of ≥42.3 Gy compared to those receiving <42.3 Gy, although the difference was not significant (p = 0.347). conclusions Adding WBRT after resection of brain oligometastases from NSCLC seems to enhance intracranial control. Furthermore, combining lower-dose WBRT with a tumor bed boost may be an attractive option. PMID:28712276

Time-dependent diffuse reflectance spectroscopy for in vivo characterization of pediatric epileptogenic brain lesions

NASA Astrophysics Data System (ADS)

Oh, Sanghoon; Ragheb, John; Bhatia, Sanjiv; Sandberg, David; Johnson, Mahlon; Fernald, Bradley; Lin, Wei-Chiang

2008-02-01

Optical spectroscopy for in vivo tissue diagnosis is performed traditionally in a static manner; a snap shot of the tissue biochemical and morphological characteristics is captured through the interaction between light and the tissue. This approach does not capture the dynamic nature of a living organ, which is critical to the studies of brain disorders such as epilepsy. Therefore, a time-dependent diffuse reflectance spectroscopy system with a fiber-optic probe was designed and developed. The system was designed to acquire broadband diffuse reflectance spectra (240 ~ 932 nm) at an acquisition rate of 33 Hz. The broadband spectral acquisition feature allows simultaneous monitoring of various physiological characteristics of tissues. The utility of such a system in guiding pediatric epilepsy surgery was tested in a pilot clinical study including 13 epilepsy patients and seven brain tumor patients. The control patients were children undergoing suregery for brain tumors in which measurements were taken from normal brain exposed during the surgery. Diffuse reflectance spectra were acquired for 12 seconds from various parts of the brain of the patients during surgery. Recorded spectra were processed and analyzed in both spectral and time domains to gain insights into the dynamic changes in, for example, hemodynamics of the investigated brain tissue. One finding from this pilot study is that unsynchronized alterations in local blood oxygenation and local blood volume were observed in epileptogenic cortex. These study results suggest the advantage of using a time-dependent diffuse reflectance spectroscopy system to study epileptogenic brain in vivo.

Brain parcellation choice affects disease-related topology differences increasingly from global to local network levels.

PubMed

Lord, Anton; Ehrlich, Stefan; Borchardt, Viola; Geisler, Daniel; Seidel, Maria; Huber, Stefanie; Murr, Julia; Walter, Martin

2016-03-30

Network-based analyses of deviant brain function have become extremely popular in psychiatric neuroimaging. Underpinning brain network analyses is the selection of appropriate regions of interest (ROIs). Although ROI selection is fundamental in network analysis, its impact on detecting disease effects remains unclear. We investigated the impact of parcellation choice when comparing results from different studies. We investigated the effects of anatomical (AAL) and literature-based (Dosenbach) parcellation schemes on comparability of group differences in 35 female patients with anorexia nervosa and 35 age- and sex-matched healthy controls. Global and local network properties, including network-based statistics (NBS), were assessed on resting state functional magnetic resonance imaging data obtained at 3T. Parcellation schemes were comparably consistent on global network properties, while NBS and local metrics differed in location, but not metric type. Location of local metric alterations varied for AAL (parietal and cingulate cortices) versus Dosenbach (insula, thalamus) parcellation approaches. However, consistency was observed for the occipital cortex. Patient-specific global network properties can be robustly observed using different parcellation schemes, while graph metrics characterizing impairments of individual nodes vary considerably. Therefore, the impact of parcellation choice on specific group differences varies depending on the level of network organization. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Source localization of intermittent rhythmic delta activity in a patient with acute confusional migraine: cross-spectral analysis using standardized low-resolution brain electromagnetic tomography (sLORETA).

PubMed

Kim, Dae-Eun; Shin, Jung-Hyun; Kim, Young-Hoon; Eom, Tae-Hoon; Kim, Sung-Hun; Kim, Jung-Min

2016-01-01

Acute confusional migraine (ACM) shows typical electroencephalography (EEG) patterns of diffuse delta slowing and frontal intermittent rhythmic delta activity (FIRDA). The pathophysiology of ACM is still unclear but these patterns suggest neuronal dysfunction in specific brain areas. We performed source localization analysis of IRDA (in the frequency band of 1-3.5 Hz) to better understand the ACM mechanism. Typical IRDA EEG patterns were recorded in a patient with ACM during the acute stage. A second EEG was obtained after recovery from ACM. To identify source localization of IRDA, statistical non-parametric mapping using standardized low-resolution brain electromagnetic tomography was performed for the delta frequency band comparisons between ACM attack and non-attack periods. A difference in the current density maximum was found in the dorsal anterior cingulated cortex (ACC). The significant differences were widely distributed over the frontal, parietal, temporal and limbic lobe, paracentral lobule and insula and were predominant in the left hemisphere. Dorsal ACC dysfunction was demonstrated for the first time in a patient with ACM in this source localization analysis of IRDA. The ACC plays an important role in the frontal attentional control system and acute confusion. This dysfunction of the dorsal ACC might represent an important ACM pathophysiology.

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

PubMed Central

Koos, Tibor; Buzsáki, György

2012-01-01

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

Graph Metrics of Structural Brain Networks in Individuals with Schizophrenia and Healthy Controls: Group Differences, Relationships with Intelligence, and Genetics.

PubMed

Yeo, Ronald A; Ryman, Sephira G; van den Heuvel, Martijn P; de Reus, Marcel A; Jung, Rex E; Pommy, Jessica; Mayer, Andrew R; Ehrlich, Stefan; Schulz, S Charles; Morrow, Eric M; Manoach, Dara; Ho, Beng-Choon; Sponheim, Scott R; Calhoun, Vince D

2016-02-01

One of the most prominent features of schizophrenia is relatively lower general cognitive ability (GCA). An emerging approach to understanding the roots of variation in GCA relies on network properties of the brain. In this multi-center study, we determined global characteristics of brain networks using graph theory and related these to GCA in healthy controls and individuals with schizophrenia. Participants (N=116 controls, 80 patients with schizophrenia) were recruited from four sites. GCA was represented by the first principal component of a large battery of neurocognitive tests. Graph metrics were derived from diffusion-weighted imaging. The global metrics of longer characteristic path length and reduced overall connectivity predicted lower GCA across groups, and group differences were noted for both variables. Measures of clustering, efficiency, and modularity did not differ across groups or predict GCA. Follow-up analyses investigated three topological types of connectivity--connections among high degree "rich club" nodes, "feeder" connections to these rich club nodes, and "local" connections not involving the rich club. Rich club and local connectivity predicted performance across groups. In a subsample (N=101 controls, 56 patients), a genetic measure reflecting mutation load, based on rare copy number deletions, was associated with longer characteristic path length. Results highlight the importance of characteristic path lengths and rich club connectivity for GCA and provide no evidence for group differences in the relationships between graph metrics and GCA.

BRCA1 Mutations Associated With Increased Risk of Brain Metastases in Breast Cancer: A 1: 2 Matched-pair Analysis.

PubMed

Zavitsanos, Peter J; Wazer, David E; Hepel, Jaroslaw T; Wang, Yihong; Singh, Kamaljeet; Leonard, Kara L

2018-05-18

Brain metastases (BM) occur in ∼5% of breast cancer patients. BRCA1-associated cancers are often basal-like and basal-like cancers are known to have a predilection for central nervous system metastases. We performed a matched-pair analysis of breast cancer patients with and without BRCA mutations and compared the frequency of BM in both groups. From a database of 1935 patients treated for localized breast cancer at our institution from 2009 to 2014 we identified 20 patients with BRCA1 or BRCA2 mutations and manually matched 40 patients without BRCA mutations accounting for age, stage, estrogen receptor expression, and human epidermal growth factor receptor 2 (HER2) expression. Comparisons of freedom from brain metastasis, brain metastasis-free survival, and overall survival were made using the log rank test. Testing for a basal-type phenotype using the immunohistochemistry definition (ER/PR/HER2 and either CK 5/6 or EGFR) was performed for BRCA patients who developed BM and their matched controls. We analyzed 60 patients: 20 BRCA and 40 were matched controls. Median follow-up was 37 and 49 months, respectively. Three years freedom from brain metastasis was 84% for BRCA patients and 97% for BRCA controls (P=0.049). Three years brain metastasis-free survival was 84% and 97% for the BRCA+ and controls, respectively (P=0.176). Mean time to brain failure was 11 months from diagnosis for the BRCA patients. All 3 BRCA1 patients who developed BM were of a basal-type triple negative phenotype. Breast cancer patients with germline BRCA1 mutations appear to have a shorter interval to brain progression while accounting for confounding factors.

Neuromechanism Study of Insect–Machine Interface: Flight Control by Neural Electrical Stimulation

PubMed Central

Zhao, Huixia; Zheng, Nenggan; Ribi, Willi A.; Zheng, Huoqing; Xue, Lei; Gong, Fan; Zheng, Xiaoxiang; Hu, Fuliang

2014-01-01

The insect–machine interface (IMI) is a novel approach developed for man-made air vehicles, which directly controls insect flight by either neuromuscular or neural stimulation. In our previous study of IMI, we induced flight initiation and cessation reproducibly in restrained honeybees (Apis mellifera L.) via electrical stimulation of the bilateral optic lobes. To explore the neuromechanism underlying IMI, we applied electrical stimulation to seven subregions of the honeybee brain with the aid of a new method for localizing brain regions. Results showed that the success rate for initiating honeybee flight decreased in the order: α-lobe (or β-lobe), ellipsoid body, lobula, medulla and antennal lobe. Based on a comparison with other neurobiological studies in honeybees, we propose that there is a cluster of descending neurons in the honeybee brain that transmits neural excitation from stimulated brain areas to the thoracic ganglia, leading to flight behavior. This neural circuit may involve the higher-order integration center, the primary visual processing center and the suboesophageal ganglion, which is also associated with a possible learning and memory pathway. By pharmacologically manipulating the electrically stimulated honeybee brain, we have shown that octopamine, rather than dopamine, serotonin and acetylcholine, plays a part in the circuit underlying electrically elicited honeybee flight. Our study presents a new brain stimulation protocol for the honeybee–machine interface and has solved one of the questions with regard to understanding which functional divisions of the insect brain participate in flight control. It will support further studies to uncover the involved neurons inside specific brain areas and to test the hypothesized involvement of a visual learning and memory pathway in IMI flight control. PMID:25409523

Neuromechanism study of insect-machine interface: flight control by neural electrical stimulation.

PubMed

Zhao, Huixia; Zheng, Nenggan; Ribi, Willi A; Zheng, Huoqing; Xue, Lei; Gong, Fan; Zheng, Xiaoxiang; Hu, Fuliang

2014-01-01

The insect-machine interface (IMI) is a novel approach developed for man-made air vehicles, which directly controls insect flight by either neuromuscular or neural stimulation. In our previous study of IMI, we induced flight initiation and cessation reproducibly in restrained honeybees (Apis mellifera L.) via electrical stimulation of the bilateral optic lobes. To explore the neuromechanism underlying IMI, we applied electrical stimulation to seven subregions of the honeybee brain with the aid of a new method for localizing brain regions. Results showed that the success rate for initiating honeybee flight decreased in the order: α-lobe (or β-lobe), ellipsoid body, lobula, medulla and antennal lobe. Based on a comparison with other neurobiological studies in honeybees, we propose that there is a cluster of descending neurons in the honeybee brain that transmits neural excitation from stimulated brain areas to the thoracic ganglia, leading to flight behavior. This neural circuit may involve the higher-order integration center, the primary visual processing center and the suboesophageal ganglion, which is also associated with a possible learning and memory pathway. By pharmacologically manipulating the electrically stimulated honeybee brain, we have shown that octopamine, rather than dopamine, serotonin and acetylcholine, plays a part in the circuit underlying electrically elicited honeybee flight. Our study presents a new brain stimulation protocol for the honeybee-machine interface and has solved one of the questions with regard to understanding which functional divisions of the insect brain participate in flight control. It will support further studies to uncover the involved neurons inside specific brain areas and to test the hypothesized involvement of a visual learning and memory pathway in IMI flight control.

Integration of chemotherapy and radiation therapy for small cell carcinoma of the lung

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

Holoye, P.Y.; Libnoch, J.A.; Byhardt, R.W.

1982-09-01

Two chemotherapy trials using cyclophosphamide, doxorubicine hydrochloride and high-dose vincristine sulfate with or without methotrexate have induced a 93% incidence of complete remission in limited disease presentation of small cell bronchogenic carcinoma of the lung and 39% incidence in extensive disease. The first without consolidation radiotherapy had a local failure rate of 65%, which dropped to 17% with consolidation radiotherapy to the primary and mediastinum. Prophylactic whole brain radiotherapy prevented local recurrence in 98% of evaluable patients. One carcinomatous meningitis and 5 intraspinal recurrences were noted among the 38 patients in the CAV-M trial. We conclude that high-dose vincristine sulfatemore » is associated with an improved incidence of complete remission; that prophylactic whole brain radiotherapy has been highly successful; that prevention of intraspinal recurrence will necessitate the use of craniospinal axis radiation therapy and consolidation radiation therapy improves local control of primary and mediastinum.« less

Magnetic Field Homogenization of the Human Prefrontal Cortex with a Set of Localized Electrical Coils

PubMed Central

Juchem, Christoph; Nixon, Terence W.; McIntyre, Scott; Rothman, Douglas L.; de Graaf, Robin A.

2011-01-01

The prefrontal cortex is a common target brain structure in psychiatry and neuroscience due to its role in working memory and cognitive control. Large differences in magnetic susceptibility between the air-filled sinuses and the tissue/bone in the frontal part of the human head cause a strong and highly localized magnetic field focus in the prefrontal cortex. As a result, image distortion and signal dropout are observed in MR imaging. A set of external, electrical coils is presented that provides localized and high amplitude shim fields in the prefrontal cortex with minimum impact on the rest of the brain when combined with regular zero-to-second order spherical harmonics shimming. The experimental realization of the new shim method strongly minimized or even eliminated signal dropout in gradient-echo images acquired at settings typically used in functional magnetic resonance at 4 Tesla. PMID:19918909

Novel active contour model based on multi-variate local Gaussian distribution for local segmentation of MR brain images

NASA Astrophysics Data System (ADS)

Zheng, Qiang; Li, Honglun; Fan, Baode; Wu, Shuanhu; Xu, Jindong

2017-12-01

Active contour model (ACM) has been one of the most widely utilized methods in magnetic resonance (MR) brain image segmentation because of its ability of capturing topology changes. However, most of the existing ACMs only consider single-slice information in MR brain image data, i.e., the information used in ACMs based segmentation method is extracted only from one slice of MR brain image, which cannot take full advantage of the adjacent slice images' information, and cannot satisfy the local segmentation of MR brain images. In this paper, a novel ACM is proposed to solve the problem discussed above, which is based on multi-variate local Gaussian distribution and combines the adjacent slice images' information in MR brain image data to satisfy segmentation. The segmentation is finally achieved through maximizing the likelihood estimation. Experiments demonstrate the advantages of the proposed ACM over the single-slice ACM in local segmentation of MR brain image series.

Photodynamic therapy: a review of applications in neurooncology and neuropathology

NASA Astrophysics Data System (ADS)

Uzdensky, Anatoly B.; Berezhnaya, Elena; Kovaleva, Vera; Neginskaya, Marya; Rudkovskii, Mikhail; Sharifulina, Svetlana

2015-06-01

Photodynamic therapy (PDT) effect is a promising adjuvant modality for diagnosis and treatment of brain cancer. It is of importance that the bright fluorescence of most photosensitizers provides visualization of brain tumors. This is successfully used for fluorescence-guided tumor resection according to the principle "to see and to treat." Non-oncologic application of PDT effect for induction of photothrombotic infarct of the brain tissue is a well-controlled and reproducible stroke model, in which a local brain lesion is produced in the predetermined brain area. Since normal neurons and glial cells may also be damaged by PDT and this can lead to unwanted neurological consequences, PDT effects on normal neurons and glial cells should be comprehensively studied. We overviewed the current literature data on the PDT effect on a range of signaling and epigenetic proteins that control various cell functions, survival, necrosis, and apoptosis. We hypothesize that using cell-specific inhibitors or activators of some signaling proteins, one can selectively protect normal neurons and glia, and simultaneously exacerbate photodynamic damage of malignant gliomas.

Characteristics and Treatments of Large Cystic Brain Metastasis: Radiosurgery and Stereotactic Aspiration

PubMed Central

Kim, Moinay; Cheok, Stephanie; Chung, Lawrance K.; Ung, Nolan; Thill, Kimberly; Voth, Brittany; Kwon, Do Hoon; Kim, Jeong Hoon; Kim, Chang Jin; Tenn, Stephen; Lee, Percy

2015-01-01

Brain metastasis represents one of the most common causes of intracranial tumors in adults, and the incidence of brain metastasis continues to rise due to the increasing survival of cancer patients. Yet, the development of cystic brain metastasis remains a relatively rare occurrence. In this review, we describe the characteristics of cystic brain metastasis and evaluate the combined use of stereotactic aspiration and radiosurgery in treating large cystic brain metastasis. The results of several studies show that stereotactic radiosurgery produces comparable local tumor control and survival rates as other surgery protocols. When the size of the tumor interferes with radiosurgery, stereotactic aspiration of the metastasis should be considered to reduce the target volume as well as decreasing the chance of radiation induced necrosis and providing symptomatic relief from mass effect. The combined use of stereotactic aspiration and radiosurgery has strong implications in improving patient outcomes. PMID:25977901

Probe-pin device for optical neurotransmitter sensing in the brain

NASA Astrophysics Data System (ADS)

Kim, Min Hyuck; Song, Kyo D.; Yoon, Hargsoon; Park, Yeonjoon; Choi, Sang H.; Lee, Dae-Sung; Shin, Kyu-Sik; Hwang, Hak-In; Lee, Uhn

2015-04-01

Development of an optical neurotransmitter sensing device using nano-plasmonic probes and a micro-spectrometer for real time monitoring of neural signals in the brain is underway. Clinical application of this device technology is to provide autonomous closed-loop feedback control to a deep brain stimulation (DBS) system and enhance the accuracy and efficacy of DBS treatment. By far, we have developed an implantable probe-pin device based on localized field enhancement of surface plasmonic resonance on a nanostructured sensing domain which can amplify neurochemical signals from evoked neural activity in the brain. In this paper, we will introduce the details of design and sensing performance of a proto-typed microspectrometer and nanostructured probing devices for real time measurement of neurotransmitter concentrations.

Localization of Asymmetric Brain Function in Emotion and Depression

PubMed Central

Herrington, John D.; Heller, Wendy; Mohanty, Aprajita; Engels, Anna S.; Banich, Marie T.; Webb, Andrew G.; Miller, Gregory A.

2011-01-01

Although numerous EEG studies have shown that depression is associated with abnormal functional asymmetries in frontal cortex, fMRI and PET studies have largely failed to identify specific brain areas showing this effect. The present study tested the hypothesis that emotion processes are related to asymmetric patterns of fMRI activity, particularly within dorsolateral prefrontal cortex (DLPFC). Eleven depressed and 18 control participants identified the color in which pleasant, neutral, and unpleasant words were printed. Both groups showed a leftward lateralization for pleasant words in DLPFC. In a neighboring DLPFC area, the depression group showed more right-lateralized activation than controls, replicating EEG findings. These data confirm that emotional stimulus processing and trait depression are associated with asymmetric brain functions in distinct subregions of the DLPFC that may go undetected unless appropriate analytic procedures are used. PMID:20070577

Localization of asymmetric brain function in emotion and depression.

PubMed

Herrington, John D; Heller, Wendy; Mohanty, Aprajita; Engels, Anna S; Banich, Marie T; Webb, Andrew G; Miller, Gregory A

2010-05-01

Although numerous EEG studies have shown that depression is associated with abnormal functional asymmetries in frontal cortex, fMRI and PET studies have largely failed to identify specific brain areas showing this effect. The present study tested the hypothesis that emotion processes are related to asymmetric patterns of fMRI activity, particularly within dorsolateral prefrontal cortex (DLPFC). Eleven depressed and 18 control participants identified the color in which pleasant, neutral, and unpleasant words were printed. Both groups showed a leftward lateralization for pleasant words in DLPFC. In a neighboring DLPFC area, the depression group showed more right-lateralized activation than controls, replicating EEG findings. These data confirm that emotional stimulus processing and trait depression are associated with asymmetric brain functions in distinct subregions of the DLPFC that may go undetected unless appropriate analytic procedures are used.

Physiology and molecular biology of barrier mechanisms in the fetal and neonatal brain.

PubMed

Saunders, Norman R; Dziegielewska, Katarzyna M; Møllgård, Kjeld; Habgood, Mark D

2018-05-17

Properties of the local internal environment of the adult brain are tightly controlled providing a stable milieu essential for its normal function. The mechanisms involved in this complex control are structural, molecular and physiological (influx and efflux transporters) frequently referred to as the "blood-brain barrier". These mechanisms include regulation of ion levels in brain interstitial fluid essential for normal neuronal function, supply of nutrients, removal of metabolic products and prevention of entry or elimination of toxic agents. A key feature is cerebrospinal fluid secretion and turnover. This is much less during development, allowing greater accumulation of permeating molecules. The overall effect of these mechanisms is to tightly control the exchange of molecules into and out of the brain. This review presents experimental evidence currently available on the status of these mechanisms in developing brain. It has been frequently stated for over nearly a century that the blood-brain barrier is not present or at least is functionally deficient in the embryo, fetus and newborn. We suggest the alternative hypothesis that the barrier mechanisms in developing brain are likely to be appropriately matched to each stage of its development. The contributions of different barrier mechanisms, such as changes in constituents of cerebrospinal fluid in relation to specific features of brain development, for example neurogenesis, are only beginning to be studied. The evidence on this previously neglected aspect of brain barrier function is outlined. We also suggest future directions this field could follow with special emphasis on potential applications in a clinical setting. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Brain-resident memory CD8+ T cells induced by congenital CMV infection prevent brain pathology and virus reactivation.

PubMed

Brizić, Ilija; Šušak, Božo; Arapović, Maja; Huszthy, Peter C; Hiršl, Lea; Kveštak, Daria; Juranić Lisnić, Vanda; Golemac, Mijo; Pernjak Pugel, Ester; Tomac, Jelena; Oxenius, Annette; Britt, William J; Arapović, Jurica; Krmpotić, Astrid; Jonjić, Stipan

2018-06-01

Congenital HCMV infection is a leading infectious cause of long-term neurodevelopmental sequelae. Infection of newborn mice with mouse cytomegalovirus (MCMV) intraperitoneally is a well-established model of congenital human cytomegalovirus infection, which best recapitulates the hematogenous route of virus spread to brain and subsequent pathology. Here, we used this model to investigate the role, dynamics, and phenotype of CD8 + T cells in the brain following infection of newborn mice. We show that CD8 + T cells infiltrate the brain and form a pool of tissue-resident memory T cells (T RM cells) that persist for lifetime. Adoptively transferred virus-specific CD8 + T cells provide protection against primary MCMV infection in newborn mice, reduce brain pathology, and remain in the brain as T RM cells. Brain CD8 + T RM cells were long-lived, slowly proliferating cells able to respond to local challenge infection. Importantly, brain CD8 + T RM cells controlled latent MCMV and their depletion resulted in virus reactivation and enhanced inflammation in brain. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Fully Automated Method for Quantifying and Localizing White Matter Hyperintensities on MR Images

PubMed Central

Wu, Minjie; Rosano, Caterina; Butters, Meryl; Whyte, Ellen; Nable, Megan; Crooks, Ryan; Meltzer, Carolyn C.; Reynolds, Charles F.; Aizenstein3, Howard J.

2006-01-01

White matter hyperintensities (WMH), commonly found on T2-weighted FLAIR brain MR images in the elderly, are associated with a number of neuropsychiatric disorders, including vascular dementia, Alzheimer’s disease, and late-life depression. Previous MRI studies of WMHs have primarily relied on the subjective and global (i.e., full-brain) ratings of WMH grade. In the current study we implement and validate an automated method for quantifying and localizing WMHs. We adapt a fuzzy connected algorithm to automate the segmentation of WMHs and use a demons-based image registration to automate the anatomic localization of the WMHs using the Johns Hopkins University White Matter Atlas. The method is validated using the brain MR images acquired from eleven elderly subjects with late-onset late-life depression (LLD) and eight elderly controls. This dataset was chosen because LLD subjects are known to have significant WMH burden. The volumes of WMH identified in our automated method are compared with the accepted gold standard (manual ratings). A significant correlation of the automated method and the manual ratings is found (P<0.0001), thus demonstrating similar WMH quantifications of both methods. As has been shown in other studies e.g. (Taylor, et al. 2003)), we found there was a significantly greater WMH burden in the LLD subjects versus the controls for both the manual and automated method. The effect size was greater for the automated method, suggesting that it is a more specific measure. Additionally, we describe the anatomic localization of the WMHs in LLD subjects as well as in the control subjects, and detect the regions of interest (ROIs) specific for the WMH burden of LLD patients. Given the emergence of large neuroimage databases, techniques, such as that described here, will allow for a better understanding of the relationship between WMHs and neuropsychiatric disorders. PMID:17097277

Modulation of functionally localized right insular cortex activity using real-time fMRI-based neurofeedback.

PubMed

Berman, Brian D; Horovitz, Silvina G; Hallett, Mark

2013-01-01

The capacity for subjects to learn to volitionally control localized brain activity using neurofeedback is actively being investigated. We aimed to investigate the ability of healthy volunteers to quickly learn to use visual feedback during real-time functional MRI (rtfMRI) to modulate brain activity within their anterior right insular cortex (RIC) localized during a blink suppression task, an approach of possible interest in the use of rtfMRI to reduce urges. The RIC region of interest (RIC-ROI) was functionally localized using a blink suppression task, and blood-oxygen level dependent (BOLD) signal changes within RIC-ROI used to create a constantly updating display fed back to the subject in the scanner. Subjects were instructed to use emotional imagery to try and increase activity within RIC-ROI during four feedback training runs (FB1-FB4). A "control" run (CNTRL) before training and a "transfer" run (XSFR) after training were performed without feedback to assess for baseline abilities and learning effects. Fourteen participants completed all neurofeedback training runs. At the group-level, increased BOLD activity was seen in the anterior RIC during all the FB runs, but a significant increase in the functionally defined RIC-ROI was only attained during FB2. In atlas-defined insular cortex ROIs, significant increases were seen bilaterally during the CNTRL, FB1, FB2, and FB4 runs. Increased activity within the insular cortices did not show lateralization. Training did, however, result in a significant increase in functional connectivity between the RIC-ROI and the medial frontal gyrus when comparing FB4 to FB1. Since neurofeedback training did not lead to an increase in BOLD signal across all feedback runs, we suggest that learning to control one's brain activity in this fashion may require longer or repeated rtfMRI training sessions.

F18 EF5 PET/CT Imaging in Patients with Brain Metastases from Breast Cancer

DTIC Science & Technology

2013-07-01

control and survival in select patients after WBRT . At present we do not have any method of determining a priori which patients may benefit from RS...boost. The development of a noninvasive imaging biomarker to identify patients that are at highest risk of local relapse after WBRT would represent a...detect residual tumor hypoxia in patients receiving WBRT . Body: Task 1. To estimate the degree of hypoxia after WBRT in patients with brain

Learning Control Over Emotion Networks Through Connectivity-Based Neurofeedback.

PubMed

Koush, Yury; Meskaldji, Djalel-E; Pichon, Swann; Rey, Gwladys; Rieger, Sebastian W; Linden, David E J; Van De Ville, Dimitri; Vuilleumier, Patrik; Scharnowski, Frank

2017-02-01

Most mental functions are associated with dynamic interactions within functional brain networks. Thus, training individuals to alter functional brain networks might provide novel and powerful means to improve cognitive performance and emotions. Using a novel connectivity-neurofeedback approach based on functional magnetic resonance imaging (fMRI), we show for the first time that participants can learn to change functional brain networks. Specifically, we taught participants control over a key component of the emotion regulation network, in that they learned to increase top-down connectivity from the dorsomedial prefrontal cortex, which is involved in cognitive control, onto the amygdala, which is involved in emotion processing. After training, participants successfully self-regulated the top-down connectivity between these brain areas even without neurofeedback, and this was associated with concomitant increases in subjective valence ratings of emotional stimuli of the participants. Connectivity-based neurofeedback goes beyond previous neurofeedback approaches, which were limited to training localized activity within a brain region. It allows to noninvasively and nonpharmacologically change interconnected functional brain networks directly, thereby resulting in specific behavioral changes. Our results demonstrate that connectivity-based neurofeedback training of emotion regulation networks enhances emotion regulation capabilities. This approach can potentially lead to powerful therapeutic emotion regulation protocols for neuropsychiatric disorders. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Scalp and Source Power Topography in Sleepwalking and Sleep Terrors: A High-Density EEG Study.

PubMed

Castelnovo, Anna; Riedner, Brady A; Smith, Richard F; Tononi, Giulio; Boly, Melanie; Benca, Ruth M

2016-10-01

To examine scalp and source power topography in sleep arousals disorders (SADs) using high-density EEG (hdEEG). Fifteen adult subjects with sleep arousal disorders (SADs) and 15 age- and gender-matched good sleeping healthy controls were recorded in a sleep laboratory setting using a 256 channel EEG system. Scalp EEG analysis of all night NREM sleep revealed a localized decrease in slow wave activity (SWA) power (1-4 Hz) over centro-parietal regions relative to the rest of the brain in SADs compared to good sleeping healthy controls. Source modelling analysis of 5-minute segments taken from N3 during the first half of the night revealed that the local decrease in SWA power was prominent at the level of the cingulate, motor, and sensori-motor associative cortices. Similar patterns were also evident during REM sleep and wake. These differences in local sleep were present in the absence of any detectable clinical or electrophysiological sign of arousal. Overall, results suggest the presence of local sleep differences in the brain of SADs patients during nights without clinical episodes. The persistence of similar topographical changes in local EEG power during REM sleep and wakefulness points to trait-like functional changes that cross the boundaries of NREM sleep. The regions identified by source imaging are consistent with the current neurophysiological understanding of SADs as a disorder caused by local arousals in motor and cingulate cortices. Persistent localized changes in neuronal excitability may predispose affected subjects to clinical episodes. © 2016 Associated Professional Sleep Societies, LLC.

Brain functional network abnormality extends beyond the sensorimotor network in brachial plexus injury patients.

PubMed

Feng, Jun-Tao; Liu, Han-Qiu; Hua, Xu-Yun; Gu, Yu-Dong; Xu, Jian-Guang; Xu, Wen-Dong

2016-12-01

Brachial plexus injury (BPI) is a type of severe peripheral nerve trauma that leads to central remodeling in the brain, as revealed by functional MRI analysis. However, previously reported remodeling is mostly restricted to sensorimotor areas of the brain. Whether this disturbance in the sensorimotor network leads to larger-scale functional remodeling remains unknown. We sought to explore the higher-level brain functional abnormality pattern of BPI patients from a large-scale network function connectivity dimension in 15 right-handed BPI patients. Resting-state functional MRI data were collected and analyzed using independent component analysis methods. Five components of interest were recognized and compared between patients and healthy subjects. Patients showed significantly altered brain local functional activities in the bilateral fronto-parietal network (FPN), sensorimotor network (SMN), and executive-control network (ECN) compared with healthy subjects. Moreover, functional connectivity between SMN and ECN were significantly less in patients compared with healthy subjects, and connectivity strength between ECN and SMN was negatively correlated with patients' residual function of the affected limb. Functional connectivity between SMN and right FPN were also significantly less than in controls, although connectivity between ECN and default mode network (DMN) was greater than in controls. These data suggested that brain functional disturbance in BPI patients extends beyond the sensorimotor network and cascades serial remodeling in the brain, which significantly correlates with residual hand function of the paralyzed limb. Furthermore, functional remodeling in these higher-level functional networks may lead to cognitive alterations in complex tasks.

Large-Scale Network Analysis of Whole-Brain Resting-State Functional Connectivity in Spinal Cord Injury: A Comparative Study.

PubMed

Kaushal, Mayank; Oni-Orisan, Akinwunmi; Chen, Gang; Li, Wenjun; Leschke, Jack; Ward, Doug; Kalinosky, Benjamin; Budde, Matthew; Schmit, Brian; Li, Shi-Jiang; Muqeet, Vaishnavi; Kurpad, Shekar

2017-09-01

Network analysis based on graph theory depicts the brain as a complex network that allows inspection of overall brain connectivity pattern and calculation of quantifiable network metrics. To date, large-scale network analysis has not been applied to resting-state functional networks in complete spinal cord injury (SCI) patients. To characterize modular reorganization of whole brain into constituent nodes and compare network metrics between SCI and control subjects, fifteen subjects with chronic complete cervical SCI and 15 neurologically intact controls were scanned. The data were preprocessed followed by parcellation of the brain into 116 regions of interest (ROI). Correlation analysis was performed between every ROI pair to construct connectivity matrices and ROIs were categorized into distinct modules. Subsequently, local efficiency (LE) and global efficiency (GE) network metrics were calculated at incremental cost thresholds. The application of a modularity algorithm organized the whole-brain resting-state functional network of the SCI and the control subjects into nine and seven modules, respectively. The individual modules differed across groups in terms of the number and the composition of constituent nodes. LE demonstrated statistically significant decrease at multiple cost levels in SCI subjects. GE did not differ significantly between the two groups. The demonstration of modular architecture in both groups highlights the applicability of large-scale network analysis in studying complex brain networks. Comparing modules across groups revealed differences in number and membership of constituent nodes, indicating modular reorganization due to neural plasticity.

Regional Homogeneity

PubMed Central

Jiang, Lili; Zuo, Xi-Nian

2015-01-01

Much effort has been made to understand the organizational principles of human brain function using functional magnetic resonance imaging (fMRI) methods, among which resting-state fMRI (rfMRI) is an increasingly recognized technique for measuring the intrinsic dynamics of the human brain. Functional connectivity (FC) with rfMRI is the most widely used method to describe remote or long-distance relationships in studies of cerebral cortex parcellation, interindividual variability, and brain disorders. In contrast, local or short-distance functional interactions, especially at a scale of millimeters, have rarely been investigated or systematically reviewed like remote FC, although some local FC algorithms have been developed and applied to the discovery of brain-based changes under neuropsychiatric conditions. To fill this gap between remote and local FC studies, this review will (1) briefly survey the history of studies on organizational principles of human brain function; (2) propose local functional homogeneity as a network centrality to characterize multimodal local features of the brain connectome; (3) render a neurobiological perspective on local functional homogeneity by linking its temporal, spatial, and individual variability to information processing, anatomical morphology, and brain development; and (4) discuss its role in performing connectome-wide association studies and identify relevant challenges, and recommend its use in future brain connectomics studies. PMID:26170004

Prefrontal cortex lesions and MAO-A modulate aggression in penetrating traumatic brain injury

PubMed Central

Pardini, M.; Krueger, F.; Hodgkinson, C.; Raymont, V.; Ferrier, C.; Goldman, D.; Strenziok, M.; Guida, S.

2011-01-01

Objective: This study investigates the interaction between brain lesion location and monoamine oxidase A (MAO-A) in the genesis of aggression in patients with penetrating traumatic brain injury (PTBI). Methods: We enrolled 155 patients with PTBI and 42 controls drawn from the Vietnam Head Injury Study registry. Patients with PTBI were divided according to lesion localization (prefrontal cortex [PFC] vs non-PFC) and were genotyped for the MAO-A polymorphism linked to low and high transcriptional activity. Aggression was assessed with the aggression/agitation subscale of the Neuropsychiatric Inventory (NPI-a). Results: Patients with the highest levels of aggression preferentially presented lesions in PFC territories. A significant interaction between MAO-A transcriptional activity and lesion localization on aggression was revealed. In the control group, carriers of the low-activity allele demonstrated higher aggression than high-activity allele carriers. In the PFC lesion group, no significant differences in aggression were observed between carriers of the 2 MAO-A alleles, whereas in the non-PFC lesion group higher aggression was observed in the high-activity allele than in the low-activity allele carriers. Higher NPI-a scores were linked to more severe childhood psychological traumatic experiences and posttraumatic stress disorder symptomatology in the control and non-PFC lesion groups but not in the PFC lesion group. Conclusions: Lesion location and MAO-A genotype interact in mediating aggression in PTBI. Importantly, PFC integrity is necessary for modulation of aggressive behaviors by genetic susceptibilities and traumatic experiences. Potentially, lesion localization and MAO-A genotype data could be combined to develop risk-stratification algorithms and individualized treatments for aggression in PTBI. PMID:21422455

Auditory P3a and P3b neural generators in schizophrenia: An adaptive sLORETA P300 localization approach.

PubMed

Bachiller, Alejandro; Romero, Sergio; Molina, Vicente; Alonso, Joan F; Mañanas, Miguel A; Poza, Jesús; Hornero, Roberto

2015-12-01

The present study investigates the neural substrates underlying cognitive processing in schizophrenia (Sz) patients. To this end, an auditory 3-stimulus oddball paradigm was used to identify P3a and P3b components, elicited by rare-distractor and rare-target tones, respectively. Event-related potentials (ERP) were recorded from 31 Sz patients and 38 healthy controls. The P3a and P3b brain-source generators were identified by time-averaging of low-resolution brain electromagnetic tomography (LORETA) current density images. In contrast with the commonly used fixed window of interest (WOI), we proposed to apply an adaptive WOI, which takes into account subjects' P300 latency variability. Our results showed different P3a and P3b source activation patterns in both groups. P3b sources included frontal, parietal and limbic lobes, whereas P3a response generators were localized over bilateral frontal and superior temporal regions. These areas have been related to the discrimination of auditory stimulus and to the inhibition (P3a) or the initiation (P3b) of motor response in a cognitive task. In addition, differences in source localization between Sz and control groups were observed. Sz patients showed lower P3b source activity in bilateral frontal structures and the cingulate. P3a generators were less widespread for Sz patients than for controls in right superior, medial and middle frontal gyrus. Our findings suggest that target and distractor processing involves distinct attentional subsystems, both being altered in Sz. Hence, the study of neuroelectric brain information can provide further insights to understand cognitive processes and underlying mechanisms in Sz. Copyright © 2015 Elsevier B.V. All rights reserved.

MicroRNA profiling reveals new aspects of HIV neurodegeneration: caspase-6 regulates astrocyte survival.

PubMed

Noorbakhsh, Farshid; Ramachandran, Rithwik; Barsby, Nicola; Ellestad, Kristofor K; LeBlanc, Andrea; Dickie, Peter; Baker, Glen; Hollenberg, Morley D; Cohen, Eric A; Power, Christopher

2010-06-01

MicroRNAs (miRNAs) are small noncoding RNA molecules, which are known to regulate gene expression in physiological and pathological conditions. miRNA profiling was performed using brain tissue from patients with HIV encephalitis (HIVE), a neuroinflammatory/degenerative disorder caused by HIV infection of the brain. Microarray analysis showed differential expression of multiple miRNAs in HIVE compared to control brains. Target prediction and gene ontology enrichment analysis disclosed targeting of several gene families/biological processes by differentially expressed miRNAs (DEMs), with cell death-related genes, including caspase-6, showing a bias toward down-regulated DEMs. Consistent with the miRNA data, HIVE brains exhibited higher levels of caspase-6 transcripts compared with control patients. Immunohistochemical analysis showed localization of the cleaved form of caspase-6 in astrocytes in HIVE brain sections. Exposure of cultured human primary astrocytes to HIV viral protein R (Vpr) induced p53 up-regulation, loss of mitochondrial membrane potential, and caspase-6 activation followed by cell injury. Transgenic mice, expressing Vpr in microglial cells, demonstrated astrocyte apoptosis in brain, which was associated with caspase-6 activation and neurobehavioral abnormalities. Overall, these data point to previously unrecognized alterations in miRNA profile in the brain during HIV infection, which contribute to cell death through dysregulation of cell death machinery.

The Virtual Brain: Modeling Biological Correlates of Recovery after Chronic Stroke

PubMed Central

Falcon, Maria Inez; Riley, Jeffrey D.; Jirsa, Viktor; McIntosh, Anthony R.; Shereen, Ahmed D.; Chen, E. Elinor; Solodkin, Ana

2015-01-01

There currently remains considerable variability in stroke survivor recovery. To address this, developing individualized treatment has become an important goal in stroke treatment. As a first step, it is necessary to determine brain dynamics associated with stroke and recovery. While recent methods have made strides in this direction, we still lack physiological biomarkers. The Virtual Brain (TVB) is a novel application for modeling brain dynamics that simulates an individual’s brain activity by integrating their own neuroimaging data with local biophysical models. Here, we give a detailed description of the TVB modeling process and explore model parameters associated with stroke. In order to establish a parallel between this new type of modeling and those currently in use, in this work we establish an association between a specific TVB parameter (long-range coupling) that increases after stroke with metrics derived from graph analysis. We used TVB to simulate the individual BOLD signals for 20 patients with stroke and 10 healthy controls. We performed graph analysis on their structural connectivity matrices calculating degree centrality, betweenness centrality, and global efficiency. Linear regression analysis demonstrated that long-range coupling is negatively correlated with global efficiency (P = 0.038), but is not correlated with degree centrality or betweenness centrality. Our results suggest that the larger influence of local dynamics seen through the long-range coupling parameter is closely associated with a decreased efficiency of the system. We thus propose that the increase in the long-range parameter in TVB (indicating a bias toward local over global dynamics) is deleterious because it reduces communication as suggested by the decrease in efficiency. The new model platform TVB hence provides a novel perspective to understanding biophysical parameters responsible for global brain dynamics after stroke, allowing the design of focused therapeutic interventions. PMID:26579071

[Brain-Computer Interface: the First Clinical Experience in Russia].

PubMed

Mokienko, O A; Lyukmanov, R Kh; Chernikova, L A; Suponeva, N A; Piradov, M A; Frolov, A A

2016-01-01

Motor imagery is suggested to stimulate the same plastic mechanisms in the brain as a real movement. The brain-computer interface (BCI) controls motor imagery by converting EEG during this process into the commands for an external device. This article presents the results of two-stage study of the clinical use of non-invasive BCI in the rehabilitation of patients with severe hemiparesis caused by focal brain damage. It was found that the ability to control BCI did not depend on the duration of a disease, brain lesion localization and the degree of neurological deficit. The first step of the study involved 36 patients; it showed that the efficacy of rehabilitation was higher in the group with the use of BCI (the score on the Action Research Arm Test (ARAT) improved from 1 [0; 2] to 5 [0; 16] points, p = 0.012; no significant improvement was observed in control group). The second step of the study involved 19 patients; the complex BCI-exoskeleton (i.e. with the kinesthetic feedback) was used for motor imagery trainings. The improvement of the motor function of hands was proved by ARAT (the score improved from 2 [0; 37] to 4 [1; 45:5] points, p = 0.005) and Fugl-Meyer scale (from 72 [63; 110 ] to 79 [68; 115] points, p = 0.005).

Altered Whole-Brain and Network-Based Functional Connectivity in Parkinson's Disease.

PubMed

de Schipper, Laura J; Hafkemeijer, Anne; van der Grond, Jeroen; Marinus, Johan; Henselmans, Johanna M L; van Hilten, Jacobus J

2018-01-01

Background: Functional imaging methods, such as resting-state functional magnetic resonance imaging, reflect changes in neural connectivity and may help to assess the widespread consequences of disease-specific network changes in Parkinson's disease. In this study we used a relatively new graph analysis approach in functional imaging: eigenvector centrality mapping. This model-free method, applied to all voxels in the brain, identifies prominent regions in the brain network hierarchy and detects localized differences between patient populations. In other neurological disorders, eigenvector centrality mapping has been linked to changes in functional connectivity in certain nodes of brain networks. Objectives: Examining changes in functional brain connectivity architecture on a whole brain and network level in patients with Parkinson's disease. Methods: Whole brain resting-state functional architecture was studied with a recently introduced graph analysis approach (eigenvector centrality mapping). Functional connectivity was further investigated in relation to eight known resting-state networks. Cross-sectional analyses included group comparison of functional connectivity measures of Parkinson's disease patients ( n = 107) with control subjects ( n = 58) and correlations with clinical data, including motor and cognitive impairment and a composite measure of predominantly non-dopaminergic symptoms. Results: Eigenvector centrality mapping revealed that frontoparietal regions were more prominent in the whole-brain network function in patients compared to control subjects, while frontal and occipital brain areas were less prominent in patients. Using standard resting-state networks, we found predominantly increased functional connectivity, namely within sensorimotor system and visual networks in patients. Regional group differences in functional connectivity of both techniques between patients and control subjects partly overlapped for highly connected posterior brain regions, in particular in the posterior cingulate cortex and precuneus. Clinico-functional imaging relations were not found. Conclusions: Changes on the level of functional brain connectivity architecture might provide a different perspective of pathological consequences of Parkinson's disease. The involvement of specific, highly connected (hub) brain regions may influence whole brain functional network architecture in Parkinson's disease.

Introducing Euro-Glo, a rare earth metal chelate with numerous applications for the fluorescent localization of myelin and amyloid plaques in brain tissue sections.

PubMed

Schmued, Larry; Raymick, James

2017-03-01

The vast majority of fluorochromes are organic in nature and none of the few existing chelates have been applied as histological tracers for localizing brain anatomy and pathology. In this study we have developed and characterized a Europium chelate with the ability to fluorescently label normal and pathological myelin in control and toxicant-exposed rats, as well as the amyloid plaques in aged AD/Tg mice. This study demonstrates how Euro-Glo can be used for the detailed labeling of both normal myelination in the control rat as well as myelin pathology in the kainic acid exposed rat. In addition, this study demonstrates how E-G will label the shell of amyloid plaques in an AD/Tg mouse model of Alzheimer's disease a red color, while the plaque core appears blue in color. The observed E-G staining pattern is compared with that of well characterized tracers specific for the localization of myelin (Black-Gold II), degenerating neurons (Fluoro-Jade C), A-beta aggregates (Amylo-Glo) and glycolipids (PAS). This study represents the first time a rare earth metal (REM) chelate has been used as a histochemical tracer in the brain. This novel tracer, Euro-Glo (E-G), exhibits numerous advantages over conventional organic fluorophores including high intensity emission, high resistance to fading, compatibility with multiple labeling protocols, high Stoke's shift value and an absence of bleed-through of the signal through other filters. Euro-Glo represents the first fluorescent metal chelate to be used as a histochemical tracer, specifically to localize normal and pathological myelin as well as amyloid plaques. Copyright © 2016. Published by Elsevier B.V.

N-isopropyl-(/sup 123/I)p-iodoamphetamine: single-pass brain uptake and washout; binding to brain synaptosomes; and localization in dog and monkey brain

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

Winchell, H.S.; Horst, W.D.; Braun, L.

1980-10-01

The kinetics of N-isopropyl-p-(/sup 123/I)iodoamphetamine in rat brains were determined by serial measurements of brain uptake index (BUI) after intracarotid injection; also studied were its effects on amine uptake and release in rat's brain cortical synaptosomes; and its in vivo distribution in the dog and monkey. No specific localization in brain nuclei of the dog was seen, but there was progressive accumulation in the eyes. Rapid initial brain uptake in the ketamine-sedated monkey was noted, and further slow brain uptake occurred during the next 20 min but without retinal localization. High levels of brain activity were maintained for several hours.more » The quantitative initial single-pass clearance of the agent in the brain suggests its use in evaluation of regional brain perfusion. Its interaction with brain amine-binding sites suggests its possible application in studies of cerebral amine metabolism.« less

Intrinsic Brain Connectivity in Chronic Pain: A Resting-State fMRI Study in Patients with Rheumatoid Arthritis

PubMed Central

Flodin, Pär; Martinsen, Sofia; Altawil, Reem; Waldheim, Eva; Lampa, Jon; Kosek, Eva; Fransson, Peter

2016-01-01

Background: Rheumatoid arthritis (RA) is commonly accompanied by pain that is discordant with the degree of peripheral pathology. Very little is known about the cerebral processes involved in pain processing in RA. Here we investigated resting-state brain connectivity associated with prolonged pain in RA. Methods: 24 RA subjects and 19 matched controls were compared with regard to both behavioral measures of pain perception and resting-resting state fMRI data acquired subsequently to fMRI sessions involving pain stimuli. The resting-state fMRI brain connectivity was investigated using 159 seed regions located in cardinal pain processing brain regions. Additional principal component based multivariate pattern analysis of the whole brain connectivity pattern was carried out in a data driven analysis to localize group differences in functional connectivity. Results: When RA patients were compared to controls, we observed significantly lower pain resilience for pressure on the affected finger joints (i.e., P50-joint) and an overall heightened level of perceived global pain in RA patients. Relative to controls, RA patients displayed increased brain connectivity predominately for the supplementary motor areas, mid-cingulate cortex, and the primary sensorimotor cortex. Additionally, we observed an increase in brain connectivity between the insula and prefrontal cortex as well as between anterior cingulate cortex and occipital areas for RA patients. None of the group differences in brain connectivity were significantly correlated with behavioral parameters. Conclusion: Our study provides experimental evidence of increased connectivity between frontal midline regions that are implicated in affective pain processing and bilateral sensorimotor regions in RA patients. PMID:27014038

Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases.

PubMed

Tsao, May N; Xu, Wei; Wong, Rebecca Ks; Lloyd, Nancy; Laperriere, Normand; Sahgal, Arjun; Rakovitch, Eileen; Chow, Edward

2018-01-25

This is an update to the review published in the Cochrane Library (2012, Issue 4).It is estimated that 20% to 40% of people with cancer will develop brain metastases during the course of their illness. The burden of brain metastases impacts quality and length of survival. To assess the effectiveness and adverse effects of whole brain radiotherapy (WBRT) given alone or in combination with other therapies to adults with newly diagnosed multiple brain metastases. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase to May 2017 and the National Cancer Institute Physicians Data Query for ongoing trials. We included phase III randomised controlled trials (RCTs) comparing WBRT versus other treatments for adults with newly diagnosed multiple brain metastases. Two review authors independently assessed trial quality and abstracted information in accordance with Cochrane methods. We added 10 RCTs to this updated review. The review now includes 54 published trials (45 fully published reports, four abstracts, and five subsets of data from previously published RCTs) involving 11,898 participants.Lower biological WBRT doses versus controlThe hazard ratio (HR) for overall survival (OS) with lower biological WBRT doses as compared with control (3000 cGy in 10 daily fractions) was 1.21 (95% confidence interval (CI) 1.04 to 1.40; P = 0.01; moderate-certainty evidence) in favour of control. The HR for neurological function improvement (NFI) was 1.74 (95% CI 1.06 to 2.84; P = 0.03; moderate-certainty evidence) in favour of control fractionation.Higher biological WBRT doses versus controlThe HR for OS with higher biological WBRT doses as compared with control (3000 cGy in 10 daily fractions) was 0.97 (95% CI 0.83 to 1.12; P = 0.65; moderate-certainty evidence). The HR for NFI was 1.14 (95% CI 0.92 to 1.42; P = 0.23; moderate-certainty evidence).WBRT and radiosensitisersThe addition of radiosensitisers to WBRT did not confer additional benefit for OS (HR 1.05, 95% CI 0.99 to 1.12; P = 0.12; moderate-certainty evidence) or for brain tumour response rates (odds ratio (OR) 0.84, 95% CI 0.63 to 1.11; P = 0.22; high-certainty evidence).Radiosurgery and WBRT versus WBRT aloneThe HR for OS with use of WBRT and radiosurgery boost as compared with WBRT alone for selected participants was 0.61 (95% CI 0.27 to 1.39; P = 0.24; moderate-certainty evidence). For overall brain control at one year, the HR was 0.39 (95% CI 0.25 to 0.60; P < 0.0001; high-certainty evidence) favouring the WBRT and radiosurgery boost group.Radiosurgery alone versus radiosurgery and WBRTThe HR for local brain control was 2.73 (95% CI 1.87 to 3.99; P < 0.00001; high-certainty evidence)favouring the addition of WBRT to radiosurgery. The HR for distant brain control was 2.34 (95% CI 1.73 to 3.18; P < 0.00001; high-certainty evidence) favouring WBRT and radiosurgery. The HR for OS was 1.00 (95% CI 0.80 to 1.25; P = 0.99; moderate-certainty evidence). Two trials reported worse neurocognitive outcomes and one trial reported worse quality of life outcomes when WBRT was added to radiosurgery.We could not pool data from trials related to chemotherapy, optimal supportive care (OSC), molecular targeted agents, neurocognitive protective agents, and hippocampal sparing WBRT. However, one trial reported no differences in quality-adjusted life-years for selected participants with brain metastases from non-small-cell lung cancer randomised to OSC and WBRT versus OSC alone. None of the trials with altered higher biological WBRT dose-fractionation schemes reported benefit for OS, NFI, or symptom control compared with standard care. However, OS and NFI were worse for lower biological WBRT dose-fractionation schemes than for standard dose schedules.The addition of WBRT to radiosurgery improved local and distant brain control in selected people with brain metastases, but data show worse neurocognitive outcomes and no differences in OS.Selected people with multiple brain metastases from non-small-cell lung cancer may show no difference in OS when OSC is given and WBRT is omitted.Use of radiosensitisers, chemotherapy, or molecular targeted agents in conjunction with WBRT remains experimental.Further trials are needed to evaluate the use of neurocognitive protective agents and hippocampal sparing with WBRT. As well, future trials should examine homogeneous participants with brain metastases with focus on prognostic features and molecular markers.

Brain activity underlying auditory perceptual learning during short period training: simultaneous fMRI and EEG recording

PubMed Central

2013-01-01

Background There is an accumulating body of evidence indicating that neuronal functional specificity to basic sensory stimulation is mutable and subject to experience. Although fMRI experiments have investigated changes in brain activity after relative to before perceptual learning, brain activity during perceptual learning has not been explored. This work investigated brain activity related to auditory frequency discrimination learning using a variational Bayesian approach for source localization, during simultaneous EEG and fMRI recording. We investigated whether the practice effects are determined solely by activity in stimulus-driven mechanisms or whether high-level attentional mechanisms, which are linked to the perceptual task, control the learning process. Results The results of fMRI analyses revealed significant attention and learning related activity in left and right superior temporal gyrus STG as well as the left inferior frontal gyrus IFG. Current source localization of simultaneously recorded EEG data was estimated using a variational Bayesian method. Analysis of current localized to the left inferior frontal gyrus and the right superior temporal gyrus revealed gamma band activity correlated with behavioral performance. Conclusions Rapid improvement in task performance is accompanied by plastic changes in the sensory cortex as well as superior areas gated by selective attention. Together the fMRI and EEG results suggest that gamma band activity in the right STG and left IFG plays an important role during perceptual learning. PMID:23316957

Using large-scale Granger causality to study changes in brain network properties in the Clinically Isolated Syndrome (CIS) stage of multiple sclerosis

NASA Astrophysics Data System (ADS)

Abidin, Anas Z.; Chockanathan, Udaysankar; DSouza, Adora M.; Inglese, Matilde; Wismüller, Axel

2017-03-01

Clinically Isolated Syndrome (CIS) is often considered to be the first neurological episode associated with Multiple sclerosis (MS). At an early stage the inflammatory demyelination occurring in the CNS can manifest as a change in neuronal metabolism, with multiple asymptomatic white matter lesions detected in clinical MRI. Such damage may induce topological changes of brain networks, which can be captured by advanced functional MRI (fMRI) analysis techniques. We test this hypothesis by capturing the effective relationships of 90 brain regions, defined in the Automated Anatomic Labeling (AAL) atlas, using a large-scale Granger Causality (lsGC) framework. The resulting networks are then characterized using graph-theoretic measures that quantify various network topology properties at a global as well as at a local level. We study for differences in these properties in network graphs obtained for 18 subjects (10 male and 8 female, 9 with CIS and 9 healthy controls). Global network properties captured trending differences with modularity and clustering coefficient (p<0.1). Additionally, local network properties, such as local efficiency and the strength of connections, captured statistically significant (p<0.01) differences in some regions of the inferior frontal and parietal lobe. We conclude that multivariate analysis of fMRI time-series can reveal interesting information about changes occurring in the brain in early stages of MS.

Clinical features of brain metastases from hepatocellular carcinoma using gamma knife surgery.

PubMed

Ogino, Akiyoshi; Hirai, Tatsuo; Serizawa, Toru; Yoshino, Atsuo

2018-05-01

Brain metastases from hepatocellular carcinoma (HCC) are rare, but their incidence is increasing because of developments in recent therapeutic advances. The purpose of this study was to investigate the characteristics of brain metastases from HCC, to evaluate the predictive factors, and to assess the efficacy of gamma knife surgery (GKS). A retrospective study was performed on patients with brain metastases from HCC who were treated at Tokyo Gamma Unit Center from 2005 to 2014. Nineteen patients were identified. The median age at diagnosis of brain metastases was 67.0 years. Fifteen patients were male and four patients were female. Six patients were infected with hepatitis B virus (HBV). Two patients were infected with hepatitis C virus (HCV). Eleven patients were not infected with HBV or HCV. The median interval from the diagnosis of HCC to brain metastases was 32.0 months. The median number of brain metastases was two. The median Karnofsky performance score at first GKS was 70. The median survival time following brain metastases was 21.0 weeks. Six-month and 1-year survival rates were 41.2 and 0%, respectively. One month after GKS, no tumor showed progressive disease. The HBV infection (positive vs. negative) was significantly associated with survival according to univariate analysis (p = 0.002). The patients having brain metastases from HCC had poor prognosis and low performance state. Therefore, GKS is an acceptable option for controlling brain metastases from HCC because GKS is noninvasive remedy and local control is reasonable.

Hierarchy of Information Processing in the Brain: A Novel 'Intrinsic Ignition' Framework.

PubMed

Deco, Gustavo; Kringelbach, Morten L

2017-06-07

A general theory of brain function has to be able to explain local and non-local network computations over space and time. We propose a new framework to capture the key principles of how local activity influences global computation, i.e., describing the propagation of information and thus the broadness of communication driven by local activity. More specifically, we consider the diversity in space (nodes or brain regions) over time using the concept of intrinsic ignition, which are naturally occurring intrinsic perturbations reflecting the capability of a given brain area to propagate neuronal activity to other regions in a given brain state. Characterizing the profile of intrinsic ignition for a given brain state provides insight into the precise nature of hierarchical information processing. Combining this data-driven method with a causal whole-brain computational model can provide novel insights into the imbalance of brain states found in neuropsychiatric disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

Lesion network localization of criminal behavior

PubMed Central

Darby, R. Ryan; Horn, Andreas; Fox, Michael D.

2018-01-01

Following brain lesions, previously normal patients sometimes exhibit criminal behavior. Although rare, these cases can lend unique insight into the neurobiological substrate of criminality. Here we present a systematic mapping of lesions with known temporal association to criminal behavior, identifying 17 lesion cases. The lesion sites were spatially heterogeneous, including the medial prefrontal cortex, orbitofrontal cortex, and different locations within the bilateral temporal lobes. No single brain region was damaged in all cases. Because lesion-induced symptoms can come from sites connected to the lesion location and not just the lesion location itself, we also identified brain regions functionally connected to each lesion location. This technique, termed lesion network mapping, has recently identified regions involved in symptom generation across a variety of lesion-induced disorders. All lesions were functionally connected to the same network of brain regions. This criminality-associated connectivity pattern was unique compared with lesions causing four other neuropsychiatric syndromes. This network includes regions involved in morality, value-based decision making, and theory of mind, but not regions involved in cognitive control or empathy. Finally, we replicated our results in a separate cohort of 23 cases in which a temporal relationship between brain lesions and criminal behavior was implied but not definitive. Our results suggest that lesions in criminals occur in different brain locations but localize to a unique resting state network, providing insight into the neurobiology of criminal behavior. PMID:29255017

Effect of whole brain radiation on local cerebral glucose utilization in the rat.

PubMed

d'Avella, D; Cicciarello, R; Albiero, F; Mesiti, M; Gagliardi, M E; Russi, E; d'Aquino, A; Princi, P; d'Aquino, S

1991-04-01

We assessed, by means of the [14C]-2-deoxy-D-glucose autoradiography method, the effect of whole-brain x-radiation on local cerebral glucose utilization in the rat brain. Animals were exposed to conventional fractionation (200 +/- 4 cGy/day, 5 days/week; total dose, 4000 cGy). Metabolic experiments were made 2 to 3 weeks after completion of the radiation exposure. In comparison with control and sham-irradiated animals, cerebral metabolic activity was diffusely decreased after irradiation. Statistically significant decreases in metabolic activity were observed in 13 of 27 brain regions studied. In general, the brain areas with the highest basal metabolic rates showed the greatest percentage of decrease in glucose utilization. The concept that radiation suppresses glucose utilization before any morphological change takes place in the cell structures was the basis of this study. Metabolic alterations after irradiation may explain the syndrome of early delayed deterioration observed in humans after whole-brain radiotherapy. These studies have applications to observations made with the [18F]-fluorodeoxyglucose method in conjunction with positron emission tomographic scans in patients receiving radiation therapy for intracranial malignancies. The data reported here also have potential clinical implications for the evaluation of a risk/benefit ratio for radiotherapy in patients with benign neurosurgical diseases or children undergoing prophylactic treatment of the central nervous system.

The sexually dimorphic impact of maltreatment on cortical thickness, surface area and gyrification.

PubMed

Kelly, Philip A; Viding, Essi; Puetz, Vanessa B; Palmer, Amy L; Samuel, Sophie; McCrory, Eamon J

2016-09-01

An extensive literature has detailed how maltreatment experience impacts brain structure in children and adolescents. However, there is a dearth of studies on the influence of maltreatment on surface based indices, and to date no study has investigated how sex influences the impact of maltreatment on cortical thickness, surface area and local gyrification. We investigated sex differences in these measures of cortical structure in a large community sample of children aged 10-14 years (n = 122) comprising 62 children with verified maltreatment experience and 60 matched non-maltreated controls. The maltreated group relative to the controls presented with a pattern of decreased cortical thickness within a region of right anterior cingulate, orbitofrontal cortex and superior frontal gyrus; decreased surface area within the right inferior parietal cortex; and increased local gyrification within left superior parietal cortex. This atypical pattern of cortical structure was similar across males and females. An interaction between maltreatment exposure and sex was found only in local gyrification, within two clusters: the right tempo-parietal junction and the left precentral gyrus. These findings suggest that maltreatment impacts cortical structure in brain areas associated with emotional regulation and theory of mind, with few differences between the sexes.

Preliminary clinical outcomes of image-guided 3-dimensional conformal radiotherapy for limited brain metastases instead of stereotactic irradiation referral.

PubMed

Ohtakara, Kazuhiro; Hoshi, Hiroaki

2014-06-01

To determine the preliminary clinical outcomes of image-guided 3-dimensional conformal radiotherapy (IG-3DCRT) for limited but variably-sized brain metastases (BM). Sixty-two lesions in 24 patients were retrospectively evaluated; out of these patients 75% were ≥ 65 years of age, and 37.5% were categorized into recursive partitioning analysis (RPA) class 3. The median value for the maximum diameter of the lesions was 19 mm (range=4-72 mm). The median sole treatment dose was 36 Gy in 10 fractions. The median survival durations after IG-3DCRT were 12.0 months and 3.2 months for patients categorized into RPA classes ≤ 2 and 3, respectively. Local recurrences occurred in two lesions with a 6-month local control probability of 93.0%. Major toxicities included radiation necrosis in two patients. IG-3DCRT is feasible even for patients with limited BM who are categorized into RPA class 3, and confers clinical outcomes comparable to those of stereotactic radiosurgery, including excellent local control and minimal toxicity even for large tumors. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Phase 3 Trials of Stereotactic Radiosurgery With or Without Whole-Brain Radiation Therapy for 1 to 4 Brain Metastases: Individual Patient Data Meta-Analysis

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

Sahgal, Arjun, E-mail: arjun.sahgal@sunnybrook.ca; Aoyama, Hidefumi; Kocher, Martin

Purpose: To perform an individual patient data (IPD) meta-analysis of randomized controlled trials evaluating stereotactic radiosurgery (SRS) with or without whole-brain radiation therapy (WBRT) for patients presenting with 1 to 4 brain metastases. Method and Materials: Three trials were identified through a literature search, and IPD were obtained. Outcomes of interest were survival, local failure, and distant brain failure. The treatment effect was estimated after adjustments for age, recursive partitioning analysis (RPA) score, number of brain metastases, and treatment arm. Results: A total of 364 of the pooled 389 patients met eligibility criteria, of whom 51% were treated with SRSmore » alone and 49% were treated with SRS plus WBRT. For survival, age was a significant effect modifier (P=.04) favoring SRS alone in patients ≤50 years of age, and no significant differences were observed in older patients. Hazard ratios (HRs) for patients 35, 40, 45, and 50 years of age were 0.46 (95% confidence interval [CI] = 0.24-0.90), 0.52 (95% CI = 0.29-0.92), 0.58 (95% CI = 0.35-0.95), and 0.64 (95% CI = 0.42-0.99), respectively. Patients with a single metastasis had significantly better survival than those who had 2 to 4 metastases. For distant brain failure, age was a significant effect modifier (P=.043), with similar rates in the 2 arms for patients ≤50 of age; otherwise, the risk was reduced with WBRT for patients >50 years of age. Patients with a single metastasis also had a significantly lower risk of distant brain failure than patients who had 2 to 4 metastases. Local control significantly favored additional WBRT in all age groups. Conclusions: For patients ≤50 years of age, SRS alone favored survival, in addition, the initial omission of WBRT did not impact distant brain relapse rates. SRS alone may be the preferred treatment for this age group.« less

Three-dimensional mapping of the lateral ventricles in autism

PubMed Central

Vidal, Christine N.; Nicolsonln, Rob; Boire, Jean-Yves; Barra, Vincent; DeVito, Timothy J.; Hayashi, Kiralee M.; Geaga, Jennifer A.; Drost, Dick J.; Williamson, Peter C.; Rajakumar, Nagalingam; Toga, Arthur W.; Thompson, Paul M.

2009-01-01

In this study, a computational mapping technique was used to examine the three-dimensional profile of the lateral ventricles in autism. T1-weighted three-dimensional magnetic resonance images of the brain were acquired from 20 males with autism (age: 10.1 ± 3.5 years) and 22 male control subjects (age: 10.7 ± 2.5 years). The lateral ventricles were delineated manually and ventricular volumes were compared between the two groups. Ventricular traces were also converted into statistical three-dimensional maps, based on anatomical surface meshes. These maps were used to visualize regional morphological differences in the thickness of the lateral ventricles between patients and controls. Although ventricular volumes measured using traditional methods did not differ significantly between groups, statistical surface maps revealed subtle, highly localized reductions in ventricular size in patients with autism in the left frontal and occipital horns. These localized reductions in the lateral ventricles may result from exaggerated brain growth early in life. PMID:18502618

Local brain connectivity across development in autism spectrum disorder: A cross-sectional investigation

PubMed Central

Dajani, Dina R.; Uddin, Lucina Q.

2015-01-01

Lay Abstract There is a general consensus that autism spectrum disorder (ASD) is accompanied by alterations in brain connectivity. Much of the neuroimaging work has focused on assessing long-range connectivity disruptions in ASD. However, evidence from both animal models and postmortem examination of the human brain suggests that local connections may also be disrupted in individuals with ASD. Here we investigated the development of local connectivity across three age cohorts of individuals with ASD and typically developing (TD) individuals. We find that in typical development, children exhibit high levels of local connectivity across the brain, while adolescents exhibit lower levels of local connectivity, similar to adult levels. On the other hand, children with ASD exhibit marginally lower local connectivity than TD children, and adolescents and adults with ASD exhibit levels of local connectivity comparable to that observed in neurotypical individuals. During all developmental stages -- childhood, adolescence, and adulthood -- individuals with ASD exhibited lower local connectivity in brain regions involved in sensory processing and higher local connectivity in brain regions involved in complex information processing. Further, higher local connectivity in ASD corresponded to more severe ASD symptomatology. Thus we demonstrate that local connectivity is disrupted in autism across development, with the most pronounced differences occurring in childhood. Scientific Abstract There is a general consensus that autism spectrum disorder (ASD) is accompanied by alterations in brain connectivity. Much of the neuroimaging work has focused on assessing long-range connectivity disruptions in ASD. However, evidence from both animal models and postmortem examination of the human brain suggests that local connections may also be disrupted in individuals with the disorder. Here we investigated how regional homogeneity (ReHo), a measure of similarity of a voxel’s timeseries to its nearest neighbors, varies across age in individuals with ASD and typically developing (TD) individuals using a cross-sectional design. Resting-state fMRI data obtained from a publicly available database were analyzed to determine group differences in ReHo between three age cohorts: children, adolescents, and adults. In typical development, ReHo across the entire brain was higher in children than in adolescents and adults. In contrast, children with ASD exhibited marginally lower ReHo than TD children, while adolescents and adults with ASD exhibited similar levels of local connectivity as age-matched neurotypical individuals. During all developmental stages, individuals with ASD exhibited lower local connectivity in sensory processing brain regions and higher local connectivity in complex information processing regions. Further, higher local connectivity in ASD corresponded to more severe ASD symptomatology. These results demonstrate that local connectivity is disrupted in ASD across development, with the most pronounced differences occurring in childhood. Developmental changes in ReHo do not mirror findings from fMRI studies of long-range connectivity in ASD, pointing to a need for more nuanced accounts of brain connectivity alterations in the disorder. PMID:26058882

Individualized Gaussian process-based prediction and detection of local and global gray matter abnormalities in elderly subjects.

PubMed

Ziegler, G; Ridgway, G R; Dahnke, R; Gaser, C

2014-08-15

Structural imaging based on MRI is an integral component of the clinical assessment of patients with potential dementia. We here propose an individualized Gaussian process-based inference scheme for clinical decision support in healthy and pathological aging elderly subjects using MRI. The approach aims at quantitative and transparent support for clinicians who aim to detect structural abnormalities in patients at risk of Alzheimer's disease or other types of dementia. Firstly, we introduce a generative model incorporating our knowledge about normative decline of local and global gray matter volume across the brain in elderly. By supposing smooth structural trajectories the models account for the general course of age-related structural decline as well as late-life accelerated loss. Considering healthy subjects' demography and global brain parameters as informative about normal brain aging variability affords individualized predictions in single cases. Using Gaussian process models as a normative reference, we predict new subjects' brain scans and quantify the local gray matter abnormalities in terms of Normative Probability Maps (NPM) and global z-scores. By integrating the observed expectation error and the predictive uncertainty, the local maps and global scores exploit the advantages of Bayesian inference for clinical decisions and provide a valuable extension of diagnostic information about pathological aging. We validate the approach in simulated data and real MRI data. We train the GP framework using 1238 healthy subjects with ages 18-94 years, and predict in 415 independent test subjects diagnosed as healthy controls, Mild Cognitive Impairment and Alzheimer's disease. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Individualized Gaussian process-based prediction and detection of local and global gray matter abnormalities in elderly subjects

PubMed Central

Ziegler, G.; Ridgway, G.R.; Dahnke, R.; Gaser, C.

2014-01-01

Structural imaging based on MRI is an integral component of the clinical assessment of patients with potential dementia. We here propose an individualized Gaussian process-based inference scheme for clinical decision support in healthy and pathological aging elderly subjects using MRI. The approach aims at quantitative and transparent support for clinicians who aim to detect structural abnormalities in patients at risk of Alzheimer's disease or other types of dementia. Firstly, we introduce a generative model incorporating our knowledge about normative decline of local and global gray matter volume across the brain in elderly. By supposing smooth structural trajectories the models account for the general course of age-related structural decline as well as late-life accelerated loss. Considering healthy subjects' demography and global brain parameters as informative about normal brain aging variability affords individualized predictions in single cases. Using Gaussian process models as a normative reference, we predict new subjects' brain scans and quantify the local gray matter abnormalities in terms of Normative Probability Maps (NPM) and global z-scores. By integrating the observed expectation error and the predictive uncertainty, the local maps and global scores exploit the advantages of Bayesian inference for clinical decisions and provide a valuable extension of diagnostic information about pathological aging. We validate the approach in simulated data and real MRI data. We train the GP framework using 1238 healthy subjects with ages 18–94 years, and predict in 415 independent test subjects diagnosed as healthy controls, Mild Cognitive Impairment and Alzheimer's disease. PMID:24742919

Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases.

PubMed

Patil, Chirag G; Pricola, Katie; Garg, Sachin K; Bryant, Andrew; Black, Keith L

2010-06-16

Historically, whole brain radiation therapy (WBRT) has been the main treatment for brain metastases. Stereotactic radiosurgery (SRS) delivers high dose focused radiation and is being increasingly utilized to treat brain metastases. The benefit of adding radiosurgery to WBRT is unclear. To assess the efficacy of WBRT plus radiosurgery versus WBRT alone in the treatment of of brain metastases. We searched the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2009), MEDLINE (1966 to 2009), EMBASE (1980 to 2009) and CancerLit (1975 to 2009) in order to identify trials for inclusion in this review. The review was restricted to randomised controlled trials (RCTs) that compared use of radiosurgery and WBRT versus WBRT alone for upfront treatment of adult patients with newly diagnosed metastases (single or multiple) in the brain resulting from any primary, extracranial cancer The Generic Inverse Variance method, random effects model in RevMan 5 was used for the meta-analysis. A meta-analysis of two trials with a total of 358 participants, found no statistically significant difference in overall survival (OS) between WBRT plus radiosurgery and WBRT alone groups (HR = 0.82, 95% CI 0.65 to 1.02). For patients with one brain metastasis median survival was significantly longer in WBRT plus SRS group (6.5 months) versus WBRT group (4.9 months, P = 0.04). Patients in the WBRT plus radiosurgery group had decreased local failure compared to patients who received WBRT alone (HR = 0.27, 95% CI 0.14 to 0.52). Furthermore, a statistically significant improvement in performance status scores and decrease in steroid use was seen in the WBRT plus SRS group. Unchanged or improved KPS at 6 months was seen in 43% of patients in the combined therapy group versus only 28% in WBRT group (P = 0.03). Overall, risk of bias in the included studies was unclear. Given the unclear risk of bias in the included studies, the results of this analysis have to be interpreted with caution. Analysis of all included patients, SRS plus WBRT, did not show a survival benefit over WBRT alone. However, performance status and local control were significantly better in the SRS plus WBRT group. Furthermore, significantly longer OS was reported in the combined treatment group for RPA Class I patients as well as patients with single metastasis.

Neuron-specific caveolin-1 overexpression improves motor function and preserves memory in mice subjected to brain trauma.

PubMed

Egawa, Junji; Schilling, Jan M; Cui, Weihua; Posadas, Edmund; Sawada, Atsushi; Alas, Basheer; Zemljic-Harpf, Alice E; Fannon-Pavlich, McKenzie J; Mandyam, Chitra D; Roth, David M; Patel, Hemal H; Patel, Piyush M; Head, Brian P

2017-08-01

Studies in vitro and in vivo demonstrate that membrane/lipid rafts and caveolin (Cav) organize progrowth receptors, and, when overexpressed specifically in neurons, Cav-1 augments neuronal signaling and growth and improves cognitive function in adult and aged mice; however, whether neuronal Cav-1 overexpression can preserve motor and cognitive function in the brain trauma setting is unknown. Here, we generated a neuron-targeted Cav-1-overexpressing transgenic (Tg) mouse [synapsin-driven Cav-1 (SynCav1 Tg)] and subjected it to a controlled cortical impact model of brain trauma and measured biochemical, anatomic, and behavioral changes. SynCav1 Tg mice exhibited increased hippocampal expression of Cav-1 and membrane/lipid raft localization of postsynaptic density protein 95, NMDA receptor, and tropomyosin receptor kinase B. When subjected to a controlled cortical impact, SynCav1 Tg mice demonstrated preserved hippocampus-dependent fear learning and memory, improved motor function recovery, and decreased brain lesion volume compared with wild-type controls. Neuron-targeted overexpression of Cav-1 in the adult brain prevents hippocampus-dependent learning and memory deficits, restores motor function after brain trauma, and decreases brain lesion size induced by trauma. Our findings demonstrate that neuron-targeted Cav-1 can be used as a novel therapeutic strategy to restore brain function and prevent trauma-associated maladaptive plasticity.-Egawa, J., Schilling, J. M., Cui, W., Posadas, E., Sawada, A., Alas, B., Zemljic-Harpf, A. E., Fannon-Pavlich, M. J., Mandyam, C. D., Roth, D. M., Patel, H. H., Patel, P. M., Head, B. P. Neuron-specific caveolin-1 overexpression improves motor function and preserves memory in mice subjected to brain trauma. © FASEB.

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

PubMed

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

2014-01-01

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

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

PubMed Central

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

2014-01-01

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

Developmental vitamin D deficiency alters multiple neurotransmitter systems in the neonatal rat brain.

PubMed

Kesby, James P; Turner, Karly M; Alexander, Suzanne; Eyles, Darryl W; McGrath, John J; Burne, Thomas H J

2017-11-01

Epidemiological evidence suggests that developmental vitamin D (DVD) deficiency is a risk factor for neuropsychiatric disorders, such as schizophrenia. DVD deficiency in rats is associated with altered brain structure and adult behaviours indicating alterations in dopamine and glutamate signalling. Developmental alterations in dopamine neurotransmission have also been observed in DVD-deficient rats but a comprehensive assessment of brain neurochemistry has not been undertaken. Thus, the current study determined the regional concentrations of dopamine, noradrenaline, serotonin, glutamine, glutamate and γ-aminobutyric acid (GABA), and associated metabolites, in DVD-deficient neonates. Sprague-Dawley rats were fed a vitamin D deficient diet or control diet six weeks prior to mating until birth and housed under UVB-free lighting conditions. Neurotransmitter concentration was assessed by high-performance liquid chromatography on post-mortem neonatal brain tissue. Ubiquitous reductions in the levels of glutamine (12-24%) were observed in DVD-deficient neonates compared with control neonates. Similarly, in multiple brain regions DVD-deficient neonates had increased levels of noradrenaline and serine compared with control neonates. In contrast, increased levels of dopamine and decreased levels of serotonin in DVD-deficient neonates were limited to striatal subregions compared with controls. Our results confirm that DVD deficiency leads to changes in multiple neurotransmitter systems in the neonate brain. Importantly, this regionally-based assessment in DVD-deficient neonates identified both widespread neurotransmitter changes (glutamine/noradrenaline) and regionally selective neurotransmitter changes (dopamine/serotonin). Thus, vitamin D may have both general and local actions depending on the neurotransmitter system being investigated. Taken together, these data suggest that DVD deficiency alters neurotransmitter systems relevant to schizophrenia in the developing rat brain. Copyright © 2017 ISDN. All rights reserved.

Attentional performance is correlated with the local regional efficiency of intrinsic brain networks.

PubMed

Xu, Junhai; Yin, Xuntao; Ge, Haitao; Han, Yan; Pang, Zengchang; Tang, Yuchun; Liu, Baolin; Liu, Shuwei

2015-01-01

Attention is a crucial brain function for human beings. Using neuropsychological paradigms and task-based functional brain imaging, previous studies have indicated that widely distributed brain regions are engaged in three distinct attention subsystems: alerting, orienting and executive control (EC). Here, we explored the potential contribution of spontaneous brain activity to attention by examining whether resting-state activity could account for individual differences of the attentional performance in normal individuals. The resting-state functional images and behavioral data from attention network test (ANT) task were collected in 59 healthy subjects. Graph analysis was conducted to obtain the characteristics of functional brain networks and linear regression analyses were used to explore their relationships with behavioral performances of the three attentional components. We found that there was no significant relationship between the attentional performance and the global measures, while the attentional performance was associated with specific local regional efficiency. These regions related to the scores of alerting, orienting and EC largely overlapped with the regions activated in previous task-related functional imaging studies, and were consistent with the intrinsic dorsal and ventral attention networks (DAN/VAN). In addition, the strong associations between the attentional performance and specific regional efficiency suggested that there was a possible relationship between the DAN/VAN and task performances in the ANT. We concluded that the intrinsic activity of the human brain could reflect the processing efficiency of the attention system. Our findings revealed a robust evidence for the functional significance of the efficiently organized intrinsic brain network for highly productive cognitions and the hypothesized role of the DAN/VAN at rest.

Intrinsic gray-matter connectivity of the brain in adults with autism spectrum disorder

PubMed Central

Ecker, Christine; Ronan, Lisa; Feng, Yue; Daly, Eileen; Murphy, Clodagh; Ginestet, Cedric E.; Brammer, Michael; Fletcher, Paul C.; Bullmore, Edward T.; Suckling, John; Baron-Cohen, Simon; Williams, Steve; Loth, Eva; Murphy, Declan G. M.; Bailey, A. J.; Baron-Cohen, S.; Bolton, P. F.; Bullmore, E. T.; Carrington, S.; Chakrabarti, B.; Daly, E. M.; Deoni, S. C.; Ecker, C.; Happe, F.; Henty, J.; Jezzard, P.; Johnston, P.; Jones, D. K.; Lai, M. C.; Lombardo, M. V.; Madden, A.; Mullins, D.; Murphy, C. M.; Murphy, D. G.; Pasco, G.; Sadek, S.; Spain, D.; Steward, R.; Suckling, J.; Wheelwright, S.; Williams, S. C.

2013-01-01

Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions that are accompanied by atypical brain connectivity. So far, in vivo evidence for atypical structural brain connectivity in ASD has mainly been based on neuroimaging studies of cortical white matter. However, genetic studies suggest that abnormal connectivity in ASD may also affect neural connections within the cortical gray matter. Such intrinsic gray-matter connections are inherently more difficult to describe in vivo but may be inferred from a variety of surface-based geometric features that can be measured using magnetic resonance imaging. Here, we present a neuroimaging study that examines the intrinsic cortico-cortical connectivity of the brain in ASD using measures of “cortical separation distances” to assess the global and local intrinsic “wiring costs” of the cortex (i.e., estimated length of horizontal connections required to wire the cortex within the cortical sheet). In a sample of 68 adults with ASD and matched controls, we observed significantly reduced intrinsic wiring costs of cortex in ASD, both globally and locally. Differences in global and local wiring cost were predominantly observed in fronto-temporal regions and also significantly predicted the severity of social and repetitive symptoms (respectively). Our study confirms that atypical cortico-cortical “connectivity” in ASD is not restricted to the development of white-matter connections but may also affect the intrinsic gray-matter architecture (and connectivity) within the cortical sheet. Thus, the atypical connectivity of the brain in ASD is complex, affecting both gray and white matter, and forms part of the core neural substrates underlying autistic symptoms. PMID:23878213

Glucose Metabolism during Resting State Reveals Abnormal Brain Networks Organization in the Alzheimer’s Disease and Mild Cognitive Impairment

PubMed Central

Martínez-Montes, Eduardo

2013-01-01

This paper aims to study the abnormal patterns of brain glucose metabolism co-variations in Alzheimer disease (AD) and Mild Cognitive Impairment (MCI) patients compared to Normal healthy controls (NC) using the Alzheimer Disease Neuroimaging Initiative (ADNI) database. The local cerebral metabolic rate for glucose (CMRgl) in a set of 90 structures belonging to the AAL atlas was obtained from Fluro-Deoxyglucose Positron Emission Tomography data in resting state. It is assumed that brain regions whose CMRgl values are significantly correlated are functionally associated; therefore, when metabolism is altered in a single region, the alteration will affect the metabolism of other brain areas with which it interrelates. The glucose metabolism network (represented by the matrix of the CMRgl co-variations among all pairs of structures) was studied using the graph theory framework. The highest concurrent fluctuations in CMRgl were basically identified between homologous cortical regions in all groups. Significant differences in CMRgl co-variations in AD and MCI groups as compared to NC were found. The AD and MCI patients showed aberrant patterns in comparison to NC subjects, as detected by global and local network properties (global and local efficiency, clustering index, and others). MCI network’s attributes showed an intermediate position between NC and AD, corroborating it as a transitional stage from normal aging to Alzheimer disease. Our study is an attempt at exploring the complex association between glucose metabolism, CMRgl covariations and the attributes of the brain network organization in AD and MCI. PMID:23894356

Intrinsic gray-matter connectivity of the brain in adults with autism spectrum disorder.

PubMed

Ecker, Christine; Ronan, Lisa; Feng, Yue; Daly, Eileen; Murphy, Clodagh; Ginestet, Cedric E; Brammer, Michael; Fletcher, Paul C; Bullmore, Edward T; Suckling, John; Baron-Cohen, Simon; Williams, Steve; Loth, Eva; Murphy, Declan G M

2013-08-06

Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions that are accompanied by atypical brain connectivity. So far, in vivo evidence for atypical structural brain connectivity in ASD has mainly been based on neuroimaging studies of cortical white matter. However, genetic studies suggest that abnormal connectivity in ASD may also affect neural connections within the cortical gray matter. Such intrinsic gray-matter connections are inherently more difficult to describe in vivo but may be inferred from a variety of surface-based geometric features that can be measured using magnetic resonance imaging. Here, we present a neuroimaging study that examines the intrinsic cortico-cortical connectivity of the brain in ASD using measures of "cortical separation distances" to assess the global and local intrinsic "wiring costs" of the cortex (i.e., estimated length of horizontal connections required to wire the cortex within the cortical sheet). In a sample of 68 adults with ASD and matched controls, we observed significantly reduced intrinsic wiring costs of cortex in ASD, both globally and locally. Differences in global and local wiring cost were predominantly observed in fronto-temporal regions and also significantly predicted the severity of social and repetitive symptoms (respectively). Our study confirms that atypical cortico-cortical "connectivity" in ASD is not restricted to the development of white-matter connections but may also affect the intrinsic gray-matter architecture (and connectivity) within the cortical sheet. Thus, the atypical connectivity of the brain in ASD is complex, affecting both gray and white matter, and forms part of the core neural substrates underlying autistic symptoms.

Brain metastases as site of first and isolated recurrence of breast cancer: the role of systemic therapy after local treatment.

PubMed

Niwińska, Anna

2016-10-01

The role of systemic treatment was assessed after local therapy for breast cancer patients who developed central nervous system (CNS) metastases as a first and isolated recurrence. Subjects were 128 breast cancer patients with brain metastases as the first and isolated site of recurrence that were selected from 673 consecutive breast cancer patients with brain metastases treated at the same institution. Median survival from brain metastases in patients with and without systemic treatment after local therapy was respectively 15 and 4 months (p < 0.001). In patients with a Karnofsky Performance Status ≥70 and those <70, survival was respectively 16 and 5.5 months (p < 0.001). The median survival from brain metastasis in patients with solitary brain metastasis, with and without systemic treatment after local therapy, was respectively 22 and 7 months (p = 0.003). Cox multivariate analysis demonstrated that good performance status, solitary brain metastasis and systemic therapy undertaken after local treatment were factors which prolonged survival. However patient survival was adversely affected by those having leptomeningeal metastasis associated with brain parenchymal lesions. Systemic therapy, undertaken after local treatment improved survival in those patients with breast cancer and brain metastases as the site of first and isolated recurrence. Further study is required in order to fully establish the role of systemic treatment for this patient group.

Dissociable effects of local inhibitory and excitatory theta-burst stimulation on large-scale brain dynamics

PubMed Central

Sale, Martin V.; Lord, Anton; Zalesky, Andrew; Breakspear, Michael; Mattingley, Jason B.

2015-01-01

Normal brain function depends on a dynamic balance between local specialization and large-scale integration. It remains unclear, however, how local changes in functionally specialized areas can influence integrated activity across larger brain networks. By combining transcranial magnetic stimulation with resting-state functional magnetic resonance imaging, we tested for changes in large-scale integration following the application of excitatory or inhibitory stimulation on the human motor cortex. After local inhibitory stimulation, regions encompassing the sensorimotor module concurrently increased their internal integration and decreased their communication with other modules of the brain. There were no such changes in modular dynamics following excitatory stimulation of the same area of motor cortex nor were there changes in the configuration and interactions between core brain hubs after excitatory or inhibitory stimulation of the same area. These results suggest the existence of selective mechanisms that integrate local changes in neural activity, while preserving ongoing communication between brain hubs. PMID:25717162

Alterations in regional homogeneity of resting-state brain activity in fatigue of Parkinson's disease.

PubMed

Li, Junyi; Yuan, Yongsheng; Wang, Min; Zhang, Jiejin; Zhang, Li; Jiang, Siming; Ding, Jian; Zhang, Kezhong

2017-10-01

Fatigue is a common complaint in patients with Parkinson's disease (PD). However, the neural bases of fatigue in PD remain uncertain. In this cross-sectional study, our aim was to study the change of the local brain function in PD patients with fatigue. Among 49 patients with PD, 17 of them had fatigue and the remaining 32 patients without fatigue, and 25 age- and gender-matched healthy controls were enrolled. All subjects were evaluated with Fatigue Severity Scale (FSS) and had a resting-state functional magnetic resonance imaging (rs-fMRI) scan. The fMRI images were analyzed using regional homogeneity (ReHo) to study the change of the local brain function. ReHo analysis controlling for gray matter volume, age, gender, and education showed decreased ReHo in the left anterior cingulate cortex (ACC) and the right superior frontal gyrus (dorsolateral part), and increased ReHo in the left postcentral gyrus and the right inferior frontal gyrus (orbital and triangular part), compared PD-F with PD-NF; In PD patients, the regional activity in the left ACC and the right superior frontal gyrus (dorsolateral part) was negatively correlated with the FSS scores, while that in the left postcentral gyrus, the right inferior frontal gyrus (orbital and triangular part) was positively correlated with the FSS scores. This study demonstrates that brain areas including frontal, postcentral and ACC regions indicative of sensory, motor, and cognitive systems are involved in fatigue in PD patients.

Intracranial control and radiographic changes with adjuvant radiation therapy for resected brain metastases: whole brain radiotherapy versus stereotactic radiosurgery alone.

PubMed

Patel, Kirtesh R; Prabhu, Roshan S; Kandula, Shravan; Oliver, Daniel E; Kim, Sungjin; Hadjipanayis, Constantinos; Olson, Jeffery J; Oyesiku, Nelson; Curran, Walter J; Khan, Mohammad K; Shu, Hui-Kuo; Crocker, Ian

2014-12-01

The aim of this study was to compare outcomes of postoperative whole brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) alone in patients with resected brain metastases (BM). We reviewed records of patients who underwent surgical resection of BM followed by WBRT or SRS alone between 2003 and 2013. Local control (LC) of the treated resected cavity, distant brain control (DBC), leptomeningeal disease (LMD), overall survival (OS), and radiographic leukoencephalopathy rates were estimated by the Kaplan-Meier method. One-hundred thirty-two patients underwent surgical resection for 141 intracranial metastases: 36 (27 %) patients received adjuvant WBRT and 96 (73 %) received SRS alone to the resection cavity. One-year OS (56 vs. 55 %, p = 0.64) and LC (83 vs. 74 %, p = 0.31) were similar between patients receiving WBRT and SRS. After controlling for number of BM, WBRT was associated with higher 1-year DBC compared with SRS (70 vs. 48 %, p = 0.03); single metastasis and WBRT were the only significant predictors for reduced distant brain recurrence in multi-variate analysis. Freedom from LMD was higher with WBRT at 18 months (87 vs. 69 %, p = 0.045), while incidence of radiographic leukoencephalopathy was higher with WBRT at 12 months (47 vs. 7 %, p = 0.001). One-year freedom from WBRT in the SRS alone group was 86 %. Compared with WBRT for patients with resected BM, SRS alone demonstrated similar LC, higher rates of LMD and inferior DBC, after controlling for the number of BM. However, OS was similar between groups. The results of ongoing clinical trials are needed to confirm these findings.

Affective Aspects of Perceived Loss of Control and Potential Implications for Brain-Computer Interfaces.

PubMed

Grissmann, Sebastian; Zander, Thorsten O; Faller, Josef; Brönstrup, Jonas; Kelava, Augustin; Gramann, Klaus; Gerjets, Peter

2017-01-01

Most brain-computer interfaces (BCIs) focus on detecting single aspects of user states (e.g., motor imagery) in the electroencephalogram (EEG) in order to use these aspects as control input for external systems. This communication can be effective, but unaccounted mental processes can interfere with signals used for classification and thereby introduce changes in the signal properties which could potentially impede BCI classification performance. To improve BCI performance, we propose deploying an approach that potentially allows to describe different mental states that could influence BCI performance. To test this approach, we analyzed neural signatures of potential affective states in data collected in a paradigm where the complex user state of perceived loss of control (LOC) was induced. In this article, source localization methods were used to identify brain dynamics with source located outside but affecting the signal of interest originating from the primary motor areas, pointing to interfering processes in the brain during natural human-machine interaction. In particular, we found affective correlates which were related to perceived LOC. We conclude that additional context information about the ongoing user state might help to improve the applicability of BCIs to real-world scenarios.

Affective Aspects of Perceived Loss of Control and Potential Implications for Brain-Computer Interfaces

PubMed Central

Grissmann, Sebastian; Zander, Thorsten O.; Faller, Josef; Brönstrup, Jonas; Kelava, Augustin; Gramann, Klaus; Gerjets, Peter

2017-01-01

Most brain-computer interfaces (BCIs) focus on detecting single aspects of user states (e.g., motor imagery) in the electroencephalogram (EEG) in order to use these aspects as control input for external systems. This communication can be effective, but unaccounted mental processes can interfere with signals used for classification and thereby introduce changes in the signal properties which could potentially impede BCI classification performance. To improve BCI performance, we propose deploying an approach that potentially allows to describe different mental states that could influence BCI performance. To test this approach, we analyzed neural signatures of potential affective states in data collected in a paradigm where the complex user state of perceived loss of control (LOC) was induced. In this article, source localization methods were used to identify brain dynamics with source located outside but affecting the signal of interest originating from the primary motor areas, pointing to interfering processes in the brain during natural human-machine interaction. In particular, we found affective correlates which were related to perceived LOC. We conclude that additional context information about the ongoing user state might help to improve the applicability of BCIs to real-world scenarios. PMID:28769776

Biotelemetry system for Epilepsy Seizure Control

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

Smith, LaCurtise; Bohnert, George W.

2009-07-02

The Biotelemetry System for Epilepsy Seizure Control Project developed and tested an automated telemetry system for use in an epileptic seizure prevention device that precisely controls localized brain temperature. This project was a result of a Department of Energy (DOE) Global Initiatives for Proliferation Prevention (GIPP) grant to the Kansas City Plant (KCP), Argonne National Laboratory (ANL), and Pacific Northwest National Laboratory (PNNL) to partner with Flint Hills Scientific, LLC, Lawrence, KS and Biophysical Laboratory Ltd (BIOFIL), Sarov, Russia to develop a method to help control epileptic seizures.

Reconfigurable visible nanophotonic switch for optogenetic applications (Conference Presentation)

NASA Astrophysics Data System (ADS)

Mohanty, Aseema; Li, Qian; Tadayon, Mohammad Amin; Bhatt, Gaurang R.; Cardenas, Jaime; Miller, Steven A.; Kepecs, Adam; Lipson, Michal

2017-02-01

High spatiotemporal resolution deep-brain optical excitation for optogenetics would enable activation of specific neural populations and in-depth study of neural circuits. Conventionally, a single fiber is used to flood light into a large area of the brain with limited resolution. The scalability of silicon photonics could enable neural excitation over large areas with single-cell resolution similar to electrical probes. However, active control of these optical circuits has yet to be demonstrated for optogenetics. Here we demonstrate the first active integrated optical switch for neural excitation at 473 nm, enabling control of multiple beams for deep-brain neural stimulation. Using a silicon nitride waveguide platform, we develop a cascaded Mach-Zehnder interferometer (MZI) network located outside the brain to direct light to 8 different grating emitters located at the tip of the neural probe. We use integrated platinum microheaters to induce a local thermo-optic phase shift in the MZI to control the switch output. We measure an ON/OFF extinction ratio of >8dB for a single switch and a switching speed of 20 microseconds. We characterize the optical output of the switch by imaging its excitation of fluorescent dye. Finally, we demonstrate in vivo single-neuron optical activation from different grating emitters using a fully packaged device inserted into a mouse brain. Directly activated neurons showed robust spike firing activities with low first-spike latency and small jitter. Active switching on a nanophotonic platform is necessary for eventually controlling highly-multiplexed reconfigurable optical circuits, enabling high-resolution optical stimulation in deep-brain regions.

Local texture descriptors for the assessment of differences in diffusion magnetic resonance imaging of the brain.

PubMed

Thomsen, Felix Sebastian Leo; Delrieux, Claudio Augusto; de Luis-García, Rodrigo

2017-03-01

Descriptors extracted from magnetic resonance imaging (MRI) of the brain can be employed to locate and characterize a wide range of pathologies. Scalar measures are typically derived within a single-voxel unit, but neighborhood-based texture measures can also be applied. In this work, we propose a new set of descriptors to compute local texture characteristics from scalar measures of diffusion tensor imaging (DTI), such as mean and radial diffusivity, and fractional anisotropy. We employ weighted rotational invariant local operators, namely standard deviation, inter-quartile range, coefficient of variation, quartile coefficient of variation and skewness. Sensitivity and specificity of those texture descriptors were analyzed with tract-based spatial statistics of the white matter on a diffusion MRI group study of elderly healthy controls, patients with mild cognitive impairment (MCI), and mild or moderate Alzheimer's disease (AD). In addition, robustness against noise has been assessed with a realistic diffusion-weighted imaging phantom and the contamination of the local neighborhood with gray matter has been measured. The new texture operators showed an increased ability for finding formerly undetected differences between groups compared to conventional DTI methods. In particular, the coefficient of variation, quartile coefficient of variation, standard deviation and inter-quartile range of the mean and radial diffusivity detected significant differences even between previously not significantly discernible groups, such as MCI versus moderate AD and mild versus moderate AD. The analysis provided evidence of low contamination of the local neighborhood with gray matter and high robustness against noise. The local operators applied here enhance the identification and localization of areas of the brain where cognitive impairment takes place and thus indicate them as promising extensions in diffusion MRI group studies.

Local Use-Dependent Sleep in Wakefulness Links Performance Errors to Learning

PubMed Central

Quercia, Angelica; Zappasodi, Filippo; Committeri, Giorgia; Ferrara, Michele

2018-01-01

Sleep and wakefulness are no longer to be considered as discrete states. During wakefulness brain regions can enter a sleep-like state (off-periods) in response to a prolonged period of activity (local use-dependent sleep). Similarly, during nonREM sleep the slow-wave activity, the hallmark of sleep plasticity, increases locally in brain regions previously involved in a learning task. Recent studies have demonstrated that behavioral performance may be impaired by off-periods in wake in task-related regions. However, the relation between off-periods in wake, related performance errors and learning is still untested in humans. Here, by employing high density electroencephalographic (hd-EEG) recordings, we investigated local use-dependent sleep in wake, asking participants to repeat continuously two intensive spatial navigation tasks. Critically, one task relied on previous map learning (Wayfinding) while the other did not (Control). Behaviorally awake participants, who were not sleep deprived, showed progressive increments of delta activity only during the learning-based spatial navigation task. As shown by source localization, delta activity was mainly localized in the left parietal and bilateral frontal cortices, all regions known to be engaged in spatial navigation tasks. Moreover, during the Wayfinding task, these increments of delta power were specifically associated with errors, whose probability of occurrence was significantly higher compared to the Control task. Unlike the Wayfinding task, during the Control task neither delta activity nor the number of errors increased progressively. Furthermore, during the Wayfinding task, both the number and the amplitude of individual delta waves, as indexes of neuronal silence in wake (off-periods), were significantly higher during errors than hits. Finally, a path analysis linked the use of the spatial navigation circuits undergone to learning plasticity to off periods in wake. In conclusion, local sleep regulation in wakefulness, associated with performance failures, could be functionally linked to learning-related cortical plasticity. PMID:29666574

Functional brain networks in Alzheimer's disease: EEG analysis based on limited penetrable visibility graph and phase space method

NASA Astrophysics Data System (ADS)

Wang, Jiang; Yang, Chen; Wang, Ruofan; Yu, Haitao; Cao, Yibin; Liu, Jing

2016-10-01

In this paper, EEG series are applied to construct functional connections with the correlation between different regions in order to investigate the nonlinear characteristic and the cognitive function of the brain with Alzheimer's disease (AD). First, limited penetrable visibility graph (LPVG) and phase space method map single EEG series into networks, and investigate the underlying chaotic system dynamics of AD brain. Topological properties of the networks are extracted, such as average path length and clustering coefficient. It is found that the network topology of AD in several local brain regions are different from that of the control group with no statistically significant difference existing all over the brain. Furthermore, in order to detect the abnormality of AD brain as a whole, functional connections among different brain regions are reconstructed based on similarity of clustering coefficient sequence (CCSS) of EEG series in the four frequency bands (delta, theta, alpha, and beta), which exhibit obvious small-world properties. Graph analysis demonstrates that for both methodologies, the functional connections between regions of AD brain decrease, particularly in the alpha frequency band. AD causes the graph index complexity of the functional network decreased, the small-world properties weakened, and the vulnerability increased. The obtained results show that the brain functional network constructed by LPVG and phase space method might be more effective to distinguish AD from the normal control than the analysis of single series, which is helpful for revealing the underlying pathological mechanism of the disease.

Photodynamic characterization and optimization using multifunctional nanoparticles for brain cancer treatment

NASA Astrophysics Data System (ADS)

Herrmann, Kristen; Lee Koo, Yong-Eun; Orringer, Daniel A.; Sagher, Oren; Philbert, Martin; Kopelman, Raoul

2013-03-01

Photosensitizer-conjugated polyacrylamide nanoparticles were prepared for in vivo characterization of the minimally invasive and localized treatment of photodynamic therapy (PDT) on brain tumors. By incorporating a variety of nanoparticle matrixes, choosing methylene blue as a photosensitizer, and targeting the nanoparticle by the use of F3 peptide we have made nanoparticle-based PDT improvements to current PDT efficiency. Quantitative growth patterns were determined through visual observation of the tumorigenic response to various treatments by the use of an animal cranial window model. PDT treatments with methylene blue-polyacrylamide (MB-PAA) nanoparticles produced significant adjournment of tumor growth over control groups, clearly demonstrating the advantages of nanoparticle-based PDT agents for the eradication of local tumors, leading to the potential palliation of the advancing disease.

Dendritic protein synthesis in the normal and diseased brain

PubMed Central

Swanger, Sharon A.; Bassell, Gary J.

2015-01-01

Synaptic activity is a spatially-limited process that requires a precise, yet dynamic, complement of proteins within the synaptic micro-domain. The maintenance and regulation of these synaptic proteins is regulated, in part, by local mRNA translation in dendrites. Protein synthesis within the postsynaptic compartment allows neurons tight spatial and temporal control of synaptic protein expression, which is critical for proper functioning of synapses and neural circuits. In this review, we discuss the identity of proteins synthesized within dendrites, the receptor-mediated mechanisms regulating their synthesis, and the possible roles for these locally synthesized proteins. We also explore how our current understanding of dendritic protein synthesis in the hippocampus can be applied to new brain regions and to understanding the pathological mechanisms underlying varied neurological diseases. PMID:23262237

Tolerance and outcomes of stereotactic radiosurgery combined with anti-programmed cell death-1 (pembrolizumab) for melanoma brain metastases.

PubMed

Nardin, Charlee; Mateus, Christine; Texier, Mathieu; Lanoy, Emilie; Hibat-Allah, Salima; Ammari, Samy; Robert, Caroline; Dhermain, Frederic

2018-04-01

Anti-programmed cell death-1 (anti-PD1) antibodies are currently the first-line treatment for patients with metastatic BRAF wild-type melanoma, alone or combined with the anti-CTLA4 monoclonal antibody, ipilimumab. To date, data on safety and the outcomes of patients treated with the anti-PD1 monoclonal antibodies, pembrolizumab (PB), or nivolumab, combined with stereotactic radiosurgery (SRS), for melanoma brain metastases (MBM) are scarce. We retrospectively reviewed all patients with MBM treated with PB combined with SRS between 2012 and 2015. The primary endpoint was neurotoxicity. The secondary endpoints were local, distant intracranial controls and overall survival (OS). Among 74 patients with MBM treated with SRS, 25 patients with a total of 58 MBM treated with PB combined with SRS within 6 months were included. Radiation necrosis, occurring within a median time of 6.5 months, was observed for four MBM (6.8%) in four patients. No other significant SRS-related adverse event was observed. After a median follow-up of 8.4 months, local control was achieved in 46 (80%) metastases and 17 (68%) patients. Perilesional oedema and intratumour haemorrhage appearing or increasing after SRS were associated with local progression (P<0.001). The median OS was 15.3 months (95% confidence interval: 4.6-26). The timing between SRS and PB administration did not seem to influence the risk of radiation necrosis, intracranial control or OS. SRS combined with PB was well tolerated and achieved local control in 80% of the lesions. Prolonged OS was observed compared with that currently yielded in this population of patients. Prospective studies are required to explore further the optimal ways to combine immunotherapy and SRS.

Stereotactic radiosurgery for small brain metastases and implications regarding management with systemic therapy alone.

PubMed

Trifiletti, Daniel M; Hill, Colin; Cohen-Inbar, Or; Xu, Zhiyuan; Sheehan, Jason P

2017-09-01

While stereotactic radiosurgery (SRS) has been shown effective in the management of brain metastases, small brain metastases (≤10 mm) can pose unique challenges. Our aim was to investigate the efficacy of SRS in the treatment of small brain metastases, as well as elucidate clinically relevant factors impacting local failure (LF). We utilized a large, single-institution cohort to perform a retrospective analysis of patients with brain metastases up to 1 cm in maximal dimension. Clinical and radiosurgical parameters were investigated for an association with LF and compared using a competing risk model to calculate cumulative incidence functions, with death and whole brain radiotherapy serving as competing risks. 1596 small brain metastases treated with SRS among 424 patients were included. Among these tumors, 33 developed LF during the follow-up period (2.4% at 12 months following SRS). Competing risk analysis demonstrated that LF was dependent on tumor size (0.7% if ≤2 mm and 3.0% if 2-10 mm at 12 months, p = 0.016). Other factors associated with increasing risk of LF were the decreasing margin dose, increasing maximal tumor diameter, volume, and radioresistant tumors (each p < 0.01). 22 tumors (0.78%) developed radiographic radiation necrosis following SRS, and this incidence did not differ by tumor size (≤2 mm and 2-10 mm, p = 0.200). This large analysis confirms that SRS remains an effective modality in treatment of small brain metastases. In light of the excellent local control and relatively low risk of toxicity, patients with small brain metastases who otherwise have a reasonable expected survival should be considered for radiosurgical management.

Plasma membrane localization of multidrug resistance-associated protein homologs in brain capillary endothelial cells.

PubMed

Zhang, Yan; Schuetz, John D; Elmquist, William F; Miller, Donald W

2004-11-01

Several multidrug resistance-associated protein (MRP) homologs are expressed in brain microvessel endothelial cells forming the blood-brain barrier (BBB). The influence of these MRP transporters on BBB permeability will be dependent on their localization within the brain microvessel endothelial cells. Using two different and complementary approaches, the localization of various MPR homologs (MRP1, MRP4, and MRP5) was examined in primary cultured bovine brain microvessel endothelial cells (BBMECs). The first approach involved centrifugal separation of apical and basolateral plasma membranes of cultured BBMECs. The membrane fractions were then subjected to Western blot analysis for MRPs. The second approach used confocal laser scanning microscopy to determine membrane localization of MRPs in BBMECs. Results show a predominantly apical plasma membrane distribution for MRP1 and MRP5, and an almost equal distribution of MRP4 on the apical and basolateral plasma membrane of BBMECs. These studies provide the first demonstration of the localization of MRP1, MRP4, and MRP5 homologs in brain microvessel endothelial cells. The present studies also indicate that the localization of MRPs in the endothelial cells forming the BBB is different from that observed in polarized epithelial cells and thus may contribute to the reduced entry and enhanced elimination of organic anions and nucleotides in the brain.

The devil is in the detail: brain dynamics in preparation for a global-local task.

PubMed

Leaver, Echo E; Low, Kathy A; DiVacri, Assunta; Merla, Arcangelo; Fabiani, Monica; Gratton, Gabriele

2015-08-01

When analyzing visual scenes, it is sometimes important to determine the relevant "grain" size. Attention control mechanisms may help direct our processing to the intended grain size. Here we used the event-related optical signal, a method possessing high temporal and spatial resolution, to examine the involvement of brain structures within the dorsal attention network (DAN) and the visual processing network (VPN) in preparation for the appropriate level of analysis. Behavioral data indicate that the small features of a hierarchical stimulus (local condition) are more difficult to process than the large features (global condition). Consistent with this finding, cues predicting a local trial were associated with greater DAN activation. This activity was bilateral but more pronounced in the left hemisphere, where it showed a frontal-to-parietal progression over time. Furthermore, the amount of DAN activation, especially in the left hemisphere and in parietal regions, was predictive of subsequent performance. Although local cues elicited left-lateralized DAN activity, no preponderantly right activity was observed for global cues; however, the data indicated an interaction between level of analysis (local vs. global) and hemisphere in VPN. They further showed that local processing involves structures in the ventral VPN, whereas global processing involves structures in the dorsal VPN. These results indicate that in our study preparation for analyzing different size features is an asymmetric process, in which greater preparation is required to focus on small rather than large features, perhaps because of their lesser salience. This preparation involves the same DAN used for other attention control operations.

What Is the Optimal Treatment of Large Brain Metastases? An Argument for a Multidisciplinary Approach

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

Choi, Clara Y.H.; Chang, Steven D.; Gibbs, Iris C.

2012-11-01

Purpose: Single-modality treatment of large brain metastases (>2 cm) with whole-brain irradiation, stereotactic radiosurgery (SRS) alone, or surgery alone is not effective, with local failure (LF) rates of 50% to 90%. Our goal was to improve local control (LC) by using multimodality therapy of surgery and adjuvant SRS targeting the resection cavity. Patients and Methods: We retrospectively evaluated 97 patients with brain metastases >2 cm in diameter treated with surgery and cavity SRS. Local and distant brain failure (DF) rates were analyzed with competing risk analysis, with death as a competing risk. The overall survival rate was calculated by themore » Kaplain-Meier product-limit method. Results: The median imaging follow-up duration for all patients was 10 months (range, 1-80 months). The 12-month cumulative incidence rates of LF, with death as a competing risk, were 9.3% (95% confidence interval [CI], 4.5%-16.1%), and the median time to LF was 6 months (range, 3-17 months). The 12-month cumulative incidence rate of DF, with death as a competing risk, was 53% (95% CI, 43%-63%). The median survival time for all patients was 15.6 months. The median survival times for recursive partitioning analysis classes 1, 2, and 3 were 33.8, 13.7, and 9.0 months, respectively (p = 0.022). On multivariate analysis, Karnofsky Performance Status ({>=}80 vs. <80; hazard ratio 0.54; 95% CI 0.31-0.94; p = 0.029) and maximum preoperative tumor diameter (hazard ratio 1.41; 95% CI 1.08-1.85; p = 0.013) were associated with survival. Five patients (5%) required intervention for Common Terminology Criteria for Adverse Events v4.02 grade 2 and 3 toxicity. Conclusion: Surgery and adjuvant resection cavity SRS yields excellent LC of large brain metastases. Compared with other multimodality treatment options, this approach allows patients to avoid or delay whole-brain irradiation without compromising LC.« less

Experimental microembolism induces localized neuritic pathology in guinea pig cerebrum

PubMed Central

Li, Jian-Ming; Cai, Yan; Liu, Fei; Yang, La; Hu, Xia; Patrylo, Peter R.; Cai, Huaibin; Luo, Xue-Gang; Xiao, Dong; Yan, Xiao-Xin

2015-01-01

Microbleeds are a common finding in aged human brains. In Alzheimer's disease (AD), neuritic plaques composed of β-amyloid (Aβ) deposits and dystrophic neurites occur frequently around cerebral vasculature, raising a compelling question as to whether, and if so, how, microvascular abnormality and amyloid/neuritic pathology might be causally related. Here we used a guinea pig model of cerebral microembolism to explore a potential inductive effect of vascular injury on neuritic and amyloid pathogenesis. Brains were examined 7-30 days after experimental microvascular embolization occupying ~0.5% of total cortical area. Compared to sham-operated controls, glial fibrillary acidic protein immunoreactivity was increased in the embolized cerebrum, evidently around intracortical vasculature. Swollen/sprouting neurites exhibiting increased reactivity of nicotinamide adenine dinucleotide phosphate diaphorase, parvalbumin, vesicular glutamate transporter 1 and choline acetyltransferase appeared locally in the embolized brains in proximity to intracortical vasculature. The embolization-induced swollen/sprouting neurites were also robustly immunoreactive for β-amyloid precursor protein and β-secretase-1, the substrate and initiating enzyme for Aβ genesis. These experimental data suggest that microvascular injury can induce multisystem neuritic pathology associated with an enhanced amyloidogenic potential in wild-type mammalian brain. PMID:25871402

Experimental microembolism induces localized neuritic pathology in guinea pig cerebrum.

PubMed

Li, Jian-Ming; Cai, Yan; Liu, Fei; Yang, La; Hu, Xia; Patrylo, Peter R; Cai, Huaibin; Luo, Xue-Gang; Xiao, Dong; Yan, Xiao-Xin

2015-05-10

Microbleeds are a common finding in aged human brains. In Alzheimer's disease (AD), neuritic plaques composed of β-amyloid (Aβ) deposits and dystrophic neurites occur frequently around cerebral vasculature, raising a compelling question as to whether, and if so, how, microvascular abnormality and amyloid/neuritic pathology might be causally related. Here we used a guinea pig model of cerebral microembolism to explore a potential inductive effect of vascular injury on neuritic and amyloid pathogenesis. Brains were examined 7-30 days after experimental microvascular embolization occupying ~0.5% of total cortical area. Compared to sham-operated controls, glial fibrillary acidic protein immunoreactivity was increased in the embolized cerebrum, evidently around intracortical vasculature. Swollen/sprouting neurites exhibiting increased reactivity of nicotinamide adenine dinucleotide phosphate diaphorase, parvalbumin, vesicular glutamate transporter 1 and choline acetyltransferase appeared locally in the embolized brains in proximity to intracortical vasculature. The embolization-induced swollen/sprouting neurites were also robustly immunoreactive for β-amyloid precursor protein and β-secretase-1, the substrate and initiating enzyme for Aβ genesis. These experimental data suggest that microvascular injury can induce multisystem neuritic pathology associated with an enhanced amyloidogenic potential in wild-type mammalian brain.

Localization and mobility of glucose-coated gold nanoparticles within the brain.

PubMed

Gromnicova, Radka; Yilmaz, Canan Ugur; Orhan, Nurcan; Kaya, Mehmet; Davies, Heather; Williams, Phil; Romero, Ignacio A; Sharrack, Basil; Male, David

2016-03-01

To identify the localization of glucose-coated gold nanoparticles within cells of the brain after intravascular infusion which may point to the mechanism by which they cross the blood-brain barrier. Tissue distribution of the nanoparticles was measured by inductively-coupled-mass spectrometry and localization within the brain by histochemistry and electron microscopy. Nanoparticles were identified within neurons and glial cells more than 10 μm from the nearest microvessel within 10 min of intracarotid infusion. Their distribution indicated movement across the endothelial cytosol, and direct transfer between cells of the brain. The rapid movement of this class of nanoparticle (<5 nm) into the brain demonstrates their potential to carry therapeutic biomolecules or imaging reagents.

Definitions of state variables and state space for brain-computer interface : Part 2. Extraction and classification of feature vectors.

PubMed

Freeman, Walter J

2007-06-01

The hypothesis is proposed that the central dynamics of the action-perception cycle has five steps: emergence from an existing macroscopic brain state of a pattern that predicts a future goal state; selection of a mesoscopic frame for action control; execution of a limb trajectory by microscopic spike activity; modification of microscopic cortical spike activity by sensory inputs; construction of mesoscopic perceptual patterns; and integration of a new macroscopic brain state. The basis is the circular causality between microscopic entities (neurons) and the mesoscopic and macroscopic entities (populations) self-organized by axosynaptic interactions. Self-organization of neural activity is bidirectional in all cortices. Upwardly the organization of mesoscopic percepts from microscopic spike input predominates in primary sensory areas. Downwardly the organization of spike outputs that direct specific limb movements is by mesoscopic fields constituting plans to achieve predicted goals. The mesoscopic fields in sensory and motor cortices emerge as frames within macroscopic activity. Part 1 describes the action-perception cycle and its derivative reflex arc qualitatively. Part 2 describes the perceptual limb of the arc from microscopic MSA to mesoscopic wave packets, and from these to macroscopic EEG and global ECoG fields that express experience-dependent knowledge in successive states. These macroscopic states are conceived to embed and control mesoscopic frames in premotor and motor cortices that are observed in local ECoG and LFP of frontoparietal areas. The fields sampled by ECoG and LFP are conceived as local patterns of neural activity in which trajectories of multiple spike activities (MSA) emerge that control limb movements. Mesoscopic frames are located by use of the analytic signal from the Hilbert transform after band pass filtering. The state variables in frames are measured to construct feature vectors by which to describe and classify frame patterns. Evidence is cited to justify use of linear analysis. The aim of the review is to enable researchers to conceive and identify goal-oriented states in brain activity for use as commands, in order to relegate the details of execution to adaptive control devices outside the brain.

Stereotactic radiosurgery alone for multiple brain metastases? A review of clinical and technical issues

PubMed Central

Ruschin, Mark; Ma, Lijun; Verbakel, Wilko; Larson, David; Brown, Paul D.

2017-01-01

Abstract Over the past three decades several randomized trials have enabled evidence-based practice for patients presenting with limited brain metastases. These trials have focused on the role of surgery or stereotactic radiosurgery (SRS) with or without whole brain radiation therapy (WBRT). As a result, it is clear that local control should be optimized with surgery or SRS in patients with optimal prognostic factors presenting with up to 4 brain metastases. The routine use of adjuvant WBRT remains debatable, as although greater distant brain control rates are observed, there is no impact on survival, and modern outcomes suggest adverse effects from WBRT on patient cognition and quality of life. With dramatic technologic advances in radiation oncology facilitating the adoption of SRS into mainstream practice, the optimal management of patients with multiple brain metastases is now being put forward. Practice is evolving to SRS alone in these patients despite a lack of level 1 evidence to support a clinical departure from WBRT. The purpose of this review is to summarize the current state of the evidence for patients presenting with limited and multiple metastases, and to present an in-depth analysis of the technology and dosimetric issues specific to the treatment of multiple metastases. PMID:28380635

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

PubMed Central

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

2011-01-01

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

Computation of an MRI brain atlas from a population of Parkinson’s disease patients

NASA Astrophysics Data System (ADS)

Angelidakis, L.; Papageorgiou, I. E.; Damianou, C.; Psychogios, M. N.; Lingor, P.; von Eckardstein, K.; Hadjidemetriou, S.

2017-11-01

Parkinson’s Disease (PD) is a degenerative disorder of the brain. This study presents an MRI-based brain atlas of PD to characterize associated alterations for diagnostic and interventional purposes. The atlas standardizes primarily the implicated subcortical regions such as the globus pallidus (GP), substantia nigra (SN), subthalamic nucleus (STN), caudate nucleus (CN), thalamus (TH), putamen (PUT), and red nucleus (RN). The data were 3.0 T MRI brain images from 16 PD patients and 10 matched controls. The images used were T1-weighted (T 1 w), T2-weighted (T 2 w) images, and Susceptibility Weighted Images (SWI). The T1w images were the reference for the inter-subject non-rigid registration available from 3DSlicer. Anatomic labeling was achieved with BrainSuite and regions were refined with the level sets segmentation of ITK-Snap. The subcortical centers were analyzed for their volume and signal intensity. Comparison with an age-matched control group unravels a significant PD-related T1w signal loss in the striatum (CN and PUT) centers, but approximately a constant volume. The results in this study improve MRI based PD localization and can lead to the development of novel biomarkers.

Scalp and Source Power Topography in Sleepwalking and Sleep Terrors: A High-Density EEG Study

PubMed Central

Castelnovo, Anna; Riedner, Brady A.; Smith, Richard F.; Tononi, Giulio; Boly, Melanie; Benca, Ruth M.

2016-01-01

Study Objectives: To examine scalp and source power topography in sleep arousals disorders (SADs) using high-density EEG (hdEEG). Methods: Fifteen adult subjects with sleep arousal disorders (SADs) and 15 age- and gender-matched good sleeping healthy controls were recorded in a sleep laboratory setting using a 256 channel EEG system. Results: Scalp EEG analysis of all night NREM sleep revealed a localized decrease in slow wave activity (SWA) power (1–4 Hz) over centro-parietal regions relative to the rest of the brain in SADs compared to good sleeping healthy controls. Source modelling analysis of 5-minute segments taken from N3 during the first half of the night revealed that the local decrease in SWA power was prominent at the level of the cingulate, motor, and sensori-motor associative cortices. Similar patterns were also evident during REM sleep and wake. These differences in local sleep were present in the absence of any detectable clinical or electrophysiological sign of arousal. Conclusions: Overall, results suggest the presence of local sleep differences in the brain of SADs patients during nights without clinical episodes. The persistence of similar topographical changes in local EEG power during REM sleep and wakefulness points to trait-like functional changes that cross the boundaries of NREM sleep. The regions identified by source imaging are consistent with the current neurophysiological understanding of SADs as a disorder caused by local arousals in motor and cingulate cortices. Persistent localized changes in neuronal excitability may predispose affected subjects to clinical episodes. Citation: Castelnovo A, Riedner BA, Smith RF, Tononi G, Boly M, Benca RM. Scalp and source power topography in sleepwalking and sleep terrors: a high-density EEG study. SLEEP 2016;39(10):1815–1825. PMID:27568805

Group-Level Progressive Alterations in Brain Connectivity Patterns Revealed by Diffusion-Tensor Brain Networks across Severity Stages in Alzheimer’s Disease

PubMed Central

Rasero, Javier; Alonso-Montes, Carmen; Diez, Ibai; Olabarrieta-Landa, Laiene; Remaki, Lakhdar; Escudero, Iñaki; Mateos, Beatriz; Bonifazi, Paolo; Fernandez, Manuel; Arango-Lasprilla, Juan Carlos; Stramaglia, Sebastiano; Cortes, Jesus M.

2017-01-01

Alzheimer’s disease (AD) is a chronically progressive neurodegenerative disease highly correlated to aging. Whether AD originates by targeting a localized brain area and propagates to the rest of the brain across disease-severity progression is a question with an unknown answer. Here, we aim to provide an answer to this question at the group-level by looking at differences in diffusion-tensor brain networks. In particular, making use of data from Alzheimer’s Disease Neuroimaging Initiative (ADNI), four different groups were defined (all of them matched by age, sex and education level): G1 (N1 = 36, healthy control subjects, Control), G2 (N2 = 36, early mild cognitive impairment, EMCI), G3 (N3 = 36, late mild cognitive impairment, LMCI) and G4 (N4 = 36, AD). Diffusion-tensor brain networks were compared across three disease stages: stage I (Control vs. EMCI), stage II (Control vs. LMCI) and stage III (Control vs. AD). The group comparison was performed using the multivariate distance matrix regression analysis, a technique that was born in genomics and was recently proposed to handle brain functional networks, but here applied to diffusion-tensor data. The results were threefold: First, no significant differences were found in stage I. Second, significant differences were found in stage II in the connectivity pattern of a subnetwork strongly associated to memory function (including part of the hippocampus, amygdala, entorhinal cortex, fusiform gyrus, inferior and middle temporal gyrus, parahippocampal gyrus and temporal pole). Third, a widespread disconnection across the entire AD brain was found in stage III, affecting more strongly the same memory subnetwork appearing in stage II, plus the other new subnetworks, including the default mode network, medial visual network, frontoparietal regions and striatum. Our results are consistent with a scenario where progressive alterations of connectivity arise as the disease severity increases and provide the brain areas possibly involved in such a degenerative process. Further studies applying the same strategy to longitudinal data are needed to fully confirm this scenario. PMID:28736521

Dieldrin and heptachlor residues in dead gray bats, Franklin County, Missouri--1976 versus 1977

USGS Publications Warehouse

Clark, D.R.; LaVal, R.K.; Krynitsky, A.J.

1980-01-01

Lethal dieldrin concentrations were found in the brains of dead gray bats (Myotis grisescens) collected during 1976 and 1977 beneath a maternity roost in a Missouri cave. In addition, residues of heptachlor epoxide, oxychlordane, cis-chlordane, and trans-nonachlor increased significantly in both brains and carcasses of bats collected during 1977. These increases appear to reflect a switch by local farmers from aldrin, dieldrin's parent compound, to heptachlor for the control of cutworms. They also constitute an additional threat to this colony of this endangered bat species.

Changes in functional and structural brain connectome along the Alzheimer's disease continuum.

PubMed

Filippi, Massimo; Basaia, Silvia; Canu, Elisa; Imperiale, Francesca; Magnani, Giuseppe; Falautano, Monica; Comi, Giancarlo; Falini, Andrea; Agosta, Federica

2018-05-09

The aim of this study was two-fold: (i) to investigate structural and functional brain network architecture in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI), stratified in converters (c-aMCI) and non-converters (nc-aMCI) to AD; and to assess the relationship between healthy brain network functional connectivity and the topography of brain atrophy in patients along the AD continuum. Ninety-four AD patients, 47 aMCI patients (25 c-aMCI within 36 months) and 53 age- and sex-matched healthy controls were studied. Graph analysis and connectomics assessed global and local, structural and functional topological network properties and regional connectivity. Healthy topological features of brain regions were assessed based on their connectivity with the point of maximal atrophy (epicenter) in AD and aMCI patients. Brain network graph analysis properties were severely altered in AD patients. Structural brain network was already altered in c-aMCI patients relative to healthy controls in particular in the temporal and parietal brain regions, while functional connectivity did not change. Structural connectivity alterations distinguished c-aMCI from nc-aMCI cases. In both AD and c-aMCI, the point of maximal atrophy was located in left hippocampus (disease-epicenter). Brain regions most strongly connected with the disease-epicenter in the healthy functional connectome were also the most atrophic in both AD and c-aMCI patients. Progressive degeneration in the AD continuum is associated with an early breakdown of anatomical brain connections and follows the strongest connections with the disease-epicenter. These findings support the hypothesis that the topography of brain connectional architecture can modulate the spread of AD through the brain.

An automated method measures variability in P-glycoprotein and ABCG2 densities across brain regions and brain matter.

PubMed

Kannan, Pavitra; Schain, Martin; Kretzschmar, Warren W; Weidner, Lora; Mitsios, Nicholas; Gulyás, Balázs; Blom, Hans; Gottesman, Michael M; Innis, Robert B; Hall, Matthew D; Mulder, Jan

2017-06-01

Changes in P-glycoprotein and ABCG2 densities may play a role in amyloid-beta accumulation in Alzheimer's disease. However, previous studies report conflicting results from different brain regions, without correcting for changes in vessel density. We developed an automated method to measure transporter density exclusively within the vascular space, thereby correcting for vessel density. We then examined variability in transporter density across brain regions, matter, and disease using two cohorts of post-mortem brains from Alzheimer's disease patients and age-matched controls. Changes in transporter density were also investigated in capillaries near plaques and on the mRNA level. P-glycoprotein density varied with brain region and matter, whereas ABCG2 density varied with brain matter. In temporal cortex, P-glycoprotein density was 53% lower in Alzheimer's disease samples than in controls, and was reduced by 35% in capillaries near plaque deposits within Alzheimer's disease samples. ABCG2 density was unaffected in Alzheimer's disease. No differences were detected at the transcript level. Our study indicates that region-specific changes in transporter densities can occur globally and locally near amyloid-beta deposits in Alzheimer's disease, providing an explanation for conflicting results in the literature. When differences in region and matter are accounted for, changes in density can be reproducibly measured using our automated method.

Differentiating prenatal exposure to methamphetamine and alcohol versus alcohol and not methamphetamine using tensor based brain morphometry and discriminant analysis

PubMed Central

Sowell, Elizabeth R.; Leow, Alex D.; Bookheimer, Susan Y.; Smith, Lynne M.; O’Connor, Mary J.; Kan, Eric; Rosso, Carly; Houston, Suzanne; Dinov, Ivo D.; Thompson, Paul M.

2010-01-01

Here we investigate the effects of prenatal exposure to methamphetamine (MA) on local brain volume using magnetic resonance imaging. Because many who use MA during pregnancy also use alcohol, a known teratogen, we examined whether local brain volumes differed among 61 children (ages 5 to 15), 21 with prenatal MA exposure, 18 with concomitant prenatal alcohol exposure (the MAA group), 13 with heavy prenatal alcohol but not MA exposure (ALC group), and 27 unexposed controls (CON group). Volume reductions were observed in both exposure groups relative to controls in striatal and thalamic regions bilaterally, and right prefrontal and left occipitoparietal cortices. Striatal volume reductions were more severe in the MAA group than in the ALC group, and within the MAA group, a negative correlation between full-scale IQ (FSIQ) scores and caudate volume was observed. Limbic structures including the anterior and posterior cingulate, the inferior frontal gyrus (IFG) and ventral and lateral temporal lobes bilaterally were increased in volume in both exposure groups. Further, cingulate and right IFG volume increases were more pronounced in the MAA than ALC group. Discriminant function analyses using local volume measurements and FSIQ were used to predict group membership, yielding factor scores that correctly classified 72% of participants in jackknife analyses. These findings suggest that striatal and limbic structures, known to be sites of neurotoxicity in adult MA abusers, may be more vulnerable to prenatal MA exposure than alcohol exposure, and that more severe striatal damage is associated with more severe cognitive deficit. PMID:20237258

Thought-Controlled Nanoscale Robots in a Living Host.

PubMed

Arnon, Shachar; Dahan, Nir; Koren, Amir; Radiano, Oz; Ronen, Matan; Yannay, Tal; Giron, Jonathan; Ben-Ami, Lee; Amir, Yaniv; Hel-Or, Yacov; Friedman, Doron; Bachelet, Ido

2016-01-01

We report a new type of brain-machine interface enabling a human operator to control nanometer-size robots inside a living animal by brain activity. Recorded EEG patterns are recognized online by an algorithm, which in turn controls the state of an electromagnetic field. The field induces the local heating of billions of mechanically-actuating DNA origami robots tethered to metal nanoparticles, leading to their reversible activation and subsequent exposure of a bioactive payload. As a proof of principle we demonstrate activation of DNA robots to cause a cellular effect inside the insect Blaberus discoidalis, by a cognitively straining task. This technology enables the online switching of a bioactive molecule on and off in response to a subject's cognitive state, with potential implications to therapeutic control in disorders such as schizophrenia, depression, and attention deficits, which are among the most challenging conditions to diagnose and treat.

Thought-Controlled Nanoscale Robots in a Living Host

PubMed Central

Giron, Jonathan; Ben-Ami, Lee; Amir, Yaniv; Hel-Or, Yacov; Friedman, Doron; Bachelet, Ido

2016-01-01

We report a new type of brain-machine interface enabling a human operator to control nanometer-size robots inside a living animal by brain activity. Recorded EEG patterns are recognized online by an algorithm, which in turn controls the state of an electromagnetic field. The field induces the local heating of billions of mechanically-actuating DNA origami robots tethered to metal nanoparticles, leading to their reversible activation and subsequent exposure of a bioactive payload. As a proof of principle we demonstrate activation of DNA robots to cause a cellular effect inside the insect Blaberus discoidalis, by a cognitively straining task. This technology enables the online switching of a bioactive molecule on and off in response to a subject’s cognitive state, with potential implications to therapeutic control in disorders such as schizophrenia, depression, and attention deficits, which are among the most challenging conditions to diagnose and treat. PMID:27525806

Emerging Trends in the Management of Brain Metastases from Non-small Cell Lung Cancer.

PubMed

Churilla, Thomas M; Weiss, Stephanie E

2018-05-07

To summarize current approaches in the management of brain metastases from non-small cell lung cancer (NSCLC). Local treatment has evolved from whole-brain radiotherapy (WBRT) to increasing use of stereotactic radiosurgery (SRS) alone for patients with limited (1-4) brain metastases. Trials have established post-operative SRS as an alternative to adjuvant WBRT following resection of brain metastases. Second-generation TKIs for ALK rearranged NSCLC have demonstrated improved CNS penetration and activity. Current brain metastasis trials are focused on reducing cognitive toxicity: hippocampal sparing WBRT, SRS for 5-15 metastases, pre-operative SRS, and use of systemic targeted agents or immunotherapy. The role for radiotherapy in the management of brain metastases is becoming better defined with local treatment shifting from WBRT to SRS alone for limited brain metastases and post-operative SRS for resected metastases. Further trials are warranted to define the optimal integration of newer systemic agents with local therapies.

Cortical grey matter and subcortical white matter brain microstructural changes in schizophrenia are localised and age independent: a case-control diffusion tensor imaging study.

PubMed

Chiapponi, Chiara; Piras, Fabrizio; Piras, Federica; Fagioli, Sabrina; Caltagirone, Carlo; Spalletta, Gianfranco

2013-01-01

It is still unknown whether the structural brain impairments that characterize schizophrenia (SZ) worsen during the lifetime. Here, we aimed to describe age-related microstructural brain changes in cortical grey matter and subcortical white matter of patients affected by SZ. In this diffusion tensor imaging study, we included 69 patients diagnosed with SZ and 69 healthy control (HC) subjects, age and gender matched. We carried out analyses of covariance, with diagnosis as fixed factor and brain diffusion-related parameters as dependent variables, and controlled for the effect of education. White matter fractional anisotropy decreased in the entire age range spanned (18-65 years) in both SZ and HC and was significantly lower in younger patients with SZ, with no interaction (age by diagnosis) effect in fiber tracts including corpus callosum, corona radiata, thalamic radiations and external capsule. Also, grey matter mean diffusivity increased in the entire age range in both SZ and HC and was significantly higher in younger patients, with no age by diagnosis interaction in the left frontal operculum cortex, left insula and left planum polare and in the right temporal pole and right intracalcarine cortex. In individuals with SZ we found that localized brain cortical and white matter subcortical microstructural impairments appear early in life but do not worsen in the 18-65 year age range.

Intensity-Modulated Radiation Therapy in Childhood Ependymoma

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

Schroeder, Thomas M.; Chintagumpala, Murali; Okcu, M. Fatih

2008-07-15

Purpose: To determine the patterns of failure after intensity-modulated radiation therapy (IMRT) for localized intracranial ependymoma. Methods and Materials: From 1994 to 2005, 22 children with pathologically proven, localized, intracranial ependymoma were treated with adjuvant IMRT. Of the patients, 12 (55%) had an infratentorial tumor and 14 (64%) had anaplastic histology. Five patients had a subtotal resection (STR), as evidenced by postoperative magnetic resonance imaging. The clinical target volume encompassed the tumor bed and any residual disease plus margin (median dose 54 Gy). Median follow-up for surviving patients was 39.8 months. Results: The 3-year overall survival rate was 87% {+-}more » 9%. The 3-year local control rate was 68% {+-} 12%. There were six local recurrences, all in the high-dose region of the treatment field. Median time to recurrence was 21.7 months. Of the 5 STR patients, 4 experienced recurrence and 3 died. Patients with a gross total resection had significantly better local control (p = 0.024) and overall survival (p = 0.008) than those with an STR. At last follow-up, no patient had developed visual loss, brain necrosis, myelitis, or a second malignancy. Conclusions: Treatment with IMRT provides local control and survival rates comparable with those in historic publications using larger treatment volumes. All failures were within the high-dose region, suggesting that IMRT does not diminish local control. The degree of surgical resection was shown to be significant for local control and survival.« less

Pharmacodynamic and Therapeutic Investigation of Focused Ultrasound-Induced Blood-Brain Barrier Opening for Enhanced Temozolomide Delivery in Glioma Treatment

PubMed Central

Liu, Hao-Li; Huang, Chiung-Yin; Chen, Ju-Yu; Wang, Hay-Yan Jack; Chen, Pin-Yuan; Wei, Kuo-Chen

2014-01-01

Focused ultrasound (FUS) exposure with the presence of microbubbles has been shown to transiently open the blood-brain barrier (BBB), and thus has potential to enhance the delivery of various kinds of therapeutic agents into brain tumors. The purpose of this study was to assess the preclinical therapeutic efficacy of FUS-BBB opening for enhanced temozolomide (TMZ) delivery in glioma treatment. FUS exposure with microbubbles was delivered to open the BBB of nude mice that were either normal or implanted with U87 human glioma cells. Different TMZ dose regimens were tested, ranging from 2.5 to 25 mg/kg. Plasma and brain samples were obtained at different time-points ranging from 0.5 to 4 hours, and the TMZ concentration within samples was quantitated via a developed LC-MS/MS procedure. Tumor progression was followed with T2-MRI, and animal survival and brain tissue histology were conducted. Results demonstrated that FUS-BBB opening caused the local TMZ accumulation in the brain to increase from 6.98 to 19 ng/mg. TMZ degradation time in the tumor core was found to increase from 1.02 to 1.56 hours. Improved tumor progression and animal survival were found at different TMZ doses (up to 15% and 30%, respectively). In conclusion, this study provides preclinical evidence that FUS-BBB opening increases the local concentration of TMZ to improve the control of tumor progression and animal survival, suggesting the potential for clinical application to improve current brain tumor treatment. PMID:25490097

Nuclear-cytoplasmic localization of acetyl coenzyme A synthetase-1 in the rat brain

PubMed Central

Ariyannur, Prasanth S.; Moffett, John R.; Madhavarao, Chikkathur N; Arun, Peethambaran; Vishnu, Nisha; Jacobowitz, David M.; Hallows, William C.; Denu, John M.; Namboodiri, Aryan M.A.

2011-01-01

Acetyl coenzyme A synthetase 1 (AceCS1) catalyzes the synthesis of acetyl coenzyme A from acetate and coenzyme A, and is thought to play diverse roles ranging from fatty acid synthesis to gene regulation. Using an affinity purified antibody generated against an 18-mer peptide sequence of AceCS1, and a polyclonal antibody directed against recombinant AceCS1 protein, we examined the expression of AceCS1 in the rat brain. AceCS1 immunoreactivity in the adult rat brain was present predominantly in cell nuclei, with only light to moderate cytoplasmic staining in some neurons, axons and oligodendrocytes. Some non-neuronal cell nuclei were very strongly immunoreactive, including those of some oligodendrocytes, whereas neuronal nuclei ranged from unstained to moderately stained. Both antibodies stained some neuronal cell bodies and axons, especially in the hindbrain. AceCS1 immunoreactivity was stronger and more widespread in the brains of 18 day old rats than in adults, with increased expression in oligodendrocytes and neurons, including cortical pyramidal cells. Expression of AceCS1 was substantially upregulated in neurons throughout the brain after controlled cortical impact injury. The strong AceCS1 expression observed in the nuclei of CNS cells during brain development and after injury is consistent with a role in nuclear histone acetylation and therefore the regulation of chromatin structure and gene expression. The cytoplasmic staining observed in some oligodendrocytes, especially during postnatal brain development, suggests an additional role in CNS lipid synthesis and myelination. Neuronal and axonal localization implicates AceCS1 in cytoplasmic acetylation reactions in some neurons. PMID:20533355

Behavioral Analysis of Genetically Modified Mice Indicates Essential Roles of Neurosteroidal Estrogen

PubMed Central

Honda, Shin-Ichiro; Wakatsuki, Toru; Harada, Nobuhiro

2011-01-01

Aromatase in the mouse brain is expressed only in the nerve cells of specific brain regions with a transient peak during the neonatal period when sexual behaviors become organized. The aromatase-knockout (ArKO) mouse, generated to shed light on the physiological functions of estrogen in the brain, exhibited various abnormal behaviors, concomitant with undetectable estrogen and increased androgen in the blood. To further elucidate the effects of neurosteroidal estrogens on behavioral phenotypes, we first prepared an brain-specific aromatase transgenic (bsArTG) mouse by introduction of a human aromatase transgene controlled under a −6.5 kb upstream region of the brain-specific promoter of the mouse aromatase gene into fertilized mouse eggs, because the −6.5 kb promoter region was previously shown to contain the minimal essential element responsible for brain-specific spatiotemporal expression. Then, an ArKO mouse expressing the human aromatase only in the brain was generated by crossing the bsArTG mouse with the ArKO mouse. The resulting mice (ArKO/bsArTG mice) nearly recovered from abnormal sexual, aggressive, and locomotive (exploratory) behaviors, in spite of having almost the same serum levels of estrogen and androgen as the adult ArKO mouse. These results suggest that estrogens locally synthesized in the specific neurons of the perinatal mouse brain directly act on the neurons and play crucial roles in the organization of neuronal networks participating in the control of sexual, aggressive, and locomotive (exploratory) behaviors. PMID:22654807

Abnormal brain synchrony in Down Syndrome☆

PubMed Central

Anderson, Jeffrey S.; Nielsen, Jared A.; Ferguson, Michael A.; Burback, Melissa C.; Cox, Elizabeth T.; Dai, Li; Gerig, Guido; Edgin, Jamie O.; Korenberg, Julie R.

2013-01-01

Down Syndrome is the most common genetic cause for intellectual disability, yet the pathophysiology of cognitive impairment in Down Syndrome is unknown. We compared fMRI scans of 15 individuals with Down Syndrome to 14 typically developing control subjects while they viewed 50 min of cartoon video clips. There was widespread increased synchrony between brain regions, with only a small subset of strong, distant connections showing underconnectivity in Down Syndrome. Brain regions showing negative correlations were less anticorrelated and were among the most strongly affected connections in the brain. Increased correlation was observed between all of the distributed brain networks studied, with the strongest internetwork correlation in subjects with the lowest performance IQ. A functional parcellation of the brain showed simplified network structure in Down Syndrome organized by local connectivity. Despite increased interregional synchrony, intersubject correlation to the cartoon stimuli was lower in Down Syndrome, indicating that increased synchrony had a temporal pattern that was not in response to environmental stimuli, but idiosyncratic to each Down Syndrome subject. Short-range, increased synchrony was not observed in a comparison sample of 447 autism vs. 517 control subjects from the Autism Brain Imaging Exchange (ABIDE) collection of resting state fMRI data, and increased internetwork synchrony was only observed between the default mode and attentional networks in autism. These findings suggest immature development of connectivity in Down Syndrome with impaired ability to integrate information from distant brain regions into coherent distributed networks. PMID:24179822

Going Local to Find Help

MedlinePlus

... Bar Home Current Issue Past Issues Cover Story: Traumatic Brain Injury Going Local to Find Help Past Issues / Fall ... all the time. From the MedlinePlus page on Traumatic Brain Injury, you can use Go Local to find specific ...

A Coordinated Action of Blood-Borne and Brain Insulin-Like Growth Factor I in the Response to Traumatic Brain Injury.

PubMed

Santi, A; Genis, L; Torres Aleman, I

2018-06-01

In response to injury, the brain produces different neuroprotective molecules, such as insulin-like growth factor I (IGF-I). However, IGF-I is also taken up by the brain from the circulation in response to physiological stimuli. Herein, we analyzed in mice the relative contribution of circulating and locally produced IGF-I to increased brain IGF-I levels after insult. Traumatic brain injury (TBI) induced by a controlled impact resulted in increased IGF-I levels in the vicinity of the lesion, but mice with low serum IGF-I showed significantly lower increases. Indeed, in normal mice, peripheral IGF-I accumulated at the lesion site after injury, and at the same time serum IGF-I levels decreased. Collectively, these data suggest that serum IGF-I enter into the brain after TBI and contributes to increased brain IGF-I levels at the injury site. This connection between central and circulating IGF-I provides an amenable route for treatment, as subcutaneous administration of IGF-I to TBI mice led to functional recovery. These latter results add further support to the use of systemic IGF-I or its mimetics for treatment of brain injuries.

Generation and evaluation of an ultra-high-field atlas with applications in DBS planning

NASA Astrophysics Data System (ADS)

Wang, Brian T.; Poirier, Stefan; Guo, Ting; Parrent, Andrew G.; Peters, Terry M.; Khan, Ali R.

2016-03-01

Purpose Deep brain stimulation (DBS) is a common treatment for Parkinson's disease (PD) and involves the use of brain atlases or intrinsic landmarks to estimate the location of target deep brain structures, such as the subthalamic nucleus (STN) and the globus pallidus pars interna (GPi). However, these structures can be difficult to localize with conventional clinical magnetic resonance imaging (MRI), and thus targeting can be prone to error. Ultra-high-field imaging at 7T has the ability to clearly resolve these structures and thus atlases built with these data have the potential to improve targeting accuracy. Methods T1 and T2-weighted images of 12 healthy control subjects were acquired using a 7T MR scanner. These images were then used with groupwise registration to generate an unbiased average template with T1w and T2w contrast. Deep brain structures were manually labelled in each subject by two raters and rater reliability was assessed. We compared the use of this unbiased atlas with two other methods of atlas-based segmentation (single-template and multi-template) for subthalamic nucleus (STN) segmentation on 7T MRI data. We also applied this atlas to clinical DBS data acquired at 1.5T to evaluate its efficacy for DBS target localization as compared to using a standard atlas. Results The unbiased templates provide superb detail of subcortical structures. Through one-way ANOVA tests, the unbiased template is significantly (p <0.05) more accurate than a single-template in atlas-based segmentation and DBS target localization tasks. Conclusion The generated unbiased averaged templates provide better visualization of deep brain nuclei and an increase in accuracy over single-template and lower field strength atlases.

[An automatic system for anatomophysiological correlation in three planes simultaneously during functional neurosurgery].

PubMed

Teijeiro, E J; Macías, R J; Morales, J M; Guerra, E; López, G; Alvarez, L M; Fernández, F; Maragoto, C; Seijo, F; Alvarez, E

The Neurosurgical Deep Recording System (NDRS) using a personal computer takes the place of complex electronic equipment for recording and processing deep cerebral electrical activity, as a guide in stereotaxic functional neurosurgery. It also permits increased possibilities of presenting information in direct graphic form with automatic management and sufficient flexibility to implement different analyses. This paper describes the possibilities of automatic simultaneous graphic representation in three almost orthogonal planes, available with the new 5.1 version of NDRS so as to facilitate the analysis of anatomophysiological correlation in the localization of deep structures of the brain during minimal access surgery. This new version can automatically show the spatial behaviour of signals registered throughout the path of the electrode inside the brain, superimposed simultaneously on sagittal, coronal and axial sections of an anatomical atlas of the brain, after adjusting the scale automatically according to the dimensions of the brain of each individual patient. This may also be shown in a tridimensional representation of the different planes themselves intercepting. The NDRS system has been successfully used in Spain and Cuba in over 300 functional neurosurgery operations. The new version further facilitates analysis of spatial anatomophysiological correlation for the localization of brain structures. This system has contributed to increase the precision and safety in selecting surgical targets in the control of Parkinson s disease and other disorders of movement.

The neuropathology of morality: Germany 1930-1960.

PubMed

Schirmann, Felix

2014-01-01

This article analyzes brain scientists' attempts to trace morality in the brain in Germany from 1930 to 1960. The debate around Karl Kleist's localization of the Gemeinschafts-Ich [community-I] in the 1930s is depicted in order to illustrate the central arguments for and against localizations of morality. The focus of this article is on the period 1936-1960 in which experts put forth specific ideas on morality's cerebral underpinnings that mirror the larger theoretical shift from strict localization doctrine to a more holistic understanding of the brain. As a result of this shift, experts avoided exact localizations of morality. Instead, they posited correlations between brain areas and morality. The analysis illustrates the dependence of neuropathological research on morality on general theories of brain functioning and marks a first contribution to the history of the neuroscience of morality for the time after 1930.

Imaging of Glial Cell Activation and White Matter Integrity in Brains of Active and Recently Retired National Football League Players.

PubMed

Coughlin, Jennifer M; Wang, Yuchuan; Minn, Il; Bienko, Nicholas; Ambinder, Emily B; Xu, Xin; Peters, Matthew E; Dougherty, John W; Vranesic, Melin; Koo, Soo Min; Ahn, Hye-Hyun; Lee, Merton; Cottrell, Chris; Sair, Haris I; Sawa, Akira; Munro, Cynthia A; Nowinski, Christopher J; Dannals, Robert F; Lyketsos, Constantine G; Kassiou, Michael; Smith, Gwenn; Caffo, Brian; Mori, Susumu; Guilarte, Tomas R; Pomper, Martin G

2017-01-01

Microglia, the resident immune cells of the central nervous system, play an important role in the brain's response to injury and neurodegenerative processes. It has been proposed that prolonged microglial activation occurs after single and repeated traumatic brain injury, possibly through sports-related concussive and subconcussive injuries. Limited in vivo brain imaging studies months to years after individuals experience a single moderate to severe traumatic brain injury suggest widespread persistent microglial activation, but there has been little study of persistent glial cell activity in brains of athletes with sports-related traumatic brain injury. To measure translocator protein 18 kDa (TSPO), a marker of activated glial cell response, in a cohort of National Football League (NFL) players and control participants, and to report measures of white matter integrity. This cross-sectional, case-control study included young active (n = 4) or former (n = 10) NFL players recruited from across the United States, and 16 age-, sex-, highest educational level-, and body mass index-matched control participants. This study was conducted at an academic research institution in Baltimore, Maryland, from January 29, 2015, to February 18, 2016. Positron emission tomography-based regional measures of TSPO using [11C]DPA-713, diffusion tensor imaging measures of regional white matter integrity, regional volumes on structural magnetic resonance imaging, and neuropsychological performance. The mean (SD) ages of the 14 NFL participants and 16 control participants were 31.3 (6.1) years and 27.6 (4.9) years, respectively. Players reported a mean (SD) of 7.0 (6.4) years (range, 1-21 years) since the last self-reported concussion. Using [11C]DPA-713 positron emission tomographic data from 12 active or former NFL players and 11 matched control participants, the NFL players showed higher total distribution volume in 8 of the 12 brain regions examined (P < .004). We also observed limited change in white matter fractional anisotropy and mean diffusivity in 13 players compared with 15 control participants. In contrast, these young players did not differ from control participants in regional brain volumes or in neuropsychological performance. The results suggest that localized brain injury and repair, indicated by higher TSPO signal and white matter changes, may be associated with NFL play. Further study is needed to confirm these findings and to determine whether TSPO signal and white matter changes in young NFL athletes are related to later onset of neuropsychiatric symptoms.

MR-guided transcranial brain HIFU in small animal models

PubMed Central

Larrat, Benoît; Pernot, Mathieu; Aubry, Jean-François; Dervishi, Elvis; Sinkus, Ralph; Seilhean, Danielle; Marie, Yannick; Boch, Anne-Laure; Fink, Mathias; Tanter, Mickaël

2010-01-01

Recent studies have demonstrated the feasibility of transcranial High Intensity Focused Ultrasound (HIFU) therapy in the brain using adaptive focusing techniques. However, the complexity of the procedures imposes to provide an accurate targeting, monitoring and control of this emerging therapeutic modality in order to ensure the safety of the treatment and avoid potential damaging effects of ultrasound on healthy tissues. For these purposes, a complete workflow and setup for HIFU treatment under Magnetic Resonance (MR) guidance is proposed and implemented in rats. For the first time, tissue displacements induced by the acoustic radiation force are detected in vivo in brain tissues and measured quantitatively using motion-sensitive MR sequences. Such a valuable target control prior to treatment assesses the quality of the focusing pattern in situ and enables to estimate the acoustic intensity at focus. This MR-Acoustic radiation force imaging is then correlated with conventional MR-Thermometry sequences which are used to follow the temperature changes during the HIFU therapeutic session. Last, pre and post treatment Magnetic Resonance Elastography (MRE) datasets are acquired and evaluated as a new potential way to non invasively control the stiffness changes due to the presence of thermal necrosis. As a proof of concept, MRguided HIFU is performed in vitro in turkey breast samples and in vivo in transcranial rat brain experiments. The experiments are conducted using a dedicated MR compatible HIFU setup in a high field MRI scanner (7T). Results obtained on rats confirmed that both the MR localization of the US focal point and the pre and post HIFU measurement of the tissue stiffness, together with temperature control during HIFU are feasible and valuable techniques for an efficient monitoring of HIFU in the brain. Brain elasticity appears to be more sensitive to the presence of oedema than to tissue necrosis. PMID:20019400

The role of the postsynaptic density in the pathology of the fragile X syndrome.

PubMed

Kindler, Stefan; Kreienkamp, Hans-Jürgen

2012-01-01

The protein repertoire of excitatory synapses controls dendritic spine morphology, synaptic plasticity and higher brain functions. In brain neurons, the RNA-associated fragile X mental retardation protein (FMRP) binds in vivo to various transcripts encoding key postsynaptic components and may thereby substantially regulate the molecular composition of dendritic spines. In agreement with this notion functional loss of FMRP in patients affected by the fragile X syndrome (FXS) causes cognitive impairment. Here we address our current understanding of the functional role of individual postsynaptic proteins. We discuss how FMRP controls the abundance of select proteins at postsynaptic sites, which signaling pathways regulate the local activity of FMRP at synapses, and how altered levels of postsynaptic proteins may contribute to FXS pathology.

Hemispheric asymmetry of electroencephalography-based functional brain networks.

PubMed

Jalili, Mahdi

2014-11-12

Electroencephalography (EEG)-based functional brain networks have been investigated frequently in health and disease. It has been shown that a number of graph theory metrics are disrupted in brain disorders. EEG-based brain networks are often studied in the whole-brain framework, where all the nodes are grouped into a single network. In this study, we studied the brain networks in two hemispheres and assessed whether there are any hemispheric-specific patterns in the properties of the networks. To this end, resting state closed-eyes EEGs from 44 healthy individuals were processed and the network structures were extracted separately for each hemisphere. We examined neurophysiologically meaningful graph theory metrics: global and local efficiency measures. The global efficiency did not show any hemispheric asymmetry, whereas the local connectivity showed rightward asymmetry for a range of intermediate density values for the constructed networks. Furthermore, the age of the participants showed significant direct correlations with the global efficiency of the left hemisphere, but only in the right hemisphere, with local connectivity. These results suggest that only local connectivity of EEG-based functional networks is associated with brain hemispheres.

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.

Abnormal regional homogeneity as a potential imaging biomarker for adolescent-onset schizophrenia: A resting-state fMRI study and support vector machine analysis.

PubMed

Wang, Shuai; Zhang, Yan; Lv, Luxian; Wu, Renrong; Fan, Xiaoduo; Zhao, Jingping; Guo, Wenbin

2018-02-01

Structural and functional abnormalities have been reported in the brain of patients with adolescent-onset schizophrenia (AOS). The brain regional functional synchronization in patients with AOS remains unclear. We analyzed resting-state functional magnetic resonance scans in 48 drug-naive patients with AOS and 31 healthy controls by using regional homogeneity (ReHo), a measurement that reflects brain local functional connectivity or synchronization and indicates regional integration of information processing. Then, receiver operating characteristic curves and support vector machines were used to evaluate the effect of abnormal regional homogeneity in differentiating patients from controls. Patients with AOS showed significantly increased ReHo values in the bilateral superior medial prefrontal cortex (MPFC) and significantly decreased ReHo values in the left superior temporal gyrus (STG), right precentral lobule, right inferior parietal lobule (IPL), and left paracentral lobule when compared with controls. A combination of the ReHo values in bilateral superior MPFC, left STG, and right IPL was able to discriminate patients from controls with the sensitivity of 88.24%, specificity of 91.89%, and accuracy of 90.14%. The brain regional functional synchronization abnormalities exist in drug-naive patients with AOS. A combination of ReHo values in these abnormal regions might serve as potential imaging biomarker to identify patients with AOS. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Proton Resonance Spectroscopy Study of the Effects of L-Ornithine-L-Aspartate on the Development of Encephalopathy, Using Localization Pulses with Reduced Specific Absorption Rate

NASA Astrophysics Data System (ADS)

Slotboom, J.; Vogels, B. A. P. M.; Dehaan, J. G.; Creyghton, J. H. N.; Quack, G.; Chamuleau, R. A. F. M.; Bovee, W. M. M. J.

Using the SADLOVE ( single-shot adiabatic localized volume excitation) localization technique with reduced specific absorption rate phase-compensated 2π pulses for localization, in vivo rat brain spectra were obtained in order to study the possible beneficial effects of L-ornithine-L-aspartate (OA) on the development of encephalopathy induced by hyperammonemia in portacaval shunted rats, an experimental model for subacute hepatic encephalopathy. The in vivo1H spectra were quantified using a conjugate-gradient-based frequency-domain fitting procedure. OA treatment resulted in an about threefold lower increase in train lactate ( P < 0.0001) and a slower increase of brain glutamine ( P = 0.022) concentration. However, these changes in brain metabolism, including a significantly lower ammonia concentration during OA treatment, were not associated with a sig significant improvement in clinical symptoms of encephalopathy, suggesting either insufficient decrease in brain ammonia concentration or another effect of OA treatment counteracting the lowering effect on blood and brain ammonia and on brain glutamine and lactate. It is concluded that localized in vivo1H MRS of the brain in combination with other analytical techniques, such as in vivo microdialysis, is helpful in explaining pathophysiological changes during hyperammonemia-induced encephalopathy.

Clinical outcomes of gastrointestinal brain metastases treated with radiotherapy.

PubMed

Sanghvi, Samrat M; Lischalk, Jonathan W; Cai, Ling; Collins, Sean; Nair, Mani; Collins, Brain; Unger, Keith

2017-02-28

Brain metastases of gastrointestinal origin are a rare occurrence. Radiation therapy (RT) in the form of stereotactic radiosurgery (SRS) or whole brain radiation therapy (WBRT) is an effective established treatment modality in either the definitive or adjuvant setting. The aim of this study is to assess the long-term clinical outcomes of patients with gastrointestinal (GI) brain metastases treated with SRS or WBRT. In this single institutional retrospective review, we detail the outcomes of patients diagnosed with metastatic brain tumors from an adenocarcinoma gastrointestinal primary. Patients were treated using stereotactic radiosurgery or whole brain radiation therapy. Initial site control (defined as lesions visualized on imaging at time of treatment), new site control (defined as new intracranial lesions visualized on follow-up imaging), and overall survival were calculated using the Kaplan-Meier method. Thirty-three patients were treated from August 2008 to December 2015. Primary malignancy locations were as follows: 18 colon, 6 esophagus, 4 rectum, 5 other. Median total dose delivered was 25 Gy (18-35 Gy) in a median of 4 fractions for SRS and 30 Gy (10.8-40 Gy) in 10 fractions for WBRT. Crude initial site control at last radiographic follow-up was 64.3% after SRS and 41.7% after WBRT. Eleven of the 28 brain lesions (39.3%) treated with SRS had resection of the SRS-treated lesion prior to radiation therapy. Five of the twelve patients (41.7%) undergoing WBRT underwent cranial resection prior to radiation therapy. Crude new site control at last radiographic follow-up was 46.4% after SRS and 83.3% after WBRT. Kaplan-Meier analysis of overall survival did not show any statistically significant difference between WBRT and SRS (p = 0.424). Median overall survival for SRS patients was 5.2 months (0.5-57.5) and for WBRT patients 4.4 months (0-15). Kaplan-Meier analysis of new site control was significantly improved with WBRT versus SRS (p = 0.017). Total dose, treatment with WBRT, and active extracranial disease were statistically significant on multivariate analysis for new site control (p < 0.05). Survival and intracranial disease control are poor following RT for brain metastases from GI primaries. In this small series, outcomes are worse than published series for other primary malignancies metastatic to the brain and further research into methods of local control improvement is warranted. Future studies should explore the utility of dose escalation or radiosensitization in this patient population.

Brain training game boosts executive functions, working memory and processing speed in the young adults: a randomized controlled trial.

PubMed

Nouchi, Rui; Taki, Yasuyuki; Takeuchi, Hikaru; Hashizume, Hiroshi; Nozawa, Takayuki; Kambara, Toshimune; Sekiguchi, Atsushi; Miyauchi, Carlos Makoto; Kotozaki, Yuka; Nouchi, Haruka; Kawashima, Ryuta

2013-01-01

Do brain training games work? The beneficial effects of brain training games are expected to transfer to other cognitive functions. Yet in all honesty, beneficial transfer effects of the commercial brain training games in young adults have little scientific basis. Here we investigated the impact of the brain training game (Brain Age) on a wide range of cognitive functions in young adults. We conducted a double-blind (de facto masking) randomized controlled trial using a popular brain training game (Brain Age) and a popular puzzle game (Tetris). Thirty-two volunteers were recruited through an advertisement in the local newspaper and randomly assigned to either of two game groups (Brain Age, Tetris). Participants in both the Brain Age and the Tetris groups played their game for about 15 minutes per day, at least 5 days per week, for 4 weeks. Measures of the cognitive functions were conducted before and after training. Measures of the cognitive functions fell into eight categories (fluid intelligence, executive function, working memory, short-term memory, attention, processing speed, visual ability, and reading ability). Our results showed that commercial brain training game improves executive functions, working memory, and processing speed in young adults. Moreover, the popular puzzle game can engender improvement attention and visuo-spatial ability compared to playing the brain training game. The present study showed the scientific evidence which the brain training game had the beneficial effects on cognitive functions (executive functions, working memory and processing speed) in the healthy young adults. Our results do not indicate that everyone should play brain training games. However, the commercial brain training game might be a simple and convenient means to improve some cognitive functions. We believe that our findings are highly relevant to applications in educational and clinical fields. UMIN Clinical Trial Registry 000005618.

Brain Training Game Boosts Executive Functions, Working Memory and Processing Speed in the Young Adults: A Randomized Controlled Trial

PubMed Central

Nouchi, Rui; Taki, Yasuyuki; Takeuchi, Hikaru; Hashizume, Hiroshi; Nozawa, Takayuki; Kambara, Toshimune; Sekiguchi, Atsushi; Miyauchi, Carlos Makoto; Kotozaki, Yuka; Nouchi, Haruka; Kawashima, Ryuta

2013-01-01

Background Do brain training games work? The beneficial effects of brain training games are expected to transfer to other cognitive functions. Yet in all honesty, beneficial transfer effects of the commercial brain training games in young adults have little scientific basis. Here we investigated the impact of the brain training game (Brain Age) on a wide range of cognitive functions in young adults. Methods We conducted a double-blind (de facto masking) randomized controlled trial using a popular brain training game (Brain Age) and a popular puzzle game (Tetris). Thirty-two volunteers were recruited through an advertisement in the local newspaper and randomly assigned to either of two game groups (Brain Age, Tetris). Participants in both the Brain Age and the Tetris groups played their game for about 15 minutes per day, at least 5 days per week, for 4 weeks. Measures of the cognitive functions were conducted before and after training. Measures of the cognitive functions fell into eight categories (fluid intelligence, executive function, working memory, short-term memory, attention, processing speed, visual ability, and reading ability). Results and Discussion Our results showed that commercial brain training game improves executive functions, working memory, and processing speed in young adults. Moreover, the popular puzzle game can engender improvement attention and visuo-spatial ability compared to playing the brain training game. The present study showed the scientific evidence which the brain training game had the beneficial effects on cognitive functions (executive functions, working memory and processing speed) in the healthy young adults. Conclusions Our results do not indicate that everyone should play brain training games. However, the commercial brain training game might be a simple and convenient means to improve some cognitive functions. We believe that our findings are highly relevant to applications in educational and clinical fields. Trial Registration UMIN Clinical Trial Registry 000005618. PMID:23405164

MaxiK channel interactome reveals its interaction with GABA transporter 3 and heat shock protein 60 in the mammalian brain.

PubMed

Singh, H; Li, M; Hall, L; Chen, S; Sukur, S; Lu, R; Caputo, A; Meredith, A L; Stefani, E; Toro, L

2016-03-11

Large conductance voltage and calcium-activated potassium (MaxiK) channels are activated by membrane depolarization and elevated cytosolic Ca(2+). In the brain, they localize to neurons and astrocytes, where they play roles such as resetting the membrane potential during an action potential, neurotransmitter release, and neurovascular coupling. MaxiK channels are known to associate with several modulatory proteins and accessory subunits, and each of these interactions can have distinct physiological consequences. To uncover new players in MaxiK channel brain physiology, we applied a directed proteomic approach and obtained MaxiK channel pore-forming α subunit brain interactome using specific antibodies. Controls included immunoprecipitations with rabbit immunoglobulin G (IgG) and with anti-MaxiK antibodies in wild type and MaxiK channel knockout mice (Kcnma1(-/-)), respectively. We have found known and unreported interactive partners that localize to the plasma membrane, extracellular space, cytosol and intracellular organelles including mitochondria, nucleus, endoplasmic reticulum and Golgi apparatus. Localization of MaxiK channel to mitochondria was further confirmed using purified brain mitochondria colabeled with MitoTracker. Independent proof of MaxiK channel interaction with previously unidentified partners is given for GABA transporter 3 (GAT3) and heat shock protein 60 (HSP60). In human embryonic kidney 293 cells containing SV40 T-antigen (HEK293T) cells, both GAT3 and HSP60 coimmunoprecipitated and colocalized with MaxiK channel; colabeling was observed mainly at the cell periphery with GAT3 and intracellularly with HSP60 with protein proximity indices of ∼ 0.6 and ∼ 0.4, respectively. In rat primary hippocampal neurons, colocalization index was identical for GAT3 (∼ 0.6) and slightly higher for HSP60 (∼ 0.5) association with MaxiK channel. The results of this study provide a complete interactome of MaxiK channel the mouse brain, further establish the localization of MaxiK channel in the mouse brain mitochondria and demonstrate the interaction of MaxiK channel with GAT3 and HSP60 in neurons. The interaction of MaxiK channel with GAT3 opens the possibility of a role of MaxiK channel in GABA homeostasis and signaling. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Metabolic Mapping of the Brain's Response to Visual Stimulation: Studies in Humans.

ERIC Educational Resources Information Center

Phelps, Michael E.; Kuhl, David E.

1981-01-01

Studies demonstrate increasing glucose metabolic rates in human primary (PVC) and association (AVC) visual cortex as complexity of visual scenes increase. AVC increased more rapidly with scene complexity than PVC and increased local metabolic activities above control subject with eyes closed; indicates wide range and metabolic reserve of visual…

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

Hussain, Aamir; Brown, Paul D.; Stafford, Scott L.

Purpose: Patients with brainstem metastases have limited treatment options. In this study, we reviewed outcomes after stereotactic radiosurgery (SRS) in the management of patients with brainstem metastases. Methods and Materials: Records were reviewed of 22 consecutive patients presenting with brainstem metastases who underwent SRS. The most frequent primary malignancy was the lung (n = 11), followed by breast (n = 3) and kidney (n = 2). Three patients (14%) also underwent whole-brain radiation therapy (WBRT). The median tumor volume was 0.9 mL (range, 0.1-3.3 mL); the median tumor margin dose was 16 Gy (range, 14-23 Gy). Results: Median survival timemore » after SRS was 8.5 months. Although local tumor control was achieved in all patients with imaging follow-up (n = 19), 5 patients died from development and progression of new brain metastases. Two patients (9%) had symptom improvement after SRS, whereas 1 patient (5%) developed a new hemiparesis after SRS. Conclusions: Radiosurgery is safe and provides a high local tumor control rate for patients with small brainstem metastases. Patients with limited systemic disease and good performance status should be strongly considered for SRS.« less

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

Trifiletti, Daniel M., E-mail: daniel.trifiletti@gmail.com; Lee, Cheng-Chia; Kano, Hideyuki

Purpose: To pool data across multiple institutions internationally and report on the cumulative experience of brainstem stereotactic radiosurgery (SRS). Methods and Materials: Data on patients with brainstem metastases treated with SRS were collected through the International Gamma Knife Research Foundation. Clinical, radiographic, and dosimetric characteristics were compared for factors prognostic for local control (LC) and overall survival (OS) using univariate and multivariate analyses. Results: Of 547 patients with 596 brainstem metastases treated with SRS, treatment of 7.4% of tumors resulted in severe SRS-induced toxicity (grade ≥3, increased odds with increasing tumor volume, margin dose, and whole-brain irradiation). Local control at 12 monthsmore » after SRS was 81.8% and was improved with increasing margin dose and maximum dose. Overall survival at 12 months after SRS was 32.7% and impacted by age, gender, number of metastases, tumor histology, and performance score. Conclusions: Our study provides additional evidence that SRS has become an option for patients with brainstem metastases, with an excellent benefit-to-risk ratio in the hands of experienced clinicians. Prior whole-brain irradiation increases the risk of severe toxicity in brainstem metastasis patients undergoing SRS.« less

AMPA receptor-induced local brain-derived neurotrophic factor signaling mediates motor recovery after stroke.

PubMed

Clarkson, Andrew N; Overman, Justine J; Zhong, Sheng; Mueller, Rudolf; Lynch, Gary; Carmichael, S Thomas

2011-03-09

Stroke is the leading cause of adult disability. Recovery after stroke shares similar molecular and cellular properties with learning and memory. A main component of learning-induced plasticity involves signaling through AMPA receptors (AMPARs). We systematically tested the role of AMPAR function in motor recovery in a mouse model of focal stroke. AMPAR function controls functional recovery beginning 5 d after the stroke. Positive allosteric modulators of AMPARs enhance recovery of limb control when administered after a delay from the stroke. Conversely, AMPAR antagonists impair motor recovery. The contributions of AMPARs to recovery are mediated by release of brain-derived neurotrophic factor (BDNF) in periinfarct cortex, as blocking local BDNF function in periinfarct cortex blocks AMPAR-mediated recovery and prevents the normal pattern of motor recovery. In contrast to a delayed AMPAR role in motor recovery, early administration of AMPAR agonists after stroke increases stroke damage. These findings indicate that the role of glutamate signaling through the AMPAR changes over time in stroke: early potentiation of AMPAR signaling worsens stroke damage, whereas later potentiation of the same signaling system improves functional recovery.

Localization of androgen receptors and estrogen receptors in the same cells of the songbird brain.

PubMed Central

Gahr, M

1990-01-01

Estrogens and androgens each have unique effects but act together for the neural differentiation and control of sexual behaviors in male vertebrates, such as the canary. The neuronal basis for these synergistic effects is elusive because the spatial relation between estrogen target cells and androgen target cells is unknown. This study localized estrogen receptor (ER)-containing cells by using immunocytochemistry and androgen receptor (AR)-containing cells by using autoradiography in the same sections of the male canary brain. Three cell types, those containing only ER, those containing only AR, and those containing both ER and AR, were found in tissue-specific frequencies. The midbrain nucleus intercollicularis exhibited the highest number of cells expressing both ER and AR, whereas ER and AR are expressed only in disjunctive cell populations in the forebrain nucleus hyperstriatalis ventrale, pars caudale. Synergistic effects of androgens and estrogens for the neural behavorial control could result from cells containing both ER and AR (intracellular) and from neural circuits containing ER and AR in different cells (intercellular). Images PMID:2251286

Periodontitis induced by bacterial infection exacerbates features of Alzheimer's disease in transgenic mice.

PubMed

Ishida, Naoyuki; Ishihara, Yuichi; Ishida, Kazuto; Tada, Hiroyuki; Funaki-Kato, Yoshiko; Hagiwara, Makoto; Ferdous, Taslima; Abdullah, Mohammad; Mitani, Akio; Michikawa, Makoto; Matsushita, Kenji

2017-01-01

Periodontitis is a localized infectious disease caused by periodontopathic bacteria, such as Porphyromonas gingivalis . Recently, it has been suggested that bacterial infections may contribute to the onset and the progression of Alzheimer's disease (AD). However, we do not have any evidence about a causative relationship between periodontitis and AD. In this study, we investigated by using a transgenic mouse model of AD whether periodontitis evoked by P. gingivalis modulates the pathological features of AD. Cognitive function was significantly impaired in periodontitis-induced APP-Tg mice, compared to that in control APP-Tg mice. Levels of Amiloid β (Aβ) deposition, Aβ40, and Aβ42 in both the hippocampus and cortex were higher in inoculated APP-Tg mice than in control APP-Tg mice. Furthermore, levels of IL-1β and TNF-α in the brain were higher in inoculated mice than in control mice. The levels of LPS were increased in the serum and brain of P. gingivalis -inoculated mice. P. gingivalis LPS-induced production of Aβ40 and Aβ42 in neural cell cultures and strongly enhanced TNF-α and IL-1β production in a culture of microglial cells primed with Aβ. Periodontitis evoked by P. gingivalis may exacerbate brain Aβ deposition, leading to enhanced cognitive impairments, by a mechanism that involves triggering brain inflammation.

A high performing brain-machine interface driven by low-frequency local field potentials alone and together with spikes

NASA Astrophysics Data System (ADS)

Stavisky, Sergey D.; Kao, Jonathan C.; Nuyujukian, Paul; Ryu, Stephen I.; Shenoy, Krishna V.

2015-06-01

Objective. Brain-machine interfaces (BMIs) seek to enable people with movement disabilities to directly control prosthetic systems with their neural activity. Current high performance BMIs are driven by action potentials (spikes), but access to this signal often diminishes as sensors degrade over time. Decoding local field potentials (LFPs) as an alternative or complementary BMI control signal may improve performance when there is a paucity of spike signals. To date only a small handful of LFP decoding methods have been tested online; there remains a need to test different LFP decoding approaches and improve LFP-driven performance. There has also not been a reported demonstration of a hybrid BMI that decodes kinematics from both LFP and spikes. Here we first evaluate a BMI driven by the local motor potential (LMP), a low-pass filtered time-domain LFP amplitude feature. We then combine decoding of both LMP and spikes to implement a hybrid BMI. Approach. Spikes and LFP were recorded from two macaques implanted with multielectrode arrays in primary and premotor cortex while they performed a reaching task. We then evaluated closed-loop BMI control using biomimetic decoders driven by LMP, spikes, or both signals together. Main results. LMP decoding enabled quick and accurate cursor control which surpassed previously reported LFP BMI performance. Hybrid decoding of both spikes and LMP improved performance when spikes signal quality was mediocre to poor. Significance. These findings show that LMP is an effective BMI control signal which requires minimal power to extract and can substitute for or augment impoverished spikes signals. Use of this signal may lengthen the useful lifespan of BMIs and is therefore an important step towards clinically viable BMIs.

Using human extra-cortical local field potentials to control a switch

NASA Astrophysics Data System (ADS)

Kennedy, Philip; Andreasen, Dinal; Ehirim, Princewill; King, Brandon; Kirby, Todd; Mao, Hui; Moore, Melody

2004-06-01

Individuals with profound paralysis and mutism require a communication channel. Traditional assistive technology devices eventually fail, especially in the case of amyotrophic lateral sclerosis (ALS) subjects who gradually become totally locked-in. A direct brain-to-computer interface that provides switch functions can provide a direct communication channel to the external world. Electroencephalographic (EEG) signals recorded from scalp electrodes are significantly degraded due to skull and scalp attenuation and ambient noise. The present system using conductive skull screws allows more reliable access to cortical local field potentials (LFPs) without entering the brain itself. We describe an almost locked-in human subject with ALS who activated a switch using online time domain detection techniques. Frequency domain analysis of his LFP activity demonstrates this to be an alternative method of detecting switch activation intentions. With this brain communicator system it is reasonable to expect that locked-in, but cognitively intact, humans will always be able to communicate. Financial disclosure. Authors PK and DA may derive some financial gain from the sale of this device. A patent has been applied under US and international law: 10/675,703.

A voxel-based investigation of brain structure in male adolescents with autistic spectrum disorder.

PubMed

Waiter, Gordon D; Williams, Justin H G; Murray, Alison D; Gilchrist, Anne; Perrett, David I; Whiten, Andrew

2004-06-01

Autistic spectrum disorder (ASD) has been associated with abnormal neuroanatomy in many imaging and neuropathological studies. Both global brain volume differences and differences in the size of specific neural structures have been reported. Here, we report a voxel-based morphometric whole brain analysis, using a group specific template, on 16 individuals of normal intelligence with autistic spectrum disorder (ASD), and a group of 16 age-, sex- and IQ-matched controls. Total grey matter volume was increased in the ASD group relative to the control group, with local volume increases in the right fusiform gyrus, the right temporo-occipital region and the left frontal pole extending to the medial frontal cortex. A local decrease in grey matter volume was found in the right thalamus. A decrease in global white matter volume in the ASD group did not reach significance. We found the increase in grey matter volume in ASD subjects was greatest in those areas recognised for their role in social cognition, particularly face recognition (right fusiform gyrus), mental state attribution: 'theory of mind' (anterior cingulate and superior temporal sulcus) and perception of eye gaze (superior temporal gyrus). The picture as a whole may reflect an abnormally functioning social cognitive neural network. We suggest that increased grey matter volume may play a pivotal role in the aetiology of the autistic syndrome.

Enriched environment improves motor function and increases neurotrophins in hemicerebellar lesioned rats.

PubMed

Gelfo, Francesca; Cutuli, Debora; Foti, Francesca; Laricchiuta, Daniela; De Bartolo, Paola; Caltagirone, Carlo; Petrosini, Laura; Angelucci, Francesco

2011-01-01

Environmental enrichment (EE) defined as "a combination of complex inanimate and social stimulation" influences brain function and anatomy by enhancing sensory, cognitive, motor, and social stimulation. The beneficial effects of EE in the presence of brain damage have been partially attributed to upregulation of neurotrophins, proteins involved in neuronal survival and in activity-dependent plasticity. The authors tested the hypothesis that EE may have advantageous effects on recovery of motor function after cerebellar damage, associated with changes in local neurotrophin production. They performed a hemicerebellectomy in rats previously exposed to EE or reared in standard conditions. The time course of compensation of motor symptoms was analyzed in both lesioned groups. Then, the local production of the nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in the spared hemicerebellum and other extracerebellar regions was evaluated. Long-term exposure to EE accelerated the motor recovery in hemicerebellectomized rats and elicited an increase in NGF levels in the spared hemicerebellum, as compared with nonenriched lesioned and control rats. BDNF levels were higher in hemicerebellectomized rats but not influenced by EE. In the frontal cortex, both NGF and BDNF levels were upregulated in hemicerebellectomized enriched rats as compared with hemicerebellectomized nonenriched and control rats. This study suggests that the beneficial effects of EE on motor symptoms after cerebellar damage may be, at least partly, because of modulation of neurotrophic proteins involved in the regeneration processes.

Local functional connectivity alterations in schizophrenia, bipolar disorder, and major depressive disorder.

PubMed

Wei, Yange; Chang, Miao; Womer, Fay Y; Zhou, Qian; Yin, Zhiyang; Wei, Shengnan; Zhou, Yifang; Jiang, Xiaowei; Yao, Xudong; Duan, Jia; Xu, Ke; Zuo, Xi-Nian; Tang, Yanqing; Wang, Fei

2018-08-15

Local functional connectivity (FC) indicates local or short-distance functional interactions and may serve as a neuroimaging marker to investigate the human brain connectome. Local FC alterations suggest a disrupted balance in the local functionality of the whole brain network and are increasingly implicated in schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). We aim to examine the similarities and differences in the local FC across SZ, BD, and MDD. In total, 537 participants (SZ, 126; BD, 97; MDD, 126; and healthy controls, 188) completed resting-state functional magnetic resonance imaging at a single site. The local FC at resting state was calculated and compared across SZ, BD, and MDD. The local FC increased across SZ, BD, and MDD within the bilateral orbital frontal cortex (OFC) and additional region in the left OFC extending to putamen and decreased in the primary visual, auditory, and motor cortices, right supplemental motor area, and bilateral thalami. There was a gradient in the extent of alterations such that SZ > BD > MDD. This cross-sectional study cannot consider medications and other clinical variables. These findings indicate a disrupted balance between network integration and segregation in SZ, BD, and MDD, including over-integration via increased local FC in the OFC and diminished segregation of neural processing with the weakening of the local FC in the primary sensory cortices and thalamus. The shared local FC abnormalities across SZ, BD, and MDD may shed new light on the potential biological mechanisms underlying these disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

Differential Impact of Whole-Brain Radiotherapy Added to Radiosurgery for Brain Metastases

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

Kong, Doo-Sik; Lee, Jung-Il, E-mail: jilee@skku.ed; Im, Yong-Seok

2010-10-01

Purpose: The authors investigated whether the addition of whole-brain radiotherapy (WBRT) to stereotactic radiosurgery (SRS) provided any therapeutic benefit according to recursive partitioning analysis (RPA) class. Methods and Materials: Two hundred forty-five patients with 1 to 10 metastases who underwent SRS between January 2002 and December 2007 were included in the study. Of those, 168 patients were treated with SRS alone and 77 patients received SRS followed by WBRT. Actuarial curves were estimated using the Kaplan-Meier method regarding overall survival (OS), distant brain control (DC), and local brain control (LC) stratified by RPA class. Analyses for known prognostic variables weremore » performed using the Cox proportional hazards model. Results: Univariate and multivariate analysis revealed that control of the primary tumor, small number of brain metastases, Karnofsky performance scale (KPS) > 70, and initial treatment modalities were significant predictors for survival. For RPA class 1, SRS plus WBRT was associated with a longer survival time compared with SRS alone (854 days vs. 426 days, p = 0.042). The SRS plus WBRT group also showed better LC rate than did the SRS-alone group (p = 0.021), although they did not show a better DC rate (p = 0.079). By contrast, for RPA class 2 or 3, no significant difference in OS, LC, or DC was found between the two groups. Conclusions: These results suggest that RPA classification should determine whether or not WBRT is added to SRS. WBRT may be recommended to be added to SRS for patients in whom long-term survival is expected on the basis of RPA classification.« less

Human Impairment from Living near Confined Animal (Hog) Feeding Operations

PubMed Central

Kilburn, Kaye H.

2012-01-01

Problem. To determine whether neighbors around manure lagoons and massive hog confinement buildings who complained of offensive odors and symptoms had impaired brain and lung functions. Method. We compared near hog manure neighbors of lagoons to people living beyond 3 kilometers in Ohio and to unexposed people controls in a nearby state for neurophysiological, cognitive, recall and memory functions, and pulmonary performance. Results. The 25 exposed subjects averaged 4.3 neurobehavioral abnormalities, significantly different from 2.5 for local controls and 2.3 for Tennessee controls. Exposed subjects mean forced vital capacity and expiratory volume in 1 sec were reduced significantly compared to local and regional controls. Conclusions. Near neighbors of hog enclosures and manure lagoon gases had impaired neurobehavioral functions and pulmonary functions and these effects extended to nearby people thought to be controls. Hydrogen sulfide must be abated because people living near lagoons cannot avoid rotten egg gas. PMID:22496706

Evaluating the diagnostic utility of applying a machine learning algorithm to diffusion tensor MRI measures in individuals with major depressive disorder.

PubMed

Schnyer, David M; Clasen, Peter C; Gonzalez, Christopher; Beevers, Christopher G

2017-06-30

Using MRI to diagnose mental disorders has been a long-term goal. Despite this, the vast majority of prior neuroimaging work has been descriptive rather than predictive. The current study applies support vector machine (SVM) learning to MRI measures of brain white matter to classify adults with Major Depressive Disorder (MDD) and healthy controls. In a precisely matched group of individuals with MDD (n =25) and healthy controls (n =25), SVM learning accurately (74%) classified patients and controls across a brain map of white matter fractional anisotropy values (FA). The study revealed three main findings: 1) SVM applied to DTI derived FA maps can accurately classify MDD vs. healthy controls; 2) prediction is strongest when only right hemisphere white matter is examined; and 3) removing FA values from a region identified by univariate contrast as significantly different between MDD and healthy controls does not change the SVM accuracy. These results indicate that SVM learning applied to neuroimaging data can classify the presence versus absence of MDD and that predictive information is distributed across brain networks rather than being highly localized. Finally, MDD group differences revealed through typical univariate contrasts do not necessarily reveal patterns that provide accurate predictive information. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Localized Cortical Thinning in Patients with Obstructive Sleep Apnea Syndrome

PubMed Central

Joo, Eun Yeon; Jeon, Seun; Kim, Sung Tae; Lee, Jong-Min; Hong, Seung Bong

2013-01-01

Study Objectives: To investigate differences in cortical thickness in patients with obstructive sleep apnea (OSA) syndrome and healthy controls. Design: Cortical thickness was measured using a three-dimensional surface-based method that enabled more accurate measurement in deep sulci and localized regional mapping. Setting: University hospital. Patients: Thirty-eight male patients with severe OSA (mean apnea-hypopnea index > 30/h) and 36 age-matched male healthy controls were enrolled. Interventions: Cortical thickness was obtained at 81,924 vertices across the entire brain by reconstructing inner and outer cortical surfaces using an automated anatomical pipeline. Measurements: Group difference in cortical thickness and correlation between patients' data and thickness were analyzed by a general linear model. Results: Localized cortical thinning in patients was found in the orbitorectal gyri, dorsolateral/ventromedial prefrontal regions, pericentral gyri, anterior cingulate, insula, inferior parietal lobule, uncus, and basolateral temporal regions at corrected P < 0.05. Patients with OSA showed impaired attention and learning difficulty in memory tests compared to healthy controls. Higher number of respiratory arousals was related to cortical thinning of the anterior cingulate and inferior parietal lobule. A significant correlation was observed between the longer apnea maximum duration and the cortical thinning of the dorsolateral prefrontal regions, pericentral gyri, and insula. Retention scores in visual memory tests were associated with cortical thickness of parahippocampal gyrus and uncus. Conclusions: Brain regions with cortical thinning may provide elucidations for prefrontal cognitive dysfunction, upper airway sensorimotor dysregulation, and cardiovascular disturbances in OSA patients, that experience sleep disruption including sleep fragmentation and oxygen desaturation. Citation: Joo EY; Jeon S; Kim ST; Lee JM; Hong SB. Localized cortical thinning in patients with obstructive sleep apnea syndrome. SLEEP 2013;36(8):1153-1162. PMID:23904675

Age-related differences in BOLD modulation to cognitive control costs in a multitasking paradigm: Global switch, local switch, and compatibility-switch costs.

PubMed

Nashiro, Kaoru; Qin, Shuo; O'Connell, Margaret A; Basak, Chandramallika

2018-05-15

It is well documented that older adults recruit additional brain regions compared to those recruited by younger adults while performing a wide variety of cognitive tasks. However, it is unclear how such age-related over-recruitment interacts with different types of cognitive control, and whether this over-recruitment is compensatory. To test this, we used a multitasking paradigm, which allowed us to examine age-related over-activation associated with three types of cognitive costs (i.e., global switch, local switch, compatibility-switch costs). We found age-related impairments in global switch cost (GSC), evidenced by slower response times for maintaining and coordinating two tasks vs. performing only one task. However, no age-related declines were observed in either local switch cost (LSC), a cognitive cost associated with switching between the two tasks while maintaining two task loads, or compatibility-switch cost (CSC), a cognitive cost associated with incompatible vs. compatible stimulus-response mappings across the two tasks. The fMRI analyses allowed for identification of distinct cognitive cost-sensitive brain regions associated with GSC and LSC. In fronto-parietal GSC and LSC regions, older adults' increased activations were associated with poorer performance (greater costs), whereas a reverse relationship was observed in younger adults. Older adults also recruited additional fronto-parietal brain regions outside the cognitive cost-sensitive areas, which was associated with poorer performance or no behavioral benefits. Our results suggest that older adults exhibit a combination of inefficient activation within cognitive cost-sensitive regions, specifically the GSC and LSC regions, and non-compensatory over-recruitment in age-sensitive regions. Age-related declines in global switching, compared to local switching, was observed earlier in old age at both neural and behavioral levels. Copyright © 2018 Elsevier Inc. All rights reserved.

Disrupted brain network functional dynamics and hyper-correlation of structural and functional connectome topology in patients with breast cancer prior to treatment.

PubMed

Kesler, Shelli R; Adams, Marjorie; Packer, Melissa; Rao, Vikram; Henneghan, Ashley M; Blayney, Douglas W; Palesh, Oxana

2017-03-01

Several previous studies have demonstrated that cancer chemotherapy is associated with brain injury and cognitive dysfunction. However, evidence suggests that cancer pathogenesis alone may play a role, even in non-CNS cancers. Using a multimodal neuroimaging approach, we measured structural and functional connectome topology as well as functional network dynamics in newly diagnosed patients with breast cancer. Our study involved a novel, pretreatment assessment that occurred prior to the initiation of any cancer therapies, including surgery with anesthesia. We enrolled 74 patients with breast cancer age 29-65 and 50 frequency-matched healthy female controls who underwent anatomic and resting-state functional MRI as well as cognitive testing. Compared to controls, patients with breast cancer demonstrated significantly lower functional network dynamics ( p  = .046) and cognitive functioning ( p  < .02, corrected). The breast cancer group also showed subtle alterations in structural local clustering and functional local clustering ( p  < .05, uncorrected) as well as significantly increased correlation between structural global clustering and functional global clustering compared to controls ( p  = .03). This hyper-correlation between structural and functional topologies was significantly associated with cognitive dysfunction ( p  = .005). Our findings could not be accounted for by psychological distress and suggest that non-CNS cancer may directly and/or indirectly affect the brain via mechanisms such as tumor-induced neurogenesis, inflammation, and/or vascular changes, for example. Our results also have broader implications concerning the importance of the balance between structural and functional connectome properties as a potential biomarker of general neurologic deficit.

Whole-brain functional connectivity identification of functional dyspepsia.

PubMed

Nan, Jiaofen; Liu, Jixin; Li, Guoying; Xiong, Shiwei; Yan, Xuemei; Yin, Qing; Zeng, Fang; von Deneen, Karen M; Liang, Fanrong; Gong, Qiyong; Qin, Wei; Tian, Jie

2013-01-01

Recent neuroimaging studies have shown local brain aberrations in functional dyspepsia (FD) patients, yet little attention has been paid to the whole-brain resting-state functional network abnormalities. The purpose of this study was to investigate whether FD disrupts the patterns of whole-brain networks and the abnormal functional connectivity could reflect the severity of the disease. The dysfunctional interactions between brain regions at rest were investigated in FD patients as compared with 40 age- and gender- matched healthy controls. Multivariate pattern analysis was used to evaluate the discriminative power of our results for classifying patients from controls. In our findings, the abnormal brain functional connections were mainly situated within or across the limbic/paralimbic system, the prefrontal cortex, the tempo-parietal areas and the visual cortex. About 96% of the subjects among the original dataset were correctly classified by a leave one-out cross-validation approach, and 88% accuracy was also validated in a replication dataset. The classification features were significantly associated with the patients' dyspepsia symptoms, the self-rating depression scale and self-rating anxiety scale, but it was not correlated with duration of FD patients (p>0.05). Our results may indicate the effectiveness of the altered brain functional connections reflecting the disease pathophysiology underling FD. These dysfunctional connections may be the epiphenomena or causative agents of FD, which may be affected by clinical severity and its related emotional dimension of the disease rather than the clinical course.

Voluntary Enhancement of Neural Signatures of Affiliative Emotion Using fMRI Neurofeedback

PubMed Central

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

2014-01-01

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

Whole brain radiotherapy plus stereotactic radiosurgery (WBRT+SRS) versus surgery plus whole brain radiotherapy (OP+WBRT) for 1-3 brain metastases: results of a matched pair analysis.

PubMed

Rades, Dirk; Kueter, Jan-Dirk; Veninga, Theo; Gliemroth, Jan; Schild, Steven E

2009-02-01

This study is the first one to compare WBRT+SRS to OP+WBRT for 1-3 brain metastases. Survival (OS), intracerebral control (IC) and local control (LC) of the treated metastases were retrospectively evaluated in 52 patients undergoing WBRT+SRS and in 52 patients undergoing OP+WBRT. Both groups were matched for WBRT schedule, age, gender, performance status, tumour, number of brain metastases, extracerebral metastases, RPA class and interval from tumour diagnosis to WBRT. One-year OS was 56% after WBRT+SRS and 47% after OP+WBRT (p=0.034). One-year IC was 66% and 50% (p=0.003). One-year LC was 82% and 66% (p=0.006). On multivariate analyses, it was found that improved OS was associated with younger age (p=0.044), no extracerebral metastases (p<0.001), RPA class 1 (p<0.001) and longer interval from tumour diagnosis to WBRT (p=0.001). IC was associated with younger age (p=0.002) and longer interval (p=0.004); WBRT+SRS achieved borderline significance (p=0.052). Improved LC was associated with longer interval (p=0.017); WBRT+SRS showed a trend (p=0.09). WBRT+SRS appears at least as effective as OP+WBRT.

Blood-brain barrier-supported neurogenesis in healthy and diseased brain.

PubMed

Pozhilenkova, Elena A; Lopatina, Olga L; Komleva, Yulia K; Salmin, Vladimir V; Salmina, Alla B

2017-05-24

Adult neurogenesis is one of the most important mechanisms contributing to brain development, learning, and memory. Alterations in neurogenesis underlie a wide spectrum of brain diseases. Neurogenesis takes place in highly specialized neurogenic niches. The concept of neurogenic niches is becoming widely accepted due to growing evidence of the important role of the microenvironment established in the close vicinity to stem cells in order to provide adequate control of cell proliferation, differentiation, and apoptosis. Neurogenic niches represent the platform for tight integration of neurogenesis and angiogenesis supported by specific properties of cerebral microvessel endothelial cells contributing to establishment of partially compromised blood-brain barrier (BBB) for the adjustment of local conditions to the current metabolic needs of stem and progenitor cells. Here, we review up-to-date data on microvascular dynamics in activity-dependent neurogenesis, specific properties of BBB in neurogenic niches, endothelial-driven mechanisms of clonogenic activity, and future perspectives for reconstructing the neurogenic niches in vitro.

Renewal Processes in the Critical Brain

NASA Astrophysics Data System (ADS)

Allegrini, Paolo; Paradisi, Paolo; Menicucci, Danilo; Gemignani, Angelo

We describe herein a multidisciplinary research, as it developes and applies concepts of the theory of complexity, in turn stemming from recent advancements of statistical physics, onto cognitive neuroscience. We discuss (define) complexity, and how the human brain is a paradigm of it. We discuss how the hypothesis of brain activity dynamically behaving as a critical system is taking momentum in literature, then we focus on a feature of critical systems (hence of the brain), which is the intermittent passage between metastable states, marked by events, locally resetting the memory, but giving rise to correlation functions with infinite correlation times. The events, extracted from multi-channel ElectroEncephaloGrams, mark (are interpreted as) a birth/death process of cooperation, namely of system elements being recruited into collective states. Finally we discuss a recently discovered form of control (in the form of a new Linear Response Theory), that allows an optimized information transmission between complex systems, named Complexity Matching.

Metabolic profiling of Alzheimer's disease brains

NASA Astrophysics Data System (ADS)

Inoue, Koichi; Tsutsui, Haruhito; Akatsu, Hiroyasu; Hashizume, Yoshio; Matsukawa, Noriyuki; Yamamoto, Takayuki; Toyo'Oka, Toshimasa

2013-08-01

Alzheimer's disease (AD) is an irreversible, progressive brain disease and can be definitively diagnosed after death through an examination of senile plaques and neurofibrillary tangles in several brain regions. It is to be expected that changes in the concentration and/or localization of low-molecular-weight molecules are linked to the pathological changes that occur in AD, and determining their identity would provide valuable information regarding AD processes. Here, we propose definitive brain metabolic profiling using ultra-performance liquid chromatography coupled with electrospray time-of-flight mass spectrometry analysis. The acquired data were subjected to principal components analysis to differentiate the frontal and parietal lobes of the AD/Control groups. Significant differences in the levels of spermine and spermidine were identified using S-plot, mass spectra, databases and standards. Based on the investigation of the polyamine metabolite pathway, these data establish that the downstream metabolites of ornithine are increased, potentially implicating ornithine decarboxylase activity in AD pathology.

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.

Techniques for detection and localization of weak hippocampal and medial frontal sources using beamformers in MEG.

PubMed

Mills, Travis; Lalancette, Marc; Moses, Sandra N; Taylor, Margot J; Quraan, Maher A

2012-07-01

Magnetoencephalography provides precise information about the temporal dynamics of brain activation and is an ideal tool for investigating rapid cognitive processing. However, in many cognitive paradigms visual stimuli are used, which evoke strong brain responses (typically 40-100 nAm in V1) that may impede the detection of weaker activations of interest. This is particularly a concern when beamformer algorithms are used for source analysis, due to artefacts such as "leakage" of activation from the primary visual sources into other regions. We have previously shown (Quraan et al. 2011) that we can effectively reduce leakage patterns and detect weak hippocampal sources by subtracting the functional images derived from the experimental task and a control task with similar stimulus parameters. In this study we assess the performance of three different subtraction techniques. In the first technique we follow the same post-localization subtraction procedures as in our previous work. In the second and third techniques, we subtract the sensor data obtained from the experimental and control paradigms prior to source localization. Using simulated signals embedded in real data, we show that when beamformers are used, subtraction prior to source localization allows for the detection of weaker sources and higher localization accuracy. The improvement in localization accuracy exceeded 10 mm at low signal-to-noise ratios, and sources down to below 5 nAm were detected. We applied our techniques to empirical data acquired with two different paradigms designed to evoke hippocampal and frontal activations, and demonstrated our ability to detect robust activations in both regions with substantial improvements over image subtraction. We conclude that removal of the common-mode dominant sources through data subtraction prior to localization further improves the beamformer's ability to project the n-channel sensor-space data to reveal weak sources of interest and allows more accurate localization.

A novel framework for the local extraction of extra-axial cerebrospinal fluid from MR brain images

NASA Astrophysics Data System (ADS)

Mostapha, Mahmoud; Shen, Mark D.; Kim, SunHyung; Swanson, Meghan; Collins, D. Louis; Fonov, Vladimir; Gerig, Guido; Piven, Joseph; Styner, Martin A.

2018-03-01

The quantification of cerebrospinal fluid (CSF) in the human brain has shown to play an important role in early postnatal brain developmental. Extr a-axial fluid (EA-CSF), which is characterized by the CSF in the subarachnoid space, is promising in the early detection of children at risk for neurodevelopmental disorders. Currently, though, there is no tool to extract local EA-CSF measurements in a way that is suitable for localized analysis. In this paper, we propose a novel framework for the localized, cortical surface based analysis of EA-CSF. In our proposed processing, we combine probabilistic brain tissue segmentation, cortical surface reconstruction as well as streamline based local EA-CSF quantification. For streamline computation, we employ the vector field generated by solving a Laplacian partial differential equation (PDE) between the cortical surface and the outer CSF hull. To achieve sub-voxel accuracy while minimizing numerical errors, fourth-order Runge-Kutta (RK4) integration was used to generate the streamlines. Finally, the local EA-CSF is computed by integrating the CSF probability along the generated streamlines. The proposed local EA-CSF extraction tool was used to study the early postnatal brain development in typically developing infants. The results show that the proposed localized EA-CSF extraction pipeline can produce statistically significant regions that are not observed in previous global approach.

[Effects of electromagnetic pulse on blood-brain barrier permeability and tight junction proteins in rats].

PubMed

Qiu, Lian-bo; Ding, Gui-rong; Zhang, Ya-mei; Zhou, Yan; Wang, Xiao-wu; Li, Kang-chu; Xu, Sheng-long; Tan, Juan; Zhou, Jia-xing; Guo, Guo-zhen

2009-09-01

To study the effect of electromagnetic pulse (EMP) on the permeability of blood-brain barrier, tight junction (TJ)-associated protein expression and localization in rats. 66 male SD rats, weighing (200 approximately 250) g, were sham or whole-body exposed to EMP at 200 kV/m for 200 pulses. The repetition rate was 1 Hz. The permeability of the blood-brain barrier in rats was assessed by albumin immunohistochemistry. The expression of typical tight junction protein ZO-1 and occludin in both cerebral cortex homogenate and cerebral cortex microvessel homogenate was analyzed by the Western blotting and the distribution of ZO-1 and occludin was examined by immunofluorescence microscopy. In the sham exposure rats, no brain capillaries showed albumin leakage, at 0.5 h after 200 kV/m EMP exposure for 200 pulses; a few brain capillaries with extravasated serum albumin was found, with the time extended, the number of brain capillaries with extravasated serum albumin increased, and reached the peak at 3 h, then began to recover at 6 h. In addition, no change in the distribution of the occludin was found after EMP exposure. Total occludin expression had no significant change compared with the control. However, the expression level of ZO-1 significantly decreased at 1 h and 3 h after EMP exposure in both cerebral cortex homogenate and cerebral cortex microvessel homogenate. Furthermore, immunofluorescence studies also showed alterations in ZO-1 protein localization in cerebral cortex microvessel. The EMP exposure (200 kV/m, 200 pulses) could increase blood-brain barrier permeability in rat, and this change is associated with specific alterations in tight junction protein ZO-1.

Low resolution brain electromagnetic tomography in a realistic geometry head model: a simulation study

NASA Astrophysics Data System (ADS)

Ding, Lei; Lai, Yuan; He, Bin

2005-01-01

It is of importance to localize neural sources from scalp recorded EEG. Low resolution brain electromagnetic tomography (LORETA) has received considerable attention for localizing brain electrical sources. However, most such efforts have used spherical head models in representing the head volume conductor. Investigation of the performance of LORETA in a realistic geometry head model, as compared with the spherical model, will provide useful information guiding interpretation of data obtained by using the spherical head model. The performance of LORETA was evaluated by means of computer simulations. The boundary element method was used to solve the forward problem. A three-shell realistic geometry (RG) head model was constructed from MRI scans of a human subject. Dipole source configurations of a single dipole located at different regions of the brain with varying depth were used to assess the performance of LORETA in different regions of the brain. A three-sphere head model was also used to approximate the RG head model, and similar simulations performed, and results compared with the RG-LORETA with reference to the locations of the simulated sources. Multi-source localizations were discussed and examples given in the RG head model. Localization errors employing the spherical LORETA, with reference to the source locations within the realistic geometry head, were about 20-30 mm, for four brain regions evaluated: frontal, parietal, temporal and occipital regions. Localization errors employing the RG head model were about 10 mm over the same four brain regions. The present simulation results suggest that the use of the RG head model reduces the localization error of LORETA, and that the RG head model based LORETA is desirable if high localization accuracy is needed.

Resected Brain Tissue, Seizure Onset Zone and Quantitative EEG Measures: Towards Prediction of Post-Surgical Seizure Control

PubMed Central

Andrzejak, Ralph G.; Hauf, Martinus; Pollo, Claudio; Müller, Markus; Weisstanner, Christian; Wiest, Roland; Schindler, Kaspar

2015-01-01

Background Epilepsy surgery is a potentially curative treatment option for pharmacoresistent patients. If non-invasive methods alone do not allow to delineate the epileptogenic brain areas the surgical candidates undergo long-term monitoring with intracranial EEG. Visual EEG analysis is then used to identify the seizure onset zone for targeted resection as a standard procedure. Methods Despite of its great potential to assess the epileptogenicty of brain tissue, quantitative EEG analysis has not yet found its way into routine clinical practice. To demonstrate that quantitative EEG may yield clinically highly relevant information we retrospectively investigated how post-operative seizure control is associated with four selected EEG measures evaluated in the resected brain tissue and the seizure onset zone. Importantly, the exact spatial location of the intracranial electrodes was determined by coregistration of pre-operative MRI and post-implantation CT and coregistration with post-resection MRI was used to delineate the extent of tissue resection. Using data-driven thresholding, quantitative EEG results were separated into normally contributing and salient channels. Results In patients with favorable post-surgical seizure control a significantly larger fraction of salient channels in three of the four quantitative EEG measures was resected than in patients with unfavorable outcome in terms of seizure control (median over the whole peri-ictal recordings). The same statistics revealed no association with post-operative seizure control when EEG channels contributing to the seizure onset zone were studied. Conclusions We conclude that quantitative EEG measures provide clinically relevant and objective markers of target tissue, which may be used to optimize epilepsy surgery. The finding that differentiation between favorable and unfavorable outcome was better for the fraction of salient values in the resected brain tissue than in the seizure onset zone is consistent with growing evidence that spatially extended networks might be more relevant for seizure generation, evolution and termination than a single highly localized brain region (i.e. a “focus”) where seizures start. PMID:26513359

The neurobiological role of the dorsolateral prefrontal cortex in recovery from trauma. Longitudinal brain imaging study among survivors of the South Korean subway disaster.

PubMed

Lyoo, In Kyoon; Kim, Jieun E; Yoon, Sujung J; Hwang, Jaeuk; Bae, Sujin; Kim, Dajung J

2011-07-01

A multiwave longitudinal neuroimaging study in a cohort of direct survivors of a South Korean subway disaster, most of whom recovered from posttraumatic stress disorder 5 years after trauma, provided a unique opportunity to investigate the brain correlates of recovery from a severe psychological trauma. To investigate region-specific brain mobilization during successful recovery from posttraumatic stress disorder by assessing cortical thickness multiple times from early after trauma to recovery, and to examine whether a brain-derived neurotrophic factor gene polymorphism was associated with this brain mobilization. Five-year follow-up case-control study conducted from 2003-2007. Seoul National University and Hospital. Thirty psychologically traumatized disaster survivors and 36 age- and sex-matched control group members recruited from the disaster registry and local community, respectively, who contributed 156 high-resolution brain magnetic resonance images during 3 waves of assessments. Cerebral cortical thickness measured in high-resolution anatomic magnetic resonance images using a validated cortical thickness analysis tool and its prospective changes from early after trauma to recovery in trauma-exposed individuals and controls. Trauma-exposed individuals had greater dorsolateral prefrontal cortical (DLPFC) thickness 1.42 years after trauma (right DLPFC, 5.4%; left superior frontal cortex, 5.8%; and left inferior frontal cortex, 5.3% [all clusters, P ≤ .01]) relative to controls. Thicknesses gradually normalized over time during recovery. We found a positive linear trend, with trauma-exposed individuals with a valine/valine genotype having the greatest DLPFC cortical thickness, followed by those with a methionine genotype and controls (P < .001 for trend). Greater DLPFC thickness was associated with greater posttraumatic stress disorder symptom reductions and better recovery. The DLPFC region might play an important role in psychological recovery from a severely traumatic event in humans.

Adaptive deep brain stimulation in advanced Parkinson disease.

PubMed

Little, Simon; Pogosyan, Alex; Neal, Spencer; Zavala, Baltazar; Zrinzo, Ludvic; Hariz, Marwan; Foltynie, Thomas; Limousin, Patricia; Ashkan, Keyoumars; FitzGerald, James; Green, Alexander L; Aziz, Tipu Z; Brown, Peter

2013-09-01

Brain-computer interfaces (BCIs) could potentially be used to interact with pathological brain signals to intervene and ameliorate their effects in disease states. Here, we provide proof-of-principle of this approach by using a BCI to interpret pathological brain activity in patients with advanced Parkinson disease (PD) and to use this feedback to control when therapeutic deep brain stimulation (DBS) is delivered. Our goal was to demonstrate that by personalizing and optimizing stimulation in real time, we could improve on both the efficacy and efficiency of conventional continuous DBS. We tested BCI-controlled adaptive DBS (aDBS) of the subthalamic nucleus in 8 PD patients. Feedback was provided by processing of the local field potentials recorded directly from the stimulation electrodes. The results were compared to no stimulation, conventional continuous stimulation (cDBS), and random intermittent stimulation. Both unblinded and blinded clinical assessments of motor effect were performed using the Unified Parkinson's Disease Rating Scale. Motor scores improved by 66% (unblinded) and 50% (blinded) during aDBS, which were 29% (p = 0.03) and 27% (p = 0.005) better than cDBS, respectively. These improvements were achieved with a 56% reduction in stimulation time compared to cDBS, and a corresponding reduction in energy requirements (p < 0.001). aDBS was also more effective than no stimulation and random intermittent stimulation. BCI-controlled DBS is tractable and can be more efficient and efficacious than conventional continuous neuromodulation for PD. Copyright © 2013 American Neurological Association.

Cortical thickness and folding deficits in conduct-disordered adolescents

PubMed Central

Hyatt, Christopher J.; Haney-Caron, Emily; Stevens, Michael C.

2012-01-01

Background Studies of pediatric conduct disorder (CD) have described frontal and temporal lobe structural abnormalities that parallel findings in antisocial adults. The purpose of this study was to examine previously unexplored cortical thickness and folding as markers for brain abnormalities in “pure CD”-diagnosed adolescents. Based on current fronto-temporal theories, we hypothesized that CD youth would have thinner cortex or less cortical folding in temporal and frontal lobes than control subjects. Methods We obtained T1-weighted brain structure images from n=24 control and n=19 CD participants aged 12–18 years, matched by overall gender and age. We measured group differences in cortical thickness and local gyrification index (regional cortical folding measure) using surface-based morphometry with clusterwise correction for multiple comparisons. Results CD participants, when compared with controls, showed both reduced cortical thickness and folding. Thinner cortex was located primarily in posterior brain regions, including left superior temporal and parietal lobes, temporoparietal junction and paracentral lobule, right superior temporal and parietal lobes, temporoparietal junction and precuneus. Folding deficits were located mainly in anterior brain regions and included left insula, ventro- and dorsomedial prefrontal, anterior cingulate and orbitofrontal cortices, temporal lobe, right superior frontal and parietal lobes and paracentral lobule. Conclusions Our findings generally agree with previous CD volumetric studies, but here show the unique contributions of cortical thickness and folding to gray matter reductions in pure CD in different brain regions. PMID:22209639

Simultaneous in vivo recording of local brain temperature and electrophysiological signals with a novel neural probe

NASA Astrophysics Data System (ADS)

Fekete, Z.; Csernai, M.; Kocsis, K.; Horváth, Á. C.; Pongrácz, A.; Barthó, P.

2017-06-01

Objective. Temperature is an important factor for neural function both in normal and pathological states, nevertheless, simultaneous monitoring of local brain temperature and neuronal activity has not yet been undertaken. Approach. In our work, we propose an implantable, calibrated multimodal biosensor that facilitates the complex investigation of thermal changes in both cortical and deep brain regions, which records multiunit activity of neuronal populations in mice. The fabricated neural probe contains four electrical recording sites and a platinum temperature sensor filament integrated on the same probe shaft within a distance of 30 µm from the closest recording site. The feasibility of the simultaneous functionality is presented in in vivo studies. The probe was tested in the thalamus of anesthetized mice while manipulating the core temperature of the animals. Main results. We obtained multiunit and local field recordings along with measurement of local brain temperature with accuracy of 0.14 °C. Brain temperature generally followed core body temperature, but also showed superimposed fluctuations corresponding to epochs of increased local neural activity. With the application of higher currents, we increased the local temperature by several degrees without observable tissue damage between 34-39 °C. Significance. The proposed multifunctional tool is envisioned to broaden our knowledge on the role of the thermal modulation of neuronal activity in both cortical and deeper brain regions.

Bilingualism tunes the anterior cingulate cortex for conflict monitoring.

PubMed

Abutalebi, Jubin; Della Rosa, Pasquale Anthony; Green, David W; Hernandez, Mireia; Scifo, Paola; Keim, Roland; Cappa, Stefano F; Costa, Albert

2012-09-01

Monitoring and controlling 2 language systems is fundamental to language use in bilinguals. Here, we reveal in a combined functional (event-related functional magnetic resonance imaging) and structural neuroimaging (voxel-based morphometry) study that dorsal anterior cingulate cortex (ACC), a structure tightly bound to domain-general executive control functions, is a common locus for language control and resolving nonverbal conflict. We also show an experience-dependent effect in the same region: Bilinguals use this structure more efficiently than monolinguals to monitor nonlinguistic cognitive conflicts. They adapted better to conflicting situations showing less ACC activity while outperforming monolinguals. Importantly, for bilinguals, brain activity in the ACC, as well as behavioral measures, also correlated positively with local gray matter volume. These results suggest that early learning and lifelong practice of 2 languages exert a strong impact upon human neocortical development. The bilingual brain adapts better to resolve cognitive conflicts in domain-general cognitive tasks.

Functional network architecture predicts psychologically mediated analgesia related to treatment in chronic knee pain patients.

PubMed

Hashmi, Javeria Ali; Kong, Jian; Spaeth, Rosa; Khan, Sheraz; Kaptchuk, Ted J; Gollub, Randy L

2014-03-12

Placebo analgesia is an indicator of how efficiently the brain translates psychological signals conveyed by a treatment procedure into pain relief. It has been demonstrated that functional connectivity between distributed brain regions predicts placebo analgesia in chronic back pain patients. Greater network efficiency in baseline brain networks may allow better information transfer and facilitate adaptive physiological responses to psychological aspects of treatment. Here, we theorized that topological network alignments in resting state scans predict psychologically conditioned analgesic responses to acupuncture treatment in chronic knee osteoarthritis pain patients (n = 45). Analgesia was induced by building positive expectations toward acupuncture treatment with verbal suggestion and heat pain conditioning on a test site of the arm. This procedure induced significantly more analgesia after sham or real acupuncture on the test site than in a control site. The psychologically conditioned analgesia was invariant to sham versus real treatment. Efficiency of information transfer within local networks calculated with graph-theoretic measures (local efficiency and clustering coefficients) significantly predicted conditioned analgesia. Clustering coefficients in regions associated with memory, motivation, and pain modulation were closely involved in predicting analgesia. Moreover, women showed higher clustering coefficients and marginally greater pain reduction than men. Overall, analgesic response to placebo cues can be predicted from a priori resting state data by observing local network topology. Such low-cost synchronizations may represent preparatory resources that facilitate subsequent performance of brain circuits in responding to adaptive environmental cues. This suggests a potential utility of network measures in predicting placebo response for clinical use.

Blood-Brain Barrier Breakdown Following Traumatic Brain Injury: A Possible Role in Posttraumatic Epilepsy

PubMed Central

Tomkins, Oren; Feintuch, Akiva; Benifla, Moni; Cohen, Avi; Friedman, Alon; Shelef, Ilan

2011-01-01

Recent animal experiments indicate a critical role for opening of the blood-brain barrier (BBB) in the pathogenesis of post-traumatic epilepsy (PTE). This study aimed to investigate the frequency, extent, and functional correlates of BBB disruption in epileptic patients following mild traumatic brain injury (TBI). Thirty-seven TBI patients were included in this study, 19 of whom suffered from PTE. All underwent electroencephalographic (EEG) recordings and brain magnetic resonance imaging (bMRI). bMRIs were evaluated for BBB disruption using novel quantitative techniques. Cortical dysfunction was localized using standardized low-resolution brain electromagnetic tomography (sLORETA). TBI patients displayed significant EEG slowing compared to controls with no significant differences between PTE and nonepileptic patients. BBB disruption was found in 82.4% of PTE compared to 25% of non-epileptic patients (P = .001) and could be observed even years following the trauma. The volume of cerebral cortex with BBB disruption was significantly larger in PTE patients (P = .001). Slow wave EEG activity was localized to the same region of BBB disruption in 70% of patients and correlated to the volume of BBB disrupted cortex. We finally present a patient suffering from early cortical dysfunction and BBB breakdown with a gradual and parallel resolution of both pathologies. Our findings demonstrate that BBB pathology is frequently found following mild TBI. Lasting BBB breakdown is found with increased frequency and extent in PTE patients. Based on recent animal studies and the colocalization found between the region of disrupted BBB and abnormal EEG activity, we suggest a role for a vascular lesion in the pathogenesis of PTE. PMID:21436875

Intraflagellar transport protein 122 antagonizes Sonic Hedgehog signaling and controls ciliary localization of pathway components.

PubMed

Qin, Jian; Lin, Yulian; Norman, Ryan X; Ko, Hyuk W; Eggenschwiler, Jonathan T

2011-01-25

Primary cilia are required for proper Sonic Hedgehog (Shh) signaling in mammals. However, their role in the signal transduction process remains unclear. We have identified sister of open brain (sopb), a null allele of mouse Intraflagellar transport protein 122 (Ift122). IFT122 negatively regulates the Shh pathway in the cilium at a step downstream of the Shh ligand and the transmembrane protein Smoothened, but upstream of the Gli2 transcription factor. Ift122(sopb) mutants generate primary cilia, but they show features of defective retrograde intraflagellar transport. IFT122 controls the ciliary localization of Shh pathway regulators in different ways. Disruption of IFT122 leads to accumulation of Gli2 and Gli3 at cilia tips while blocking the ciliary localization of the antagonist TULP3. Suppressor of Fused and Smoothened localize to the cilium through an IFT122-independent mechanism. We propose that the balance between positive and negative regulators of the Shh pathway at the cilium tip controls the output of the pathway and that Shh signaling regulates this balance through intraflagellar transport.

Engaging Neuroscience to Advance Translational Research in Brain Barrier Biology

PubMed Central

Neuwelt, Edward A.; Bauer, Björn; Fahlke, Christoph; Fricker, Gert; Iadecola, Constantino; Janigro, Damir; Leybaert, Luc; Molnar, Zoltan; O’Donnell, Martha; Povlishock, John; Saunders, Norman; Sharp, Frank; Stanimirovic, Danica; Watts, Ryan; Drewes, Lester

2012-01-01

Preface The delivery of many potentially therapeutic and diagnostic compounds to specific areas of the brain is restricted by brain barriers, the most well known of which are the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier. Recent studies have shown numerous additional roles of these barriers, including an involvement in neurodevelopment, control of cerebral blood flow, and, when barrier integrity is impaired, a contribution to the pathology of many common CNS disorders such as Alzheimer’s disease, Parkinson’s disease and stroke. Thus, many key areas of neuroscientific investigation are shared with the ‘brain barriers sciences’. However, despite this overlap there has been little crosstalk. This lack of crosstalk is of more than academic interest as our emerging understanding of the neurovascular unit (NVU), composed of local neuronal circuits, glia, pericytes and the endothelium, illustrates how the brain dynamically modulates its blood flow, metabolism, and electrophysiological regulation. A key insight is that the barriers are an essential part of the NVU and as such are influenced by all cellular elements of this unit. PMID:21331083

Histamine Induces Alzheimer's Disease-Like Blood Brain Barrier Breach and Local Cellular Responses in Mouse Brain Organotypic Cultures

PubMed Central

Sedeyn, Jonathan C.; Wu, Hao; Hobbs, Reilly D.; Levin, Eli C.; Nagele, Robert G.; Venkataraman, Venkat

2015-01-01

Among the top ten causes of death in the United States, Alzheimer's disease (AD) is the only one that cannot be cured, prevented, or even slowed down at present. Significant efforts have been exerted in generating model systems to delineate the mechanism as well as establishing platforms for drug screening. In this study, a promising candidate model utilizing primary mouse brain organotypic (MBO) cultures is reported. For the first time, we have demonstrated that the MBO cultures exhibit increased blood brain barrier (BBB) permeability as shown by IgG leakage into the brain parenchyma, astrocyte activation as evidenced by increased expression of glial fibrillary acidic protein (GFAP), and neuronal damage-response as suggested by increased vimentin-positive neurons occur upon histamine treatment. Identical responses—a breakdown of the BBB, astrocyte activation, and neuronal expression of vimentin—were then demonstrated in brains from AD patients compared to age-matched controls, consistent with other reports. Thus, the histamine-treated MBO culture system may provide a valuable tool in combating AD. PMID:26697497

A Wireless 32-Channel Implantable Bidirectional Brain Machine Interface

PubMed Central

Su, Yi; Routhu, Sudhamayee; Moon, Kee S.; Lee, Sung Q.; Youm, WooSub; Ozturk, Yusuf

2016-01-01

All neural information systems (NIS) rely on sensing neural activity to supply commands and control signals for computers, machines and a variety of prosthetic devices. Invasive systems achieve a high signal-to-noise ratio (SNR) by eliminating the volume conduction problems caused by tissue and bone. An implantable brain machine interface (BMI) using intracortical electrodes provides excellent detection of a broad range of frequency oscillatory activities through the placement of a sensor in direct contact with cortex. This paper introduces a compact-sized implantable wireless 32-channel bidirectional brain machine interface (BBMI) to be used with freely-moving primates. The system is designed to monitor brain sensorimotor rhythms and present current stimuli with a configurable duration, frequency and amplitude in real time to the brain based on the brain activity report. The battery is charged via a novel ultrasonic wireless power delivery module developed for efficient delivery of power into a deeply-implanted system. The system was successfully tested through bench tests and in vivo tests on a behaving primate to record the local field potential (LFP) oscillation and stimulate the target area at the same time. PMID:27669264

BDNF and its pro-peptide are stored in presynaptic dense core vesicles in brain neurons

PubMed Central

Dieni, Sandra; Matsumoto, Tomoya; Dekkers, Martijn; Rauskolb, Stefanie; Ionescu, Mihai S.; Deogracias, Ruben; Gundelfinger, Eckart D.; Kojima, Masami; Nestel, Sigrun; Frotscher, Michael

2012-01-01

Although brain-derived neurotrophic factor (BDNF) regulates numerous and complex biological processes including memory retention, its extremely low levels in the mature central nervous system have greatly complicated attempts to reliably localize it. Using rigorous specificity controls, we found that antibodies reacting either with BDNF or its pro-peptide both stained large dense core vesicles in excitatory presynaptic terminals of the adult mouse hippocampus. Both moieties were ∼10-fold more abundant than pro-BDNF. The lack of postsynaptic localization was confirmed in Bassoon mutants, a seizure-prone mouse line exhibiting markedly elevated levels of BDNF. These findings challenge previous conclusions based on work with cultured neurons, which suggested activity-dependent dendritic synthesis and release of BDNF. They instead provide an ultrastructural basis for an anterograde mode of action of BDNF, contrasting with the long-established retrograde model derived from experiments with nerve growth factor in the peripheral nervous system. PMID:22412021

Differential effects of deep brain stimulation on verbal fluency.

PubMed

Ehlen, Felicitas; Schoenecker, Thomas; Kühn, Andrea A; Klostermann, Fabian

2014-07-01

We aimed at gaining insights into principles of subcortical lexical processing. Therefore, effects of deep brain stimulation (DBS) in different target structures on verbal fluency (VF) were tested. VF was assessed with active vs. inactivated DBS in 13 and 14 patients with DBS in the vicinity of the thalamic ventral intermediate nucleus (VIM) and, respectively, of the subthalamic nucleus (STN). Results were correlated to electrode localizations in postoperative MRI, and compared to those of 12 age-matched healthy controls. Patients' VF performance was generally below normal. However, while activation of DBS in the vicinity of VIM provoked marked VF decline, it induced subtle phonemic VF enhancement in the vicinity of STN. The effects correlated with electrode localizations in left hemispheric stimulation sites. The results show distinct dependencies of VF on DBS in the vicinity of VIM vs. STN. Particular risks for deterioration occur in patients with relatively ventromedial thalamic electrodes. Copyright © 2014 Elsevier Inc. All rights reserved.

Radiosurgery with flattening-filter-free techniques in the treatment of brain metastases : Plan comparison and early clinical evaluation.

PubMed

Rieber, J; Tonndorf-Martini, E; Schramm, O; Rhein, B; Stefanowicz, S; Kappes, J; Hoffmann, H; Lindel, K; Debus, J; Rieken, S

2016-11-01

Radiosurgical treatment of brain metastases is well established in daily clinical routine. Utilization of flattening-filter-free beams (FFF) may allow for more rapid delivery of treatment doses and improve clinical comfort. Hence, we compared plan quality and efficiency of radiosurgery in FFF mode to FF techniques. Between November 2014 and June 2015, 21 consecutive patients with 25 brain metastases were treated with stereotactic radiosurgery (SRS) in FFF mode. Brain metastases received dose-fractionation schedules of 1 × 20 Gy or 1 × 18 Gy, delivered to the conformally enclosing 80 % isodose. Three patients with critically localized or large (>3 cm) brain metastases were treated with 6 × 5 Gy. Plan quality and efficiency were evaluated by analyzing conformity, dose gradients, dose to healthy brain tissue, treatment delivery time, and number of monitor units. FFF plans were compared to those using the FF method, and early clinical outcome and toxicity were assessed. FFF mode resulted in significant reductions in beam-on time (p < 0.001) and mean brain dose (p = 0.001) relative to FF-mode comparison plans. Furthermore, significant improvements in dose gradients and sharper dose falloffs were found for SRS in FFF mode (-1.1 %, -29.6 %; p ≤ 0.003), but conformity was slightly superior in SRS in FF mode (-1.3 %; p = 0.001). With a median follow-up time of 5.1 months, 6‑month overall survival was 63.3 %. Local control was observed in 24 of 25 brain metastases (96 %). SRS in FFF mode is time efficient and provides similar plan quality with the opportunity of slightly reduced dose exposure to healthy brain tissue when compared to SRS in FF mode. Clinical outcomes appear promising and show only modest treatment-related toxicity.

A New Treatment Paradigm: Neoadjuvant Radiosurgery Before Surgical Resection of Brain Metastases With Analysis of Local Tumor Recurrence

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

Asher, Anthony L., E-mail: asher@cnsa.com; Carolina Neurosurgery and Spine Associates, Charlotte, North Carolina; Burri, Stuart H.

Purpose: Resected brain metastases (BM) require radiation therapy to reduce local recurrence. Whole brain radiation therapy (WBRT) reduces recurrence, but with potential toxicity. Postoperative stereotactic radiosurgery (SRS) is a strategy without prospective data and problematic target delineation. SRS delivered in the preoperative setting (neoadjuvant, or NaSRS) allows clear target definition and reduction of intraoperative dissemination of tumor cells. Methods and Materials: Our treatment of resectable BM with NaSRS was begun in 2005. Subsequently, a prospective trial of NaSRS was undertaken. A total of 47 consecutively treated patients (23 database and 24 prospective trial) with a total of 51 lesions weremore » reviewed. No statistical difference was observed between the 2 cohorts, and they were combined for analysis. The median follow-up time was 12 months (range, 1-58 months), and the median age was 57. A median of 1 day elapsed between NaSRS and resection. The median diameter of lesions was 3.04 cm (range, 1.34-5.21 cm), and the median volume was 8.49 cc (range, 0.89-46.7 cc). A dose reduction strategy was used, with a median dose of 14 Gy (range, 11.6-18 Gy) prescribed to 80% isodose. Results: Kaplan-Meier overall survival was 77.8% and 60.0% at 6 and 12 months. Kaplan-Meier local control was 97.8%, 85.6%, and 71.8% at 6, 12, and 24 months, respectively. Five of 8 failures were proved pathologically without radiation necrosis. There were no perioperative adverse events. Ultimately, 14.8% of the patients were treated with WBRT. Local failure was more likely with lesions >10 cc (P=.01), >3.4 cm (P=.014), with a trend in surface lesions (P=.066) and eloquent areas (P=.052). Six of the 8 failures had an obvious dural attachment or proximity to draining veins. Conclusions: NaSRS can be performed safely and effectively with excellent results without documented radiation necrosis. Local control was excellent even in the setting of large (>3 cm) lesions. The strong majority of patients were able to avoid WBRT. NaSRS merits consideration in a multi-institution trial.« less

A new treatment paradigm: neoadjuvant radiosurgery before surgical resection of brain metastases with analysis of local tumor recurrence.

PubMed

Asher, Anthony L; Burri, Stuart H; Wiggins, Walter F; Kelly, Renee P; Boltes, Margaret O; Mehrlich, Melissa; Norton, H James; Fraser, Robert W

2014-03-15

Resected brain metastases (BM) require radiation therapy to reduce local recurrence. Whole brain radiation therapy (WBRT) reduces recurrence, but with potential toxicity. Postoperative stereotactic radiosurgery (SRS) is a strategy without prospective data and problematic target delineation. SRS delivered in the preoperative setting (neoadjuvant, or NaSRS) allows clear target definition and reduction of intraoperative dissemination of tumor cells. Our treatment of resectable BM with NaSRS was begun in 2005. Subsequently, a prospective trial of NaSRS was undertaken. A total of 47 consecutively treated patients (23 database and 24 prospective trial) with a total of 51 lesions were reviewed. No statistical difference was observed between the 2 cohorts, and they were combined for analysis. The median follow-up time was 12 months (range, 1-58 months), and the median age was 57. A median of 1 day elapsed between NaSRS and resection. The median diameter of lesions was 3.04 cm (range, 1.34-5.21 cm), and the median volume was 8.49 cc (range, 0.89-46.7 cc). A dose reduction strategy was used, with a median dose of 14 Gy (range, 11.6-18 Gy) prescribed to 80% isodose. Kaplan-Meier overall survival was 77.8% and 60.0% at 6 and 12 months. Kaplan-Meier local control was 97.8%, 85.6%, and 71.8% at 6, 12, and 24 months, respectively. Five of 8 failures were proved pathologically without radiation necrosis. There were no perioperative adverse events. Ultimately, 14.8% of the patients were treated with WBRT. Local failure was more likely with lesions >10 cc (P=.01), >3.4 cm (P=.014), with a trend in surface lesions (P=.066) and eloquent areas (P=.052). Six of the 8 failures had an obvious dural attachment or proximity to draining veins. NaSRS can be performed safely and effectively with excellent results without documented radiation necrosis. Local control was excellent even in the setting of large (>3 cm) lesions. The strong majority of patients were able to avoid WBRT. NaSRS merits consideration in a multi-institution trial. Copyright © 2014 Elsevier Inc. All rights reserved.

A trade-off between local and distributed information processing associated with remote episodic versus semantic memory.

PubMed

Heisz, Jennifer J; Vakorin, Vasily; Ross, Bernhard; Levine, Brian; McIntosh, Anthony R

2014-01-01

Episodic memory and semantic memory produce very different subjective experiences yet rely on overlapping networks of brain regions for processing. Traditional approaches for characterizing functional brain networks emphasize static states of function and thus are blind to the dynamic information processing within and across brain regions. This study used information theoretic measures of entropy to quantify changes in the complexity of the brain's response as measured by magnetoencephalography while participants listened to audio recordings describing past personal episodic and general semantic events. Personal episodic recordings evoked richer subjective mnemonic experiences and more complex brain responses than general semantic recordings. Critically, we observed a trade-off between the relative contribution of local versus distributed entropy, such that personal episodic recordings produced relatively more local entropy whereas general semantic recordings produced relatively more distributed entropy. Changes in the relative contributions of local and distributed entropy to the total complexity of the system provides a potential mechanism that allows the same network of brain regions to represent cognitive information as either specific episodes or more general semantic knowledge.

Development of drug-loaded polymer microcapsules for treatment of epilepsy.

PubMed

Chen, Yu; Gu, Qi; Yue, Zhilian; Crook, Jeremy M; Moulton, Simon E; Cook, Mark J; Wallace, Gordon G

2017-09-26

Despite significant progress in developing new drugs for seizure control, epilepsy still affects 1% of the global population and is drug-resistant in more than 30% of cases. To improve the therapeutic efficacy of epilepsy medication, a promising approach is to deliver anti-epilepsy drugs directly to affected brain areas using local drug delivery systems. The drug delivery systems must meet a number of criteria, including high drug loading efficiency, biodegradability, neuro-cytocompatibility and predictable drug release profiles. Here we report the development of fibre- and sphere-based microcapsules that exhibit controllable uniform morphologies and drug release profiles as predicted by mathematical modelling. Importantly, both forms of fabricated microcapsules are compatible with human brain derived neural stem cells and differentiated neurons and neuroglia, indicating clinical compliance for neural implantation and therapeutic drug delivery.

[The Dual Nature of the Electrical Signals of the Brain (Electrical and Electrochemical) Which Were Recorded With the Help Polarizable Electrodes From Inert Metals].

PubMed

Dubinin, A G; Reutov, V P; Svinov, M M; Troshin, G I; Shvets-Teneta-Gurii, T B

2015-01-01

In the modern neurophysiology opinion was confirmed that the electrical signals of the brain in the frequency band from DC to electroencephalogram recorded with metallic conductors of inert metal implanted in the brain are formed solely by changes in the electric field of the brain. This paper presents a review of the literature and our own data, according to which the formation of these signals involves two factors. One factor is a change in the charge of the electric double layer electrode having a capacitor property and change the value of its charge with changes in the electric field volume conductor--the brain. Another factor is an electrochemical signal is defined by local changes in the redox potential (E) neuronal-glial populations surrounding the electrode. The paper provides an overviews the electrical and electrochemical properties of the electrodes of the inert metals used in electrophysiology. It is shown that each of these factors has the characteristic parameters over time and amplitude. The data of own studies of local changes in E cortex accompanying brain's response to the implantation of electrodes in the brain's cortex, the natural behavior of animals in the wake-sleep, integrative brain function and effect of pharmacological agents. These results give evidence of the highly informative study of local changes in brain E in order to study energy metabolism in the brain of waking animals, and lay the foundation for the study of local changes in brain energy metabolism in free animal behavior.

Enhanced-locality fiber-optic two-photon-fluorescence live-brain interrogation

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

Fedotov, I. V.; Doronina-Amitonova, L. V.; Russian Quantum Center, ul. Novaya 100, Skolkovo, Moscow Region 1430125

2014-02-24

Two-photon excitation is shown to substantially enhance the locality of fiber-based optical interrogation of strongly scattering biotissues. In our experiments, a high-numerical-aperture, large-core-are fiber probe is used to deliver the 200-fs output of a 100-MHz mode-locked ytterbium fiber laser to samples of live mouse brain, induce two-photon fluorescence of nitrogen–vacancy centers in diamond markers in brain sample. Fiber probes with a high numerical aperture and a large core area are shown to enable locality enhancement in fiber-laser–fiber-probe two-photon brain excitation and interrogation without sacrificing the efficiency of fluorescence response collection.

Reconstruction of human brain spontaneous activity based on frequency-pattern analysis of magnetoencephalography data

PubMed Central

Llinás, Rodolfo R.; Ustinin, Mikhail N.; Rykunov, Stanislav D.; Boyko, Anna I.; Sychev, Vyacheslav V.; Walton, Kerry D.; Rabello, Guilherme M.; Garcia, John

2015-01-01

A new method for the analysis and localization of brain activity has been developed, based on multichannel magnetic field recordings, over minutes, superimposed on the MRI of the individual. Here, a high resolution Fourier Transform is obtained over the entire recording period, leading to a detailed multi-frequency spectrum. Further analysis implements a total decomposition of the frequency components into functionally invariant entities, each having an invariant field pattern localizable in recording space. The method, addressed as functional tomography, makes it possible to find the distribution of magnetic field sources in space. Here, the method is applied to the analysis of simulated data, to oscillating signals activating a physical current dipoles phantom, and to recordings of spontaneous brain activity in 10 healthy adults. In the analysis of simulated data, 61 dipoles are localized with 0.7 mm precision. Concerning the physical phantom the method is able to localize three simultaneously activated current dipoles with 1 mm precision. Spatial resolution 3 mm was attained when localizing spontaneous alpha rhythm activity in 10 healthy adults, where the alpha peak was specified for each subject individually. Co-registration of the functional tomograms with each subject's head MRI localized alpha range activity to the occipital and/or posterior parietal brain region. This is the first application of this new functional tomography to human brain activity. The method successfully provides an overall view of brain electrical activity, a detailed spectral description and, combined with MRI, the localization of sources in anatomical brain space. PMID:26528119

Task-Dependent Changes in Cross-Level Coupling between Single Neurons and Oscillatory Activity in Multiscale Networks

PubMed Central

Canolty, Ryan T.; Ganguly, Karunesh; Carmena, Jose M.

2012-01-01

Understanding the principles governing the dynamic coordination of functional brain networks remains an important unmet goal within neuroscience. How do distributed ensembles of neurons transiently coordinate their activity across a variety of spatial and temporal scales? While a complete mechanistic account of this process remains elusive, evidence suggests that neuronal oscillations may play a key role in this process, with different rhythms influencing both local computation and long-range communication. To investigate this question, we recorded multiple single unit and local field potential (LFP) activity from microelectrode arrays implanted bilaterally in macaque motor areas. Monkeys performed a delayed center-out reach task either manually using their natural arm (Manual Control, MC) or under direct neural control through a brain-machine interface (Brain Control, BC). In accord with prior work, we found that the spiking activity of individual neurons is coupled to multiple aspects of the ongoing motor beta rhythm (10–45 Hz) during both MC and BC, with neurons exhibiting a diversity of coupling preferences. However, here we show that for identified single neurons, this beta-to-rate mapping can change in a reversible and task-dependent way. For example, as beta power increases, a given neuron may increase spiking during MC but decrease spiking during BC, or exhibit a reversible shift in the preferred phase of firing. The within-task stability of coupling, combined with the reversible cross-task changes in coupling, suggest that task-dependent changes in the beta-to-rate mapping play a role in the transient functional reorganization of neural ensembles. We characterize the range of task-dependent changes in the mapping from beta amplitude, phase, and inter-hemispheric phase differences to the spike rates of an ensemble of simultaneously-recorded neurons, and discuss the potential implications that dynamic remapping from oscillatory activity to spike rate and timing may hold for models of computation and communication in distributed functional brain networks. PMID:23284276

Brain network connectivity in individuals with schizophrenia and their siblings.

PubMed

Repovs, Grega; Csernansky, John G; Barch, Deanna M

2011-05-15

Research on brain activity in schizophrenia has shown that changes in the function of any single region cannot explain the range of cognitive and affective impairments in this illness. Rather, neural circuits that support sensory, cognitive, and emotional processes are now being investigated as substrates for cognitive and affective impairments in schizophrenia, a shift in focus consistent with long-standing hypotheses about schizophrenia as a disconnection syndrome. Our goal was to further examine alterations in functional connectivity within and between the default mode network and three cognitive control networks (frontal-parietal, cingulo-opercular, and cerebellar) as a basis for such impairments. Resting state functional magnetic resonance imaging was collected from 40 individuals with DSM-IV-TR schizophrenia, 31 siblings of individuals with schizophrenia, 15 healthy control subjects, and 18 siblings of healthy control subjects while they rested quietly with their eyes closed. Connectivity metrics were compared between patients and control subjects for both within- and between-network connections and were used to predict clinical symptoms and cognitive function. Individuals with schizophrenia showed reduced distal and somewhat enhanced local connectivity between the cognitive control networks compared with control subjects. Additionally, greater connectivity between the frontal-parietal and cerebellar regions was robustly predictive of better cognitive performance across groups and predictive of fewer disorganization symptoms among patients. These results are consistent with the hypothesis that impairments of executive function and cognitive control result from disruption in the coordination of activity across brain networks and additionally suggest that these might reflect impairments in normal pattern of brain connectivity development. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Stereotactic Radiosurgery in the Management of Limited (1-4) Brain Metasteses: Systematic Review and International Stereotactic Radiosurgery Society Practice Guideline.

PubMed

Chao, Samuel T; De Salles, Antonio; Hayashi, Motohiro; Levivier, Marc; Ma, Lijun; Martinez, Roberto; Paddick, Ian; Régis, Jean; Ryu, Samuel; Slotman, Ben J; Sahgal, Arjun

2017-11-03

Guidelines regarding stereotactic radiosurgery (SRS) for brain metastases are missing recently published evidence. To conduct a systematic review and provide an objective summary of publications regarding SRS in managing patients with 1 to 4 brain metastases. Using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was conducted using PubMed and Medline up to November 2016. A separate search was conducted for SRS for larger brain metastases. Twenty-seven prospective studies, critical reviews, meta-analyses, and published consensus guidelines were reviewed. Four key points came from these studies. First, there is no detriment to survival by withholding whole brain radiation (WBRT) in the upfront management of brain metastases with SRS. Second, while SRS on its own provides a high rate of local control (LC), WBRT may provide further increase in LC. Next, WBRT does provide distant brain control with less need for salvage therapy. Finally, the addition of WBRT does affect neurocognitive function and quality of life more than SRS alone. For larger brain metastases, surgical resection should be considered, especially when factoring lower LC with single-session radiosurgery. There is emerging data showing good LC and/or decreased toxicity with multisession radiosurgery. A number of well-conducted prospective and meta-analyses studies demonstrate good LC, without compromising survival, using SRS alone for patients with a limited number of brain metastases. Some also demonstrated less impact on neurocognitive function with SRS alone. Practice guidelines were developed using these data with International Stereotactic Radiosurgery Society consensus. Copyright © 2017 by the Congress of Neurological Surgeons

Localization of HIV-1 co-receptors CCR5 and CXCR4 in the brain of children with AIDS.

PubMed Central

Vallat, A. V.; De Girolami, U.; He, J.; Mhashilkar, A.; Marasco, W.; Shi, B.; Gray, F.; Bell, J.; Keohane, C.; Smith, T. W.; Gabuzda, D.

1998-01-01

The chemokine receptors CCR5 and CXCR4 are co-receptors together with CD4 for human immunodeficiency virus (HIV)-1 entry into target cells. Macrophage-tropic HIV-1 viruses use CCR5 as a co-receptor, whereas T-cell-line tropic viruses use CXCR4. HIV-1 infects the brain and causes a progressive encephalopathy in 20 to 30% of infected children and adults. Most of the HIV-1-infected cells in the brain are macrophages and microglia. We examined expression of CCR5 and CXCR4 in brain tissue from 20 pediatric acquired immune deficiency syndrome (AIDS) patients in relation to neuropathological consequences of HIV-1 infection. The overall frequency of CCR5-positive perivascular mononuclear cells and macrophages was increased in the brains of children with severe HIV-1 encephalitis (HIVE) compared with children with mild HIVE or non-AIDS controls, whereas the frequency of CXCR4-positive perivascular cells did not correlate with disease severity. CCR5- and CXCR4-positive macrophages and microglia were detected in inflammatory lesions in the brain of children with severe HIVE. In addition, CXCR4 was detected in a subpopulation of neurons in autopsy brain tissue and primary human brain cultures. Similar findings were demonstrated in the brain of adult AIDS patients and controls. These findings suggest that CCR5-positive mononuclear cells, macrophages, and microglia contribute to disease progression in the central nervous system of children and adults with AIDS by serving as targets for virus replication. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 8 PMID:9422534

Visual processing during recovery from vegetative state to consciousness: comparing behavioral indices to brain responses.

PubMed

Wijnen, V J M; Eilander, H J; de Gelder, B; van Boxtel, G J M

2014-11-01

Auditory stimulation is often used to evoke responses in unresponsive patients who have suffered severe brain injury. In order to investigate visual responses, we examined visual evoked potentials (VEPs) and behavioral responses to visual stimuli in vegetative patients during recovery to consciousness. Behavioral responses to visual stimuli (visual localization, comprehension of written commands, and object manipulation) and flash VEPs were repeatedly examined in eleven vegetative patients every two weeks for an average period of 2.6months, and patients' VEPs were compared to a healthy control group. Long-term outcome of the patients was assessed 2-3years later. Visual response scores increased during recovery to consciousness for all scales: visual localization, comprehension of written commands, and object manipulation. VEP amplitudes were smaller, and latencies were longer in the patient group relative to the controls. VEPs characteristics at first measurement were related to long-term outcome up to three years after injury. Our findings show the improvement of visual responding with recovery from the vegetative state to consciousness. Elementary visual processing is present, yet according to VEP responses, poorer in vegetative and minimally conscious state than in healthy controls, and remains poorer when patients recovered to consciousness. However, initial VEPs are related to long-term outcome. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

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

PubMed

Başar, Erol; Düzgün, Aysel

2016-05-01

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

Food-induced changes of lipids in rat neuronal tissue visualized by ToF-SIMS imaging.

PubMed

Dowlatshahi Pour, Masoumeh; Jennische, Eva; Lange, Stefan; Ewing, Andrew G; Malmberg, Per

2016-09-06

Time of flight secondary ion mass spectrometry (ToF-SIMS) was used to image the lipid localization in brain tissue sections from rats fed specially processed cereals (SPC). An IonTof 5 instrument equipped with a Bi cluster ion gun was used to analyze the tissue sections. Data from 15 brain samples from control and cereal-fed rats were recorded and exported to principal components analysis (PCA). The data clearly show changes of certain lipids in the brain following cereal feeding. PCA score plots show a good separation in lipid distribution between the control and the SPC-fed group. The loadings plot reveal that the groups separated mainly due to changes in cholesterol, vitamin E and c18:2, c16:0 fatty acid distribution as well as some short chain monocarboxylic fatty acid compositions. These insights relate to the working mechanism of SPC as a dietary supplement. SPC is thought to activate antisecretory factor (AF), an endogenous protein with regulatory function for inflammation and fluid secretion. These data provide insights into lipid content in brain following SPC feeding and suggest a relation to activating AF.

Localization and regulation of PML bodies in the adult mouse brain.

PubMed

Hall, Małgorzata H; Magalska, Adriana; Malinowska, Monika; Ruszczycki, Błażej; Czaban, Iwona; Patel, Satyam; Ambrożek-Latecka, Magdalena; Zołocińska, Ewa; Broszkiewicz, Hanna; Parobczak, Kamil; Nair, Rajeevkumar R; Rylski, Marcin; Pawlak, Robert; Bramham, Clive R; Wilczyński, Grzegorz M

2016-06-01

PML is a tumor suppressor protein involved in the pathogenesis of promyelocytic leukemia. In non-neuronal cells, PML is a principal component of characteristic nuclear bodies. In the brain, PML has been implicated in the control of embryonic neurogenesis, and in certain physiological and pathological phenomena in the adult brain. Yet, the cellular and subcellular localization of the PML protein in the brain, including its presence in the nuclear bodies, has not been investigated comprehensively. Because the formation of PML bodies appears to be a key aspect in the function of the PML protein, we investigated the presence of these structures and their anatomical distribution, throughout the adult mouse brain. We found that PML is broadly expressed across the gray matter, with the highest levels in the cerebral and cerebellar cortices. In the cerebral cortex PML is present exclusively in neurons, in which it forms well-defined nuclear inclusions containing SUMO-1, SUMO 2/3, but not Daxx. At the ultrastructural level, the appearance of neuronal PML bodies differs from the classic one, i.e., the solitary structure with more or less distinctive capsule. Rather, neuronal PML bodies have the form of small PML protein aggregates located in the close vicinity of chromatin threads. The number, size, and signal intensity of neuronal PML bodies are dynamically influenced by immobilization stress and seizures. Our study indicates that PML bodies are broadly involved in activity-dependent nuclear phenomena in adult neurons.

Electroencephalographic inverse localization of brain activity in acute traumatic brain injury as a guide to surgery, monitoring and treatment

PubMed Central

Irimia, Andrei; Goh, S.-Y. Matthew; Torgerson, Carinna M.; Stein, Nathan R.; Chambers, Micah C.; Vespa, Paul M.; Van Horn, John D.

2013-01-01

Objective To inverse-localize epileptiform cortical electrical activity recorded from severe traumatic brain injury (TBI) patients using electroencephalography (EEG). Methods Three acute TBI cases were imaged using computed tomography (CT) and multimodal magnetic resonance imaging (MRI). Semi-automatic segmentation was performed to partition the complete TBI head into 25 distinct tissue types, including 6 tissue types accounting for pathology. Segmentations were employed to generate a finite element method model of the head, and EEG activity generators were modeled as dipolar currents distributed over the cortical surface. Results We demonstrate anatomically faithful localization of EEG generators responsible for epileptiform discharges in severe TBI. By accounting for injury-related tissue conductivity changes, our work offers the most realistic implementation currently available for the inverse estimation of cortical activity in TBI. Conclusion Whereas standard localization techniques are available for electrical activity mapping in uninjured brains, they are rarely applied to acute TBI. Modern models of TBI-induced pathology can inform the localization of epileptogenic foci, improve surgical efficacy, contribute to the improvement of critical care monitoring and provide guidance for patient-tailored treatment. With approaches such as this, neurosurgeons and neurologists can study brain activity in acute TBI and obtain insights regarding injury effects upon brain metabolism and clinical outcome. PMID:24011495

Electroencephalographic inverse localization of brain activity in acute traumatic brain injury as a guide to surgery, monitoring and treatment.

PubMed

Irimia, Andrei; Goh, S-Y Matthew; Torgerson, Carinna M; Stein, Nathan R; Chambers, Micah C; Vespa, Paul M; Van Horn, John D

2013-10-01

To inverse-localize epileptiform cortical electrical activity recorded from severe traumatic brain injury (TBI) patients using electroencephalography (EEG). Three acute TBI cases were imaged using computed tomography (CT) and multimodal magnetic resonance imaging (MRI). Semi-automatic segmentation was performed to partition the complete TBI head into 25 distinct tissue types, including 6 tissue types accounting for pathology. Segmentations were employed to generate a finite element method model of the head, and EEG activity generators were modeled as dipolar currents distributed over the cortical surface. We demonstrate anatomically faithful localization of EEG generators responsible for epileptiform discharges in severe TBI. By accounting for injury-related tissue conductivity changes, our work offers the most realistic implementation currently available for the inverse estimation of cortical activity in TBI. Whereas standard localization techniques are available for electrical activity mapping in uninjured brains, they are rarely applied to acute TBI. Modern models of TBI-induced pathology can inform the localization of epileptogenic foci, improve surgical efficacy, contribute to the improvement of critical care monitoring and provide guidance for patient-tailored treatment. With approaches such as this, neurosurgeons and neurologists can study brain activity in acute TBI and obtain insights regarding injury effects upon brain metabolism and clinical outcome. Published by Elsevier B.V.

Rapid and efficient gene delivery into the adult mouse brain via focal electroporation

PubMed Central

Nomura, Tadashi; Nishimura, Yusuke; Gotoh, Hitoshi; Ono, Katsuhiko

2016-01-01

In vivo gene delivery is required for studying the cellular and molecular mechanisms of various biological events. Virus-mediated gene transfer or generation of transgenic animals is widely used; however, these methods are time-consuming and expensive. Here we show an improved electroporation technique for acute gene delivery into the adult mouse brain. Using a syringe-based microelectrode, local DNA injection and the application of electric current can be performed simultaneously; this allows rapid and efficient gene transduction of adult non-neuronal cells. Combining this technique with various expression vectors that carry specific promoters resulted in targeted gene expression in astrocytic cells. Our results constitute a powerful strategy for the genetic manipulation of adult brains in a spatio-temporally controlled manner. PMID:27430903

Promising approaches to circumvent the blood-brain barrier: progress, pitfalls and clinical prospects in brain cancer

PubMed Central

Papademetriou, Iason T; Porter, Tyrone

2015-01-01

Brain drug delivery is a major challenge for therapy of central nervous system (CNS) diseases. Biochemical modifications of drugs or drug nanocarriers, methods of local delivery, and blood–brain barrier (BBB) disruption with focused ultrasound and microbubbles are promising approaches which enhance transport or bypass the BBB. These approaches are discussed in the context of brain cancer as an example in CNS drug development. Targeting to receptors enabling transport across the BBB offers noninvasive delivery of small molecule and biological cancer therapeutics. Local delivery methods enable high dose delivery while avoiding systemic exposure. BBB disruption with focused ultrasound and microbubbles offers local and noninvasive treatment. Clinical trials show the prospects of these technologies and point to challenges for the future. PMID:26488496

Promising approaches to circumvent the blood-brain barrier: progress, pitfalls and clinical prospects in brain cancer.

PubMed

Papademetriou, Iason T; Porter, Tyrone

2015-01-01

Brain drug delivery is a major challenge for therapy of central nervous system (CNS) diseases. Biochemical modifications of drugs or drug nanocarriers, methods of local delivery, and blood-brain barrier (BBB) disruption with focused ultrasound and microbubbles are promising approaches which enhance transport or bypass the BBB. These approaches are discussed in the context of brain cancer as an example in CNS drug development. Targeting to receptors enabling transport across the BBB offers noninvasive delivery of small molecule and biological cancer therapeutics. Local delivery methods enable high dose delivery while avoiding systemic exposure. BBB disruption with focused ultrasound and microbubbles offers local and noninvasive treatment. Clinical trials show the prospects of these technologies and point to challenges for the future.

Quantification of changes in language-related brain areas in autism spectrum disorders using large-scale network analysis.

PubMed

Goch, Caspar J; Stieltjes, Bram; Henze, Romy; Hering, Jan; Poustka, Luise; Meinzer, Hans-Peter; Maier-Hein, Klaus H

2014-05-01

Diagnosis of autism spectrum disorders (ASD) is difficult, as symptoms vary greatly and are difficult to quantify objectively. Recent work has focused on the assessment of non-invasive diffusion tensor imaging-based biomarkers that reflect the microstructural characteristics of neuronal pathways in the brain. While tractography-based approaches typically analyze specific structures of interest, a graph-based large-scale network analysis of the connectome can yield comprehensive measures of larger-scale architectural patterns in the brain. Commonly applied global network indices, however, do not provide any specificity with respect to functional areas or anatomical structures. Aim of this work was to assess the concept of network centrality as a tool to perform locally specific analysis without disregarding the global network architecture and compare it to other popular network indices. We create connectome networks from fiber tractographies and parcellations of the human brain and compute global network indices as well as local indices for Wernicke's Area, Broca's Area and the Motor Cortex. Our approach was evaluated on 18 children suffering from ASD and 18 typically developed controls using magnetic resonance imaging-based cortical parcellations in combination with diffusion tensor imaging tractography. We show that the network centrality of Wernicke's area is significantly (p<0.001) reduced in ASD, while the motor cortex, which was used as a control region, did not show significant alterations. This could reflect the reduced capacity for comprehension of language in ASD. The betweenness centrality could potentially be an important metric in the development of future diagnostic tools in the clinical context of ASD diagnosis. Our results further demonstrate the applicability of large-scale network analysis tools in the domain of region-specific analysis with a potential application in many different psychological disorders.

Long-Term Stability of Motor Cortical Activity: Implications for Brain Machine Interfaces and Optimal Feedback Control.

PubMed

Flint, Robert D; Scheid, Michael R; Wright, Zachary A; Solla, Sara A; Slutzky, Marc W

2016-03-23

The human motor system is capable of remarkably precise control of movements--consider the skill of professional baseball pitchers or surgeons. This precise control relies upon stable representations of movements in the brain. Here, we investigated the stability of cortical activity at multiple spatial and temporal scales by recording local field potentials (LFPs) and action potentials (multiunit spikes, MSPs) while two monkeys controlled a cursor either with their hand or directly from the brain using a brain-machine interface. LFPs and some MSPs were remarkably stable over time periods ranging from 3 d to over 3 years; overall, LFPs were significantly more stable than spikes. We then assessed whether the stability of all neural activity, or just a subset of activity, was necessary to achieve stable behavior. We showed that projections of neural activity into the subspace relevant to the task (the "task-relevant space") were significantly more stable than were projections into the task-irrelevant (or "task-null") space. This provides cortical evidence in support of the minimum intervention principle, which proposes that optimal feedback control (OFC) allows the brain to tightly control only activity in the task-relevant space while allowing activity in the task-irrelevant space to vary substantially from trial to trial. We found that the brain appears capable of maintaining stable movement representations for extremely long periods of time, particularly so for neural activity in the task-relevant space, which agrees with OFC predictions. It is unknown whether cortical signals are stable for more than a few weeks. Here, we demonstrate that motor cortical signals can exhibit high stability over several years. This result is particularly important to brain-machine interfaces because it could enable stable performance with infrequent recalibration. Although we can maintain movement accuracy over time, movement components that are unrelated to the goals of a task (such as elbow position during reaching) often vary from trial to trial. This is consistent with the minimum intervention principle of optimal feedback control. We provide evidence that the motor cortex acts according to this principle: cortical activity is more stable in the task-relevant space and more variable in the task-irrelevant space. Copyright © 2016 the authors 0270-6474/16/363623-10$15.00/0.

A method for monitoring of oxygen saturation changes in brain tissue using diffuse reflectance spectroscopy.

PubMed

Rejmstad, Peter; Johansson, Johannes D; Haj-Hosseini, Neda; Wårdell, Karin

2017-03-01

Continuous measurement of local brain oxygen saturation (SO 2 ) can be used to monitor the status of brain trauma patients in the neurocritical care unit. Currently, micro-oxygen-electrodes are considered as the "gold standard" in measuring cerebral oxygen pressure (pO 2 ), which is closely related to SO 2 through the oxygen dissociation curve (ODC) of hemoglobin, but with the drawback of slow in response time. The present study suggests estimation of SO 2 in brain tissue using diffuse reflectance spectroscopy (DRS) for finding an analytical relation between measured spectra and the SO 2 for different blood concentrations. The P 3 diffusion approximation is used to generate a set of spectra simulating brain tissue for various levels of blood concentrations in order to estimate SO 2 . The algorithm is evaluated on optical phantoms mimicking white brain matter (blood volume of 0.5-2%) where pO 2 and temperature is controlled and on clinical data collected during brain surgery. The suggested method is capable of estimating the blood fraction and oxygen saturation changes from the spectroscopic signal and the hemoglobin absorption profile. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A novel PGC-1α isoform in brain localizes to mitochondria and associates with PINK1 and VDAC

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

Choi, Joungil, E-mail: jochoi@som.umaryland.edu; Veterans Affairs Medical Center, Baltimore, MD 21201; Batchu, Vera Venkatanaresh Kumar

2013-06-14

Highlights: •Novel 35 kDa PGC-1α localizes to mitochondrial inner membrane and matrix in brain. •Mitochondrial localization of 35 kDa PGC-1α depends on VDAC protein. •Mitochondrial localization of 35 kDa PGC-1α depends on membrane potential. •The 35 kDa PGC-1α associates and colocalizes with PINK in brain mitochondria. -- Abstract: Peroxisome proliferator-activated receptor-gamma co-activator 1α (PGC-1α) and PTEN-induced putative kinase 1 (PINK1) are powerful regulators of mitochondrial function. Here, we report that a previously unrecognized, novel 35 kDa PGC-1α isoform localizes to the mitochondrial inner membrane and matrix in brain as determined by protease protection and carbonate extraction assays, as well asmore » by immunoelectron microscopy. Immunoelectron microscopy and import experiments in vitro revealed that 35 kDa PGC-1α colocalizes and interacts with the voltage-dependent anion channel (VDAC), and that its import depends on VDAC. Valinomycin treatment which depolarizes the membrane potential, abolished mitochondrial localization of the 35 kDa PGC-1α. Using blue native-PAGE, co-immunoprecipitation, and immunoelectron microscopy analyses, we found that the 35 kDa PGC-1α binds and colocalizes with PINK1 in brain mitochondria. This is the first report regarding mitochondrial localization of a novel 35 kDa PGC-1α isoform and its association with PINK1, suggesting possible regulatory roles for mitochondrial function in the brain.« less

Self-regulation of inter-hemispheric visual cortex balance through real-time fMRI neurofeedback training.

PubMed

Robineau, F; Rieger, S W; Mermoud, C; Pichon, S; Koush, Y; Van De Ville, D; Vuilleumier, P; Scharnowski, F

2014-10-15

Recent advances in neurofeedback based on real-time functional magnetic resonance imaging (fMRI) allow for learning to control spatially localized brain activity in the range of millimeters across the entire brain. Real-time fMRI neurofeedback studies have demonstrated the feasibility of self-regulating activation in specific areas that are involved in a variety of functions, such as perception, motor control, language, and emotional processing. In most of these previous studies, participants trained to control activity within one region of interest (ROI). In the present study, we extended the neurofeedback approach by now training healthy participants to control the interhemispheric balance between their left and right visual cortices. This was accomplished by providing feedback based on the difference in activity between a target visual ROI and the corresponding homologue region in the opposite hemisphere. Eight out of 14 participants learned to control the differential feedback signal over the course of 3 neurofeedback training sessions spread over 3 days, i.e., they produced consistent increases in the visual target ROI relative to the opposite visual cortex. Those who learned to control the differential feedback signal were subsequently also able to exert that control in the absence of neurofeedback. Such learning to voluntarily control the balance between cortical areas of the two hemispheres might offer promising rehabilitation approaches for neurological or psychiatric conditions associated with pathological asymmetries in brain activity patterns, such as hemispatial neglect, dyslexia, or mood disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

Functional Brain Connectome and Its Relation to Hoehn and Yahr Stage in Parkinson Disease.

PubMed

Suo, Xueling; Lei, Du; Li, Nannan; Cheng, Lan; Chen, Fuqin; Wang, Meiyun; Kemp, Graham J; Peng, Rong; Gong, Qiyong

2017-12-01

Purpose To use resting-state functional magnetic resonance (MR) imaging and graph theory approaches to investigate the brain functional connectome and its potential relation to disease severity in Parkinson disease (PD). Materials and Methods This case-control study was approved by the local research ethics committee, and all participants provided informed consent. There were 153 right-handed patients with PD and 81 healthy control participants recruited who were matched for age, sex, and handedness to undergo a 3-T resting-state functional MR examination. The whole-brain functional connectome was constructed by thresholding the Pearson correlation matrices of 90 brain regions, and the topologic properties were analyzed by using graph theory approaches. Nonparametric permutation tests were used to compare topologic properties, and their relationship to disease severity was assessed. Results The functional connectome in PD showed abnormalities at the global level (ie, decrease in clustering coefficient, global efficiency, and local efficiency, and increase in characteristic path length) and at the nodal level (decreased nodal centralities in the sensorimotor cortex, default mode, and temporal-occipital regions; P < .001, false discovery rate corrected). Further, the nodal centralities in left postcentral gyrus and left superior temporal gyrus correlated negatively with Unified Parkinson's Disease Rating Scale III score (P = .038, false discovery rate corrected, r = -0.198; and P = .009, false discovery rate corrected, r = -0.270, respectively) and decreased with increasing Hoehn and Yahr stage in patients with PD. Conclusion The configurations of brain functional connectome in patients with PD were perturbed and correlated with disease severity, notably with those responsible for motor functions. These results provide topologic insights into understanding the neural functional changes in relation to disease severity of PD. © RSNA, 2017 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on September 11, 2017.

The Population Benefit of Radiotherapy for Malignant Brain Tumors: Local Control and Survival Estimates for Guideline-Based Use.

PubMed

Hanna, Timothy Paul; Delaney, Geoffrey Paul; Barton, Michael Bernard

2016-09-01

To estimate the population benefit of radiotherapy (RT) for primary malignant brain tumors if evidence-based guidelines were routinely followed. This study investigated 5-year local control (LC) and 2- and 5-year overall survival (OS) benefits. RT benefit was the absolute proportional benefit of RT alone over no RT for radical indications, and over surgery alone for adjuvant indications. Chemoradiotherapy (CRT) benefit was the absolute incremental benefit of concurrent chemotherapy and RT over RT alone. Decision tree models were adapted to define the incidence of each indication. Citation databases were systematically queried for the highest level of evidence defining indication benefits. Meta-analysis was performed if there were multiple sources of the same evidence level, and deterministic and probabilistic sensitivity analysis was also performed. Among all patients with malignant brain tumors, 82% had indications for curative- or adjuvant-intent RT. The magnitude of benefit was based on level I or II evidence in 44% of all patients. A total of 25 relevant studies were used to quantify indication benefits. All RT benefit included in the model was irreplaceable. For malignant brain tumors, the estimated population benefit for RT alone was 9% for 5-year LC (95% CI, 7%-10%), 9% for 2-year OS (95% CI, 8%-11%), and 5% for 5-year OS (95% CI, 4%-5%). The incremental benefit of CRT was 1% for 5-year LC (95% CI, 0%-2%), 7% for 2-year OS (95% CI, 4%-11%), and 3% for 5-year OS (95% CI, 1%-5%). The model was robust in sensitivity analysis. When optimally used, RT provides an important benefit for many patients with malignant brain tumors. The model provided a robust means for estimating the magnitude of this benefit. Copyright © 2016 by the National Comprehensive Cancer Network.

Neurosteroid hydroxylase CYP7B: vivid reporter activity in dentate gyrus of gene-targeted mice and abolition of a widespread pathway of steroid and oxysterol hydroxylation.

PubMed

Rose, K; Allan, A; Gauldie, S; Stapleton, G; Dobbie, L; Dott, K; Martin, C; Wang, L; Hedlund, E; Seckl, J R; Gustafsson, J A; Lathe, R

2001-06-29

The major adrenal steroid dehydroepiandrosterone (DHEA) enhances memory and immune function but has no known dedicated receptor; local metabolism may govern its activity. We described a cytochrome P450 expressed in brain and other tissues, CYP7B, that catalyzes the 7alpha-hydroxylation of oxysterols and 3beta-hydroxysteroids including DHEA. We report here that CYP7B mRNA and 7alpha-hydroxylation activity are widespread in rat tissues. However, steroids related to DHEA are reported to be modified at positions other than 7alpha, exemplified by prominent 6alpha-hydroxylation of 5alpha-androstane-3beta,17beta-diol (A/anediol) in some rodent tissues including brain. To determine whether CYP7B is responsible for these and other activities we disrupted the mouse Cyp7b gene by targeted insertion of an IRES-lacZ reporter cassette, placing reporter enzyme activity (beta-galactosidase) under Cyp7b promoter control. In heterozygous mouse brain, chromogenic detection of reporter activity was strikingly restricted to the dentate gyrus. Staining did not exactly reproduce the in situ hybridization expression pattern; post-transcriptional control is inferred. Lower level staining was detected in cerebellum, liver, and kidney, and which largely paralleled mRNA distribution. Liver and kidney expression was sexually dimorphic. Mice homozygous for the insertion are viable and superficially normal, but ex vivo metabolism of DHEA to 7alpha-hydroxy-DHEA was abolished in brain, spleen, thymus, heart, lung, prostate, uterus, and mammary gland; lower abundance metabolites were also eliminated. 7alpha-Hydroxylation of 25-hydroxycholesterol and related substrates was also abolished, as was presumed 6alpha-hydroxylation of A/anediol. These different enzyme activities therefore derive from the Cyp7b gene. CYP7B is thus a major extrahepatic steroid and oxysterol hydroxylase and provides the predominant route for local metabolism of DHEA and related molecules in brain and other tissues.

Gadolinium Deposition in Human Brain Tissues after Contrast-enhanced MR Imaging in Adult Patients without Intracranial Abnormalities.

PubMed

McDonald, Robert J; McDonald, Jennifer S; Kallmes, David F; Jentoft, Mark E; Paolini, Michael A; Murray, David L; Williamson, Eric E; Eckel, Laurence J

2017-11-01

Purpose To determine whether gadolinium deposits in neural tissues of patients with intracranial abnormalities following intravenous gadolinium-based contrast agent (GBCA) exposure might be related to blood-brain barrier integrity by studying adult patients with normal brain pathologic characteristics. Materials and Methods After obtaining antemortem consent and institutional review board approval, the authors compared postmortem neuronal tissue samples from five patients who had undergone four to 18 gadolinium-enhanced magnetic resonance (MR) examinations between 2005 and 2014 (contrast group) with samples from 10 gadolinium-naive patients who had undergone at least one MR examination during their lifetime (control group). All patients in the contrast group had received gadodiamide. Neuronal tissues from the dentate nuclei, pons, globus pallidus, and thalamus were harvested and analyzed with inductively coupled plasma mass spectrometry (ICP-MS), transmission electron microscopy with energy-dispersive x-ray spectroscopy, and light microscopy to quantify, localize, and assess the effects of gadolinium deposition. Results Tissues from the four neuroanatomic regions of gadodiamide-exposed patients contained 0.1-19.4 μg of gadolinium per gram of tissue in a statistically significant dose-dependent relationship (globus pallidus: ρ = 0.90, P = .04). In contradistinction, patients in the control group had undetectable levels of gadolinium with ICP-MS. All patients had normal brain pathologic characteristics at autopsy. Three patients in the contrast group had borderline renal function (estimated glomerular filtration rate <45 mL/min/1.73 m 2 ) and hepatobiliary dysfunction at MR examination. Gadolinium deposition in the contrast group was localized to the capillary endothelium and neuronal interstitium and, in two cases, within the nucleus of the cell. Conclusion Gadolinium deposition in neural tissues after GBCA administration occurs in the absence of intracranial abnormalities that might affect the permeability of the blood-brain barrier. These findings challenge current understanding of the biodistribution of these contrast agents and their safety. © RSNA, 2017.

Rapid Postnatal Expansion of Neural Networks Occurs in an Environment of Altered Neurovascular and Neurometabolic Coupling.

PubMed

Kozberg, Mariel G; Ma, Ying; Shaik, Mohammed A; Kim, Sharon H; Hillman, Elizabeth M C

2016-06-22

In the adult brain, increases in neural activity lead to increases in local blood flow. However, many prior measurements of functional hemodynamics in the neonatal brain, including functional magnetic resonance imaging (fMRI) in human infants, have noted altered and even inverted hemodynamic responses to stimuli. Here, we demonstrate that localized neural activity in early postnatal mice does not evoke blood flow increases as in the adult brain, and elucidate the neural and metabolic correlates of these altered functional hemodynamics as a function of developmental age. Using wide-field GCaMP imaging, the development of neural responses to somatosensory stimulus is visualized over the entire bilaterally exposed cortex. Neural responses are observed to progress from tightly localized, unilateral maps to bilateral responses as interhemispheric connectivity becomes established. Simultaneous hemodynamic imaging confirms that spatiotemporally coupled functional hyperemia is not present during these early stages of postnatal brain development, and develops gradually as cortical connectivity is established. Exploring the consequences of this lack of functional hyperemia, measurements of oxidative metabolism via flavoprotein fluorescence suggest that neural activity depletes local oxygen to below baseline levels at early developmental stages. Analysis of hemoglobin oxygenation dynamics at the same age confirms oxygen depletion for both stimulus-evoked and resting-state neural activity. This state of unmet metabolic demand during neural network development poses new questions about the mechanisms of neurovascular development and its role in both normal and abnormal brain development. These results also provide important insights for the interpretation of fMRI studies of the developing brain. This work demonstrates that the postnatal development of neuronal connectivity is accompanied by development of the mechanisms that regulate local blood flow in response to neural activity. Novel in vivo imaging reveals that, in the developing mouse brain, strong and localized GCaMP neural responses to stimulus fail to evoke local blood flow increases, leading to a state in which oxygen levels become locally depleted. These results demonstrate that the development of cortical connectivity occurs in an environment of altered energy availability that itself may play a role in shaping normal brain development. These findings have important implications for understanding the pathophysiology of abnormal developmental trajectories, and for the interpretation of functional magnetic resonance imaging data acquired in the developing brain. Copyright © 2016 the authors 0270-6474/16/366704-14$15.00/0.

Overall survival and the response to radiotherapy among molecular subtypes of breast cancer brain metastases treated with targeted therapies.

PubMed

Miller, Jacob A; Kotecha, Rupesh; Ahluwalia, Manmeet S; Mohammadi, Alireza M; Chao, Samuel T; Barnett, Gene H; Murphy, Erin S; Vogelbaum, Michael A; Angelov, Lilyana; Peereboom, David M; Suh, John H

2017-06-15

The current study was conducted to investigate survival and the response to radiotherapy among patients with molecular subtypes of breast cancer brain metastases treated with or without targeted therapies. Patients diagnosed with breast cancer brain metastases at a single tertiary care institution were included. The primary outcome was overall survival, whereas secondary outcomes included the cumulative incidences of distant intracranial failure, local failure, and radiation necrosis. Competing risks regression was used to model secondary outcomes. Within the study period, 547 patients presented with 3224 brain metastases and met inclusion criteria. Among patients with human epidermal growth factor receptor 2 (HER2)-amplified disease, 80% received HER2 antibodies and 38% received HER2/epidermal growth factor receptor tyrosine kinase inhibitors (TKIs). The median survival was significantly shorter in the basal cohort (8.4 months), and progressively increased in the luminal A (12.3 months), HER2-positive (15.4 months), and luminal B (18.8 months) cohorts (P<.001). Among patients with HER2-amplified disease, the median survival was extended with the use of both HER2 antibodies (17.9 months vs 15.1 months; P = .04) and TKIs (21.1 months vs 15.4 months; P = .03). The 12-month cumulative incidences of local failure among molecular subtypes were 6.0% in the luminal A cohort, 10.3% in the luminal B cohort, 15.4% in the HER2-positive cohort, and 9.9% in the basal cohort (P = .01). Concurrent HER2/epidermal growth factor receptor TKIs with stereotactic radiosurgery significantly decreased the 12-month cumulative incidence of local failure from 15.1% to 5.7% (P<.001). Molecular subtypes appear to be prognostic for survival and predictive of the response to radiotherapy. TKIs were found to improve survival and local control, and may decrease the rate of distant failure. To preserve neurocognition, these results support a paradigm of upfront radiosurgery and HER2-directed therapy in the HER2-amplified population, reserving whole-brain radiotherapy for salvage. Cancer 2017;123:2283-2293. © 2017 American Cancer Society. © 2017 American Cancer Society.

Age-related differences in the topological efficiency of the brain structural connectome in amnestic mild cognitive impairment.

PubMed

Zhao, Tengda; Sheng, Can; Bi, Qiuhui; Niu, Weili; Shu, Ni; Han, Ying

2017-11-01

Amnestic mild cognitive impairment (aMCI) is accompanied by the accelerated cognitive decline and rapid brain degeneration with aging. However, the age-related alterations of the topological organization of the brain connectome in aMCI patients remained largely unknown. In this study, we constructed the brain structural connectome in 51 aMCI patients and 51 healthy controls by diffusion magnetic resonance imaging and deterministic tractography. The different age-related alteration patterns of the global and regional network metrics between aMCI patients and healthy controls were assessed by a linear regression model. Compared with healthy controls, significantly decreased global and local network efficiency in aMCI patients were found. When correlating network efficiency with age, we observed a significant decline in network efficiency with aging in the aMCI patients, while not in the healthy controls. The age-related decreases of nodal efficiency in aMCI patients were mainly distributed in the key regions of the default-mode network, such as precuneus, anterior cingulate gyrus, and parahippocampal gyrus. In addition, age-related decreases in the connection strength of the edges between peripheral nodes were observed in aMCI patients. Moreover, the decreased regional efficiency of the parahippocampal gyrus was correlated with impaired memory performances in patients. The present study suggests an age-related disruption of the topological organization of the brain structural connectome in aMCI patients, which may provide evidence for different neural mechanisms underlying aging in aMCI and may serve as a potential imaging marker for the early diagnosis of Alzheimer's disease. Copyright © 2017 Elsevier Inc. All rights reserved.

White matter alterations in narcolepsy patients with cataplexy: tract-based spatial statistics.

PubMed

Park, Yun K; Kwon, Oh-Hun; Joo, Eun Yeon; Kim, Jae-Hun; Lee, Jong M; Kim, Sung T; Hong, Seung B

2016-04-01

Functional imaging studies and voxel-based morphometry analysis of brain magnetic resonance imaging showed abnormalities in the hypothalamus-thalamus-orbitofrontal pathway, demonstrating altered hypocretin pathway in narcolepsy. Those distinct morphometric changes account for problems in wake-sleep control, attention and memory. It also raised the necessity to evaluate white matter changes. To investigate brain white matter alterations in drug-naïve narcolepsy patients with cataplexy and to explore relationships between white matter changes and patient clinical characteristics, drug-naïve narcolepsy patients with cataplexy (n = 22) and healthy age- and gender-matched controls (n = 26) were studied. Fractional anisotropy and mean diffusivity images were obtained from whole-brain diffusion tensor imaging, and tract-based spatial statistics were used to localize white matter abnormalities. Compared with controls, patients showed significant decreases in fractional anisotropy of white matter of the bilateral anterior cingulate, fronto-orbital area, frontal lobe, anterior limb of the internal capsule and corpus callosum, as well as the left anterior and medial thalamus. Patients and controls showed no differences in mean diffusivity. Among patients, mean diffusivity values of white matter in the bilateral superior frontal gyri, bilateral fronto-orbital gyri and right superior parietal gyrus were positively correlated with depressive mood. This tract-based spatial statistics study demonstrated that drug-naïve patients with narcolepsy had reduced fractional anisotropy of white matter in multiple brain areas and significant relationship between increased mean diffusivity of white matter in frontal/cingulate and depression. It suggests the widespread disruption of white matter integrity and prevalent brain degeneration of frontal lobes according to a depressive symptom in narcolepsy. © 2015 European Sleep Research Society.

Three-dimensional brain growth abnormalities in childhood-onset schizophrenia visualized by using tensor-based morphometry.

PubMed

Gogtay, Nitin; Lu, Allen; Leow, Alex D; Klunder, Andrea D; Lee, Agatha D; Chavez, Alex; Greenstein, Deanna; Giedd, Jay N; Toga, Arthur W; Rapoport, Judith L; Thompson, Paul M

2008-10-14

Earlier studies revealed progressive cortical gray matter (GM) loss in childhood-onset schizophrenia (COS) across both lateral and medial surfaces of the developing brain. Here, we use tensor-based morphometry to visualize white matter (WM) growth abnormalities in COS throughout the brain. Using high-dimensional elastic image registration, we compared 3D maps of local WM growth rates in COS patients and healthy children over a 5-year period, based on analyzing longitudinal brain MRIs from 12 COS patients and 12 healthy controls matched for age, gender, and scan interval. COS patients showed up to 2.2% slower growth rates per year than healthy controls in WM (P = 0.02, all P values corrected). The greatest differences were in the right hemisphere (P = 0.006). This asymmetry was attributable to a right slower than left hemisphere growth rate mapped in COS patients (P = 0.037) but not in healthy controls. WM growth rates reached 2.6% per year in healthy controls (P = 0.0002). COS patients showed only a 1.3% per year trend for growth in the left hemisphere (P = 0.066). In COS, WM growth rates were associated with improvement in the Children's Global Assessment Scale (R = 0.64, P = 0.029). Growth rates were reduced throughout the brain in COS, but this process appeared to progress in a front-to-back (frontal-parietal) fashion, and this effect was not attributable to lower IQ. Growth rates were correlated with functional prognosis and were visualized as detailed 3D maps. Finally, these findings also confirm that the progressive GM deficits seen in schizophrenia are not the result of WM overgrowth.

Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases.

PubMed

Patil, Chirag G; Pricola, Katie; Sarmiento, J Manuel; Garg, Sachin K; Bryant, Andrew; Black, Keith L

2012-09-12

Historically, whole brain radiation therapy (WBRT) has been the main treatment for brain metastases. Stereotactic radiosurgery (SRS) delivers high-dose focused radiation and is being increasingly utilized to treat brain metastases. The benefit of adding SRS to WBRT is unclear. This is an updated version of the original Cochrane review published in Issue 6, 2010. To assess the efficacy of WBRT plus SRS versus WBRT alone in the treatment of brain metastases. In the original review we searched the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2009), MEDLINE (1966 to 2009), EMBASE (1980 to 2009), and CancerLit (1975 to 2009) in order to identify trials for inclusion in this review.In this update we searched the following electronic databases in May 2012: Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 5, 2012), MEDLINE (2009 to May week 4 2012), and EMBASE (2009 to 2012 week 21) in order to identify trials for inclusion in the review. The review was restricted to randomized controlled trials (RCTs) that compared use of WBRT plus SRS versus WBRT alone for upfront treatment of adult patients with newly diagnosed metastases (single or multiple) in the brain resulting from any primary, extracranial cancer. The Generic Inverse Variance method, random-effects model in RevMan 5 was used for the meta-analysis. A meta-analysis of two trials with a total of 358 participants, found no statistically significant difference in overall survival (OS) between WBRT plus SRS and WBRT alone groups (hazard ratio (HR) 0.82; 95% confidence interval (CI) 0.65 to 1.02). For patients with one brain metastasis median survival was significantly longer in WBRT plus SRS group (6.5 months) versus WBRT group (4.9 months; P = 0.04). Patients in the WBRT plus SRS group had decreased local failure compared to patients who received WBRT alone (HR 0.27; 95% CI 0.14 to 0.52). Furthermore, a statistically significant improvement in performance status scores and decrease in steroid use was seen in the WBRT plus SRS group. Unchanged or improved Karnofsky Performance Scale (KPS) at 6 months was seen in 43% of patients in the combined therapy group versus only 28% in WBRT group (P = 0.03). Overall, risk of bias in the included studies was unclear. Since the last version of this review no new studies were found that met the inclusion criteria. Given the unclear risk of bias in the included studies, the results of this analysis have to be interpreted with caution. Analysis of all included patients, SRS plus WBRT, did not show a survival benefit over WBRT alone. However, performance status and local control were significantly better in the SRS plus WBRT group. Furthermore, significantly longer OS was reported in the combined treatment group for recursive partitioning analysis (RPA) Class I patients as well as patients with single metastasis.

Spatial cluster analysis of nanoscopically mapped serotonin receptors for classification of fixed brain tissue

NASA Astrophysics Data System (ADS)

Sams, Michael; Silye, Rene; Göhring, Janett; Muresan, Leila; Schilcher, Kurt; Jacak, Jaroslaw

2014-01-01

We present a cluster spatial analysis method using nanoscopic dSTORM images to determine changes in protein cluster distributions within brain tissue. Such methods are suitable to investigate human brain tissue and will help to achieve a deeper understanding of brain disease along with aiding drug development. Human brain tissue samples are usually treated postmortem via standard fixation protocols, which are established in clinical laboratories. Therefore, our localization microscopy-based method was adapted to characterize protein density and protein cluster localization in samples fixed using different protocols followed by common fluorescent immunohistochemistry techniques. The localization microscopy allows nanoscopic mapping of serotonin 5-HT1A receptor groups within a two-dimensional image of a brain tissue slice. These nanoscopically mapped proteins can be confined to clusters by applying the proposed statistical spatial analysis. Selected features of such clusters were subsequently used to characterize and classify the tissue. Samples were obtained from different types of patients, fixed with different preparation methods, and finally stored in a human tissue bank. To verify the proposed method, samples of a cryopreserved healthy brain have been compared with epitope-retrieved and paraffin-fixed tissues. Furthermore, samples of healthy brain tissues were compared with data obtained from patients suffering from mental illnesses (e.g., major depressive disorder). Our work demonstrates the applicability of localization microscopy and image analysis methods for comparison and classification of human brain tissues at a nanoscopic level. Furthermore, the presented workflow marks a unique technological advance in the characterization of protein distributions in brain tissue sections.

Local sleep homeostasis in the avian brain: convergence of sleep function in mammals and birds?

PubMed

Lesku, John A; Vyssotski, Alexei L; Martinez-Gonzalez, Dolores; Wilzeck, Christiane; Rattenborg, Niels C

2011-08-22

The function of the brain activity that defines slow wave sleep (SWS) and rapid eye movement (REM) sleep in mammals is unknown. During SWS, the level of electroencephalogram slow wave activity (SWA or 0.5-4.5 Hz power density) increases and decreases as a function of prior time spent awake and asleep, respectively. Such dynamics occur in response to waking brain use, as SWA increases locally in brain regions used more extensively during prior wakefulness. Thus, SWA is thought to reflect homeostatically regulated processes potentially tied to maintaining optimal brain functioning. Interestingly, birds also engage in SWS and REM sleep, a similarity that arose via convergent evolution, as sleeping reptiles and amphibians do not show similar brain activity. Although birds deprived of sleep show global increases in SWA during subsequent sleep, it is unclear whether avian sleep is likewise regulated locally. Here, we provide, to our knowledge, the first electrophysiological evidence for local sleep homeostasis in the avian brain. After staying awake watching David Attenborough's The Life of Birds with only one eye, SWA and the slope of slow waves (a purported marker of synaptic strength) increased only in the hyperpallium--a primary visual processing region--neurologically connected to the stimulated eye. Asymmetries were specific to the hyperpallium, as the non-visual mesopallium showed a symmetric increase in SWA and wave slope. Thus, hypotheses for the function of mammalian SWS that rely on local sleep homeostasis may apply also to birds.

Scoring Systems to Estimate Intracerebral Control and Survival Rates of Patients Irradiated for Brain Metastases;Brain metastases; Radiation therapy; Local control; Survival; Prognostic scores

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

Rades, Dirk, E-mail: Rades.Dirk@gmx.net; Dziggel, Liesa; Haatanen, Tiina

2011-07-15

Purpose: To create and validate scoring systems for intracerebral control (IC) and overall survival (OS) of patients irradiated for brain metastases. Methods and Materials: In this study, 1,797 patients were randomly assigned to the test (n = 1,198) or the validation group (n = 599). Two scoring systems were developed, one for IC and another for OS. The scores included prognostic factors found significant on multivariate analyses. Age, performance status, extracerebral metastases, interval tumor diagnosis to RT, and number of brain metastases were associated with OS. Tumor type, performance status, interval, and number of brain metastases were associated with IC.more » The score for each factor was determined by dividing the 6-month IC or OS rate (given in percent) by 10. The total score represented the sum of the scores for each factor. The score groups of the test group were compared with the corresponding score groups of the validation group. Results: In the test group, 6-month IC rates were 17% for 14-18 points, 49% for 19-23 points, and 77% for 24-27 points (p < 0.0001). IC rates in the validation group were 19%, 52%, and 77%, respectively (p < 0.0001). In the test group, 6-month OS rates were 9% for 15-19 points, 41% for 20-25 points, and 78% for 26-30 points (p < 0.0001). OS rates in the validation group were 7%, 39%, and 79%, respectively (p < 0.0001). Conclusions: Patients irradiated for brain metastases can be given scores to estimate OS and IC. IC and OS rates of the validation group were similar to the test group demonstrating the validity and reproducibility of both scores.« less

Topographical distribution of decrements and recovery in muscarinic receptors from rat brains repeatedly exposed to sublethal doses of soman

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

Churchill, L.; Pazdernik, T.L.; Jackson, J.L.

1984-08-01

(3H)Quinuclidinyl benzilate binding to rat brain muscarinic receptors decreased after repeated exposure to soman, a potent organophosphorus cholinesterase inhibitor. The topographical distribution of this decrement was analyzed by quantitative receptor autoradiography. After 4 weeks of soman, three times a week, quinuclidinyl benzilate binding decreased to 67 to 80% of control in frontal and parietal cortex, caudate-putamen, lateral septum, hippocampal body, dentate gyrus, superior colliculus, nucleus of the fifth nerve, and central grey. Minor or no decreases were observed in thalamic or hypothalamic nuclei, reticular formation, pontine nuclei, inferior colliculus, nucleus of the seventh nerve, and cerebellum. Scatchard analyses of saturationmore » curves using frontal cortex sections from soman-treated rats revealed a decrease in maximal quinuclidinyl benzilate binding from that in control rats and a return toward control levels by 24 days without any significant change in affinity. These brain areas showing significant decrements in muscarinic receptors recovered with a similar time course. An estimate of the time for 50% recovery for some of the brain areas was 14 days for superior colliculus, 16 days for cortex, and 19 days for hippocampal body. The application of quantitative receptor autoradiography to analyze receptor alterations has been valuable in localizing the telencephalon as a region more susceptible to change in receptor concentration.« less

Updates in the management of brain metastases

PubMed Central

Arvold, Nils D.; Lee, Eudocia Q.; Mehta, Minesh P.; Margolin, Kim; Alexander, Brian M.; Lin, Nancy U.; Anders, Carey K.; Soffietti, Riccardo; Camidge, D. Ross; Vogelbaum, Michael A.; Dunn, Ian F.; Wen, Patrick Y.

2016-01-01

The clinical management/understanding of brain metastases (BM) has changed substantially in the last 5 years, with key advances and clinical trials highlighted in this review. Several of these changes stem from improvements in systemic therapy, which have led to better systemic control and longer overall patient survival, associated with increased time at risk for developing BM. Development of systemic therapies capable of preventing BM and controlling both intracranial and extracranial disease once BM are diagnosed is paramount. The increase in use of stereotactic radiosurgery alone for many patients with multiple BM is an outgrowth of the desire to employ treatments focused on local control while minimizing cognitive effects associated with whole brain radiotherapy. Complications from BM and their treatment must be considered in comprehensive patient management, especially with greater awareness that the majority of patients do not die from their BM. Being aware of significant heterogeneity in prognosis and therapeutic options for patients with BM is crucial for appropriate management, with greater attention to developing individual patient treatment plans based on predicted outcomes; in this context, recent prognostic models of survival have been extensively revised to incorporate molecular markers unique to different primary cancers. PMID:27382120

Examining frontotemporal connectivity and rTMS in healthy controls: implications for auditory hallucinations in schizophrenia.

PubMed

Gromann, Paula M; Tracy, Derek K; Giampietro, Vincent; Brammer, Michael J; Krabbendam, Lydia; Shergill, Sukhwinder S

2012-01-01

Repetitive transcranial magnetic stimulation (rTMS) has been shown to have clinically beneficial effects in altering the perception of auditory hallucinations (AH) in patients with schizophrenia. However, the mode of action is not clear. Recent neuroimaging findings indicate that rTMS has the potential to induce not only local effects but also changes in remote, functionally connected brain regions. Frontotemporal dysconnectivity has been proposed as a mechanism leading to psychotic symptoms in schizophrenia. The current study examines functional connectivity between temporal and frontal brain regions after rTMS and the implications for AH in schizophrenia. A connectivity analysis was conducted on the fMRI data of 11 healthy controls receiving rTMS, compared with 11 matched subjects receiving sham TMS, to the temporoparietal junction, before engaging in a task associated with robust frontotemporal activation. Compared to the control group, the rTMS group showed an altered frontotemporal connectivity with stronger connectivity between the right temporoparietal cortex and the dorsolateral prefrontal cortex and the angular gyrus. This finding provides preliminary evidence for the hypothesis that normalizing the functional connectivity between the temporoparietal and frontal brain regions may underlie the therapeutic effect of rTMS on AH in schizophrenia.

Comparison of the activation of somatostatin- and neuropeptide Y-containing neuronal populations of the rat amygdala following two different anxiogenic stressors

PubMed Central

Butler, Ryan K.; White, L. Casey; Frederick-Duus, Dani; Kaigler, Kris F.; Fadel, Jim R.; Wilson, Marlene A.

2012-01-01

Rats exposed to the odor of a predator or to the elevated plus maze express fear behaviors without a prior exposure to either stimulus. The expression of innate fear provides for an ideal model of anxiety which can aid in the elucidation of brain circuits involved in anxiety-related behaviors. The current experiments compared activation of neuropeptide-containing neuronal populations in the amygdala of rats exposed to either the elevated plus maze (EPM; 5 minutes) versus home cage controls, or predator ferret odor versus butyric acid, or no odor (30 minutes). Sections of the brains were prepared for dual-labeled immunohistochemistry and counts of c-Fos co-localized with somatostatin (SOM) or neuropeptide Y (NPY) were made in the basolateral (BLA), central (CEA), medial (MEA) nucleus of the amygdala. Ferret odor and butyric acid exposure significantly decreased the percentage of SOM–positive neurons also immunoreactive for c-Fos in the anterior BLA compared to controls, whereas EPM exposure yielded a significant increase in the activation of SOM-positive neurons versus home cage controls. In the CEA, ferret odor and butyric exposure significantly decreased the percentage of SOM-positive neurons also immunoreactive for c-Fos compared to no-odor controls whereas EPM exposure yielded no change versus controls. In the MEA, both ferret odor exposure and EPM exposure resulted in increased SOM co-localized with c-Fos compared to control groups whereas NPY co-localized with c-Fos occurred following ferret odor exposure, but not EPM exposure. These results indicate that phenotypically distinct neuronal populations of the amygdala are differentially activated following exposure to different anxiogenic stimuli. These studies further elucidate the fundamental neurocircuitry of anxiety and could possibly explain the differential behavioral effects of predator versus novelty-induced stress. PMID:22917777

Cognitive control related network analysis: A novel way to measure neuron fiber connection of Alzheimer's disease.

PubMed

Changle Zhang; Tao Chai; Na Gao; Ma, Heather T

2017-07-01

Effective measurement of cognitive impairment caused by Alzheimer's disease (AD) will provide a chance for early medical intervention and delay the disease onset. Diffusion tensor imaging (DTI) provides a non-intrusive examination of cranial nerve diseases which can help us observe the microstructure of neuron fibers. Cognitive control network (CCN) consists of the brain regions that highly related to human self-control. In this study, hub-and-spoke model which was widely used in transportation and sociology area had been employed to analyze the relationship of CCN and other regions under its control, cognitive control related network (CCRN) was built by applying this model. Local and global graph theoretical parameters were calculated and went through statistical analysis. Significant difference had been found in the scale of local as well as global which may represent the impairment of cognitive control ability. This result may provide a potential bio-marker for the loss of connection caused by Alzheimer's disease.

Investigating neuronal function with optically controllable proteins

PubMed Central

Zhou, Xin X.; Pan, Michael; Lin, Michael Z.

2015-01-01

In the nervous system, protein activities are highly regulated in space and time. This regulation allows for fine modulation of neuronal structure and function during development and adaptive responses. For example, neurite extension and synaptogenesis both involve localized and transient activation of cytoskeletal and signaling proteins, allowing changes in microarchitecture to occur rapidly and in a localized manner. To investigate the role of specific protein regulation events in these processes, methods to optically control the activity of specific proteins have been developed. In this review, we focus on how photosensory domains enable optical control over protein activity and have been used in neuroscience applications. These tools have demonstrated versatility in controlling various proteins and thereby cellular functions, and possess enormous potential for future applications in nervous systems. Just as optogenetic control of neuronal firing using opsins has changed how we investigate the function of cellular circuits in vivo, optical control may yet yield another revolution in how we study the circuitry of intracellular signaling in the brain. PMID:26257603

Immunohistochemical characterization of the arcuate kisspeptin/neurokinin B/dynorphin (KNDy) and preoptic kisspeptin neuronal populations in the hypothalamus during the estrous cycle in heifers

PubMed Central

HASSANEEN, A; NANIWA, Yousuke; SUETOMI, Yuta; MATSUYAMA, Shuichi; KIMURA, Koji; IEDA, Nahoko; INOUE, Naoko; UENOYAMA, Yoshihisa; TSUKAMURA, Hiroko; MAEDA, Kei-ichiro; MATSUDA, Fuko; OHKURA, Satoshi

2016-01-01

Elucidating the physiological mechanisms that control reproduction is an obvious strategy for improving the fertility of cattle and developing new agents to control reproductive functions. The present study aimed to identify kisspeptin neurons in the bovine hypothalamus, clarifying that a central mechanism is also present in the cattle brain, as kisspeptin is known to play an important role in the stimulation of gonadotropin-releasing hormone (GnRH)/gonadotropin secretion in other mammals. To characterize kisspeptin neurons in the bovine hypothalamus, the co-localizations of kisspeptin and neurokinin B (NKB) or kisspeptin and dynorphin A (Dyn) were examined. Hypothalamic tissue was collected from Japanese Black or Japanese Black × Holstein crossbred cows during the follicular and luteal phases. Brain sections, including the arcuate nucleus (ARC) and the preoptic area (POA), were dual immunostained with kisspeptin and either NKB or Dyn. In the ARC, both NKB and Dyn were co-localized in kisspeptin neurons during both the follicular and luteal phases, demonstrating the presence of kisspeptin/NKB/Dyn-containing neurons, referred to as KNDy neurons, in cows. In the POA, no co-localization of kisspeptin with either NKB or Dyn was detected. Kisspeptin expression in the follicular phase was higher than that in the luteal phase, suggesting that kisspeptin expression in the POA is positively controlled by estrogen in cows. The kisspeptin neuronal populations in the ARC and POA likely play important roles in regulating the GnRH pulse and surge, respectively, in cows. PMID:27349533

Global and regional alterations of hippocampal anatomy in long-term meditation practitioners.

PubMed

Luders, Eileen; Thompson, Paul M; Kurth, Florian; Hong, Jui-Yang; Phillips, Owen R; Wang, Yalin; Gutman, Boris A; Chou, Yi-Yu; Narr, Katherine L; Toga, Arthur W

2013-12-01

Studies linking meditation and brain structure are still relatively sparse, but the hippocampus is consistently implicated as one of the structures altered in meditation practitioners. To explore hippocampal features in the framework of meditation, we analyzed high-resolution structural magnetic resonance imaging data from 30 long-term meditators and 30 controls, closely matched for sex, age, and handedness. Hippocampal formations were manually traced following established protocols. In addition to calculating left and right hippocampal volumes (global measures), regional variations in surface morphology were determined by measuring radial distances from the hippocampal core to spatially matched surface points (local measures). Left and right hippocampal volumes were larger in meditators than in controls, significantly so for the left hippocampus. The presence and direction of this global effect was confirmed locally by mapping the exact spatial locations of the group differences. Altogether, radial distances were larger in meditators compared to controls, with up to 15% difference. These local effects were observed in several hippocampal regions in the left and right hemisphere though achieved significance primarily in the left hippocampal head. Larger hippocampal dimensions in long-term meditators may constitute part of the underlying neurological substrate for cognitive skills, mental capacities, and/or personal traits associated with the practice of meditation. Alternatively, given that meditation positively affects autonomic regulation and immune activity, altered hippocampal dimensions may be one result of meditation-induced stress reduction. However, given the cross-sectional design, the lack of individual stress measures, and the limited resolution of brain data, the exact underlying neuronal mechanisms remain to be established. Copyright © 2012 Wiley Periodicals, Inc.

Global and Regional Alterations of Hippocampal Anatomy in Long-Term Meditation Practitioners

PubMed Central

Luders, Eileen; Thompson, Paul M.; Kurth, Florian; Hong, Jui-Yang; Phillips, Owen R.; Wang, Yalin; Gutman, Boris A.; Chou, Yi-Yu; Narr, Katherine L.; Toga, Arthur W.

2014-01-01

Studies linking meditation and brain structure are still relatively sparse, but the hippocampus is consistently implicated as one of the structures altered in meditation practitioners. To explore hippocampal features in the framework of meditation, we analyzed high-resolution structural magnetic resonance imaging data from 30 long-term meditators and 30 controls, closely matched for sex, age, and handedness. Hippocampal formations were manually traced following established protocols. In addition to calculating left and right hippocampal volumes (global measures), regional variations in surface morphology were determined by measuring radial distances from the hippocampal core to spatially matched surface points (local measures). Left and right hippocampal volumes were larger in meditators than in controls, significantly so for the left hippocampus. The presence and direction of this global effect was confirmed locally by mapping the exact spatial locations of the group differences. Altogether, radial distances were larger in meditators compared to controls, with up to 15% difference. These local effects were observed in several hippocampal regions in the left and right hemisphere though achieved significance primarily in the left hippocampal head. Larger hippocampal dimensions in long-term meditators may constitute part of the underlying neurological substrate for cognitive skills, mental capacities, and/or personal traits associated with the practice of meditation. Alternatively, given that meditation positively affects autonomic regulation and immune activity, altered hippocampal dimensions may be one result of meditation-induced stress reduction. However, given the cross-sectional design, the lack of individual stress measures, and the limited resolution of brain data, the exact underlying neuronal mechanisms remain to be established. PMID:22815233

Three-dimensional reconstruction of brain-wide wiring networks in Drosophila at single-cell resolution.

PubMed

Chiang, Ann-Shyn; Lin, Chih-Yung; Chuang, Chao-Chun; Chang, Hsiu-Ming; Hsieh, Chang-Huain; Yeh, Chang-Wei; Shih, Chi-Tin; Wu, Jian-Jheng; Wang, Guo-Tzau; Chen, Yung-Chang; Wu, Cheng-Chi; Chen, Guan-Yu; Ching, Yu-Tai; Lee, Ping-Chang; Lin, Chih-Yang; Lin, Hui-Hao; Wu, Chia-Chou; Hsu, Hao-Wei; Huang, Yun-Ann; Chen, Jing-Yi; Chiang, Hsin-Jung; Lu, Chun-Fang; Ni, Ru-Fen; Yeh, Chao-Yuan; Hwang, Jenn-Kang

2011-01-11

Animal behavior is governed by the activity of interconnected brain circuits. Comprehensive brain wiring maps are thus needed in order to formulate hypotheses about information flow and also to guide genetic manipulations aimed at understanding how genes and circuits orchestrate complex behaviors. To assemble this map, we deconstructed the adult Drosophila brain into approximately 16,000 single neurons and reconstructed them into a common standardized framework to produce a virtual fly brain. We have constructed a mesoscopic map and found that it consists of 41 local processing units (LPUs), six hubs, and 58 tracts covering the whole Drosophila brain. Despite individual local variation, the architecture of the Drosophila brain shows invariance for both the aggregation of local neurons (LNs) within specific LPUs and for the connectivity of projection neurons (PNs) between the same set of LPUs. An open-access image database, named FlyCircuit, has been constructed for online data archiving, mining, analysis, and three-dimensional visualization of all single neurons, brain-wide LPUs, their wiring diagrams, and neural tracts. We found that the Drosophila brain is assembled from families of multiple LPUs and their interconnections. This provides an essential first step in the analysis of information processing within and between neurons in a complete brain. Copyright © 2011 Elsevier Ltd. All rights reserved.

Novel Intrinsic Ignition Method Measuring Local-Global Integration Characterizes Wakefulness and Deep Sleep

PubMed Central

Tagliazucchi, Enzo; Sanjuán, Ana

2017-01-01

Abstract A precise definition of a brain state has proven elusive. Here, we introduce the novel local-global concept of intrinsic ignition characterizing the dynamical complexity of different brain states. Naturally occurring intrinsic ignition events reflect the capability of a given brain area to propagate neuronal activity to other regions, giving rise to different levels of integration. The ignitory capability of brain regions is computed by the elicited level of integration for each intrinsic ignition event in each brain region, averaged over all events. This intrinsic ignition method is shown to clearly distinguish human neuroimaging data of two fundamental brain states (wakefulness and deep sleep). Importantly, whole-brain computational modelling of this data shows that at the optimal working point is found where there is maximal variability of the intrinsic ignition across brain regions. Thus, combining whole brain models with intrinsic ignition can provide novel insights into underlying mechanisms of brain states. PMID:28966977

Novel Intrinsic Ignition Method Measuring Local-Global Integration Characterizes Wakefulness and Deep Sleep.

PubMed

Deco, Gustavo; Tagliazucchi, Enzo; Laufs, Helmut; Sanjuán, Ana; Kringelbach, Morten L

2017-01-01

A precise definition of a brain state has proven elusive. Here, we introduce the novel local-global concept of intrinsic ignition characterizing the dynamical complexity of different brain states. Naturally occurring intrinsic ignition events reflect the capability of a given brain area to propagate neuronal activity to other regions, giving rise to different levels of integration. The ignitory capability of brain regions is computed by the elicited level of integration for each intrinsic ignition event in each brain region, averaged over all events. This intrinsic ignition method is shown to clearly distinguish human neuroimaging data of two fundamental brain states (wakefulness and deep sleep). Importantly, whole-brain computational modelling of this data shows that at the optimal working point is found where there is maximal variability of the intrinsic ignition across brain regions. Thus, combining whole brain models with intrinsic ignition can provide novel insights into underlying mechanisms of brain states.

PET/CT imaging evidence of FUS-mediated (18)F-FDG uptake changes in rat brain

PubMed Central

Kim, Hyungmin; Park, Mi-Ae; Wang, Shuyan; Chiu, Alan; Fischer, Krisztina; Yoo, Seung-Schik

2013-01-01

Purpose: Transcranial focused ultrasound (FUS) delivers highly focused acoustic energy to a small region of the brain in a noninvasive manner. Recent studies have revealed that FUS, which is administered either in pulsed or continuous waves, can elicit or suppress neural tissue excitability. This neuromodulatory property of FUS has been demonstrated via direct motion detection, electrophysiological recordings, functional magnetic resonance imaging (fMRI), confocal imaging, and microdialysis sampling of neurotransmitters. This study presents new evidence of local increase in glucose metabolism induced by FUS to the rat brain using FDG (18-fludeoxyglucose) positron emission tomography (PET). Methods: Sprague–Dawley rats underwent sonication to a unilateral hemispheric area of the brain prior to PET scan. The pulsed sonication (350 kHz, tone burst duration of 0.5 ms, pulse repetition frequency of 1 kHz, and duration of 300 ms) was applied in 2 s intervals for 40 min immediately after the FDG injection via tail vein. Subsequently, the PET was acquired in dynamic list-mode to image FDG activity for an hour, and reconstructed into a single volume representing standardized uptake value (SUV). The raw SUV as well as its asymmetry index (AI) were measured from five different volume-of-interests (VOIs) of the brain for both hemispheres, and compared between sonicated and unsonicated groups. Results: Statistically significant hemispheric changes in SUV were observed only at the center of sonication focus within the FUS group [paired t-test; t(7) = 3.57, p < 0.05]. There were no significant hemispheric differences in SUV within the control group in any of the VOIs. A statistically significant elevation in AI (t-test; t(7) = 3.40, p < 0.05) was observed at the center of sonication focus (7.9 ± 2.5%, the deviations are in standard error) among the FUS group when compared to the control group (−0.8 ± 1.2%). Conclusions: Spatially distinct increases in the glucose metabolic activity in the rat brain is present only at the center of sonication focus, suggesting localized functional neuromodulation mediated by the sonication. PMID:23464343

Birdsong and the neural production of steroids

PubMed Central

Remage-Healey, Luke; London, Sarah E.; Schinger, Barney A.

2009-01-01

The forebrain circuits involved in singing and audition (the ‘song system’) in songbirds exhibit a remarkable capacity to synthesize and respond to steroid hormones. This review considers how local brain steroid production impacts the development, sexual differentiation, and activity of song system circuitry. The songbird forebrain contains all of the enzymes necessary for the de novo synthesis of steroids - including neuroestrogens - from cholesterol. Steroid production enzymes are found in neuronal cell bodies, but they are also expressed in pre-synaptic terminals in the song system, indicating a novel mode of brain steroid delivery to local circuits. The song system expresses nuclear hormone receptors, consistent with local action of brain-derived steroids. Local steroid production also occurs in brain regions that do not express nuclear hormone receptors, suggesting a non-classical mode-of-action. Recent evidence indicates that local steroid levels can change rapidly within the forebrain, in a manner similar to traditional neuromodulators. Lastly, we consider growing evidence for modulatory interactions between brain-derived steroids and neurotransmitter/neuropeptide networks within the song system. Songbirds have therefore emerged as a rich and powerful model system to explore the neural and neurochemical regulation of social behavior. PMID:19589382

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-08-24

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

BRAPH: A graph theory software for the analysis of brain connectivity

PubMed Central

Mijalkov, Mite; Kakaei, Ehsan; Pereira, Joana B.; Westman, Eric; Volpe, Giovanni

2017-01-01

The brain is a large-scale complex network whose workings rely on the interaction between its various regions. In the past few years, the organization of the human brain network has been studied extensively using concepts from graph theory, where the brain is represented as a set of nodes connected by edges. This representation of the brain as a connectome can be used to assess important measures that reflect its topological architecture. We have developed a freeware MatLab-based software (BRAPH–BRain Analysis using graPH theory) for connectivity analysis of brain networks derived from structural magnetic resonance imaging (MRI), functional MRI (fMRI), positron emission tomography (PET) and electroencephalogram (EEG) data. BRAPH allows building connectivity matrices, calculating global and local network measures, performing non-parametric permutations for group comparisons, assessing the modules in the network, and comparing the results to random networks. By contrast to other toolboxes, it allows performing longitudinal comparisons of the same patients across different points in time. Furthermore, even though a user-friendly interface is provided, the architecture of the program is modular (object-oriented) so that it can be easily expanded and customized. To demonstrate the abilities of BRAPH, we performed structural and functional graph theory analyses in two separate studies. In the first study, using MRI data, we assessed the differences in global and nodal network topology in healthy controls, patients with amnestic mild cognitive impairment, and patients with Alzheimer’s disease. In the second study, using resting-state fMRI data, we compared healthy controls and Parkinson’s patients with mild cognitive impairment. PMID:28763447

BRAPH: A graph theory software for the analysis of brain connectivity.

PubMed

Mijalkov, Mite; Kakaei, Ehsan; Pereira, Joana B; Westman, Eric; Volpe, Giovanni

2017-01-01

The brain is a large-scale complex network whose workings rely on the interaction between its various regions. In the past few years, the organization of the human brain network has been studied extensively using concepts from graph theory, where the brain is represented as a set of nodes connected by edges. This representation of the brain as a connectome can be used to assess important measures that reflect its topological architecture. We have developed a freeware MatLab-based software (BRAPH-BRain Analysis using graPH theory) for connectivity analysis of brain networks derived from structural magnetic resonance imaging (MRI), functional MRI (fMRI), positron emission tomography (PET) and electroencephalogram (EEG) data. BRAPH allows building connectivity matrices, calculating global and local network measures, performing non-parametric permutations for group comparisons, assessing the modules in the network, and comparing the results to random networks. By contrast to other toolboxes, it allows performing longitudinal comparisons of the same patients across different points in time. Furthermore, even though a user-friendly interface is provided, the architecture of the program is modular (object-oriented) so that it can be easily expanded and customized. To demonstrate the abilities of BRAPH, we performed structural and functional graph theory analyses in two separate studies. In the first study, using MRI data, we assessed the differences in global and nodal network topology in healthy controls, patients with amnestic mild cognitive impairment, and patients with Alzheimer's disease. In the second study, using resting-state fMRI data, we compared healthy controls and Parkinson's patients with mild cognitive impairment.

Atypical vertical sound localization and sound-onset sensitivity in people with autism spectrum disorders.

PubMed

Visser, Eelke; Zwiers, Marcel P; Kan, Cornelis C; Hoekstra, Liesbeth; van Opstal, A John; Buitelaar, Jan K

2013-11-01

Autism spectrum disorders (ASDs) are associated with auditory hyper- or hyposensitivity; atypicalities in central auditory processes, such as speech-processing and selective auditory attention; and neural connectivity deficits. We sought to investigate whether the low-level integrative processes underlying sound localization and spatial discrimination are affected in ASDs. We performed 3 behavioural experiments to probe different connecting neural pathways: 1) horizontal and vertical localization of auditory stimuli in a noisy background, 2) vertical localization of repetitive frequency sweeps and 3) discrimination of horizontally separated sound stimuli with a short onset difference (precedence effect). Ten adult participants with ASDs and 10 healthy control listeners participated in experiments 1 and 3; sample sizes for experiment 2 were 18 adults with ASDs and 19 controls. Horizontal localization was unaffected, but vertical localization performance was significantly worse in participants with ASDs. The temporal window for the precedence effect was shorter in participants with ASDs than in controls. The study was performed with adult participants and hence does not provide insight into the developmental aspects of auditory processing in individuals with ASDs. Changes in low-level auditory processing could underlie degraded performance in vertical localization, which would be in agreement with recently reported changes in the neuroanatomy of the auditory brainstem in individuals with ASDs. The results are further discussed in the context of theories about abnormal brain connectivity in individuals with ASDs.

Hypertonic sodium lactate reverses brain oxygenation and metabolism dysfunction after traumatic brain injury.

PubMed

Millet, A; Cuisinier, A; Bouzat, P; Batandier, C; Lemasson, B; Stupar, V; Pernet-Gallay, K; Crespy, T; Barbier, E L; Payen, J F

2018-06-01

The mechanisms by which hypertonic sodium lactate (HSL) solution act in injured brain are unclear. We investigated the effects of HSL on brain metabolism, oxygenation, and perfusion in a rodent model of diffuse traumatic brain injury (TBI). Thirty minutes after trauma, anaesthetised adult rats were randomly assigned to receive a 3 h infusion of either a saline solution (TBI-saline group) or HSL (TBI-HSL group). The sham-saline and sham-HSL groups received no insult. Three series of experiments were conducted up to 4 h after TBI (or equivalent) to investigate: 1) brain oedema using diffusion-weighted magnetic resonance imaging and brain metabolism using localized 1 H-magnetic resonance spectroscopy (n = 10 rats per group). The respiratory control ratio was then determined using oxygraphic analysis of extracted mitochondria, 2) brain oxygenation and perfusion using quantitative blood-oxygenation-level-dependent magnetic resonance approach (n = 10 rats per group), and 3) mitochondrial ultrastructural changes (n = 1 rat per group). Compared with the TBI-saline group, the TBI-HSL and the sham-operated groups had reduced brain oedema. Concomitantly, the TBI-HSL group had lower intracellular lactate/creatine ratio [0.049 (0.047-0.098) vs 0.097 (0.079-0.157); P < 0.05], higher mitochondrial respiratory control ratio, higher tissue oxygen saturation [77% (71-79) vs 66% (55-73); P < 0.05], and reduced mitochondrial cristae thickness in astrocytes [27.5 (22.5-38.4) nm vs 38.4 (31.0-47.5) nm; P < 0.01] compared with the TBI-saline group. Serum sodium and lactate concentrations and serum osmolality were higher in the TBI-HSL than in the TBI-saline group. These findings indicate that the hypertonic sodium lactate solution can reverse brain oxygenation and metabolism dysfunction after traumatic brain injury through vasodilatory, mitochondrial, and anti-oedema effects. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

[Cerebral metabolism and permeability of the hemato-encephalic barrier in an experimental model for brain radiotherapy].

PubMed

Cicciarello, R; Russi, E; Albiero, F; Mesiti, M; Torre, E; D'Aquino, A; Raffaele, L; Bertolani, S; D'Avella, D

1990-11-01

Whole brain irradiation (WBR) can produce acute and chronic neurological adverse effects, which are usually divided into acute, early delayed and late delayed reactions according to the time of onset. To assess the impact of WBR on brain functional parameters during the early-delayed phase, we employed the [14C]-2-deoxyglucose (2-DG) and the [14C]-alfa-aminoisobutyric (AIB) acid quantitative autoradiographic techniques to study local cerebral glucose utilization and blood-brain barrier permeability, respectively. Sprague-Dowley albino rats were exposed to conventional fractionation (200 Gy/day 5 days a week) for a total dose of 4000 Gy. Experiments were made 3 weeks after completion of the radiation exposure. In comparison with control and sham-irradiated animals, cerebral metabolic activity was diffusely decreased following irradiation. As a rule, brain areas with the highest basal metabolic rates showed the highest percentage drop in glucose utilization. Changes in blood-brain barrier function, as assessed by an increased transcapillary transport of AIB, were also demonstrated in specific brain regions. This study illustrates how moderate doses of WBR induce well-defined changes in brain metabolism and BBB function, which are possibly involved in the pathogenesis of the early-delayed radiation-induced cerebral dysfunction in humans.

Towards hyperpolarized 13C-succinate imaging of brain cancer

PubMed Central

Bhattacharya, Pratip; Chekmenev, Eduard Y.; Perman, William H.; Harris, Kent C.; Lin, Alexander P.; Norton, Valerie A.; Tan, Chou T.; Ross, Brian D.; Weitekamp, Daniel P.

2009-01-01

We describe a novel 13C enriched precursor molecule, sodium 1-13C acetylenedicarboxylate, which after hydrogenation by PASADE-NA (Parahydrogen and Synthesis Allows Dramatically Enhanced Nuclear Alignment) under controlled experimental conditions, becomes hyperpolarized 13C sodium succinate. Fast in vivo 3D FIESTA MR imaging demonstrated that, following carotid arterial injection, the hyperpolarized 13C-succinate appeared in the head and cerebral circulation of normal and tumor-bearing rats. At this time, no in vivo hyperpolarized signal has been localized to normal brain or brain tumor. On the other hand, ex vivo samples of brain harvested from rats bearing a 9L brain tumor, 1 h or more following in vivo carotid injection of hyperpolarized 13C sodium succinate, contained significant concentrations of the injected substrate, 13C sodium succinate, together with 13C maleate and succinate metabolites 1-13C-glutamate, 5-13C-glutamate, 1-13C-glutamine and 5-13C-glutamine. The 13C substrates and products were below the limits of NMR detection in ex vivo samples of normal brain consistent with an intact blood–brain barrier. These ex vivo results indicate that hyperpolarized 13C sodium succinate may become a useful tool for rapid in vivo identification of brain tumors, providing novel biomarkers in 13C MR spectral-spatial images. PMID:17303454

Towards hyperpolarized 13C-succinate imaging of brain cancer

NASA Astrophysics Data System (ADS)

Bhattacharya, Pratip; Chekmenev, Eduard Y.; Perman, William H.; Harris, Kent C.; Lin, Alexander P.; Norton, Valerie A.; Tan, Chou T.; Ross, Brian D.; Weitekamp, Daniel P.

2007-05-01

We describe a novel 13C enriched precursor molecule, sodium 1- 13C acetylenedicarboxylate, which after hydrogenation by PASADENA (Parahydrogen and Synthesis Allows Dramatically Enhanced Nuclear Alignment) under controlled experimental conditions, becomes hyperpolarized 13C sodium succinate. Fast in vivo 3D FIESTA MR imaging demonstrated that, following carotid arterial injection, the hyperpolarized 13C-succinate appeared in the head and cerebral circulation of normal and tumor-bearing rats. At this time, no in vivo hyperpolarized signal has been localized to normal brain or brain tumor. On the other hand, ex vivo samples of brain harvested from rats bearing a 9L brain tumor, 1 h or more following in vivo carotid injection of hyperpolarized 13C sodium succinate, contained significant concentrations of the injected substrate, 13C sodium succinate, together with 13C maleate and succinate metabolites 1- 13C-glutamate, 5- 13C-glutamate, 1- 13C-glutamine and 5- 13C-glutamine. The 13C substrates and products were below the limits of NMR detection in ex vivo samples of normal brain consistent with an intact blood-brain barrier. These ex vivo results indicate that hyperpolarized 13C sodium succinate may become a useful tool for rapid in vivo identification of brain tumors, providing novel biomarkers in 13C MR spectral-spatial images.

Linear accelerator-based stereotactic radiosurgery for brainstem metastases: the Dana-Farber/Brigham and Women's Cancer Center experience.

PubMed

Kelly, Paul J; Lin, Yijie Brittany; Yu, Alvin Y C; Ropper, Alexander E; Nguyen, Paul L; Marcus, Karen J; Hacker, Fred L; Weiss, Stephanie E

2011-09-01

To review the safety and efficacy of linear accelerator-based stereotactic radiosurgery (SRS) for brainstem metastases. We reviewed all patients with brain metastases treated with SRS at DF/BWCC from 2001 to 2009 to identify patients who had SRS to a single brainstem metastasis. Overall survival and freedom-from-local failure rates were calculated from the date of SRS using the Kaplan-Meier method. Prognostic factors were evaluated using the log-rank test and Cox proportional hazards model. A total of 24 consecutive patients with brainstem metastases had SRS. At the time of SRS, 21/24 had metastatic lesions elsewhere within the brain. 23/24 had undergone prior WBRT. Primary diagnoses included eight NSCLC, eight breast cancer, three melanoma, three renal cell carcinoma and two others. Median dose was 13 Gy (range, 8-16). One patient had fractionated SRS 5 Gy ×5. Median target volume was 0.2 cc (range, 0.02-2.39). The median age was 57 years (range, 42-92). Follow-up information was available in 22/24 cases. At the time of analysis, 18/22 patients (82%) had died. The median overall survival time was 5.3 months (range, 0.8-21.1 months). The only prognostic factor that trended toward statistical significance for overall survival was the absence of synchronous brain metastasis at the time of SRS; 1-year overall survival was 31% with versus 67% without synchronous brain metastasis (log rank P = 0.11). Non-significant factors included primary tumor histology and status of extracranial disease (progressing vs. stable/absent). Local failure occurred in 4/22 cases (18%). Actuarial freedom from local failure for all cases was 78.6% at 1 year. RTOG grade 3 toxicities were recorded in two patients (ataxia, confusion). Linac-based SRS for small volume brainstem metastases using a median dose of 13 Gy is associated with acceptable local control and low morbidity.

Brain networks, structural realism, and local approaches to the scientific realism debate.

PubMed

Yan, Karen; Hricko, Jonathon

2017-08-01

We examine recent work in cognitive neuroscience that investigates brain networks. Brain networks are characterized by the ways in which brain regions are functionally and anatomically connected to one another. Cognitive neuroscientists use various noninvasive techniques (e.g., fMRI) to investigate these networks. They represent them formally as graphs. And they use various graph theoretic techniques to analyze them further. We distinguish between knowledge of the graph theoretic structure of such networks (structural knowledge) and knowledge of what instantiates that structure (nonstructural knowledge). And we argue that this work provides structural knowledge of brain networks. We explore the significance of this conclusion for the scientific realism debate. We argue that our conclusion should not be understood as an instance of a global structural realist claim regarding the structure of the unobservable part of the world, but instead, as a local structural realist attitude towards brain networks in particular. And we argue that various local approaches to the realism debate, i.e., approaches that restrict realist commitments to particular theories and/or entities, are problematic insofar as they don't allow for the possibility of such a local structural realist attitude. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Brain plastic alterations in subjects with chronic right-sided sensorineural hearing loss: a resting-state MRI study].

PubMed

Zhang, L L; Gong, J P; Xu, Y W; Liu, B

2016-06-21

To investigate the nodal properties and reorganization of whole-brain functional network in subjects with severe right-sided SNHL. From June 2012 to June 2013, a total of 19 patients with severe right-sided SNHL were collected from Zhongda Hospital or the recruitment advertising along with 31 healthy controls.Based on the graph-theoretical analysis, the whole-brain functional networks were constructed using the BOLD-fMRI data of all subjects.Two sample two-tailed t-tests were used to investigate the differences between two groups in nodal metrics, such as node degree, node betweenness, node global efficiency and node local efficiency.All metrics were corrected by multiple comparisons.Partial correlation analysis was used to estimate the relationship between the significant metrics and the duration or severity of hearing loss. The right-sided SNHL showed significantly increased betweenness centrality in left supramarginal gyrus and right fusiform.However, other nodal parameters showed no statistical difference.Besides, patients exhibited no significant association between the altered metrics and clinical variables. Alterations of local topological properties may underlie cerebral cross-modal plastic reorganization in visual or speech-related regions in severe right-sided SNHL patients.

Localized reductions in resting-state functional connectivity in children with prenatal alcohol exposure.

PubMed

Fan, Jia; Taylor, Paul A; Jacobson, Sandra W; Molteno, Christopher D; Gohel, Suril; Biswal, Bharat B; Jacobson, Joseph L; Meintjes, Ernesta M

2017-10-01

Fetal alcohol spectrum disorders (FASD) are characterized by impairment in cognitive function that may or may not be accompanied by craniofacial anomalies, microcephaly, and/or growth retardation. Resting-state functional MRI (rs-fMRI), which examines the low-frequency component of the blood oxygen level dependent (BOLD) signal in the absence of an explicit task, provides an efficient and powerful mechanism for studying functional brain networks even in low-functioning and young subjects. Studies using independent component analysis (ICA) have identified a set of resting-state networks (RSNs) that have been linked to distinct domains of cognitive and perceptual function, which are believed to reflect the intrinsic functional architecture of the brain. This study is the first to examine resting-state functional connectivity within these RSNs in FASD. Rs-fMRI scans were performed on 38 children with FASD (19 with either full fetal alcohol syndrome (FAS) or partial FAS (PFAS), 19 nonsyndromal heavily exposed (HE)), and 19 controls, mean age 11.3 ± 0.9 years, from the Cape Town Longitudinal Cohort. Nine resting-state networks were generated by ICA. Voxelwise group comparison between a combined FAS/PFAS group and controls revealed localized dose-dependent functional connectivity reductions in five regions in separate networks: anterior default mode, salience, ventral and dorsal attention, and R executive control. The former three also showed lower connectivity in the HE group. Gray matter connectivity deficits in four of the five networks appear to be related to deficits in white matter tracts that provide intra-RSN connections. Hum Brain Mapp 38:5217-5233, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

EEG Cortical Connectivity Analysis of Working Memory Reveals Topological Reorganization in Theta and Alpha Bands

PubMed Central

Dai, Zhongxiang; de Souza, Joshua; Lim, Julian; Ho, Paul M.; Chen, Yu; Li, Junhua; Thakor, Nitish; Bezerianos, Anastasios; Sun, Yu

2017-01-01

Numerous studies have revealed various working memory (WM)-related brain activities that originate from various cortical regions and oscillate at different frequencies. However, multi-frequency band analysis of the brain network in WM in the cortical space remains largely unexplored. In this study, we employed a graph theoretical framework to characterize the topological properties of the brain functional network in the theta and alpha frequency bands during WM tasks. Twenty-eight subjects performed visual n-back tasks at two difficulty levels, i.e., 0-back (control task) and 2-back (WM task). After preprocessing, Electroencephalogram (EEG) signals were projected into the source space and 80 cortical brain regions were selected for further analysis. Subsequently, the theta- and alpha-band networks were constructed by calculating the Pearson correlation coefficients between the power series (obtained by concatenating the power values of all epochs in each session) of all pairs of brain regions. Graph theoretical approaches were then employed to estimate the topological properties of the brain networks at different WM tasks. We found higher functional integration in the theta band and lower functional segregation in the alpha band in the WM task compared with the control task. Moreover, compared to the 0-back task, altered regional centrality was revealed in the 2-back task in various brain regions that mainly resided in the frontal, temporal and occipital lobes, with distinct presentations in the theta and alpha bands. In addition, significant negative correlations were found between the reaction time with the average path length of the theta-band network and the local clustering of the alpha-band network, which demonstrates the potential for using the brain network metrics as biomarkers for predicting the task performance during WM tasks. PMID:28553215

EEG Cortical Connectivity Analysis of Working Memory Reveals Topological Reorganization in Theta and Alpha Bands.

PubMed

Dai, Zhongxiang; de Souza, Joshua; Lim, Julian; Ho, Paul M; Chen, Yu; Li, Junhua; Thakor, Nitish; Bezerianos, Anastasios; Sun, Yu

2017-01-01

Numerous studies have revealed various working memory (WM)-related brain activities that originate from various cortical regions and oscillate at different frequencies. However, multi-frequency band analysis of the brain network in WM in the cortical space remains largely unexplored. In this study, we employed a graph theoretical framework to characterize the topological properties of the brain functional network in the theta and alpha frequency bands during WM tasks. Twenty-eight subjects performed visual n -back tasks at two difficulty levels, i.e., 0-back (control task) and 2-back (WM task). After preprocessing, Electroencephalogram (EEG) signals were projected into the source space and 80 cortical brain regions were selected for further analysis. Subsequently, the theta- and alpha-band networks were constructed by calculating the Pearson correlation coefficients between the power series (obtained by concatenating the power values of all epochs in each session) of all pairs of brain regions. Graph theoretical approaches were then employed to estimate the topological properties of the brain networks at different WM tasks. We found higher functional integration in the theta band and lower functional segregation in the alpha band in the WM task compared with the control task. Moreover, compared to the 0-back task, altered regional centrality was revealed in the 2-back task in various brain regions that mainly resided in the frontal, temporal and occipital lobes, with distinct presentations in the theta and alpha bands. In addition, significant negative correlations were found between the reaction time with the average path length of the theta-band network and the local clustering of the alpha-band network, which demonstrates the potential for using the brain network metrics as biomarkers for predicting the task performance during WM tasks.

Tai Chi Chuan optimizes the functional organization of the intrinsic human brain architecture in older adults

PubMed Central

Wei, Gao-Xia; Dong, Hao-Ming; Yang, Zhi; Luo, Jing; Zuo, Xi-Nian

2014-01-01

Whether Tai Chi Chuan (TCC) can influence the intrinsic functional architecture of the human brain remains unclear. To examine TCC-associated changes in functional connectomes, resting-state functional magnetic resonance images were acquired from 40 older individuals including 22 experienced TCC practitioners (experts) and 18 demographically matched TCC-naïve healthy controls, and their local functional homogeneities across the cortical mantle were compared. Compared to the controls, the TCC experts had significantly greater and more experience-dependent functional homogeneity in the right post-central gyrus (PosCG) and less functional homogeneity in the left anterior cingulate cortex (ACC) and the right dorsal lateral prefrontal cortex. Increased functional homogeneity in the PosCG was correlated with TCC experience. Intriguingly, decreases in functional homogeneity (improved functional specialization) in the left ACC and increases in functional homogeneity (improved functional integration) in the right PosCG both predicted performance gains on attention network behavior tests. These findings provide evidence for the functional plasticity of the brain’s intrinsic architecture toward optimizing locally functional organization, with great implications for understanding the effects of TCC on cognition, behavior and health in aging population. PMID:24860494

Increased densities of monocarboxylate transporter MCT1 after chronic hyperglycemia in rat brain.

PubMed

Canis, Martin; Maurer, Martin H; Kuschinsky, Wolfgang; Duembgen, Lutz; Duelli, Roman

2009-02-27

The brain is capable of taking up monocarboxylates as energy substrates. Under physiological conditions, plasma levels of monocarboxylates are very low and glucose is the primary energy substrate in brain metabolism. However, given conditions such as hyperglycemia and ketosis, levels of circulating monocarboxylates such as lactate and pyruvate are elevated. Previous studies reported an increased expression of monocarboxylate transporter MCT1 in brain following ketotic diet. The major aim of the present study was to answer the question whether chronic hyperglycemia is likewise sufficient to change local densities of MCT1 in the brain. Moreover, chronic hyperglycemia increases local cerebral glucose utilization (LCGU) in particular brain areas. Glucose hereby enters the brain parenchyma via glucose transporters and is partially metabolised by astrocytes, which then release lactate to meet the energetic demands of surrounding neurons. Streptozotocin was given intravenously to induce chronic hyperglycemia and local densities of MCT1 were measured by immunoautoradiographic methods in cryosections of rat brains. The density of monocarboxylate transporter MCT1 was significantly increased in 10 of 24 brain structures investigated (median increase 11.7+/-3.4 %). Immunocytochemical stainings of these substructures revealed an expression of MCT1 within endothelial cells and astrocytes. A comparison of MCT1 densities with LCGU measured in a previous study under normo- and hyperglycemic conditions revealed a partial correlation between both parameters and under both conditions. Four out of 10 brain areas, which showed a significant increase in MCT1 density due to hyperglycemia, also showed a significant increase in LCGU. In summary, our data show that chronic hyperglycemia induces a moderate increase of local and global density of MCT1 in several brain structures. However, in terms of brain topologies and substructures this phenomenon did only partially match with increased LCGU. It is concluded that MCT1 transporters were up-regulated during chronic hyperglycemia at the level of brain substructures and independently of LCGU.

Functional disorganization of small-world brain networks in mild Alzheimer's Disease and amnestic Mild Cognitive Impairment: an EEG study using Relative Wavelet Entropy (RWE).

PubMed

Frantzidis, Christos A; Vivas, Ana B; Tsolaki, Anthoula; Klados, Manousos A; Tsolaki, Magda; Bamidis, Panagiotis D

2014-01-01

Previous neuroscientific findings have linked Alzheimer's Disease (AD) with less efficient information processing and brain network disorganization. However, pathological alterations of the brain networks during the preclinical phase of amnestic Mild Cognitive Impairment (aMCI) remain largely unknown. The present study aimed at comparing patterns of the detection of functional disorganization in MCI relative to Mild Dementia (MD). Participants consisted of 23 cognitively healthy adults, 17 aMCI and 24 mild AD patients who underwent electroencephalographic (EEG) data acquisition during a resting-state condition. Synchronization analysis through the Orthogonal Discrete Wavelet Transform (ODWT), and directional brain network analysis were applied on the EEG data. This computational model was performed for networks that have the same number of edges (N = 500, 600, 700, 800 edges) across all participants and groups (fixed density values). All groups exhibited a small-world (SW) brain architecture. However, we found a significant reduction in the SW brain architecture in both aMCI and MD patients relative to the group of Healthy controls. This functional disorganization was also correlated with the participant's generic cognitive status. The deterioration of the network's organization was caused mainly by deficient local information processing as quantified by the mean cluster coefficient value. Functional hubs were identified through the normalized betweenness centrality metric. Analysis of the local characteristics showed relative hub preservation even with statistically significant reduced strength. Compensatory phenomena were also evident through the formation of additional hubs on left frontal and parietal regions. Our results indicate a declined functional network organization even during the prodromal phase. Degeneration is evident even in the preclinical phase and coexists with transient network reorganization due to compensation.

Single-subject-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mild traumatic brain injury

PubMed Central

Huang, Ming-Xiong; Nichols, Sharon; Baker, Dewleen G.; Robb, Ashley; Angeles, Annemarie; Yurgil, Kate A.; Drake, Angela; Levy, Michael; Song, Tao; McLay, Robert; Theilmann, Rebecca J.; Diwakar, Mithun; Risbrough, Victoria B.; Ji, Zhengwei; Huang, Charles W.; Chang, Douglas G.; Harrington, Deborah L.; Muzzatti, Laura; Canive, Jose M.; Christopher Edgar, J.; Chen, Yu-Han; Lee, Roland R.

2014-01-01

Traumatic brain injury (TBI) is a leading cause of sustained impairment in military and civilian populations. However, mild TBI (mTBI) can be difficult to detect using conventional MRI or CT. Injured brain tissues in mTBI patients generate abnormal slow-waves (1–4 Hz) that can be measured and localized by resting-state magnetoencephalography (MEG). In this study, we develop a voxel-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mTBI on a single-subject basis. A normative database of resting-state MEG source magnitude images (1–4 Hz) from 79 healthy control subjects was established for all brain voxels. The high-resolution MEG source magnitude images were obtained by our recent Fast-VESTAL method. In 84 mTBI patients with persistent post-concussive symptoms (36 from blasts, and 48 from non-blast causes), our method detected abnormalities at the positive detection rates of 84.5%, 86.1%, and 83.3% for the combined (blast-induced plus with non-blast causes), blast, and non-blast mTBI groups, respectively. We found that prefrontal, posterior parietal, inferior temporal, hippocampus, and cerebella areas were particularly vulnerable to head trauma. The result also showed that MEG slow-wave generation in prefrontal areas positively correlated with personality change, trouble concentrating, affective lability, and depression symptoms. Discussion is provided regarding the neuronal mechanisms of MEG slow-wave generation due to deafferentation caused by axonal injury and/or blockages/limitations of cholinergic transmission in TBI. This study provides an effective way for using MEG slow-wave source imaging to localize affected areas and supports MEG as a tool for assisting the diagnosis of mTBI. PMID:25009772

Local brain connectivity across development in autism spectrum disorder: A cross-sectional investigation.

PubMed

Dajani, Dina R; Uddin, Lucina Q

2016-01-01

There is a general consensus that autism spectrum disorder (ASD) is accompanied by alterations in brain connectivity. Much of the neuroimaging work has focused on assessing long-range connectivity disruptions in ASD. However, evidence from both animal models and postmortem examination of the human brain suggests that local connections may also be disrupted in individuals with the disorder. Here, we investigated how regional homogeneity (ReHo), a measure of similarity of a voxel's timeseries to its nearest neighbors, varies across age in individuals with ASD and typically developing (TD) individuals using a cross-sectional design. Resting-state fMRI data obtained from a publicly available database were analyzed to determine group differences in ReHo between three age cohorts: children, adolescents, and adults. In typical development, ReHo across the entire brain was higher in children than in adolescents and adults. In contrast, children with ASD exhibited marginally lower ReHo than TD children, while adolescents and adults with ASD exhibited similar levels of local connectivity as age-matched neurotypical individuals. During all developmental stages, individuals with ASD exhibited lower local connectivity in sensory processing brain regions and higher local connectivity in complex information processing regions. Further, higher local connectivity in ASD corresponded to more severe ASD symptomatology. These results demonstrate that local connectivity is disrupted in ASD across development, with the most pronounced differences occurring in childhood. Developmental changes in ReHo do not mirror findings from fMRI studies of long-range connectivity in ASD, pointing to a need for more nuanced accounts of brain connectivity alterations in the disorder. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

A high-resolution computational localization method for transcranial magnetic stimulation mapping.

PubMed

Aonuma, Shinta; Gomez-Tames, Jose; Laakso, Ilkka; Hirata, Akimasa; Takakura, Tomokazu; Tamura, Manabu; Muragaki, Yoshihiro

2018-05-15

Transcranial magnetic stimulation (TMS) is used for the mapping of brain motor functions. The complexity of the brain deters determining the exact localization of the stimulation site using simplified methods (e.g., the region below the center of the TMS coil) or conventional computational approaches. This study aimed to present a high-precision localization method for a specific motor area by synthesizing computed non-uniform current distributions in the brain for multiple sessions of TMS. Peritumoral mapping by TMS was conducted on patients who had intra-axial brain neoplasms located within or close to the motor speech area. The electric field induced by TMS was computed using realistic head models constructed from magnetic resonance images of patients. A post-processing method was implemented to determine a TMS hotspot by combining the computed electric fields for the coil orientations and positions that delivered high motor-evoked potentials during peritumoral mapping. The method was compared to the stimulation site localized via intraoperative direct brain stimulation and navigated TMS. Four main results were obtained: 1) the dependence of the computed hotspot area on the number of peritumoral measurements was evaluated; 2) the estimated localization of the hand motor area in eight non-affected hemispheres was in good agreement with the position of a so-called "hand-knob"; 3) the estimated hotspot areas were not sensitive to variations in tissue conductivity; and 4) the hand motor areas estimated by this proposal and direct electric stimulation (DES) were in good agreement in the ipsilateral hemisphere of four glioma patients. The TMS localization method was validated by well-known positions of the "hand-knob" in brains for the non-affected hemisphere, and by a hotspot localized via DES during awake craniotomy for the tumor-containing hemisphere. Copyright © 2018 Elsevier Inc. All rights reserved.

Disrupted topological organization in whole-brain functional networks of heroin-dependent individuals: a resting-state FMRI study.

PubMed

Jiang, Guihua; Wen, Xue; Qiu, Yingwei; Zhang, Ruibin; Wang, Junjing; Li, Meng; Ma, Xiaofen; Tian, Junzhang; Huang, Ruiwang

2013-01-01

Neuroimaging studies have shown that heroin addiction is related to abnormalities in widespread local regions and in the functional connectivity of the brain. However, little is known about whether heroin addiction changes the topological organization of whole-brain functional networks. Seventeen heroin-dependent individuals (HDIs) and 15 age-, gender-matched normal controls (NCs) were enrolled, and the resting-state functional magnetic resonance images (RS-fMRI) were acquired from these subjects. We constructed the brain functional networks of HDIs and NCs, and compared the between-group differences in network topological properties using graph theory method. We found that the HDIs showed decreases in the normalized clustering coefficient and in small-worldness compared to the NCs. Furthermore, the HDIs exhibited significantly decreased nodal centralities primarily in regions of cognitive control network, including the bilateral middle cingulate gyrus, left middle frontal gyrus, and right precuneus, but significantly increased nodal centralities primarily in the left hippocampus. The between-group differences in nodal centralities were not corrected by multiple comparisons suggesting these should be considered as an exploratory analysis. Moreover, nodal centralities in the left hippocampus were positively correlated with the duration of heroin addiction. Overall, our results indicated that disruptions occur in the whole-brain functional networks of HDIs, findings which may be helpful in further understanding the mechanisms underlying heroin addiction.

Exercise increases blood flow to locomotor, vestibular, cardiorespiratory and visual regions of the brain in miniature swine

PubMed Central

Delp, Michael D; Armstrong, R B; Godfrey, Donald A; Laughlin, M Harold; Ross, C David; Wilkerson, M Keith

2001-01-01

The purpose of these experiments was to use radiolabelled microspheres to measure blood flow distribution within the brain, and in particular to areas associated with motor function, maintenance of equilibrium, cardiorespiratory control, vision, hearing and smell, at rest and during exercise in miniature swine. Exercise consisted of steady-state treadmill running at intensities eliciting 70 and 100 % maximal oxygen consumption (). Mean arterial pressure was elevated by 17 and 26 % above that at rest during exercise at 70 and 100 %, respectively. Mean brain blood flow increased 24 and 25 % at 70 and 100 %, respectively. Blood flow was not locally elevated to cortical regions associated with motor and somatosensory functions during exercise, but was increased to several subcortical areas that are involved in the control of locomotion. Exercise elevated perfusion and diminished vascular resistance in several regions of the brain related to the maintenance of equilibrium (vestibular nuclear area, cerebellar ventral vermis and floccular lobe), cardiorespiratory control (medulla and pons), and vision (dorsal occipital cortex, superior colliculi and lateral geniculate body). Conversely, blood flow to regions related to hearing (cochlear nuclei, inferior colliculi and temporal cortex) and smell (olfactory bulbs and rhinencephalon) were unaltered by exercise and associated with increases in vascular resistance. The data indicate that blood flow increases as a function of exercise intensity to several areas of the brain associated with integrating sensory input and motor output (anterior and dorsal cerebellar vermis) and the maintenance of equilibrium (vestibular nuclei). Additionally, there was an intensity-dependent decrease of vascular resistance in the dorsal cerebellar vermis. PMID:11410640

Brain anatomical networks in world class gymnasts: a DTI tractography study.

PubMed

Wang, Bin; Fan, Yuanyuan; Lu, Min; Li, Shumei; Song, Zheng; Peng, Xiaoling; Zhang, Ruibin; Lin, Qixiang; He, Yong; Wang, Jun; Huang, Ruiwang

2013-01-15

The excellent motor skills of world class gymnasts amaze everyone. People marvel at the way they precisely control their movements and wonder how the brain structure and function of these elite athletes differ from those of non-athletes. In this study, we acquired diffusion images from thirteen world class gymnasts and fourteen matched controls, constructed their anatomical networks, and calculated the topological properties of each network based on graph theory. From a connectivity-based analysis, we found that most of the edges with increased connection density in the champions were linked to brain regions that are located in the sensorimotor, attentional, and default-mode systems. From graph-based metrics, we detected significantly greater global and local efficiency but shorter characteristic path length in the anatomical networks of the champions compared with the controls. Moreover, in the champions we found a significantly higher nodal degree and greater regional efficiency in several brain regions that correspond to motor and attention functions. These included the left precentral gyrus, left postcentral gyrus, right anterior cingulate gyrus and temporal lobes. In addition, we revealed an increase in the mean fractional anisotropy of the corticospinal tract in the champions, possibly in response to long-term gymnastic training. Our study indicates that neuroanatomical adaptations and plastic changes occur in gymnasts' brain anatomical networks either in response to long-term intensive gymnastic training or as an innate predisposition or both. Our findings may help to explain gymnastic skills at the highest levels of performance and aid in understanding the neural mechanisms that distinguish expert gymnasts from novices. Copyright © 2012 Elsevier Inc. All rights reserved.

A multi-purpose electromagnetic actuator for magnetic resonance elastography.

PubMed

Feng, Yuan; Zhu, Mo; Qiu, Suhao; Shen, Ping; Ma, Shengyuan; Zhao, Xuefeng; Hu, Chun-Hong; Guo, Liang

2018-04-19

An electromagnetic actuator was designed for magnetic resonance elastography (MRE). The actuator is unique in that it is simple, portable, and capable of brain, abdomen, and phantom imagings. A custom-built control unit was used for controlling the vibration frequency and synchronizing the trigger signals. An actuation unit was built and mounted on the specifically designed clamp and holders for different imaging applications. MRE experiments with respect to gel phantoms, brain, and liver showed that the actuator could produce stable and consistent mechanical waves. Estimated shear modulus using local frequency estimate method demonstrated that the measurement results were in line with that from MRE studies using different actuation systems. The relatively easy setup procedure and simple design indicated that the actuator system had the potential to be applied in many different clinical studies. Copyright © 2018 Elsevier Inc. All rights reserved.

Identification of a novel synaptic protein, TMTC3, involved in periventricular nodular heterotopia with intellectual disability and epilepsy

PubMed Central

Farhan, Sali M K; Nixon, Kevin C J; Everest, Michelle; Edwards, Tara N; Long, Shirley; Segal, Dmitri; Knip, Maria J; Arts, Heleen H; Chakrabarti, Rana; Wang, Jian; Robinson, John F; Lee, Donald; Mirsattari, Seyed M; Rupar, C Anthony; Siu, Victoria M; Poulter, Michael O; Hegele, Robert A; Kramer, Jamie M

2017-01-01

Abstract Defects in neuronal migration cause brain malformations, which are associated with intellectual disability (ID) and epilepsy. Using exome sequencing, we identified compound heterozygous variants (p.Arg71His and p. Leu729ThrfsTer6) in TMTC3, encoding transmembrane and tetratricopeptide repeat containing 3, in four siblings with nocturnal seizures and ID. Three of the four siblings have periventricular nodular heterotopia (PVNH), a common brain malformation caused by failure of neurons to migrate from the ventricular zone to the cortex. Expression analysis using patient-derived cells confirmed reduced TMTC3 transcript levels and loss of the TMTC3 protein compared to parental and control cells. As TMTC3 function is currently unexplored in the brain, we gathered support for a neurobiological role for TMTC3 by generating flies with post-mitotic neuron-specific knockdown of the highly conserved Drosophila melanogaster TMTC3 ortholog, CG4050/tmtc3. Neuron-specific knockdown of tmtc3 in flies resulted in increased susceptibility to induced seizures. Importantly, this phenotype was rescued by neuron-specific expression of human TMTC3, suggesting a role for TMTC3 in seizure biology. In addition, we observed co-localization of TMTC3 in the rat brain with vesicular GABA transporter (VGAT), a presynaptic marker for inhibitory synapses. TMTC3 is localized at VGAT positive pre-synaptic terminals and boutons in the rat hypothalamus and piriform cortex, suggesting a role for TMTC3 in the regulation of GABAergic inhibitory synapses. TMTC3 did not co-localize with Vglut2, a presynaptic marker for excitatory neurons. Our data identified TMTC3 as a synaptic protein that is involved in PVNH with ID and epilepsy, in addition to its previously described association with cobblestone lissencephaly. PMID:28973161

Use of diffusion-weighted MRI to modify radiosurgery planning in brain metastases may reduce local recurrence.

PubMed

Zakaria, Rasheed; Pomschar, Andreas; Jenkinson, Michael D; Tonn, Jörg-Christian; Belka, Claus; Ertl-Wagner, Birgit; Niyazi, Maximilian

2017-02-01

Stereotactic radiosurgery (SRS) is an effective and well tolerated treatment for selected brain metastases; however, local recurrence still occurs. We investigated the use of diffusion weighted MRI (DWI) as an adjunct for SRS treatment planning in brain metastases. Seventeen consecutive patients undergoing complete surgical resection of a solitary brain metastasis underwent image analysis retrospectively. SRS treatment plans were generated based on standard 3D post-contrast T1-weighted sequences at 1.5T and then separately using apparent diffusion coefficient (ADC) maps in a blinded fashion. Control scans immediately post operation confirmed complete tumour resection. Treatment plans were compared to one another and with volume of local recurrence at progression quantitatively and qualitatively by calculating the conformity index (CI), the overlapping volume as a proportion of the total combined volume, where 1 = identical plans and 0 = no conformation whatsoever. Gross tumour volumes (GTVs) using ADC and post-contrast T1-weighted sequences were quantitatively the same (related samples Wilcoxon signed rank test = -0.45, p = 0.653) but showed differing conformations (CI 0.53, p < 0.001). The diffusion treatment volume (DTV) obtained by combining the two target volumes was significantly greater than the treatment volume based on post contrast T1-weighted MRI alone, both quantitatively (median 13.65 vs. 9.52 cm 3 , related samples Wilcoxon signed rank test p < 0.001) and qualitatively (CI 0.74, p = 0.001). This DTV covered a greater volume of subsequent tumour recurrence than the standard plan (median 3.53 cm 3 vs. 3.84 cm 3 , p = 0.002). ADC maps may be a useful tool in addition to the standard post-contrast T1-weighted sequence used for SRS planning.

Identification of a novel synaptic protein, TMTC3, involved in periventricular nodular heterotopia with intellectual disability and epilepsy.

PubMed

Farhan, Sali M K; Nixon, Kevin C J; Everest, Michelle; Edwards, Tara N; Long, Shirley; Segal, Dmitri; Knip, Maria J; Arts, Heleen H; Chakrabarti, Rana; Wang, Jian; Robinson, John F; Lee, Donald; Mirsattari, Seyed M; Rupar, C Anthony; Siu, Victoria M; Poulter, Michael O; Hegele, Robert A; Kramer, Jamie M

2017-11-01

Defects in neuronal migration cause brain malformations, which are associated with intellectual disability (ID) and epilepsy. Using exome sequencing, we identified compound heterozygous variants (p.Arg71His and p. Leu729ThrfsTer6) in TMTC3, encoding transmembrane and tetratricopeptide repeat containing 3, in four siblings with nocturnal seizures and ID. Three of the four siblings have periventricular nodular heterotopia (PVNH), a common brain malformation caused by failure of neurons to migrate from the ventricular zone to the cortex. Expression analysis using patient-derived cells confirmed reduced TMTC3 transcript levels and loss of the TMTC3 protein compared to parental and control cells. As TMTC3 function is currently unexplored in the brain, we gathered support for a neurobiological role for TMTC3 by generating flies with post-mitotic neuron-specific knockdown of the highly conserved Drosophila melanogaster TMTC3 ortholog, CG4050/tmtc3. Neuron-specific knockdown of tmtc3 in flies resulted in increased susceptibility to induced seizures. Importantly, this phenotype was rescued by neuron-specific expression of human TMTC3, suggesting a role for TMTC3 in seizure biology. In addition, we observed co-localization of TMTC3 in the rat brain with vesicular GABA transporter (VGAT), a presynaptic marker for inhibitory synapses. TMTC3 is localized at VGAT positive pre-synaptic terminals and boutons in the rat hypothalamus and piriform cortex, suggesting a role for TMTC3 in the regulation of GABAergic inhibitory synapses. TMTC3 did not co-localize with Vglut2, a presynaptic marker for excitatory neurons. Our data identified TMTC3 as a synaptic protein that is involved in PVNH with ID and epilepsy, in addition to its previously described association with cobblestone lissencephaly. © The Author 2017. Published by Oxford University Press.

Localization of Cognitive Operations in the Human Brain.

ERIC Educational Resources Information Center

Posner, Michael I.; And Others

1988-01-01

Hypothesizes that the human brain localizes mental operations which are integrated in the performance of cognitive tasks such as reading. Provides support of this hypothesis from studies in neural imaging, mental imagery, timing, and memory. (RT)

Increased brain edema following 5-aminolevulinic acid mediated photodynamic in normal and tumor bearing rats

NASA Astrophysics Data System (ADS)

Hirschberg, Henry; Angell-Petersen, Even; Spetalen, Signe; Mathews, Marlon; Madsen, Steen J.

2007-02-01

Introduction: Failure of treatment for high grade gliomas is usually due to local recurrence at the site of surgical resection indicating that a more aggressive form of local therapy, such as PDT, could be of benefit. PDT causes damage to both tumor cells as well as cerebral blood vessels leading to degradation of the blood brain barrier with subsequent increase of brain edema. The increase in brain edema following ALA-PDT was evaluated in terms of animal survival, histopatological changes in normal brain and tumor tissue and MRI scanning. The effect of steroid treatment, to reduce post-treatment PDT induced edema, was also examined. Methods:Tumors were established in the brains of inbred BD-IX and Fisher rats. At various times following tumor induction the animals were injected with ALA ip. and four hours later light treatment at escalating fluences and fluence rates were given. Nontumor bearing control animals were also exposed to ALA-PDT in a similar manner to evaluate damage to normal brain and degree of blood brain barrier (BBB) disruption. Results: Despite a very low level of PpIX production in normal brain, with a 200:1 tumor to normal tissue selectivity ratio measured at a distance of 2 mm from the tumor border, many animals succumbed shortly after treatment. A total radiant energy of 54 J to non-tumor bearing animals resulted in 50% mortality within 5 days of treatment. Treatment of tumor bearing animals with moderate fluence levels produced similar brain edema compared to higher fluence levels. ALA PDT in nontumor bearing animals produced edema that was light dose dependent. PDT appeared to open the BBB for a period of 24-48 hrs after which it was restored. The addition of post operative steroid treatment reduced the incident of post treatment morbidity and mortality. Conclusions: T2 and contrast enhanced T1 MRI scanning proved to be a highly effective and non-evasive modality in following the development of the edema reaction and the degree and time course of BBB dysfunction thus allowing the use of fewer animals.

Neuropeptide Signaling Networks and Brain Circuit Plasticity.

PubMed

McClard, Cynthia K; Arenkiel, Benjamin R

2018-01-01

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

Whole-brain radiotherapy and stereotactic radiosurgery in brain metastases: what is the evidence?

PubMed

Mehta, Minesh P; Ahluwalia, Manmeet S

2015-01-01

The overall local treatment paradigm of brain metastases, which includes whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS), continues to evolve. Local therapies play an important role in the management of brain metastases. The choice of local therapy depends on factors that involve the patient (performance status, expected survival, and age), the prior treatment history, and the tumor (type and subtype, number, size, location of metastases, and extracranial disease status). Multidisciplinary collaboration is required to facilitate an individualized plan to improve the outcome of disease in patients with this life-limiting complication. There has been concern about the neurocognitive effects of WBRT. A number of approaches that mitigate cognitive dysfunction, such as pharmacologic intervention (memantine) or a hippocampal-sparing strategy, have been studied in a prospective manner with WBRT. Although there has been an increase in the use of SRS in the management of brain metastases in recent years, WBRT retains an important therapeutic role.

Brain tumor segmentation based on local independent projection-based classification.

PubMed

Huang, Meiyan; Yang, Wei; Wu, Yao; Jiang, Jun; Chen, Wufan; Feng, Qianjin

2014-10-01

Brain tumor segmentation is an important procedure for early tumor diagnosis and radiotherapy planning. Although numerous brain tumor segmentation methods have been presented, enhancing tumor segmentation methods is still challenging because brain tumor MRI images exhibit complex characteristics, such as high diversity in tumor appearance and ambiguous tumor boundaries. To address this problem, we propose a novel automatic tumor segmentation method for MRI images. This method treats tumor segmentation as a classification problem. Additionally, the local independent projection-based classification (LIPC) method is used to classify each voxel into different classes. A novel classification framework is derived by introducing the local independent projection into the classical classification model. Locality is important in the calculation of local independent projections for LIPC. Locality is also considered in determining whether local anchor embedding is more applicable in solving linear projection weights compared with other coding methods. Moreover, LIPC considers the data distribution of different classes by learning a softmax regression model, which can further improve classification performance. In this study, 80 brain tumor MRI images with ground truth data are used as training data and 40 images without ground truth data are used as testing data. The segmentation results of testing data are evaluated by an online evaluation tool. The average dice similarities of the proposed method for segmenting complete tumor, tumor core, and contrast-enhancing tumor on real patient data are 0.84, 0.685, and 0.585, respectively. These results are comparable to other state-of-the-art methods.

Calvarial and skull base metastases: expanding the clinical utility of Gamma Knife surgery.

PubMed

Kotecha, Rupesh; Angelov, Lilyana; Barnett, Gene H; Reddy, Chandana A; Suh, John H; Murphy, Erin S; Neyman, Gennady; Chao, Samuel T

2014-12-01

Traditionally, the treatment of choice for patients with metastases to the calvaria or skull base has been conventional radiation therapy. Because patients with systemic malignancies are also at risk for intracranial metastases, the utility of Gamma Knife surgery (GKS) for these patients has been explored to reduce excess radiation exposure to the perilesional brain parenchyma. The purpose of this study was to report the efficacy of GKS for the treatment of calvarial metastases and skull base lesions. The authors performed a retrospective chart review of 21 patients with at least 1 calvarial or skull base metastatic lesion treated with GKS during 2001-2013. For 7 calvarial lesions, a novel technique, in which a bolus was placed over the treatment site, was used. For determination of local control or disease progression, radiation therapy data were examined and posttreatment MR images and oncology records were reviewed. Survival times from the date of procedure were estimated by using Kaplan-Meier analyses. The median patient age at treatment was 57 years (range 29-84 years). A total of 19 (90%) patients received treatment for single lesions, 1 patient received treatment for 3 lesions, and 1 patient received treatment for 4 lesions. The most common primary tumor was breast cancer (24% of patients). Per lesion, the median clinical and radiographic follow-up times were 10.3 months (range 0-71.9 months) and 7.1 months (range 0-61.3 months), respectively. Of the 26 lesions analyzed, 14 (54%) were located in calvarial bones and 12 (46%) were located in the skull base. The median lesion volume was 5.3 cm(3) (range 0.3-55.6 cm(3)), and the median prescription margin dose was 15 Gy (range 13-24 Gy). The median overall survival time for all patients was 35.9 months, and the 1-year local control rate was 88.9% (95% CI 74.4%-100%). Local control rates did not differ between lesions treated with the bolus technique and those treated with traditional methods or between calvarial lesions and skull base lesions (p > 0.05). Of the 3 patients for whom local treatment failed, 1 patient received no further treatment and 2 patients responded to salvage chemotherapy. Subsequent brain parenchymal metastases developed in 2 patients, who then underwent GKS. GKS is an effective treatment modality for patients with metastases to the calvarial bones or skull base. For patients with superficial calvarial lesions, a novel approach with bolus application resulted in excellent rates of local control. GKS provides an effective therapeutic alternative to conventional radiation therapy and should be considered for patients at risk for calvarial metastases and brain parenchymal metastases.

Joint source based analysis of multiple brain structures in studying major depressive disorder

NASA Astrophysics Data System (ADS)

Ramezani, Mahdi; Rasoulian, Abtin; Hollenstein, Tom; Harkness, Kate; Johnsrude, Ingrid; Abolmaesumi, Purang

2014-03-01

We propose a joint Source-Based Analysis (jSBA) framework to identify brain structural variations in patients with Major Depressive Disorder (MDD). In this framework, features representing position, orientation and size (i.e. pose), shape, and local tissue composition are extracted. Subsequently, simultaneous analysis of these features within a joint analysis method is performed to generate the basis sources that show signi cant di erences between subjects with MDD and those in healthy control. Moreover, in a cross-validation leave- one-out experiment, we use a Fisher Linear Discriminant (FLD) classi er to identify individuals within the MDD group. Results show that we can classify the MDD subjects with an accuracy of 76% solely based on the information gathered from the joint analysis of pose, shape, and tissue composition in multiple brain structures.

Impact of 2-staged stereotactic radiosurgery for treatment of brain metastases ≥ 2 cm.

PubMed

Angelov, Lilyana; Mohammadi, Alireza M; Bennett, Elizabeth E; Abbassy, Mahmoud; Elson, Paul; Chao, Samuel T; Montgomery, Joshua S; Habboub, Ghaith; Vogelbaum, Michael A; Suh, John H; Murphy, Erin S; Ahluwalia, Manmeet S; Nagel, Sean J; Barnett, Gene H

2017-09-22

OBJECTIVE Stereotactic radiosurgery (SRS) is the primary modality for treating brain metastases. However, effective radiosurgical control of brain metastases ≥ 2 cm in maximum diameter remains challenging and is associated with suboptimal local control (LC) rates of 37%-62% and an increased risk of treatment-related toxicity. To enhance LC while limiting adverse effects (AEs) of radiation in these patients, a dose-dense treatment regimen using 2-staged SRS (2-SSRS) was used. The objective of this study was to evaluate the efficacy and toxicity of this treatment strategy. METHODS Fifty-four patients (with 63 brain metastases ≥ 2 cm) treated with 2-SSRS were evaluated as part of an institutional review board-approved retrospective review. Volumetric measurements at first-stage stereotactic radiosurgery (first SSRS) and second-stage SRS (second SSRS) treatments and on follow-up imaging studies were determined. In addition to patient demographic data and tumor characteristics, the study evaluated 3 primary outcomes: 1) response at first follow-up MRI, 2) time to local progression (TTP), and 3) overall survival (OS) with 2-SSRS. Response was analyzed using methods for binary data, TTP was analyzed using competing-risks methods to account for patients who died without disease progression, and OS was analyzed using conventional time-to-event methods. When needed, analyses accounted for multiple lesions in the same patient. RESULTS Among 54 patients, 46 (85%) had 1 brain metastasis treated with 2-SSRS, 7 patients (13%) had 2 brain metastases concurrently treated with 2-SSRS, and 1 patient underwent 2-SSRS for 3 concurrent brain metastases ≥ 2 cm. The median age was 63 years (range 23-83 years), 23 patients (43%) had non-small cell lung cancer, and 14 patients (26%) had radioresistant tumors (renal or melanoma). The median doses at first and second SSRS were 15 Gy (range 12-18 Gy) and 15 Gy (range 12-15 Gy), respectively. The median duration between stages was 34 days, and median tumor volumes at the first and second SSRS were 10.5 cm 3 (range 2.4-31.3 cm 3 ) and 7.0 cm 3 (range 1.0-29.7 cm 3 ). Three-month follow-up imaging results were available for 43 lesions; the median volume was 4.0 cm 3 (range 0.1-23.1 cm 3 ). The median change in volume compared with baseline was a decrease of 54.9% (range -98.2% to 66.1%; p < 0.001). Overall, 9 lesions (14.3%) demonstrated local progression, with a median of 5.2 months (range 1.3-7.4 months), and 7 (11.1%) demonstrated AEs (6.4% Grade 1 and 2 toxicity; 4.8% Grade 3). The estimated cumulative incidence of local progression at 6 months was 12% ± 4%, corresponding to an LC rate of 88%. Shorter TTP was associated with greater tumor volume at baseline (p = 0.01) and smaller absolute (p = 0.006) and relative (p = 0.05) decreases in tumor volume from baseline to second SSRS. Estimated OS rates at 6 and 12 months were 65% ± 7% and 49% ± 8%, respectively. CONCLUSIONS 2-SSRS is an effective treatment modality that resulted in significant reduction of brain metastases ≥ 2 cm, with excellent 3-month (95%) and 6-month (88%) LC rates and an overall AE rate of 11%. Prospective studies with larger cohorts and longer follow-up are necessary to assess the durability and toxicities of 2-SSRS.

Local Versus Global Effects of Isoflurane Anesthesia on Visual Processing in the Fly Brain

PubMed Central

2016-01-01

Abstract What characteristics of neural activity distinguish the awake and anesthetized brain? Drugs such as isoflurane abolish behavioral responsiveness in all animals, implying evolutionarily conserved mechanisms. However, it is unclear whether this conservation is reflected at the level of neural activity. Studies in humans have shown that anesthesia is characterized by spatially distinct spectral and coherence signatures that have also been implicated in the global impairment of cortical communication. We questioned whether anesthesia has similar effects on global and local neural processing in one of the smallest brains, that of the fruit fly (Drosophila melanogaster). Using a recently developed multielectrode technique, we recorded local field potentials from different areas of the fly brain simultaneously, while manipulating the concentration of isoflurane. Flickering visual stimuli (‘frequency tags’) allowed us to track evoked responses in the frequency domain and measure the effects of isoflurane throughout the brain. We found that isoflurane reduced power and coherence at the tagging frequency (13 or 17 Hz) in central brain regions. Unexpectedly, isoflurane increased power and coherence at twice the tag frequency (26 or 34 Hz) in the optic lobes of the fly, but only for specific stimulus configurations. By modeling the periodic responses, we show that the increase in power in peripheral areas can be attributed to local neuroanatomy. We further show that the effects on coherence can be explained by impacted signal-to-noise ratios. Together, our results show that general anesthesia has distinct local and global effects on neuronal processing in the fruit fly brain. PMID:27517084

Local Versus Global Effects of Isoflurane Anesthesia on Visual Processing in the Fly Brain.

PubMed

Cohen, Dror; Zalucki, Oressia H; van Swinderen, Bruno; Tsuchiya, Naotsugu

2016-01-01

What characteristics of neural activity distinguish the awake and anesthetized brain? Drugs such as isoflurane abolish behavioral responsiveness in all animals, implying evolutionarily conserved mechanisms. However, it is unclear whether this conservation is reflected at the level of neural activity. Studies in humans have shown that anesthesia is characterized by spatially distinct spectral and coherence signatures that have also been implicated in the global impairment of cortical communication. We questioned whether anesthesia has similar effects on global and local neural processing in one of the smallest brains, that of the fruit fly (Drosophila melanogaster). Using a recently developed multielectrode technique, we recorded local field potentials from different areas of the fly brain simultaneously, while manipulating the concentration of isoflurane. Flickering visual stimuli ('frequency tags') allowed us to track evoked responses in the frequency domain and measure the effects of isoflurane throughout the brain. We found that isoflurane reduced power and coherence at the tagging frequency (13 or 17 Hz) in central brain regions. Unexpectedly, isoflurane increased power and coherence at twice the tag frequency (26 or 34 Hz) in the optic lobes of the fly, but only for specific stimulus configurations. By modeling the periodic responses, we show that the increase in power in peripheral areas can be attributed to local neuroanatomy. We further show that the effects on coherence can be explained by impacted signal-to-noise ratios. Together, our results show that general anesthesia has distinct local and global effects on neuronal processing in the fruit fly brain.

Brain bioavailability of human intravenous immunoglobulin and its transport through the murine blood–brain barrier

PubMed Central

St-Amour, Isabelle; Paré, Isabelle; Alata, Wael; Coulombe, Katherine; Ringuette-Goulet, Cassandra; Drouin-Ouellet, Janelle; Vandal, Milène; Soulet, Denis; Bazin, Renée; Calon, Frédéric

2013-01-01

Intravenous immunoglobulin (IVIg) is currently evaluated in clinical trials for the treatment of various disorders of the central nervous system. To assess its capacity to reach central therapeutic targets, the brain bioavailability of IVIg must be determined. We thus quantified the passage of IVIg through the blood–brain barrier (BBB) of C57Bl/6 mice using complementary quantitative and qualitative methodologies. As determined by enzyme-linked immunosorbent assay, a small proportion of systemically injected IVIg was detected in the brain of mice (0.009±0.001% of injected dose in the cortex) whereas immunostaining revealed localization mainly within microvessels and less frequently in neurons. Pharmacokinetic analyses evidenced a low elimination rate constant (0.0053  per hour) in the cortex, consistent with accumulation within cerebral tissue. In situ cerebral perfusion experiments revealed that a fraction of IVIg crossed the BBB without causing leakage. A dose-dependent decrease of brain uptake was consistent with a saturable blood-to-brain transport mechanism. Finally, brain uptake of IVIg after a subchronic treatment was similar in the 3xTg-AD mouse model of Alzheimer disease compared with nontransgenic controls. In summary, our results provide evidence of BBB passage and bioavailability of IVIg into the brain in the absence of BBB leakage and in sufficient concentration to interact with the therapeutic targets. PMID:24045402

FXR1P Limits Long-Term Memory, Long-Lasting Synaptic Potentiation, and de novo GluA2 Translation

PubMed Central

Jones, Emma V.; Altimimi, Haider F.; Farmer, W. Todd; Gandin, Valentina; Hanna, Edith; Zong, Ruiting; Barbon, Alessandro; Nelson, David L.; Topisirovic, Ivan; Rochford, Joseph; Stellwagen, David; Béïque, Jean-Claude; Murai, Keith K.

2014-01-01

SUMMARY Translational control of mRNAs allows for rapid and selective changes in synaptic protein expression, changes that are required for long-lasting plasticity and memory formation in the brain. Fragile X Related Protein 1 (FXR1P) is an RNA-binding protein that controls mRNA translation in non-neuronal cells and co-localizes with translational machinery in neurons. However, its neuronal mRNA targets and role in the brain are unknown. Here, we demonstrate that removal of FXR1P from the forebrain of postnatal mice selectively enhances long-term storage of spatial memories, hippocampal late-phase LTP (L-LTP) and de novo GluA2 synthesis. Furthermore, FXR1P binds specifically to the 5’UTR of GluA2 mRNA to repress translation and limit the amount of GluA2 incorporated at potentiated synapses. This study uncovers a new mechanism for regulating long-lasting synaptic plasticity and spatial memory formation and reveals an unexpected divergent role of FXR1P among Fragile X proteins in brain plasticity. PMID:25456134

Characteristic changes in brain electrical activity due to chronic hypoxia in patients with obstructive sleep apnea syndrome (OSAS): a combined EEG study using LORETA and omega complexity.

PubMed

Toth, Marton; Faludi, Bela; Wackermann, Jiri; Czopf, Jozsef; Kondakor, Istvan

2009-11-01

EEG background activity of patients with obstructive sleep apnea syndrome (OSAS, N = 25) was compared to that of normal controls (N = 14) to reflect alterations of brain electrical activity caused by chronic intermittent hypoxia in OSAS. Global and regional (left vs. right, anterior vs. posterior) measures of spatial complexity (Omega) were used to characterize the degree of spatial synchrony of EEG. Low resolution electromagnetic tomography (LORETA) was used to localize generators of EEG activity in separate frequency bands. Comparing patients to controls, lower Omega complexity was found globally and in the right hemisphere. Using LORETA, an increased medium frequency activity was seen bilaterally in the precuneus, paracentral and posterior cingulate cortex. These findings indicate that alterations caused by chronic hypoxia in brain electrical activity in regions associated with influencing emotional regulation, long-term memory and the default mode network. Global synchronization (lower Omega complexity) may indicate a significantly reduced number of relatively independent, parallel neural processes due to chronic global hypoxic state in apneic patients as well as over the right hemisphere.

Chemotherapy and biological treatment options in breast cancer patients with brain metastasis: an update.

PubMed

Arslan, Cagatay; Dizdar, Omer; Altundag, Kadri

2014-08-01

Breast cancer (BC) is the second most common cause of CNS metastasis. Ten to 20% of all, and 38% of human epidermal growth factor-2(+), metastatic BC patients experience brain metastasis (BM). Prolonged survival with better control of systemic disease and limited penetration of drugs to CNS increased the probability of CNS metastasis as a sanctuary site of relapse. Treatment of CNS disease has become an important component of overall disease control and quality of life. Current standard therapy for BM is whole-brain radiotherapy, surgery, stereotactic body radiation therapy for selected cases, corticosteroids and systemic chemotherapy. Little progress has been made in chemotherapy for the treatment of BM in patients with BC. Nevertheless, new treatment choices have emerged. In this review, we aimed to update current and future treatment options in systemic treatment for BM of BC. Cornerstone local treatment options for BM of BC are radiotherapy and surgery in selected cases. Efficacy of cytotoxic chemotherapeutics is limited. Among targeted therapies, lapatinib has activity in systemic treatment of BM particularly when used in combination with capecitabine. Novel agents are currently investigated.

Estimate the effective connectivity in multi-coupled neural mass model using particle swarm optimization

NASA Astrophysics Data System (ADS)

Shan, Bonan; Wang, Jiang; Deng, Bin; Zhang, Zhen; Wei, Xile

2017-03-01

Assessment of the effective connectivity among different brain regions during seizure is a crucial problem in neuroscience today. As a consequence, a new model inversion framework of brain function imaging is introduced in this manuscript. This framework is based on approximating brain networks using a multi-coupled neural mass model (NMM). NMM describes the excitatory and inhibitory neural interactions, capturing the mechanisms involved in seizure initiation, evolution and termination. Particle swarm optimization method is used to estimate the effective connectivity variation (the parameters of NMM) and the epileptiform dynamics (the states of NMM) that cannot be directly measured using electrophysiological measurement alone. The estimated effective connectivity includes both the local connectivity parameters within a single region NMM and the remote connectivity parameters between multi-coupled NMMs. When the epileptiform activities are estimated, a proportional-integral controller outputs control signal so that the epileptiform spikes can be inhibited immediately. Numerical simulations are carried out to illustrate the effectiveness of the proposed framework. The framework and the results have a profound impact on the way we detect and treat epilepsy.

Photon dynamics in tissue imaging

NASA Astrophysics Data System (ADS)

Chance, Britton; Haselgrove, John C.; Wang, NaiGuang; Maris, Michael B.; Sevick-Muraca, Eva M.

1991-11-01

The emerging need for a fast, safe economical approach to global and localized measures of desaturation of hemoglobin with oxygen (HbO2) in the human brain motivates further research on time-resolved spectroscopy in four areas of study. (1) To afford quantization of hemoglobin saturation through time-resolved spectroscopy in the time domain (TD) and in the frequency domain (FD). Evaluation of dual-wavelength TD and FD spectrometers for determining quantitatively hemoglobin desaturation and blood-volume changes by calculations that are insensitive to mutual interference is proposed. The diffusion equation, as it applies especially to TD studies, and the absorption ((mu) a) and scattering ((mu) s) coefficients provide their independent determination from the late and early respective portions of the kinetics of the emergent photons in response to a short input pulse (50-100 psec). (2) The identification of the photon-pathlength change due to the arterial pulse in the brain tissue by FD methods with Fourier transformation affords an opportunity to employ principles of pulse oximetry to vessels localized deep within the brain tissue. (3) Localization of desaturation of hemoglobin in portions of the brain can be achieved through dual-wavelength scanning of the input/output optical fibers across the head for an X-Y coordinate and varying the distance between input and output ((rho) ) or the time delay in data acquisition to afford an in-depth Z scan. Localizations of shed blood, which have an effective concentration of over 10 times that of capillary-bed blood, are identified by X, Y, Z scans using only a single wavelength. (4) Independent measurements of absorption ((mu) a) and scattering ((mu) s) coefficients, particularly by TD techniques, affords structural mapping of the brain, which can be used to diagnose brain tumor and neuronal degeneration. Two experimental systems are used to critically evaluate these studies; the first, a hemoglobin/lipid/yeast model in which intermittent oxygenation gives saturation/desaturation effects and addition of hemoglobin simulates increased blood volume. These models can be global or may contain localized ''black'' absorbers simulating brain bleeds or model-stroke volumes in which oxygenation/deoxygenation simulates normoxia/hypoxia. Secondly, animal brains are used to model the following changes in vivo: global or localized hypoxia, brain bleeding, and hematomas by epidural blood injection, and physiological changes by epilepsy. Neuronal degeneration causing scattering effects is modeled by injection, epidurally or into the animal model brain, highly scattering material such as polystyrene spheres. The proposal envisages a basic science study of photon migration in the brain with important applications to stroke, epilepsy, brain trauma, and neuronal degenerative disease.

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

PubMed

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

2014-10-15

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

Local cerebral glucose metabolism in patients with long-term behavioral and cognitive deficits following mild traumatic brain injury.

PubMed

Gross, H; Kling, A; Henry, G; Herndon, C; Lavretsky, H

1996-01-01

A retrospective study of 20 patients with mild traumatic brain injury (MTBI) examined brain regions of interest by comparing [18F]-2-deoxyglucose PET, neuropsychological test results, and continuing behavioral dysfunction. Abnormal local cerebral metabolic rates (rLCMs) were most prominent in midtemporal, anterior cingulate, precuneus, anterior temporal, frontal white, and corpus callosum brain regions. Abnormal rLCMs were significantly correlated statistically with 1) overall clinical complaints, most specifically with inconsistent attention/concentration and 2) overall neuropsychological test results. The authors conclude that 1) even mild TBI may result in continuing brain behavioral deficits; 2) PET can help elucidate dysfunctional brain circuitry in neurobehavioral disorders; and 3) specific brain areas may correlate with deficits in daily neurobehavioral functioning and neuropsychological test findings.

Evidence of a bigenomic regulation of mitochondrial gene expression by thyroid hormone during rat brain development.

PubMed

Sinha, Rohit Anthony; Pathak, Amrita; Mohan, Vishwa; Babu, Satish; Pal, Amit; Khare, Drirh; Godbole, Madan M

2010-07-02

Hypothyroidism during early mammalian brain development is associated with decreased expression of various mitochondrial encoded genes along with evidence for mitochondrial dysfunction. However, in-spite of the similarities between neurological disorders caused by perinatal hypothyroidism and those caused by various genetic mitochondrial defects we still do not know as to how thyroid hormone (TH) regulates mitochondrial transcription during development and whether this regulation by TH is nuclear mediated or through mitochondrial TH receptors? We here in rat cerebellum show that hypothyroidism causes reduction in expression of nuclear encoded genes controlling mitochondrial biogenesis like PGC-1alpha, NRF-1alpha and Tfam. Also, we for the first time demonstrate a mitochondrial localization of thyroid hormone receptor (mTR) isoform in developing brain capable of binding a TH response element (DR2) present in D-loop region of mitochondrial DNA. These results thus indicate an integrated nuclear-mitochondrial cross talk in regulation of mitochondrial transcription by TH during brain development. Copyright 2010 Elsevier Inc. All rights reserved.

Synthetic tactile perception induced by transcranial alternating-current stimulation can substitute for natural sensory stimulus in behaving rabbits.

PubMed

Márquez-Ruiz, Javier; Ammann, Claudia; Leal-Campanario, Rocío; Ruffini, Giulio; Gruart, Agnès; Delgado-García, José M

2016-01-21

The use of brain-derived signals for controlling external devices has long attracted the attention from neuroscientists and engineers during last decades. Although much effort has been dedicated to establishing effective brain-to-computer communication, computer-to-brain communication feedback for "closing the loop" is now becoming a major research theme. While intracortical microstimulation of the sensory cortex has already been successfully used for this purpose, its future application in humans partly relies on the use of non-invasive brain stimulation technologies. In the present study, we explore the potential use of transcranial alternating-current stimulation (tACS) for synthetic tactile perception in alert behaving animals. More specifically, we determined the effects of tACS on sensory local field potentials (LFPs) and motor output and tested its capability for inducing tactile perception using classical eyeblink conditioning in the behaving animal. We demonstrated that tACS of the primary somatosensory cortex vibrissa area could indeed substitute natural stimuli during training in the associative learning paradigm.

Evidence of a bigenomic regulation of mitochondrial gene expression by thyroid hormone during rat brain development

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

Sinha, Rohit Anthony; Pathak, Amrita; Mohan, Vishwa

Hypothyroidism during early mammalian brain development is associated with decreased expression of various mitochondrial encoded genes along with evidence for mitochondrial dysfunction. However, in-spite of the similarities between neurological disorders caused by perinatal hypothyroidism and those caused by various genetic mitochondrial defects we still do not know as to how thyroid hormone (TH) regulates mitochondrial transcription during development and whether this regulation by TH is nuclear mediated or through mitochondrial TH receptors? We here in rat cerebellum show that hypothyroidism causes reduction in expression of nuclear encoded genes controlling mitochondrial biogenesis like PGC-1{alpha}, NRF-1{alpha} and Tfam. Also, we for themore » first time demonstrate a mitochondrial localization of thyroid hormone receptor (mTR) isoform in developing brain capable of binding a TH response element (DR2) present in D-loop region of mitochondrial DNA. These results thus indicate an integrated nuclear-mitochondrial cross talk in regulation of mitochondrial transcription by TH during brain development.« less

Disruption of astrocyte-vascular coupling and the blood-brain barrier by invading glioma cells

PubMed Central

Watkins, Stacey; Robel, Stefanie; Kimbrough, Ian F.; Robert, Stephanie M.; Ellis-Davies, Graham; Sontheimer, Harald

2014-01-01

Astrocytic endfeet cover the entire cerebral vasculature and serve as exchange sites for ions, metabolites, and energy substrates from the blood to the brain. They maintain endothelial tight junctions that form the blood-brain barrier (BBB) and release vasoactive molecules that regulate vascular tone. Malignant gliomas are highly invasive tumors that use the perivascular space for invasion and co-opt existing vessels as satellite tumors form. Here we use a clinically relevant mouse model of glioma and find that glioma cells, as they populate the perivascular space of pre-existing vessels, displace astrocytic endfeet from endothelial or vascular smooth muscle cells. This causes a focal breach in the BBB. Furthermore, astrocyte-mediated gliovascular coupling is lost, and glioma cells seize control over regulation of vascular tone through Ca2+-dependent release of K+. These findings have important clinical implications regarding blood flow in the tumor-associated brain and the ability to locally deliver chemotherapeutic drugs in disease. PMID:24943270

Expression of CXCL4 in microglia in vitro and in vivo and its possible signaling through CXCR3.

PubMed

de Jong, Eiko K; de Haas, Alexander H; Brouwer, Nieske; van Weering, Hilmar R J; Hensens, Marjolein; Bechmann, Ingo; Pratley, Pierre; Wesseling, Evelyn; Boddeke, Hendrikus W G M; Biber, Knut

2008-06-01

Signaling through chemokine receptor CXCR3 in the brain has been implicated in various brain diseases, as CXCR3 and its ligands are found under these conditions. Recently, a new chemokine ligand for CXCR3 was reported. In humans, an alternatively spliced variant of CXCR3 expressed on microvascular endothelial cells, named CXCR3b, was shown to bind CXCL4. In the periphery, the cellular expression and functions of CXCL4 are well described but in the brain its expression and function are unknown. Here, we show that brain microglia are a cellular source of CXCL4 in vitro and in vivo under neurodegenerating conditions. Microglial migration induced by CXCL4 is absent in CXCR3-deficient microglia, indicating a role of CXCR3. CXCL4 furthermore attenuates lipopolysaccharide-induced microglial phagocytosis and nitric oxide production in microglia and BV-2 cells. Based on these findings, it is proposed that locally released CXCL4 may control microglia responses.

Locally optimal extracellular stimulation for chaotic desynchronization of neural populations.

PubMed

Wilson, Dan; Moehlis, Jeff

2014-10-01

We use optimal control theory to design a methodology to find locally optimal stimuli for desynchronization of a model of neurons with extracellular stimulation. This methodology yields stimuli which lead to positive Lyapunov exponents, and hence desynchronizes a neural population. We analyze this methodology in the presence of interneuron coupling to make predictions about the strength of stimulation required to overcome synchronizing effects of coupling. This methodology suggests a powerful alternative to pulsatile stimuli for deep brain stimulation as it uses less energy than pulsatile stimuli, and could eliminate the time consuming tuning process.

Blood-brain barrier disruption with focused ultrasound enhances delivery of chemotherapeutic drugs for glioblastoma treatment.

PubMed

Liu, Hao-Li; Hua, Mu-Yi; Chen, Pin-Yuan; Chu, Po-Chun; Pan, Chia-Hsin; Yang, Hung-Wei; Huang, Chiung-Yin; Wang, Jiun-Jie; Yen, Tzu-Chen; Wei, Kuo-Chen

2010-05-01

To demonstrate the feasibility of using focused ultrasound to enhance delivery of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to glioblastomas in rats with induced tumors and determine if such an approach increases treatment efficacy. All animal experiments were approved by the animal committee and adhered to the experimental animal care guidelines. A 400-kHz focused ultrasound generator was used to transcranially disrupt the blood-brain barrier (BBB) in rat brains by delivering burst-tone ultrasound energy in the presence of microbubbles. The process was monitored in vivo by using magnetic resonance (MR) imaging. Cultured C6 glioma cells implanted in Sprague-Dawley rats were used as the tumor model. BCNU (13.5 mg/kg) was administered intravenously and its concentration in brains was quantified by using high-performance liquid chromatography. MR imaging was used to evaluate the effect of treatments longitudinally, including analysis of tumor progression and animal survival, and brain tissues were histologically examined. Methods including the two-tailed unpaired t test and the Mantel-Cox test were used for statistical analyses, with a significance level of .05. Focused ultrasound significantly enhanced the penetration of BCNU through the BBB in normal (by 340%) and tumor-implanted (by 202%) brains without causing hemorrhaging. Treatment of tumor-implanted rats with focused ultrasound alone had no beneficial effect on tumor progression or on animal survival up to 60 days. Administration of BCNU only transiently controlled tumor progression; nevertheless, relative to untreated controls, animal survival was improved by treatment with BCNU alone (increase in median survival time [IST(median)], 15.7%, P = .023). Treatment with focused ultrasound before BCNU administration controlled tumor progression (day 31: 0.05 cm(3) + or - 0.1 [standard deviation] vs 0.28 cm(3) + or - 0.1) and improved animal survival relative to untreated controls (IST(median), 85.9%, P = .0015). This study demonstrates a means of increasing localized chemotherapeutic drug delivery for brain tumor treatment and strongly supports the feasibility of this treatment in a clinical setting.

Fiber-array based optogenetic prosthetic system for stimulation therapy

NASA Astrophysics Data System (ADS)

Gu, Ling; Cote, Chris; Tejeda, Hector; Mohanty, Samarendra

2012-02-01

Recent advent of optogenetics has enabled activation of genetically-targeted neuronal cells using low intensity blue light with high temporal precision. Since blue light is attenuated rapidly due to scattering and absorption in neural tissue, optogenetic treatment of neurological disorders may require stimulation of specific cell types in multiple regions of the brain. Further, restoration of certain neural functions (vision, and auditory etc) requires accurate spatio-temporal stimulation patterns rather than just precise temporal stimulation. In order to activate multiple regions of the central nervous system in 3D, here, we report development of an optogenetic prosthetic comprising of array of fibers coupled to independently-controllable LEDs. This design avoids direct contact of LEDs with the brain tissue and thus does not require electrical and heat isolation, which can non-specifically stimulate and damage the local brain regions. The intensity, frequency, and duty cycle of light pulses from each fiber in the array was controlled independently using an inhouse developed LabView based program interfaced with a microcontroller driving the individual LEDs. While the temporal profile of the light pulses was controlled by varying the current driving the LED, the beam profile emanating from each fiber tip could be sculpted by microfabrication of the fiber tip. The fiber array was used to stimulate neurons, expressing channelrhodopsin-2, in different locations within the brain or retina. Control of neural activity in the mice cortex, using the fiber-array based prosthetic, is evaluated from recordings made with multi-electrode array (MEA). We also report construction of a μLED array based prosthetic for spatio-temporal stimulation of cortex.

Circadian Regulation of Pineal Gland Rhythmicity

PubMed Central

Borjigin, Jimo; Zhang, L. Samantha; Calinescu, Anda-Alexandra

2011-01-01

The pineal gland is a neuroendocrine organ of the brain. Its main task is to synthesize and secrete melatonin, a nocturnal hormone with diverse physiological functions. This review will focus on the central and pineal mechanisms in generation of mammalian pineal rhythmicity including melatonin production. In particular, this review covers the following topics: (1) local control of serotonin and melatonin rhythms; (2) neurotransmitters involved in central control of melatonin; (3) plasticity of the neural circuit controlling melatonin production; (4) role of clock genes in melatonin formation; (5) phase control of pineal rhythmicity; (6) impact of light at night on pineal rhythms; and (7) physiological function of the pineal rhythmicity. PMID:21782887

Degree connectivity in body dysmorphic disorder and relationships with obsessive and compulsive symptoms.

PubMed

Beucke, Jan C; Sepulcre, Jorge; Buhlmann, Ulrike; Kathmann, Norbert; Moody, Teena; Feusner, Jamie D

2016-10-01

Individuals with body dysmorphic disorder (BDD) and obsessive-compulsive disorder (OCD) are categorized within the same major diagnostic group and both show regional brain hyperactivity in the orbitofrontal cortex (OFC) and the basal ganglia during symptom provocation. While recent studies revealed that degree connectivity of these areas is abnormally high in OCD and positively correlates with symptom severity, no study has investigated degree connectivity in BDD. We used functional magnetic resonance imaging (fMRI) to compare the local and distant degree of functional connectivity in all brain areas between 28 unmedicated BDD participants and 28 demographically matched healthy controls during a face-processing task. Correlational analyses tested for associations between degree connectivity and symptom severity assessed by the BDD version of the Yale-Brown obsessive-compulsive scale (BDD-Y-BOCS). Reduced local amygdalar connectivity was found in participants with BDD. No differences in distant connectivity were found. BDD-Y-BOCS scores significantly correlated with the local connectivity of the posterior-lateral OFC, and distant connectivity of the posterior-lateral and post-central OFC, respectively. These findings represent preliminary evidence that individuals with BDD exhibit brain-behavioral associations related to obsessive thoughts and compulsive behaviors that are highly similar to correlations previously found in OCD, further underscoring their related pathophysiology. This relationship could be further elucidated through investigation of resting-state functional connectivity in BDD, ideally in direct comparison with OCD and other obsessive-compulsive and related disorders. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

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

PubMed

Simões, R V; Delgado-Goñi, T; Lope-Piedrafita, S; Arús, C

2010-01-01

MR spectroscopic Imaging (MRSI), with PRESS localization, is used here to monitor the effects of acute hyperglycemia in the spectral pattern of 11 mice bearing GL261 gliomas at normothermia (36.5-37.5 degrees C) and at hypothermia (28.5-29.5 degrees C). These in vivo studies were complemented by ex vivo high resolution magic angle spinning (HR-MAS) analysis of GL261 tumor samples from 6 animals sacrificed by focused microwave irradiation, and blood glucose measurements in 12 control mice. Apparent glucose levels, monitored by in vivo MRSI in brain tumors during acute hyperglycemia, rose to an average of 1.6-fold during hypothermia (p < 0.05), while no significant changes were detected at normothermia, or in control experiments performed at euglycemia, or in normal/peritumoral brain regions. Ex vivo analysis of glioma-bearing mouse brains at hypothermia revealed higher glucose increases in distinct regions during the acute hyperglycemic challenge (up to 6.6-fold at the tumor center), in agreement with maximal in vivo blood glucose changes (5-fold). Phantom studies on taurine plus glucose containing solutions explained the differences between in vivo and ex vivo measurements. Our results also indicate brain tumor heterogeneity in the four animal tumors investigated in response to a defined metabolic challenge.

Reinforcement of the Brain's Rich-Club Architecture Following Early Neurodevelopmental Disruption Caused by Very Preterm Birth

PubMed Central

Karolis, Vyacheslav R.; Froudist-Walsh, Sean; Brittain, Philip J.; Kroll, Jasmin; Ball, Gareth; Edwards, A. David; Dell'Acqua, Flavio; Williams, Steven C.; Murray, Robin M.; Nosarti, Chiara

2016-01-01

The second half of pregnancy is a crucial period for the development of structural brain connectivity, and an abrupt interruption of the typical processes of development during this phase caused by the very preterm birth (<33 weeks of gestation) is likely to result in long-lasting consequences. We used structural and diffusion imaging data to reconstruct the brain structural connectome in very preterm-born adults. We assessed its rich-club organization and modularity as 2 characteristics reflecting the capacity to support global and local information exchange, respectively. Our results suggest that the establishment of global connectivity patterns is prioritized over peripheral connectivity following early neurodevelopmental disruption. The very preterm brain exhibited a stronger rich-club architecture than the control brain, despite possessing a relative paucity of white matter resources. Using a simulated lesion approach, we also investigated whether putative structural reorganization takes place in the very preterm brain in order to compensate for its anatomical constraints. We found that connections between the basal ganglia and (pre-) motor regions, as well as connections between subcortical regions, assumed an altered role in the structural connectivity of the very preterm brain, and that such alterations had functional implications for information flow, rule learning, and verbal IQ. PMID:26742566

Adaptive estimation of hand movement trajectory in an EEG based brain-computer interface system

NASA Astrophysics Data System (ADS)

Robinson, Neethu; Guan, Cuntai; Vinod, A. P.

2015-12-01

Objective. The various parameters that define a hand movement such as its trajectory, speed, etc, are encoded in distinct brain activities. Decoding this information from neurophysiological recordings is a less explored area of brain-computer interface (BCI) research. Applying non-invasive recordings such as electroencephalography (EEG) for decoding makes the problem more challenging, as the encoding is assumed to be deep within the brain and not easily accessible by scalp recordings. Approach. EEG based BCI systems can be developed to identify the neural features underlying movement parameters that can be further utilized to provide a detailed and well defined control command set to a BCI output device. A real-time continuous control is better suited for practical BCI systems, and can be achieved by continuous adaptive reconstruction of movement trajectory than discrete brain activity classifications. In this work, we adaptively reconstruct/estimate the parameters of two-dimensional hand movement trajectory, namely movement speed and position, from multi-channel EEG recordings. The data for analysis is collected by performing an experiment that involved center-out right-hand movement tasks in four different directions at two different speeds in random order. We estimate movement trajectory using a Kalman filter that models the relation between brain activity and recorded parameters based on a set of defined predictors. We propose a method to define these predictor variables that includes spatial, spectral and temporally localized neural information and to select optimally informative variables. Main results. The proposed method yielded correlation of (0.60 ± 0.07) between recorded and estimated data. Further, incorporating the proposed predictor subset selection, the correlation achieved is (0.57 ± 0.07, p {\\lt }0.004) with significant gain in stability of the system, as well as dramatic reduction in number of predictors (76%) for the savings of computational time. Significance. The proposed system provides a real time movement control system using EEG-BCI with control over movement speed and position. These results are higher and statistically significant compared to existing techniques in EEG based systems and thus promise the applicability of the proposed method for efficient estimation of movement parameters and for continuous motor control.

APPLICATION OF ISOTOPE ENCEPHALOGRAPHY AND ELECTROENCEPHALOSCOPY FOR LOCALIZATION OF BRAIN TUMOURS

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

Shamov, V.N.; Badmayev, C.N.; Bekhtereva, N.P.

1959-10-31

The problems of diagnosis and localization of brain tumors in some cases present many difficulities and make the neurosurgeon seek for additional methods of investigation. In such circumstances usage of the tracer technique in diagnostics is of considerable help, as it has obvious advantages compared with other methods of investigation, such as safety, painlessness, non-traumatism, absence of undesirable after effects, accuracy, and relative simplicity. The present communication is based on the results of clinical observations on 150 patients with verified brain tumors. Analyses of the data show that the accuracy of the brain tumor localizations vary, depending upon the depthmore » of the tumor site and conceniration of labelled material in the area of tumor growth. The diagnostic value of the method is doubtful in cases of tumors of posterior fossa, base of the brain, or the lesions of median line. The application of isotope encephalography is successfully supplemented by the new method of investigations, i.e., electroencephaloscopy, which allows the localization of deeply set tumors. Possibilities and limitations of the method are discussed. It is concluded that the isotope encephalography and electroencephaloscopy represent very valuable diagnostic methods which alongside with other auxiliary methods are widely used in diagnosis of brain tumors. (C.H.)« less

Mid-sagittal plane and mid-sagittal surface optimization in brain MRI using a local symmetry measure

NASA Astrophysics Data System (ADS)

Stegmann, Mikkel B.; Skoglund, Karl; Ryberg, Charlotte

2005-04-01

This paper describes methods for automatic localization of the mid-sagittal plane (MSP) and mid-sagittal surface (MSS). The data used is a subset of the Leukoaraiosis And DISability (LADIS) study consisting of three-dimensional magnetic resonance brain data from 62 elderly subjects (age 66 to 84 years). Traditionally, the mid-sagittal plane is localized by global measures. However, this approach fails when the partitioning plane between the brain hemispheres does not coincide with the symmetry plane of the head. We instead propose to use a sparse set of profiles in the plane normal direction and maximize the local symmetry around these using a general-purpose optimizer. The plane is parameterized by azimuth and elevation angles along with the distance to the origin in the normal direction. This approach leads to solutions confirmed as the optimal MSP in 98 percent of the subjects. Despite the name, the mid-sagittal plane is not always planar, but a curved surface resulting in poor partitioning of the brain hemispheres. To account for this, this paper also investigates an optimization strategy which fits a thin-plate spline surface to the brain data using a robust least median of squares estimator. Albeit computationally more expensive, mid-sagittal surface fitting demonstrated convincingly better partitioning of curved brains into cerebral hemispheres.

Stereotactic interstitial radiosurgery for cerebral metastases.

PubMed

Curry, William T; Cosgrove, Garth Rees; Hochberg, Fred H; Loeffler, Jay; Zervas, Nicholas T

2005-10-01

The Photon Radiosurgery System (PRS) is a miniature x-ray generator that can stereotactically irradiate intracranial tumors by using low-energy photons. Treatment with the PRS typically occurs in conjunction with stereotactic biopsy, thereby providing diagnosis and treatment in one procedure. The authors review the treatment of patients with brain metastases with the aid of the PRS and discuss the indications, advantages, and limitations of this technique. Clinical characteristics, treatment parameters, neuroimaging-confirmed outcome, and survival were reviewed in all patients with histologically verified brain metastases who were treated with the PRS at the Massachusetts General Hospital between December 1992 and November 2000. Local control of lesions was defined as either stabilization or diminution in the size of the treated tumor as confirmed by Gd-enhanced magnetic resonance imaging. Between December 1992 and November 2000, 72 intracranial metastatic lesions in 60 patients were treated with the PRS. Primary tumors included lung (33 patients), melanoma (15 patients), renal cell (five patients), breast (two patients), esophageal (two patients), colon (one patient), and Merkle cell (one patient) cancers, and malignant fibrous histiocytoma (one patient). Supratentorial metastases were distributed throughout the cerebrum, with only one cerebellar metastasis. The lesions ranged in diameter from 6 to 40 mm and were treated with a minimal peripheral dose of 16 Gy (range 10-20 Gy). At the last follow-up examination (median 6 months), local disease control had been achieved in 48 (81%) of 59 tumors. An actuarial analysis demonstrated that the survival rates at 6 and 12 months were 63 and 34%, respectively. Patients with a single brain metastasis survived a mean of 11 months. Complications included four patients with postoperative seizures, three with symptomatic cerebral edema, two with hemorrhagic events, and three with symptomatic radiation necrosis requiring surgery. Stereotactic interstitial radiosurgery performed using the PRS can obtain local control of cerebral metastases at rates that are comparable to those achieved through open resection and external stereotactic radiosurgery. The major advantage of using the PRS is that effective treatment can be accomplished at the time of stereotactic biopsy.

Brain segmentation and the generation of cortical surfaces

NASA Technical Reports Server (NTRS)

Joshi, M.; Cui, J.; Doolittle, K.; Joshi, S.; Van Essen, D.; Wang, L.; Miller, M. I.

1999-01-01

This paper describes methods for white matter segmentation in brain images and the generation of cortical surfaces from the segmentations. We have developed a system that allows a user to start with a brain volume, obtained by modalities such as MRI or cryosection, and constructs a complete digital representation of the cortical surface. The methodology consists of three basic components: local parametric modeling and Bayesian segmentation; surface generation and local quadratic coordinate fitting; and surface editing. Segmentations are computed by parametrically fitting known density functions to the histogram of the image using the expectation maximization algorithm [DLR77]. The parametric fits are obtained locally rather than globally over the whole volume to overcome local variations in gray levels. To represent the boundary of the gray and white matter we use triangulated meshes generated using isosurface generation algorithms [GH95]. A complete system of local parametric quadratic charts [JWM+95] is superimposed on the triangulated graph to facilitate smoothing and geodesic curve tracking. Algorithms for surface editing include extraction of the largest closed surface. Results for several macaque brains are presented comparing automated and hand surface generation. Copyright 1999 Academic Press.

Organic electronics for high-resolution electrocorticography of the human brain.

PubMed

Khodagholy, Dion; Gelinas, Jennifer N; Zhao, Zifang; Yeh, Malcolm; Long, Michael; Greenlee, Jeremy D; Doyle, Werner; Devinsky, Orrin; Buzsáki, György

2016-11-01

Localizing neuronal patterns that generate pathological brain signals may assist with tissue resection and intervention strategies in patients with neurological diseases. Precise localization requires high spatiotemporal recording from populations of neurons while minimizing invasiveness and adverse events. We describe a large-scale, high-density, organic material-based, conformable neural interface device ("NeuroGrid") capable of simultaneously recording local field potentials (LFPs) and action potentials from the cortical surface. We demonstrate the feasibility and safety of intraoperative recording with NeuroGrids in anesthetized and awake subjects. Highly localized and propagating physiological and pathological LFP patterns were recorded, and correlated neural firing provided evidence about their local generation. Application of NeuroGrids to brain disorders, such as epilepsy, may improve diagnostic precision and therapeutic outcomes while reducing complications associated with invasive electrodes conventionally used to acquire high-resolution and spiking data.

Spatio-temporal Reconstruction of Neural Sources Using Indirect Dominant Mode Rejection.

PubMed

Jafadideh, Alireza Talesh; Asl, Babak Mohammadzadeh

2018-04-27

Adaptive minimum variance based beamformers (MVB) have been successfully applied to magnetoencephalogram (MEG) and electroencephalogram (EEG) data to localize brain activities. However, the performance of these beamformers falls down in situations where correlated or interference sources exist. To overcome this problem, we propose indirect dominant mode rejection (iDMR) beamformer application in brain source localization. This method by modifying measurement covariance matrix makes MVB applicable in source localization in the presence of correlated and interference sources. Numerical results on both EEG and MEG data demonstrate that presented approach accurately reconstructs time courses of active sources and localizes those sources with high spatial resolution. In addition, the results of real AEF data show the good performance of iDMR in empirical situations. Hence, iDMR can be reliably used for brain source localization especially when there are correlated and interference sources.

Blood-brain barrier dysfunction and cerebral small vessel disease (arteriolosclerosis) in brains of older people.

PubMed

Bridges, Leslie R; Andoh, Joycelyn; Lawrence, Andrew J; Khoong, Cheryl H L; Poon, Wayne; Esiri, Margaret M; Markus, Hugh S; Hainsworth, Atticus H

2014-11-01

The blood-brain barrier protects brain tissue from potentially harmful plasma components. Small vessel disease (SVD; also termed arteriolosclerosis) is common in the brains of older people and is associated with lacunar infarcts, leukoaraiosis, and vascular dementia. To determine whether plasma extravasation is associated with SVD, we immunolabeled the plasma proteins fibrinogen and immunoglobulin G, which are assumed to reflect blood-brain barrier dysfunction, in deep gray matter (DGM; anterior caudate-putamen) and deep subcortical white matter (DWM) in the brains of a well-characterized cohort of donated brains with minimal Alzheimer disease pathology (Braak Stages 0-II) (n = 84; aged 65 years or older). Morphometric measures of fibrinogen labeling were compared between people with neuropathologically defined SVD and aged control subjects. Parenchymal cellular labeling with fibrinogen and immunoglobulin G was detectable in DGM and DWM in many subjects (>70%). Quantitative measures of fibrinogen were not associated with SVD in DGM or DWM; SVD severity was correlated between DGM and DWM (p < 0.0001). Fibrinogen in DGM showed a modest association with a history of hypertension; DWM fibrinogen was associated with dementia and cerebral amyloid angiopathy (all p < 0.05). In DWM, SVD was associated with leukoaraiosis identified in life (p < 0.05), but fibrinogen was not. Our data suggest that, in aged brains, plasma extravasation and hence local blood-brain barrier dysfunction are common but do not support an association with SVD.

BAG3 is involved in neuronal differentiation and migration.

PubMed

Santoro, Antonietta; Nicolin, Vanessa; Florenzano, Fulvio; Rosati, Alessandra; Capunzo, Mario; Nori, Stefania L

2017-05-01

Bcl2-associated athanogene 3 (BAG3) protein belongs to the family of co-chaperones interacting with several heat shock proteins. It plays a key role in protein quality control and mediates the clearance of misfolded proteins. Little is known about the expression and cellular localization of BAG3 during nervous system development and differentiation. Therefore, we analyze the subcellular distribution and expression of BAG3 in nerve-growth-factor-induced neurite outgrowth in PC12 cells and in developing and adult cortex of mouse brain. In differentiated PC12 cells, BAG3 was localized mainly in the neuritic domain rather than the cell body, whereas in control cells, it appeared to be confined to the cytoplasm near the nuclear membrane. Interestingly, the change of BAG3 localization during neuronal differentiation was associated only with a slight increase in total BAG3 expression. These data were coroborated by transmission electron microscopy showing that BAG3 was confined mainly within large dense-core vesicles of the axon in differentiated PC12 cells. In mouse developing cortex, BAG3 appeared to be intensely expressed in cellular processes of migrating cells, whereas in adult brain, a diffuse expression of low to medium intensity was detected in neuronal cell bodies. These findings suggest that BAG3 expression is required for neuronal differentiation and migration and that its role is linked to a change in its distribution pattern rather than to an increase in its protein expression levels.

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

PubMed Central

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

2015-01-01

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

Mapping 22q11.2 Gene Dosage Effects on Brain Morphometry.

PubMed

Lin, Amy; Ching, Christopher R K; Vajdi, Ariana; Sun, Daqiang; Jonas, Rachel K; Jalbrzikowski, Maria; Kushan-Wells, Leila; Pacheco Hansen, Laura; Krikorian, Emma; Gutman, Boris; Dokoru, Deepika; Helleman, Gerhard; Thompson, Paul M; Bearden, Carrie E

2017-06-28

Reciprocal chromosomal rearrangements at the 22q11.2 locus are associated with elevated risk of neurodevelopmental disorders. The 22q11.2 deletion confers the highest known genetic risk for schizophrenia, but a duplication in the same region is strongly associated with autism and is less common in schizophrenia cases than in the general population. Here we conducted the first study of 22q11.2 gene dosage effects on brain structure in a sample of 143 human subjects: 66 with 22q11.2 deletions (22q-del; 32 males), 21 with 22q11.2 duplications (22q-dup; 14 males), and 56 age- and sex-matched controls (31 males). 22q11.2 gene dosage varied positively with intracranial volume, gray and white matter volume, and cortical surface area (deletion < control < duplication). In contrast, gene dosage varied negatively with mean cortical thickness (deletion > control > duplication). Widespread differences were observed for cortical surface area with more localized effects on cortical thickness. These diametric patterns extended into subcortical regions: 22q-dup carriers had a significantly larger right hippocampus, on average, but lower right caudate and corpus callosum volume, relative to 22q-del carriers. Novel subcortical shape analysis revealed greater radial distance (thickness) of the right amygdala and left thalamus, and localized increases and decreases in subregions of the caudate, putamen, and hippocampus in 22q-dup relative to 22q-del carriers. This study provides the first evidence that 22q11.2 is a genomic region associated with gene-dose-dependent brain phenotypes. Pervasive effects on cortical surface area imply that this copy number variant affects brain structure early in the course of development. SIGNIFICANCE STATEMENT Probing naturally occurring reciprocal copy number variation in the genome may help us understand mechanisms underlying deviations from typical brain and cognitive development. The 22q11.2 genomic region is particularly susceptible to chromosomal rearrangements and contains many genes crucial for neuronal development and migration. Not surprisingly, reciprocal genomic imbalances at this locus confer some of the highest known genetic risks for developmental neuropsychiatric disorders. Here we provide the first evidence that brain morphology differs meaningfully as a function of reciprocal genomic variation at the 22q11.2 locus. Cortical thickness and surface area were affected in opposite directions with more widespread effects of gene dosage on cortical surface area. Copyright © 2017 the authors 0270-6474/17/376184-17$15.00/0.

Enhanced Energy Localization in Hyperthermia Treatment Based on Hybrid Electromagnetic and Ultrasonic System: Proof of Concept with Numerical Simulations.

PubMed

Nizam-Uddin, N; Elshafiey, Ibrahim

2017-01-01

This paper proposes a hybrid hyperthermia treatment system, utilizing two noninvasive modalities for treating brain tumors. The proposed system depends on focusing electromagnetic (EM) and ultrasound (US) energies. The EM hyperthermia subsystem enhances energy localization by incorporating a multichannel wideband setting and coherent-phased-array technique. A genetic algorithm based optimization tool is developed to enhance the specific absorption rate (SAR) distribution by reducing hotspots and maximizing energy deposition at tumor regions. The treatment performance is also enhanced by augmenting an ultrasonic subsystem to allow focused energy deposition into deep tumors. The therapeutic faculty of ultrasonic energy is assessed by examining the control of mechanical alignment of transducer array elements. A time reversal (TR) approach is then investigated to address challenges in energy focus in both subsystems. Simulation results of the synergetic effect of both modalities assuming a simplified model of human head phantom demonstrate the feasibility of the proposed hybrid technique as a noninvasive tool for thermal treatment of brain tumors.

Enhanced Energy Localization in Hyperthermia Treatment Based on Hybrid Electromagnetic and Ultrasonic System: Proof of Concept with Numerical Simulations

PubMed Central

Elshafiey, Ibrahim

2017-01-01

This paper proposes a hybrid hyperthermia treatment system, utilizing two noninvasive modalities for treating brain tumors. The proposed system depends on focusing electromagnetic (EM) and ultrasound (US) energies. The EM hyperthermia subsystem enhances energy localization by incorporating a multichannel wideband setting and coherent-phased-array technique. A genetic algorithm based optimization tool is developed to enhance the specific absorption rate (SAR) distribution by reducing hotspots and maximizing energy deposition at tumor regions. The treatment performance is also enhanced by augmenting an ultrasonic subsystem to allow focused energy deposition into deep tumors. The therapeutic faculty of ultrasonic energy is assessed by examining the control of mechanical alignment of transducer array elements. A time reversal (TR) approach is then investigated to address challenges in energy focus in both subsystems. Simulation results of the synergetic effect of both modalities assuming a simplified model of human head phantom demonstrate the feasibility of the proposed hybrid technique as a noninvasive tool for thermal treatment of brain tumors. PMID:28840125

An event-related potential study of deception to self preferences.

PubMed

Tu, Shen; Li, Hong; Jou, Jerwen; Zhang, Qinglin; Wang, Ting; Yu, Caiyun; Qiu, Jiang

2009-01-09

The spatiotemporal analysis of brain activation during the execution of deceptive decision-making was performed in 14 normal young adult subjects by using high-density event-related brain potentials (ERPs) with a delayed-response paradigm (subjects were required to hide their true attitudes for a moment). Our results showed that between 400 and 700 ms after stimulus onset, Deceptive items elicited a more negative ERP deflection (N400-700) than Truthful items, and between 1000 and 2000 ms, Deceptive items elicited a more positive ERP deflection (P1000-2000) than Truthful items. Analyses using dipole locations indicated that: (1) the generators of N400-700 were localized in the medial frontal gyrus (GFM) and middle temporal gyrus (GTM), which might be involved in conflict detection and control during deceptive decision-making; and (2) the generators of P1000-2000 were localized near the cuneus (CU) and the cingulate gyrus, which might be involved in conflict coordination in working memory due to deception.

Brain signature and functional impact of centralized pain: a multidisciplinary approach to the study of chronic pelvic pain (MAPP) network study.

PubMed

Kutch, Jason J; Ichesco, Eric; Hampson, Johnson P; Labus, Jennifer S; Farmer, Melissa A; Martucci, Katherine T; Ness, Timothy J; Deutsch, Georg; Apkarian, A Vania; Mackey, Sean C; Klumpp, David J; Schaeffer, Anthony J; Rodriguez, Larissa V; Kreder, Karl J; Buchwald, Dedra; Andriole, Gerald L; Lai, H Henry; Mullins, Chris; Kusek, John W; Landis, J Richard; Mayer, Emeran A; Clemens, J Quentin; Clauw, Daniel J; Harris, Richard E

2017-10-01

Chronic pain is often measured with a severity score that overlooks its spatial distribution across the body. This widespread pain is believed to be a marker of centralization, a central nervous system process that decouples pain perception from nociceptive input. Here, we investigated whether centralization is manifested at the level of the brain using data from 1079 participants in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network (MAPP) study. Participants with a clinical diagnosis of urological chronic pelvic pain syndrome (UCPPS) were compared to pain-free controls and patients with fibromyalgia, the prototypical centralized pain disorder. Participants completed questionnaires capturing pain severity, function, and a body map of pain. A subset (UCPPS N = 110; fibromyalgia N = 23; healthy control N = 49) underwent functional and structural magnetic resonance imaging. Patients with UCPPS reported pain ranging from localized (pelvic) to widespread (throughout the body). Patients with widespread UCPPS displayed increased brain gray matter volume and functional connectivity involving sensorimotor and insular cortices (P < 0.05 corrected). These changes translated across disease diagnoses as identical outcomes were present in patients with fibromyalgia but not pain-free controls. Widespread pain was also associated with reduced physical and mental function independent of pain severity. Brain pathology in patients with centralized pain is related to pain distribution throughout the body. These patients may benefit from interventions targeting the central nervous system.

Functional brain abnormalities in major depressive disorder using the Hilbert-Huang transform.

PubMed

Yu, Haibin; Li, Feng; Wu, Tong; Li, Rui; Yao, Li; Wang, Chuanyue; Wu, Xia

2018-02-09

Major depressive disorder is a common disease worldwide, which is characterized by significant and persistent depression. Non-invasive accessory diagnosis of depression can be performed by resting-state functional magnetic resonance imaging (rs-fMRI). However, the fMRI signal may not satisfy linearity and stationarity. The Hilbert-Huang transform (HHT) is an adaptive time-frequency localization analysis method suitable for nonlinear and non-stationary signals. The objective of this study was to apply the HHT to rs-fMRI to find the abnormal brain areas of patients with depression. A total of 35 patients with depression and 37 healthy controls were subjected to rs-fMRI. The HHT was performed to extract the Hilbert-weighted mean frequency of the rs-fMRI signals, and multivariate receiver operating characteristic analysis was applied to find the abnormal brain regions with high sensitivity and specificity. We observed differences in Hilbert-weighted mean frequency between the patients and healthy controls mainly in the right hippocampus, right parahippocampal gyrus, left amygdala, and left and right caudate nucleus. Subsequently, the above-mentioned regions were included in the results obtained from the compared region homogeneity and the fractional amplitude of low frequency fluctuation method. We found brain regions with differences in the Hilbert-weighted mean frequency, and examined their sensitivity and specificity, which suggested a potential neuroimaging biomarker to distinguish between patients with depression and healthy controls. We further clarified the pathophysiological abnormality of these regions for the population with major depressive disorder.

iELVis: An open source MATLAB toolbox for localizing and visualizing human intracranial electrode data.

PubMed

Groppe, David M; Bickel, Stephan; Dykstra, Andrew R; Wang, Xiuyuan; Mégevand, Pierre; Mercier, Manuel R; Lado, Fred A; Mehta, Ashesh D; Honey, Christopher J

2017-04-01

Intracranial electrical recordings (iEEG) and brain stimulation (iEBS) are invaluable human neuroscience methodologies. However, the value of such data is often unrealized as many laboratories lack tools for localizing electrodes relative to anatomy. To remedy this, we have developed a MATLAB toolbox for intracranial electrode localization and visualization, iELVis. NEW METHOD: iELVis uses existing tools (BioImage Suite, FSL, and FreeSurfer) for preimplant magnetic resonance imaging (MRI) segmentation, neuroimaging coregistration, and manual identification of electrodes in postimplant neuroimaging. Subsequently, iELVis implements methods for correcting electrode locations for postimplant brain shift with millimeter-scale accuracy and provides interactive visualization on 3D surfaces or in 2D slices with optional functional neuroimaging overlays. iELVis also localizes electrodes relative to FreeSurfer-based atlases and can combine data across subjects via the FreeSurfer average brain. It takes 30-60min of user time and 12-24h of computer time to localize and visualize electrodes from one brain. We demonstrate iELVis's functionality by showing that three methods for mapping primary hand somatosensory cortex (iEEG, iEBS, and functional MRI) provide highly concordant results. COMPARISON WITH EXISTING METHODS: iELVis is the first public software for electrode localization that corrects for brain shift, maps electrodes to an average brain, and supports neuroimaging overlays. Moreover, its interactive visualizations are powerful and its tutorial material is extensive. iELVis promises to speed the progress and enhance the robustness of intracranial electrode research. The software and extensive tutorial materials are freely available as part of the EpiSurg software project: https://github.com/episurg/episurg. Copyright © 2017 Elsevier B.V. All rights reserved.

[Locally administered lentivirus-mediated siRNA inhibits wear debris-induced inflammation].

PubMed

Peng, Xiao-chun; Zhang, Xian-long; Tao, Kun; Cheng, Tao; Zhu, Jun-feng; Zeng, Bing-fang

2009-03-01

To determine the safety and efficacy of local administration of lentivirus-mediated small interfering RNA (siRNA) targeting tumor necrosis factor-alpha (TNF-alpha) in murine air pouch model. From May 2007 to April 2008 a siRNA targeting TNF-alpha and a missense siRNA were designed, and recombine lentivirus which coexpressed the green fluorescent protein (GFP) as a marker gene was constructed. Air pouches were established and stimulated by Ti-6Al-4V particles. Pouches were divided into 3 groups randomly. Lentivirus-mediated siRNA targeting TNF-alpha (TNF-alpha group) or lentivirus-mediated missense siRNA (MS group), or virus-free saline (control group) were injected into pouches respectively. Pouch membrane, peripheral blood, heart, liver, spleen, kidney, lung and brain were harvested at 28 d after transfection, and assayed for markers of inflammation using histological, molecular, immunological techniques and Xenogen in vivo imaging system (IVIS) 50 vivo bioluminescent assay system. Xenogen IVIS 50 vivo image revealed strong expression of GFP localized in pouch areas and no expression in other parts of mice both in TNF-alpha group and MS group at 4 weeks after transfection, while no expression of GFP was found in control group. By RT-PCR and ELISA, the mRNA and protein levels of TNF-alpha in TNF-alpha group decreased by 81.6% and 82.6% respectively compared to control group (P < 0.01), and decreased by 78.9% and 84.0% respectively compared to MS group (P < 0.01), whereas TNF-alpha level in peripheral blood, heart, liver, spleen, kidney, lung and brain remained invariant (P > 0.05). Less inflammatory responses (thinner pouch membrane and decreased cellular infiltration) were observed in TNF-alpha group. Efficient local delivery of lentivirus-mediated siRNA targeting TNF-alpha into modified murine air pouch can inhibit debris-induced inflammation effectively, with no systemic adverse effects.

Gyration of the feline brain: localization, terminology and variability.

PubMed

Pakozdy, A; Angerer, C; Klang, A; König, E H; Probst, A

2015-12-01

The terminology of feline brain gyration is not consistent and individual variability has not been systematically examined. The aim of the study was to identify the gyri and sulci of cat brains and describe them using the current terminology. The brains of 15 cats including 10 European shorthairs, 2 Siamese, 2 Maine coons and one Norvegian forest cat without clinical evidence of brain disease were examined post-mortem and photographed for documentation. For description, the terms of the most recent Nomina Anatomica Veterinaria (NAV, 2012) were used, and comparisons with previous anatomical texts were also performed. In addition to the lack of comparative morphology in the NAV, veterinary and human nomenclature are used interchangeably and inconsistently in the literature. This presents a challenge for neurologists and anatomists in localizing gyri and sulci. A comparative analysis of brain gyration showed only minor individual variability among the cats. High-quality labelled figures are provided to facilitate the identification of cat brain gyration. Our work consolidates the current and more consistent gyration terminology for reporting the localization of a cortical lesion based on magnetic resonance imaging or histopathology. This will facilitate not only morphological but also functional research using accurate anatomical reporting. © 2014 Blackwell Verlag GmbH.

Association between increased EEG signal complexity and cannabis dependence.

PubMed

Laprevote, Vincent; Bon, Laura; Krieg, Julien; Schwitzer, Thomas; Bourion-Bedes, Stéphanie; Maillard, Louis; Schwan, Raymund

2017-12-01

Both acute and regular cannabis use affects the functioning of the brain. While several studies have demonstrated that regular cannabis use can impair the capacity to synchronize neural assemblies during specific tasks, less is known about spontaneous brain activity. This can be explored by measuring EEG complexity, which reflects the spontaneous variability of human brain activity. A recent study has shown that acute cannabis use can affect that complexity. Since the characteristics of cannabis use can affect the impact on brain functioning, this study sets out to measure EEG complexity in regular cannabis users with or without dependence, in comparison with healthy controls. We recruited 26 healthy controls, 25 cannabis users without cannabis dependence and 14 cannabis users with cannabis dependence, based on DSM IV TR criteria. The EEG signal was extracted from at least 250 epochs of the 500ms pre-stimulation phase during a visual evoked potential paradigm. Brain complexity was estimated using Lempel-Ziv Complexity (LZC), which was compared across groups by non-parametric Kruskall-Wallis ANOVA. The analysis revealed a significant difference between the groups, with higher LZC in participants with cannabis dependence than in non-dependent cannabis users. There was no specific localization of this effect across electrodes. We showed that cannabis dependence is associated to an increased spontaneous brain complexity in regular users. This result is in line with previous results in acute cannabis users. It may reflect increased randomness of neural activity in cannabis dependence. Future studies should explore whether this effect is permanent or diminishes with cannabis cessation. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

Hemispheric Asymmetry of Human Brain Anatomical Network Revealed by Diffusion Tensor Tractography

PubMed Central

Liu, Yaou; Duan, Yunyun; Li, Kuncheng

2015-01-01

The topological architecture of the cerebral anatomical network reflects the structural organization of the human brain. Recently, topological measures based on graph theory have provided new approaches for quantifying large-scale anatomical networks. However, few studies have investigated the hemispheric asymmetries of the human brain from the perspective of the network model, and little is known about the asymmetries of the connection patterns of brain regions, which may reflect the functional integration and interaction between different regions. Here, we utilized diffusion tensor imaging to construct binary anatomical networks for 72 right-handed healthy adult subjects. We established the existence of structural connections between any pair of the 90 cortical and subcortical regions using deterministic tractography. To investigate the hemispheric asymmetries of the brain, statistical analyses were performed to reveal the brain regions with significant differences between bilateral topological properties, such as degree of connectivity, characteristic path length, and betweenness centrality. Furthermore, local structural connections were also investigated to examine the local asymmetries of some specific white matter tracts. From the perspective of both the global and local connection patterns, we identified the brain regions with hemispheric asymmetries. Combined with the previous studies, we suggested that the topological asymmetries in the anatomical network may reflect the functional lateralization of the human brain. PMID:26539535

Independent component analysis of EEG dipole source localization in resting and action state of brain

NASA Astrophysics Data System (ADS)

Almurshedi, Ahmed; Ismail, Abd Khamim

2015-04-01

EEG source localization was studied in order to determine the location of the brain sources that are responsible for the measured potentials at the scalp electrodes using EEGLAB with Independent Component Analysis (ICA) algorithm. Neuron source locations are responsible in generating current dipoles in different states of brain through the measured potentials. The current dipole sources localization are measured by fitting an equivalent current dipole model using a non-linear optimization technique with the implementation of standardized boundary element head model. To fit dipole models to ICA components in an EEGLAB dataset, ICA decomposition is performed and appropriate components to be fitted are selected. The topographical scalp distributions of delta, theta, alpha, and beta power spectrum and cross coherence of EEG signals are observed. In close eyes condition it shows that during resting and action states of brain, alpha band was activated from occipital (O1, O2) and partial (P3, P4) area. Therefore, parieto-occipital area of brain are active in both resting and action state of brain. However cross coherence tells that there is more coherence between right and left hemisphere in action state of brain than that in the resting state. The preliminary result indicates that these potentials arise from the same generators in the brain.

Atypical vertical sound localization and sound-onset sensitivity in people with autism spectrum disorders

PubMed Central

Visser, Eelke; Zwiers, Marcel P.; Kan, Cornelis C.; Hoekstra, Liesbeth; van Opstal, A. John; Buitelaar, Jan K.

2013-01-01

Background Autism spectrum disorders (ASDs) are associated with auditory hyper- or hyposensitivity; atypicalities in central auditory processes, such as speech-processing and selective auditory attention; and neural connectivity deficits. We sought to investigate whether the low-level integrative processes underlying sound localization and spatial discrimination are affected in ASDs. Methods We performed 3 behavioural experiments to probe different connecting neural pathways: 1) horizontal and vertical localization of auditory stimuli in a noisy background, 2) vertical localization of repetitive frequency sweeps and 3) discrimination of horizontally separated sound stimuli with a short onset difference (precedence effect). Results Ten adult participants with ASDs and 10 healthy control listeners participated in experiments 1 and 3; sample sizes for experiment 2 were 18 adults with ASDs and 19 controls. Horizontal localization was unaffected, but vertical localization performance was significantly worse in participants with ASDs. The temporal window for the precedence effect was shorter in participants with ASDs than in controls. Limitations The study was performed with adult participants and hence does not provide insight into the developmental aspects of auditory processing in individuals with ASDs. Conclusion Changes in low-level auditory processing could underlie degraded performance in vertical localization, which would be in agreement with recently reported changes in the neuroanatomy of the auditory brainstem in individuals with ASDs. The results are further discussed in the context of theories about abnormal brain connectivity in individuals with ASDs. PMID:24148845

Elevation of GM2 ganglioside during ethanol-induced apoptotic neurodegeneration in the developing mouse brain

PubMed Central

Saito, Mitsuo; Chakraborty, Goutam; Shah, Relish; Mao, Rui-Fen; Kumar, Asok; Yang, Dun-Sheng; Dobrenis, Kostantin; Saito, Mariko

2012-01-01

GM2 ganglioside in the brain increased during ethanol-induced acute apoptotic neurodegeneration in 7-day-old mice. A small but a significant increase observed 2 h after ethanol exposure was followed by a marked increase around 24 h. Subcellular fractionation of the brain 24 h after ethanol treatment indicated that GM2 increased in synaptic and non-synaptic mitochondrial fractions as well as in a lysosome-enriched fraction characteristic to the ethanol-exposed brain. Immunohistochemical staining of GM2 in the ethanol-treated brain showed strong punctate staining mainly in activated microglia, in which it partially overlapped with staining for LAMP1, a late endosomal/lysosomal marker. Also, there was weaker neuronal staining, which partially co-localized with complex IV, a mitochondrial marker, and was augmented in cleaved caspase-3-positive neurons. In contrast, the control brain showed only faint and diffuse GM2 staining in neurons. Incubation of isolated brain mitochondria with GM2 in vitro induced cytochrome c release in a manner similar to that of GD3 ganglioside. Because ethanol is known to trigger mitochondria-mediated apoptosis with cytochrome c release and caspase-3 activation in the 7-day–old mouse brain, the GM2 elevation in mitochondria may be relevant to neuroapoptosis. Subsequently, activated microglia accumulated GM2, indicating a close relationship between GM2 and ethanol-induced neurodegeneration. PMID:22372857

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

PubMed

Rossitti, Sandro

2013-01-01

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

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

PubMed Central

Rossitti, Sandro

2013-01-01

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

A comparative study of theoretical graph models for characterizing structural networks of human brain.

PubMed

Li, Xiaojin; Hu, Xintao; Jin, Changfeng; Han, Junwei; Liu, Tianming; Guo, Lei; Hao, Wei; Li, Lingjiang

2013-01-01

Previous studies have investigated both structural and functional brain networks via graph-theoretical methods. However, there is an important issue that has not been adequately discussed before: what is the optimal theoretical graph model for describing the structural networks of human brain? In this paper, we perform a comparative study to address this problem. Firstly, large-scale cortical regions of interest (ROIs) are localized by recently developed and validated brain reference system named Dense Individualized Common Connectivity-based Cortical Landmarks (DICCCOL) to address the limitations in the identification of the brain network ROIs in previous studies. Then, we construct structural brain networks based on diffusion tensor imaging (DTI) data. Afterwards, the global and local graph properties of the constructed structural brain networks are measured using the state-of-the-art graph analysis algorithms and tools and are further compared with seven popular theoretical graph models. In addition, we compare the topological properties between two graph models, namely, stickiness-index-based model (STICKY) and scale-free gene duplication model (SF-GD), that have higher similarity with the real structural brain networks in terms of global and local graph properties. Our experimental results suggest that among the seven theoretical graph models compared in this study, STICKY and SF-GD models have better performances in characterizing the structural human brain network.

Locally adaptive MR intensity models and MRF-based segmentation of multiple sclerosis lesions

NASA Astrophysics Data System (ADS)

Galimzianova, Alfiia; Lesjak, Žiga; Likar, Boštjan; Pernuš, Franjo; Špiclin, Žiga

2015-03-01

Neuroimaging biomarkers are an important paraclinical tool used to characterize a number of neurological diseases, however, their extraction requires accurate and reliable segmentation of normal and pathological brain structures. For MR images of healthy brains the intensity models of normal-appearing brain tissue (NABT) in combination with Markov random field (MRF) models are known to give reliable and smooth NABT segmentation. However, the presence of pathology, MR intensity bias and natural tissue-dependent intensity variability altogether represent difficult challenges for a reliable estimation of NABT intensity model based on MR images. In this paper, we propose a novel method for segmentation of normal and pathological structures in brain MR images of multiple sclerosis (MS) patients that is based on locally-adaptive NABT model, a robust method for the estimation of model parameters and a MRF-based segmentation framework. Experiments on multi-sequence brain MR images of 27 MS patients show that, compared to whole-brain model and compared to the widely used Expectation-Maximization Segmentation (EMS) method, the locally-adaptive NABT model increases the accuracy of MS lesion segmentation.

Low-Dose and Limited-Volume Radiotherapy Alone for Primary Dural Marginal Zone Lymphoma: Treatment Approach and Review of Published Data

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

Puri, Dev R.; Tereffe, Welela; Yahalom, Joachim

2008-08-01

Purpose: Primary dural lymphoma is a rare intracranial lymphoma that almost always has a marginal zone histologic type and immunophenotype and often remains localized and is thus potentially curable with radiotherapy (RT) alone. The unusual location and histologic type of primary dural marginal zone lymphoma (PDMZL) distinguish it from primary central nervous system lymphoma and poses treatment dilemmas of technique, volume, and dose that have not been well addressed. We set out to analyze our recent experience in treating PDMZL and reviewed the limited published data available. Methods and Materials: Between 2002 and 2006, we treated 5 patients with localizedmore » PDMZL. Of these 5 patients, 3 had unilateral and 2 had bilateral/multifocal involvement, and 3 underwent subtotal tumor resection and 2 biopsy only. Whole brain RT was given before involved-field RT (IFRT) in 4 patients and 1 received IFRT alone. The median whole brain RT, IFRT, and total RT dose was 20, 12, and 30 Gy, respectively. The planning computed tomography scan was always fused with the post-gadolinium magnetic resonance imaging scan to assist in the IFRT volume determination. We also analyzed the published data from 27 additional patients. Results: The median follow-up was 34 months (range, 31-52). All obtained lasting local control. One patient developed a relapse in the soft tissue of the flank and additional systemic progression but no central nervous system recurrence. At last follow-up, no significant treatment-related neurotoxicity was detected. Conclusion: The results of our study have demonstrated that a combination of whole brain RT/IFRT or even low-dose IFRT alone provides excellent durable local control of PDMZL. This approach is potentially curative, possibly without significant neurotoxicity. Additional study and longer follow-up are needed to determine the appropriate RT dose and volume parameters for this rare, debilitating, and yet potentially curable lymphoma.« less

Mitochondrial angiotensin receptors in dopaminergic neurons. Role in cell protection and aging-related vulnerability to neurodegeneration

PubMed Central

Valenzuela, Rita; Costa-Besada, Maria A; Iglesias-Gonzalez, Javier; Perez-Costas, Emma; Villar-Cheda, Begoña; Garrido-Gil, Pablo; Melendez-Ferro, Miguel; Soto-Otero, Ramon; Lanciego, Jose L; Henrion, Daniel; Franco, Rafael; Labandeira-Garcia, Jose L

2016-01-01

The renin–angiotensin system (RAS) was initially considered as a circulating humoral system controlling blood pressure, being kidney the key control organ. In addition to the ‘classical' humoral RAS, a second level in RAS, local or tissular RAS, has been identified in a variety of tissues, in which local RAS play a key role in degenerative and aging-related diseases. The local brain RAS plays a major role in brain function and neurodegeneration. It is normally assumed that the effects are mediated by the cell-surface-specific G-protein-coupled angiotensin type 1 and 2 receptors (AT1 and AT2). A combination of in vivo (rats, wild-type mice and knockout mice) and in vitro (primary mesencephalic cultures, dopaminergic neuron cell line cultures) experimental approaches (confocal microscopy, electron microscopy, laser capture microdissection, transfection of fluorescent-tagged receptors, treatments with fluorescent angiotensin, western blot, polymerase chain reaction, HPLC, mitochondrial respirometry and other functional assays) were used in the present study. We report the discovery of AT1 and AT2 receptors in brain mitochondria, particularly mitochondria of dopaminergic neurons. Activation of AT1 receptors in mitochondria regulates superoxide production, via Nox4, and increases respiration. Mitochondrial AT2 receptors are much more abundant and increase after treatment of cells with oxidative stress inducers, and produce, via nitric oxide, a decrease in mitochondrial respiration. Mitochondria from the nigral region of aged rats displayed altered expression of AT1 and AT2 receptors. AT2-mediated regulation of mitochondrial respiration represents an unrecognized primary line of defence against oxidative stress, which may be particularly important in neurons with increased levels of oxidative stress such as dopaminergic neurons. Altered expression of AT1 and AT2 receptors with aging may induce mitochondrial dysfunction, the main risk factor for neurodegeneration. PMID:27763643

Effects of vibratory stimulation-induced kinesthetic illusions on the neural activities of patients with stroke.

PubMed

Kodama, Takayuki; Nakano, Hideki; Ohsugi, Hironori; Murata, Shin

2016-01-01

[Purpose] This study evaluated the influence of vibratory stimulation-induced kinesthetic illusion on brain function after stroke. [Subjects] Twelve healthy individuals and 13 stroke patients without motor or sensory loss participated. [Methods] Electroencephalograms were taken at rest and during vibratory stimulation. As a neurophysiological index of brain function, we measured the μ-rhythm, which is present mainly in the kinesthetic cortex and is attenuated by movement or motor imagery and compared the data using source localization analyses in the Standardized Low Resolution Brain Electromagnetic Tomography (sLORETA) program. [Results] At rest, μ-rhythms appeared in the sensorimotor and supplementary motor cortices in both healthy controls and stroke patients. Under vibratory stimulation, no μ-rhythm appeared in the sensorimotor cortex of either group. Moreover, in the supplementary motor area, which stores the motor imagery required for kinesthetic illusions, the μ-rhythms of patients were significantly stronger than those of the controls, although the μ-rhythms of both groups were reduced. Thus, differences in neural activity in the supplementary motor area were apparent between the subject groups. [Conclusion] Kinesthetic illusions do occur in patients with motor deficits due to stroke. The neural basis of the supplementary motor area in stroke patients may be functionally different from that found in healthy controls.

Effects of vibratory stimulation-induced kinesthetic illusions on the neural activities of patients with stroke

PubMed Central

Kodama, Takayuki; Nakano, Hideki; Ohsugi, Hironori; Murata, Shin

2016-01-01

[Purpose] This study evaluated the influence of vibratory stimulation-induced kinesthetic illusion on brain function after stroke. [Subjects] Twelve healthy individuals and 13 stroke patients without motor or sensory loss participated. [Methods] Electroencephalograms were taken at rest and during vibratory stimulation. As a neurophysiological index of brain function, we measured the μ-rhythm, which is present mainly in the kinesthetic cortex and is attenuated by movement or motor imagery and compared the data using source localization analyses in the Standardized Low Resolution Brain Electromagnetic Tomography (sLORETA) program. [Results] At rest, μ-rhythms appeared in the sensorimotor and supplementary motor cortices in both healthy controls and stroke patients. Under vibratory stimulation, no μ-rhythm appeared in the sensorimotor cortex of either group. Moreover, in the supplementary motor area, which stores the motor imagery required for kinesthetic illusions, the μ-rhythms of patients were significantly stronger than those of the controls, although the μ-rhythms of both groups were reduced. Thus, differences in neural activity in the supplementary motor area were apparent between the subject groups. [Conclusion] Kinesthetic illusions do occur in patients with motor deficits due to stroke. The neural basis of the supplementary motor area in stroke patients may be functionally different from that found in healthy controls. PMID:27065525

Insulin-regulated aminopeptidase immunoreactivity is abundantly present in human hypothalamus and posterior pituitary gland, with reduced expression in paraventricular and suprachiasmatic neurons in chronic schizophrenia.

PubMed

Bernstein, Hans-Gert; Müller, Susan; Dobrowolny, Hendrik; Wolke, Carmen; Lendeckel, Uwe; Bukowska, Alicja; Keilhoff, Gerburg; Becker, Axel; Trübner, Kurt; Steiner, Johann; Bogerts, Bernhard

2017-08-01

The vasopressin- and oxytocin-degrading enzyme insulin-regulated aminopeptidase (IRAP) is expressed in various organs including the brain. However, knowledge about its presence in human hypothalamus is fragmentary. Functionally, for a number of reasons (genetic linkage, hydrolysis of oxytocin and vasopressin, its role as angiotensin IV receptor in learning and memory and others) IRAP might play a role in schizophrenia. We studied the regional and cellular localization of IRAP in normal human brain with special emphasis on the hypothalamus and determined numerical densities of IRAP-expressing cells in the paraventricular, supraoptic and suprachiasmatic nuclei in schizophrenia patients and controls. By using immunohistochemistry and Western blot analysis, IRAP was immunolocalized in postmortem human brains. Cell countings were performed to estimate numbers and numerical densities of IRAP immunoreactive hypothalamic neurons in schizophrenia patients and control cases. Shape, size and regional distribution of IRAP-expressing cells, as well the lack of co-localization with the glia marker glutamine synthetase, show that IRAP is expressed in neurons. IRAP immunoreactive cells were observed in the hippocampal formation, cerebral cortex, thalamus, amygdala and, abundantly, hypothalamus. Double labeling experiments (IRAP and oxytocin/neurophysin 1, IRAP with vasopressin/neurophysin 2) revealed that IRAP is present in oxytocinergic and in vasopressinergic neurons. In schizophrenia patients, the numerical density of IRAP-expressing neurons in the paraventricular and the suprachiasmatic nuclei is significantly reduced, which might be associated with the reduction in neurophysin-containing neurons in these nuclei in schizophrenia. The pathophysiological role of lowered hypothalamic IRAP expression in schizophrenia remains to be established.

Local Effect of Neurotrophin-3 in Neuronal Inflammation of Allergic Rhinitis: Preliminary Report.

PubMed

İsmi, Onur; Özcan, Cengiz; Karabacak, Tuba; Polat, Gürbüz; Vayisoğlu, Yusuf; Güçlütürk, Taylan; Görür, Kemal

2015-10-01

Allergic rhinitis is a common inflammatory nasal mucosal disease characterized by sneezing, watery nasal discharge, nasal obstruction and itching. Although allergen-specific antibodies play a main role in the allergic airway inflammation, neuronal inflammation may also contribute to the symptoms of allergic rhinitis. Neuronal inflammation is primarily caused by the stimulation of sensory nerve endings with histamine. It has been shown that neurotrophins may also have a role in allergic reactions and neuronal inflammation. Nerve growth factor, neurotrophin 3 (NT-3), neurotrophin 4/5 and brain-derived neurotrophic factor are members of the neurotrophin family. Although nerve growth factor and brain-derived neurotrophic factor are well studied in allergic rhinitis patients, the exact role of Neurotrophin-3 is not known. To investigate the possible roles of neurotrophin-3 in allergic rhinitis patients. Case-control study. Neurotrophin-3 levels were studied in the inferior turbinate and serum samples of 20 allergic rhinitis and 13 control patients. Neurotrophin-3 staining of nasal tissues was evaluated by immunohistochemistry and ELISA was used for the determination of serum Neurotrophin-3 levels. Neurotrophin-3 staining scores were statistically higher in the study group than in the control patients (p=0.001). Regarding serum Neurotrophin-3 levels, no statistically significant difference could be determined between allergic rhinitis and control patients (p=0.156). When comparing the serum NT-3 levels with tissue staining scores, there were no statistically significant differences in the allergic rhinitis and control groups (p=0.254 for allergic rhinitis and p=0.624 for control groups). We suggest that Neurotrophin-3 might affect the nasal mucosa locally without being released into the systemic circulation in allergic rhinitis patients.

Handedness- and brain size-related efficiency differences in small-world brain networks: a resting-state functional magnetic resonance imaging study.

PubMed

Li, Meiling; Wang, Junping; Liu, Feng; Chen, Heng; Lu, Fengmei; Wu, Guorong; Yu, Chunshui; Chen, Huafu

2015-05-01

The human brain has been described as a complex network, which integrates information with high efficiency. However, the relationships between the efficiency of human brain functional networks and handedness and brain size remain unclear. Twenty-one left-handed and 32 right-handed healthy subjects underwent a resting-state functional magnetic resonance imaging scan. The whole brain functional networks were constructed by thresholding Pearson correlation matrices of 90 cortical and subcortical regions. Graph theory-based methods were employed to further analyze their topological properties. As expected, all participants demonstrated small-world topology, suggesting a highly efficient topological structure. Furthermore, we found that smaller brains showed higher local efficiency, whereas larger brains showed higher global efficiency, reflecting a suitable efficiency balance between local specialization and global integration of brain functional activity. Compared with right-handers, significant alterations in nodal efficiency were revealed in left-handers, involving the anterior and median cingulate gyrus, middle temporal gyrus, angular gyrus, and amygdala. Our findings indicated that the functional network organization in the human brain was associated with handedness and brain size.

Disrupted subject-specific gray matter network properties and cognitive dysfunction in type 1 diabetes patients with and without proliferative retinopathy.

PubMed

van Duinkerken, Eelco; Ijzerman, Richard G; Klein, Martin; Moll, Annette C; Snoek, Frank J; Scheltens, Philip; Pouwels, Petra J W; Barkhof, Frederik; Diamant, Michaela; Tijms, Betty M

2016-03-01

Type 1 diabetes mellitus (T1DM) patients, especially with concomitant microvascular disease, such as proliferative retinopathy, have an increased risk of cognitive deficits. Local cortical gray matter volume reductions only partially explain these cognitive dysfunctions, possibly because volume reductions do not take into account the complex connectivity structure of the brain. This study aimed to identify gray matter network alterations in relation to cognition in T1DM. We investigated if subject-specific structural gray matter network properties, constructed from T1-weighted MRI scans, were different between T1DM patients with (n = 51) and without (n = 53) proliferative retinopathy versus controls (n = 49), and were associated to cognitive decrements and fractional anisotropy, as measured by voxel-based TBSS. Global normalized and local (45 bilateral anatomical regions) clustering coefficient and path length were assessed. These network properties measure how the organization of connections in a network differs from that of randomly connected networks. Global gray matter network topology was more randomly organized in both T1DM patient groups versus controls, with the largest effects seen in patients with proliferative retinopathy. Lower local path length values were widely distributed throughout the brain. Lower local clustering was observed in the middle frontal, postcentral, and occipital areas. Complex network topology explained up to 20% of the variance of cognitive decrements, beyond other predictors. Exploratory analyses showed that lower fractional anisotropy was associated with a more random gray matter network organization. T1DM and proliferative retinopathy affect cortical network organization that may consequently contribute to clinically relevant changes in cognitive functioning in these patients. © 2015 Wiley Periodicals, Inc.

Global Efficiency of Structural Networks Mediates Cognitive Control in Mild Cognitive Impairment

PubMed Central

Berlot, Rok; Metzler-Baddeley, Claudia; Ikram, M. Arfan; Jones, Derek K.; O’Sullivan, Michael J.

2016-01-01

Background: Cognitive control has been linked to both the microstructure of individual tracts and the structure of whole-brain networks, but their relative contributions in health and disease remain unclear. Objective: To determine the contribution of both localized white matter tract damage and disruption of global network architecture to cognitive control, in older age and Mild Cognitive Impairment (MCI). Materials and Methods: Twenty-five patients with MCI and 20 age, sex, and intelligence-matched healthy volunteers were investigated with 3 Tesla structural magnetic resonance imaging (MRI). Cognitive control and episodic memory were evaluated with established tests. Structural network graphs were constructed from diffusion MRI-based whole-brain tractography. Their global measures were calculated using graph theory. Regression models utilized both global network metrics and microstructure of specific connections, known to be critical for each domain, to predict cognitive scores. Results: Global efficiency and the mean clustering coefficient of networks were reduced in MCI. Cognitive control was associated with global network topology. Episodic memory, in contrast, correlated with individual temporal tracts only. Relationships between cognitive control and network topology were attenuated by addition of single tract measures to regression models, consistent with a partial mediation effect. The mediation effect was stronger in MCI than healthy volunteers, explaining 23-36% of the effect of cingulum microstructure on cognitive control performance. Network clustering was a significant mediator in the relationship between tract microstructure and cognitive control in both groups. Conclusion: The status of critical connections and large-scale network topology are both important for maintenance of cognitive control in MCI. Mediation via large-scale networks is more important in patients with MCI than healthy volunteers. This effect is domain-specific, and true for cognitive control but not for episodic memory. Interventions to improve cognitive control will need to address both dysfunction of local circuitry and global network architecture to be maximally effective. PMID:28018208

In Situ Activation of Antigen-Specific CD8+ T Cells in the Presence of Antigen in Organotypic Brain Slices1

PubMed Central

Ling, Changying; Verbny, Yakov I.; Banks, Matthew I.; Sandor, Matyas; Fabry, Zsuzsanna

2012-01-01

The activation of Ag-specific T cells locally in the CNS could potentially contribute to the development of immune-mediated brain diseases. We addressed whether Ag-specific T cells could be stimulated in the CNS in the absence of peripheral lymphoid tissues by analyzing Ag-specific T cell responses in organotypic brain slice cultures. Organotypic brain slice cultures were established 1 h after intracerebral OVA Ag microinjection. We showed that when OVA-specific CD8+ T cells were added to Ag-containing brain slices, these cells became activated and migrated into the brain to the sites of their specific Ags. This activation of OVA-specific T cells was abrogated by the deletion of CD11c+ cells from the brain slices of the donor mice. These data suggest that brain-resident CD11c+ cells stimulate Ag-specific naive CD8+ T cells locally in the CNS and may contribute to immune responses in the brain. PMID:18523307

Application of intracerebral microdialysis to study regional distribution kinetics of drugs in rat brain.

PubMed Central

de Lange, E. C.; Bouw, M. R.; Mandema, J. W.; Danhof, M.; de Boer, A. G.; Breimer, D. D.

1995-01-01

1. The purpose of the present study was to determine whether intracerebral microdialysis can be used for the assessment of local differences in drug concentrations within the brain. 2. Two transversal microdialysis probes were implanted in parallel into the frontal cortex of male Wistar rats, and used as a local infusion and detection device respectively. Within one rat, three different concentrations of atenolol or acetaminophen were infused in randomized order. By means of the detection probe, concentration-time profiles of the drug in the brain were measured at interprobe distances between 1 and 2 mm. 3. Drug concentrations were found to be dependent on the drug as well as on the interprobe distance. It was found that the outflow concentration from the detection probe decreased with increasing lateral spacing between the probes and this decay was much steeper for acetaminophen than for atenolol. A model was developed which allows estimation of kbp/Deff (transfer coefficient from brain to blood/effective diffusion coefficient in brain extracellular fluid), which was considerably larger for the more lipohilic drug, acetaminophen. In addition, in vivo recovery values for both drugs were determined. 4. The results show that intracerebral microdialysis is able to detect local differences in drug concentrations following infusion into the brain. Furthermore, the potential use of intracerebral microdialysis to obtain pharmacokinetic parameters of drug distribution in brain by means of monitoring local concentrations of drugs in time is demonstrated. PMID:8581296

Cerebral localization, then and now.

PubMed

Marshall, John C; Fink, Gereon R

2003-11-01

We review some of the progress made in understanding the nature of functional specialization in the human brain, beginning with the anatomical claim that all mental faculties have their own distinct material substrate in different regions of the brain and the psychological claim that each mental faculty is characterized by the content domain with which it deals. This conceptual framework led behavioral neurologists to show how discrete brain lesions provoked different types of language, praxic, gnostic, spatial, and memory disorders. The simplest way of interpreting these anatomoclinical associations was to conjecture that the normal function (now impaired by brain damage) was localized within that lesioned region. It was also realized that cognitive impairments could arise from lesions that spared the functional centers themselves but disconnected them from other centers. Nonetheless, many neuroscientists remained skeptical of the entire paradigm. Accordingly, in the late 19th century functional localization began to be studied in the intact human brain by such techniques as measuring the temperature of different brain regions when different cognitive tasks were performed. During the 20th century these crude techniques gave way to positron emission tomography, functional magnetic resonance imaging, and magnetoencephalography. The relatively precise spatial and temporal resolution of modern methods now raises a crucial question: Do the functional localizations obtained by the anatomoclinical method converge with those implied by the functional neuroimaging of cognition in healthy volunteers? We then conclude with some recent suggestions that functional specialization is not such a fixed property of brain regions as previously supposed.

Oxidative Burst of Circulating Neutrophils Following Traumatic Brain Injury in Human

PubMed Central

Liao, Yiliu; Liu, Peng; Guo, Fangyuan; Zhang, Zhi-Yuan; Zhang, Zhiren

2013-01-01

Besides secondary injury at the lesional site, Traumatic brain injury (TBI) can cause a systemic inflammatory response, which may cause damage to initially unaffected organs and potentially further exacerbate the original injury. Here we investigated plasma levels of important inflammatory mediators, oxidative activity of circulating leukocytes, particularly focusing on neutrophils, from TBI subjects and control subjects with general trauma from 6 hours to 2 weeks following injury, comparing with values from uninjured subjects. We observed increased plasma level of inflammatory cytokines/molecules TNF-α, IL-6 and CRP, dramatically increased circulating leukocyte counts and elevated expression of TNF-α and iNOS in circulating leukocytes from TBI patients, which suggests a systemic inflammatory response following TBI. Our data further showed increased free radical production in leukocyte homogenates and elevated expression of key oxidative enzymes iNOS, COX-2 and NADPH oxidase (gp91phox) in circulating leukocytes, indicating an intense induction of oxidative burst following TBI, which is significantly greater than that in control subjects with general trauma. Furthermore, flow cytometry assay proved neutrophils as the largest population in circulation after TBI and showed significantly up-regulated oxidative activity and suppressed phagocytosis rate for circulating neutrophils following brain trauma. It suggests that the highly activated neutrophils might play an important role in the secondary damage, even outside the injured brain. Taken together, the potent systemic inflammatory response induced by TBI, especially the intensively increase oxidative activity of circulating leukocytes, mainly neutrophils, may lead to a systemic damage, dysfunction/damage of bystander tissues/organs and even further exacerbate secondary local damage. Controlling these pathophysiological processes may be a promising therapeutic strategy and will protect unaffected organs and the injured brain from the secondary damage. PMID:23894384

N-acetylaspartate (NAA) levels in selected areas of the brain in patients with chronic schizophrenia treated with typical and atypical neuroleptics: a proton magnetic resonance spectroscopy (1H MRS) study.

PubMed

Szulc, Agata; Galińska, Beata; Tarasów, Eugeniusz; Kubas, Bozena; Dzienis, Wojciech; Konarzewska, Beata; Poplawska, Regina; Tomczak, Anna A; Czernikiewicz, Andrzej; Walecki, Jerzy

2007-05-01

NAA, marker of neurons integrity and viability, is one of the most important brain metabolites visible in 1H MRS. In most studies of schizophrenia, the decrease of NAA level was observed in the temporal, frontal lobes and in the thalamus. This finding was observed more often among chronic patients, what suggests the influence of disease duration or the effect of neuroleptic treatment. The aim of the present study was the comparison of NAA levels in brain of schizophrenic patients taking typical and atypical neuroleptics. We analyzed the NAA levels in selected brain areas in 58 schizophrenic patients and 21 healthy controls. 10 patients were treated with typical neuroleptics, 10 patients with clozapine, 17 received olanzapine and 21 - risperidone. 1H MRS was performed on a 1,5 MR scanner with PRESS sequence. Voxels of 2x2x2 cm were localized in the left frontal, left temporal lobe and left thalamus. There were no differences in NAA levels between patients on typical and atypical medications analyzed together and separately (olanzapine, clozapine and risperidone groups). We also did not find any differences between patients taking selected atypical neuroleptics and controls. The NAA level in the thalamus in the group of patients receiving typical antipsychotics was the lowest among all groups and differed significantly from healthy controls. The results of our study suggest that atypical neuroleptics may have favorable effect on NAA concentration in brain of schizophrenic patients. Decrease in NAA level in patients taking typical medication may be caused by the progression of the disease or by the direct action of these drugs.

Limbic grey matter changes in early Parkinson's disease.

PubMed

Li, Xingfeng; Xing, Yue; Schwarz, Stefan T; Auer, Dorothee P

2017-05-02

The purpose of this study was to investigate local and network-related changes of limbic grey matter in early Parkinson's disease (PD) and their inter-relation with non-motor symptom severity. We applied voxel-based morphometric methods in 538 T1 MRI images retrieved from the Parkinson's Progression Markers Initiative website. Grey matter densities and cross-sectional estimates of age-related grey matter change were compared between subjects with early PD (n = 366) and age-matched healthy controls (n = 172) within a regression model, and associations of grey matter density with symptoms were investigated. Structural brain networks were obtained using covariance analysis seeded in regions showing grey matter abnormalities in PD subject group. Patients displayed focally reduced grey matter density in the right amygdala, which was present from the earliest stages of the disease without further advance in mild-moderate disease stages. Right amygdala grey matter density showed negative correlation with autonomic dysfunction and positive with cognitive performance in patients, but no significant interrelations were found with anxiety scores. Patients with PD also demonstrated right amygdala structural disconnection with less structural connectivity of the right amygdala with the cerebellum and thalamus but increased covariance with bilateral temporal cortices compared with controls. Age-related grey matter change was also increased in PD preferentially in the limbic system. In conclusion, detailed brain morphometry in a large group of early PD highlights predominant limbic grey matter deficits with stronger age associations compared with controls and associated altered structural connectivity pattern. This provides in vivo evidence for early limbic grey matter pathology and structural network changes that may reflect extranigral disease spread in PD. Hum Brain Mapp, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Convection-enhanced delivery of sorafenib and suppression of tumor progression in a murine model of brain melanoma through the inhibition of signal transducer and activator of transcription 3.

PubMed

Zou, Zhaoxia; Yin, Yufang; Lin, Jenny; Hsu, Li-Chen J; Brandon, Vanessa L; Yang, Fan; Jove, Richard; Jandial, Rahul; Li, Gang; Chen, Mike Y

2016-05-01

OBJECT Despite recent advances, metastatic melanoma remains a terminal disease, in which life-threatening brain metastasis occurs in approximately half of patients. Sorafenib is a multikinase inhibitor that induces apoptosis of melanoma cells in vitro. However, systemic administration has been ineffective because adequate tissue concentrations cannot be achieved. This study investigated if convection-enhanced delivery (CED) of sorafenib would enhance tumor control and survival via inhibition of the signal transducer and activator of transcription 3 (Stat3) pathway in a murine model of metastatic brain melanoma. METHODS Melanoma cells treated with sorafenib in vitro were examined for signaling and survival changes. The effect of sorafenib given by CED was assessed by bioluminescent imaging and animal survival. RESULTS The results showed that sorafenib induced cell death in the 4 established melanoma cell lines and in 1 primary cultured melanoma cell line. Sorafenib inhibited Stat3 phosphorylation in HTB65, WYC1, and B16 cells. Accordingly, sorafenib treatment also decreased expression of Mcl-1 mRNA in melanoma cell lines. Because sorafenib targets multiple pathways, the present study demonstrated the contribution of the Stat3 pathway by showing that mouse embryonic fibroblast (MEF) Stat3 +/+ cells were significantly more sensitive to sorafenib than MEF Stat3 -/- cells. In the murine model of melanoma brain metastasis used in this study, CED of sorafenib increased survival by 150% in the treatment group compared with animals receiving the vehicle control (p < 0.01). CED of sorafenib also significantly abrogated tumor growth. CONCLUSIONS The data from this study indicate that local delivery of sorafenib effectively controls brain melanoma. These findings validate further investigation of the use of CED to distribute molecularly targeted agents.

The impact of ADHD persistence, recent cannabis use, and age of regular cannabis use onset on subcortical volume and cortical thickness in young adults.

PubMed

Lisdahl, Krista M; Tamm, Leanne; Epstein, Jeffery N; Jernigan, Terry; Molina, Brooke S G; Hinshaw, Stephen P; Swanson, James M; Newman, Erik; Kelly, Clare; Bjork, James M

2016-04-01

Both Attention Deficit Hyperactivity Disorder (ADHD) and chronic cannabis (CAN) use have been associated with brain structural abnormalities, although little is known about the effects of both in young adults. Participants included: those with a childhood diagnosis of ADHD who were CAN users (ADHD_CAN; n=37) and non-users (NU) (ADHD_NU; n=44) and a local normative comparison group (LNCG) who did (LNCG_CAN; n=18) and did not (LNCG_NU; n=21) use CAN regularly. Multiple regressions and MANCOVAs were used to examine the independent and interactive effects of a childhood ADHD diagnosis and CAN group status and age of onset (CUO) on subcortical volumes and cortical thickness. After controlling for age, gender, total brain volume, nicotine use, and past-year binge drinking, childhood ADHD diagnosis did not predict brain structure; however, persistence of ADHD was associated with smaller left precentral/postcentral cortical thickness. Compared to all non-users, CAN users had decreased cortical thickness in right hemisphere superior frontal sulcus, anterior cingulate, and isthmus of cingulate gyrus regions and left hemisphere superior frontal sulcus and precentral gyrus regions. Early cannabis use age of onset (CUO) in those with ADHD predicted greater right hemisphere superior frontal and postcentral cortical thickness. Young adults with persistent ADHD demonstrated brain structure abnormalities in regions underlying motor control, working memory and inhibitory control. Further, CAN use was linked with abnormal brain structure in regions with high concentrations of cannabinoid receptors. Additional large-scale longitudinal studies are needed to clarify how substance use impacts neurodevelopment in youth with and without ADHD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Exercise increases blood flow to locomotor, vestibular, cardiorespiratory and visual regions of the brain in miniature swine

NASA Technical Reports Server (NTRS)

Delp, M. D.; Armstrong, R. B.; Godfrey, D. A.; Laughlin, M. H.; Ross, C. D.; Wilkerson, M. K.

2001-01-01

1. The purpose of these experiments was to use radiolabelled microspheres to measure blood flow distribution within the brain, and in particular to areas associated with motor function, maintenance of equilibrium, cardiorespiratory control, vision, hearing and smell, at rest and during exercise in miniature swine. Exercise consisted of steady-state treadmill running at intensities eliciting 70 and 100 % maximal oxygen consumption (V(O(2),max)). 2. Mean arterial pressure was elevated by 17 and 26 % above that at rest during exercise at 70 and 100 % V(O(2),max), respectively. 3. Mean brain blood flow increased 24 and 25 % at 70 and 100 % V(O(2),max), respectively. Blood flow was not locally elevated to cortical regions associated with motor and somatosensory functions during exercise, but was increased to several subcortical areas that are involved in the control of locomotion. 4. Exercise elevated perfusion and diminished vascular resistance in several regions of the brain related to the maintenance of equilibrium (vestibular nuclear area, cerebellar ventral vermis and floccular lobe), cardiorespiratory control (medulla and pons), and vision (dorsal occipital cortex, superior colliculi and lateral geniculate body). Conversely, blood flow to regions related to hearing (cochlear nuclei, inferior colliculi and temporal cortex) and smell (olfactory bulbs and rhinencephalon) were unaltered by exercise and associated with increases in vascular resistance. 5. The data indicate that blood flow increases as a function of exercise intensity to several areas of the brain associated with integrating sensory input and motor output (anterior and dorsal cerebellar vermis) and the maintenance of equilibrium (vestibular nuclei). Additionally, there was an intensity-dependent decrease of vascular resistance in the dorsal cerebellar vermis.

The Impact of ADHD Persistence, Recent Cannabis Use, and Age of Regular Cannabis Use Onset on Subcortical Volume and Cortical Thickness in Young Adults

PubMed Central

Lisdahl, Krista M.; Tamm, Leanne; Epstein, Jeffery N.; Jernigan, Terry; Molina, Brooke S.G.; Hinshaw, Stephen P.; Swanson, James M.; Newman, Erik; Kelly, Clare; Bjork, James M.

2017-01-01

Background Both Attention Deficit Hyperactivity Disorder (ADHD) and chronic cannabis (CAN) use have been associated with brain structural abnormalities, although little is known about the effects of both in young adults. Methods Participants included: those with a childhood diagnosis of ADHD who were CAN users (ADHD_CAN; n=37) and non-users (NU) (ADHD_NU; n=44) and a local normative comparison group (LNCG) who did (LNCG_CAN; n=18) and did not (LNCG_NU; n=21) use CAN regularly. Multiple regressions and MANCOVAs were used to examine the independent and interactive effects of a childhood ADHD diagnosis and CAN group status and age of onset (CUO) on subcortical volumes and cortical thickness. Results After controlling for age, gender, total brain volume, nicotine use, and past-year binge drinking, childhood ADHD diagnosis did not predict brain structure; however, persistence of ADHD was associated with smaller left precentral/postcentral cortical thickness. Compared to all non-users, CAN users had decreased cortical thickness in right hemisphere superior frontal sulcus, anterior cingulate, and isthmus of cingulate gyrus regions and left hemisphere superior frontal sulcus and precentral gyrus regions. Early cannabis use age of onset (CUO) in those with ADHD predicted greater right hemisphere superior frontal and postcentral cortical thickness. Discussion Young adults with persistent ADHD demonstrated brain structure abnormalities in regions underlying motor control, working memory and inhibitory control. Further, CAN use was linked with abnormal brain structure in regions with high concentrations of cannabinoid receptors. Additional large-scale longitudinal studies are needed to clarify how substance use impacts neurodevelopment in youth with and without ADHD. PMID:26897585

Soluble Megalin is Reduced in Cerebrospinal Fluid Samples of Alzheimer's Disease Patients.

PubMed

Spuch, Carlos; Antequera, Desireé; Pascual, Consuelo; Abilleira, Soledad; Blanco, María; Moreno-Carretero, María José; Romero-López, Jesús; Ishida, Tetsuya; Molina, Jose Antonio; Villarejo, Alberto; Bermejo-Pareja, Felix; Carro, Eva

2015-01-01

Megalin or low-density lipoprotein receptor-related protein-2 is a member of the low-density lipoprotein receptor family, which has been linked to Alzheimer's disease (AD) by clearing brain amyloid β-peptide (Aβ) across the blood-cerebrospinal fluid barrier at the choroid plexus. Here, we found a soluble form of megalin secreted from choroid plexus epithelial cells. Soluble megalin levels were also localized in the human cerebrospinal fluid (CSF), being reduced in AD patients. We have also shown that soluble megalin binding to Aβ is decreased in the CSF of AD patients, suggesting that decreased sequestration of Aβ in the CSF could be associated with defective clearance of Aβ and an increase of brain Aβ levels. Thus, therapies, which increase megalin expression, at the choroid plexus and/or enhance circulating soluble megalin hold potential to control brain Aβ-related pathologies in AD.

Soluble Megalin is Reduced in Cerebrospinal Fluid Samples of Alzheimer’s Disease Patients

PubMed Central

Spuch, Carlos; Antequera, Desireé; Pascual, Consuelo; Abilleira, Soledad; Blanco, María; Moreno-Carretero, María José; Romero-López, Jesús; Ishida, Tetsuya; Molina, Jose Antonio; Villarejo, Alberto; Bermejo-Pareja, Felix; Carro, Eva

2015-01-01

Megalin or low-density lipoprotein receptor-related protein-2 is a member of the low-density lipoprotein receptor family, which has been linked to Alzheimer’s disease (AD) by clearing brain amyloid β-peptide (Aβ) across the blood–cerebrospinal fluid barrier at the choroid plexus. Here, we found a soluble form of megalin secreted from choroid plexus epithelial cells. Soluble megalin levels were also localized in the human cerebrospinal fluid (CSF), being reduced in AD patients. We have also shown that soluble megalin binding to Aβ is decreased in the CSF of AD patients, suggesting that decreased sequestration of Aβ in the CSF could be associated with defective clearance of Aβ and an increase of brain Aβ levels. Thus, therapies, which increase megalin expression, at the choroid plexus and/or enhance circulating soluble megalin hold potential to control brain Aβ-related pathologies in AD. PMID:25926771

Spatial Working Memory Performance and fMRI Activation Interactions in Abstinent Adolescent Marijuana Users

PubMed Central

Padula, Claudia B.; Schweinsburg, Alecia D.; Tapert, Susan F.

2008-01-01

Previous studies have suggested neural disruption and reorganization in adult marijuana users. However, it remains unclear whether these effects persist in adolescents after 28 days of abstinence and, if they do, what Performance × Brain Response interactions occur. Adolescent marijuana users (n = 17) and controls (n = 17) aged 16–18 years were recruited from local schools. Functional magnetic resonance imaging data were collected after 28 days’ monitored abstinence as participants performed a spatial working memory task. Marijuana users show Performance × Brain Response interactions in the bilateral temporal lobes, left anterior cingulate, left parahippocampal gyrus, and right thalamus (clusters ≥ 1358 μl; p <.05), although groups do not differ on behavioral measures of task performance. Marijuana users show differences in brain response to a spatial working memory task despite adequate performance, suggesting a different approach to the task via altered neural pathways. PMID:18072830

Computing the shape of brain networks using graph filtration and Gromov-Hausdorff metric.

PubMed

Lee, Hyekyoung; Chung, Moo K; Kang, Hyejin; Kim, Boong-Nyun; Lee, Dong Soo

2011-01-01

The difference between networks has been often assessed by the difference of global topological measures such as the clustering coefficient, degree distribution and modularity. In this paper, we introduce a new framework for measuring the network difference using the Gromov-Hausdorff (GH) distance, which is often used in shape analysis. In order to apply the GH distance, we define the shape of the brain network by piecing together the patches of locally connected nearest neighbors using the graph filtration. The shape of the network is then transformed to an algebraic form called the single linkage matrix. The single linkage matrix is subsequently used in measuring network differences using the GH distance. As an illustration, we apply the proposed framework to compare the FDG-PET based functional brain networks out of 24 attention deficit hyperactivity disorder (ADHD) children, 26 autism spectrum disorder (ASD) children and 11 pediatric control subjects.

Somatostatin, tau, and beta-amyloid within the anterior olfactory nucleus in Alzheimer disease.

PubMed

Saiz-Sanchez, D; Ubeda-Bañon, I; de la Rosa-Prieto, C; Argandoña-Palacios, L; Garcia-Muñozguren, S; Insausti, R; Martinez-Marcos, A

2010-06-01

Impaired olfaction is an early symptom of Alzheimer disease (AD). This likely to reflect neurodegenerative processes taking place in basal telencephalic structures that mediate olfactory processing, including the anterior olfactory nucleus. Betaeta-amyloid (Abeta) accumulation in AD brain may relate to decline in somatostatin levels: somatostatin induces the expression of the Abeta-degrading enzyme neprilysin and somatostatin deficiency in AD may therefore reduce Abeta clearance. We have investigated the expression of somatostatin in the anterior olfactory nucleus of AD and control brain. We report that somatostatin levels were reduced by approximately 50% in AD brain. Furthermore, triple-immunofluorescence revealed co-localization of somatostatin expression with Abeta (65.43%) with Abeta and tau (19.75%) and with tau (2.47%). These data indicate that somatostatin decreases in AD and its expression may be linked with Abeta deposition. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Top-down alpha oscillatory network interactions during visuospatial attention orienting.

PubMed

Doesburg, Sam M; Bedo, Nicolas; Ward, Lawrence M

2016-05-15

Neuroimaging and lesion studies indicate that visual attention is controlled by a distributed network of brain areas. The covert control of visuospatial attention has also been associated with retinotopic modulation of alpha-band oscillations within early visual cortex, which are thought to underlie inhibition of ignored areas of visual space. The relation between distributed networks mediating attention control and more focal oscillatory mechanisms, however, remains unclear. The present study evaluated the hypothesis that alpha-band, directed, network interactions within the attention control network are systematically modulated by the locus of visuospatial attention. We localized brain areas involved in visuospatial attention orienting using magnetoencephalographic (MEG) imaging and investigated alpha-band Granger-causal interactions among activated regions using narrow-band transfer entropy. The deployment of attention to one side of visual space was indexed by lateralization of alpha power changes between about 400ms and 700ms post-cue onset. The changes in alpha power were associated, in the same time period, with lateralization of anterior-to-posterior information flow in the alpha-band from various brain areas involved in attention control, including the anterior cingulate cortex, left middle and inferior frontal gyri, left superior temporal gyrus, and right insula, and inferior parietal lobule, to early visual areas. We interpreted these results to indicate that distributed network interactions mediated by alpha oscillations exert top-down influences on early visual cortex to modulate inhibition of processing for ignored areas of visual space. Copyright © 2016. Published by Elsevier Inc.

Cerebellum as a forward but not inverse model in visuomotor adaptation task: a tDCS-based and modeling study.

PubMed

Yavari, Fatemeh; Mahdavi, Shirin; Towhidkhah, Farzad; Ahmadi-Pajouh, Mohammad-Ali; Ekhtiari, Hamed; Darainy, Mohammad

2016-04-01

Despite several pieces of evidence, which suggest that the human brain employs internal models for motor control and learning, the location of these models in the brain is not yet clear. In this study, we used transcranial direct current stimulation (tDCS) to manipulate right cerebellar function, while subjects adapt to a visuomotor task. We investigated the effect of this manipulation on the internal forward and inverse models by measuring two kinds of behavior: generalization of training in one direction to neighboring directions (as a proxy for inverse models) and localization of the hand position after movement without visual feedback (as a proxy for forward model). The experimental results showed no effect of cerebellar tDCS on generalization, but significant effect on localization. These observations support the idea that the cerebellum is a possible brain region for internal forward, but not inverse model formation. We also used a realistic human head model to calculate current density distribution in the brain. The result of this model confirmed the passage of current through the cerebellum. Moreover, to further explain some observed experimental results, we modeled the visuomotor adaptation process with the help of a biologically inspired method known as population coding. The effect of tDCS was also incorporated in the model. The results of this modeling study closely match our experimental data and provide further evidence in line with the idea that tDCS manipulates FM's function in the cerebellum.

Interval From Imaging to Treatment Delivery in the Radiation Surgery Age: How Long Is Too Long?

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

Seymour, Zachary A., E-mail: seymourz@radonc.ucsf.edu; Fogh, Shannon E.; Westcott, Sarah K.

Purpose: The purpose of this study was to evaluate workflow and patient outcomes related to frameless stereotactic radiation surgery (SRS) for brain metastases. Methods and Materials: We reviewed all treatment demographics, clinical outcomes, and workflow timing, including time from magnetic resonance imaging (MRI), computed tomography (CT) simulation, insurance authorization, and consultation to the start of SRS for brain metastases. Results: A total of 82 patients with 151 brain metastases treated with SRS were evaluated. The median times from consultation, insurance authorization, CT simulation, and MRI for treatment planning were 15, 7, 6, and 11 days to SRS. Local freedom from progressionmore » (LFFP) was lower in metastases with MRI ≥14 days before treatment (P=.0003, log rank). The 6- and 12-month LFFP rate were 95% and 75% for metastasis with interval of <14 days from MRI to treatment compared to 56% and 34% for metastases with MRI ≥14 days before treatment. On multivariate analysis, LFFP remained significantly lower for lesions with MRI ≥14 days at SRS (P=.002, Cox proportional hazards; hazard ratio: 3.4, 95% confidence interval: 1.6-7.3). Conclusions: Delay from MRI to SRS treatment delivery for brain metastases appears to reduce local control. Future studies should monitor the timing from imaging acquisition to treatment delivery. Our experience suggests that the time from MRI to treatment should be <14 days.« less

Possible psycho-physiological consequences of human long-term space missions

NASA Astrophysics Data System (ADS)

Belisheva, N. K.; Lammer, H.; Biernat, H. K.; Kachanova, T. L.; Kalashnikova, I. V.

Experiments carried out on the Earth s surface during different years and under contrast periods of solar activity have shown that the functional state of biosystems including the human organisms are controlled by global and local geocosmical agents Our finding have a close relation to space research because they demonstrate the reactions of biosystems on variations of global and local geocosmical agents and the mechanisms of modulations of biosystems state by geocosmical agents We revealed the role of variations of the geomagnetic field for the stimulation of immune systems functional state of peripheral blood human brain growth of microflora skin covers and pathogenic microorganisms The study of the psycho-physiological state of the human organism has demonstrated that an increase of the neutron intensity near the Earth s surface is associated with anxiety decrease of normal and increase of paradox reactions of examinees The analysis of the human brain functional state in dependent on the geomagnetic variation structure dose under exposure to the variations of geomagnetic field in a certain amplitude-frequency range and also the intensity of the nucleon component of secondary cosmic rays showed that the stable and unstable states of the human brain are determined by geomagnetic field variations and the intensity of the nucleon component The stable state of the brain manifested under the periodic oscillations of the geomagnetic field in a certain amplitude-frequency range The low level of geomagnetic activity associated with an

COB231 targets amyloid plaques in post-mortem human brain tissue and in an Alzheimer mouse model.

PubMed

Garin, Dominique; Virgone-Carlotta, Angélique; Gözel, Bülent; Oukhatar, Fatima; Perret, Pascale; Marti-Battle, Danièle; Touret, Monique; Millet, Philippe; Dubois-Dauphin, Michel; Meyronet, David; Streichenberger, Nathalie; Laferla, Frank M; Demeunynck, Martine; Chierici, Sabine; Sallanon Moulin, Marcelle; Ghezzi, Catherine

2015-03-01

Previous works have shown the interest of naturally fluorescent proflavine derivatives to label Abeta deposits in vitro. This study aimed to further characterize the properties of the proflavine 3-acetylamino-6-[3-(propargylamino)propanoyl]aminoacridine (COB231) derivative as a probe. This compound was therefore evaluated on human post-mortem and mice brain slices and in vivo in 18-month-old triple transgenic mice APPswe, PS1M146V and tauP301L (3xTgAD) mice presenting the main characteristics of Alzheimer's disease (AD). COB231 labelled amyloid plaques on brain slices of AD patients, and 3xTgAD mice at 10 and 0.1 μM respectively. However, no labelling of the neurofibrillary tangle-rich areas was observed either at high concentration or in the brain of fronto-temporal dementia patients. The specificity of this mapping was attested in mice using Thioflavin S and IMPY as positive controls of amyloid deposits. After intravenous injection of COB231 in old 3xTgAD mice, fluorescent amyloid plaques were detected in the cortex and hippocampus, demonstrating COB231 blood–brain barrier permeability. We also controlled the cellular localization of COB231 on primary neuronal cultures and showed that COB231 accumulates into the cytoplasm and not into the nucleus. Finally, using a viability assay, we only detected a slight cytotoxic effect of COB231 (< 10%) for the highest concentration (100 μM).

Response of brain metastasis from lung cancer patients to an oral nutraceutical product containing silibinin.

PubMed

Bosch-Barrera, Joaquim; Sais, Elia; Cañete, Noemí; Marruecos, Jordi; Cuyàs, Elisabet; Izquierdo, Angel; Porta, Rut; Haro, Manel; Brunet, Joan; Pedraza, Salvador; Menendez, Javier A

2016-05-31

Despite multimodal treatment approaches, the prognosis of brain metastases (BM) from non-small cell lung cancer (NSCLC) remains poor. Untreated patients with BM have a median survival of about 1 month, with almost all patients dying from neurological causes. We herein present the first report describing the response of BM from NSCLC patients to an oral nutraceutical product containing silibinin, a flavonoid extracted from the seeds of the milk thistle. We present evidence of how the use of the silibinin-based nutraceutical Legasil® resulted in significant clinical and radiological improvement of BM from NSCLC patients with poor performance status that progressed after whole brain radiotherapy and chemotherapy. The suppressive effects of silibinin on progressive BM, which involved a marked reduction of the peritumoral brain edema, occurred without affecting the primary lung tumor outgrowth in NSCLC patients. Because BM patients have an impaired survival prognosis and are in need for an immediate tumor control, the combination of brain radiotherapy with silibinin-based nutraceuticals might not only alleviate BM edema but also prove local control and time for either classical chemotherapeutics with immunostimulatory effects or new immunotherapeutic agents such as checkpoint blockers to reveal their full therapeutic potential in NSCLC BM patients. New studies aimed to illuminate the mechanistic aspects underlying the regulatory effects of silibinin on the cellular and molecular pathobiology of BM might expedite the entry of new formulations of silibinin into clinical testing for progressive BM from lung cancer patients.

Response of brain metastasis from lung cancer patients to an oral nutraceutical product containing silibinin

PubMed Central

Bosch-Barrera, Joaquim; Sais, Elia; Cañete, Noemí; Marruecos, Jordi; Cuyàs, Elisabet; Izquierdo, Angel; Porta, Rut; Haro, Manel; Brunet, Joan; Pedraza, Salvador; Menendez, Javier A.

2016-01-01

Despite multimodal treatment approaches, the prognosis of brain metastases (BM) from non-small cell lung cancer (NSCLC) remains poor. Untreated patients with BM have a median survival of about 1 month, with almost all patients dying from neurological causes. We herein present the first report describing the response of BM from NSCLC patients to an oral nutraceutical product containing silibinin, a flavonoid extracted from the seeds of the milk thistle. We present evidence of how the use of the silibinin-based nutraceutical Legasil® resulted in significant clinical and radiological improvement of BM from NSCLC patients with poor performance status that progressed after whole brain radiotherapy and chemotherapy. The suppressive effects of silibinin on progressive BM, which involved a marked reduction of the peritumoral brain edema, occurred without affecting the primary lung tumor outgrowth in NSCLC patients. Because BM patients have an impaired survival prognosis and are in need for an immediate tumor control, the combination of brain radiotherapy with silibinin-based nutraceuticals might not only alleviate BM edema but also prove local control and time for either classical chemotherapeutics with immunostimulatory effects or new immunotherapeutic agents such as checkpoint blockers to reveal their full therapeutic potential in NSCLC BM patients. New studies aimed to illuminate the mechanistic aspects underlying the regulatory effects of silibinin on the cellular and molecular pathobiology of BM might expedite the entry of new formulations of silibinin into clinical testing for progressive BM from lung cancer patients. PMID:26959886