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Sample records for age-matched control brains

  1. RELN-expressing Neuron Density in Layer I of the Superior Temporal Lobe is Similar in Human Brains with Autism and in Age-Matched Controls

    PubMed Central

    Camacho, Jasmin; Ejaz, Ehsan; Ariza, Jeanelle; Noctor, Stephen C.; Martínez-Cerdeño, Verónica

    2015-01-01

    Reelin protein (RELN) level is reduced in the cerebral cortex and cerebellum of subjects with autism. RELN is synthesized and secreted by a subpopulation of neurons in the developing cerebral cortex termed Cajal-Retzius (CR) cells. These cells are abundant in the marginal zone during cortical development, many die after development is complete, but a small population persists into adulthood. In adult brains, RELN is secreted by the surviving CR cells, by a subset of GABAergic interneurons in layer I, and by pyramidal cells and GABAergic interneurons in deeper cortical layers. It is widely believed that decreased RELN in layer I of the cerebral cortex of subjects with autism may result from a decrease in the density of RELN expressing neurons in layer I; however, this hypothesis has not been tested. We examined RELN expression in layer I of the adult human cortex and found that 70% of cells express RELN in both control and autistic subjects. We quantified the density of neurons in layer I of the superior temporal cortex of subjects with autism and age-matched control subjects. Our data show that there is no change in the density of neurons in layer I of the cortex of subjects with autism, and therefore suggest that reduced RELN expression in the cerebral cortex of subjects with autism is not a consequence of decreased numbers of RELN-expressing neurons in layer I. Instead reduced RELN may result from abnormal RELN processing, or a decrease in the number of other RELN-expressing neuronal cell types. PMID:25067827

  2. A comparative autoradiography study in post mortem whole hemisphere human brain slices taken from Alzheimer patients and age-matched controls using two radiolabelled DAA1106 analogues with high affinity to the peripheral benzodiazepine receptor (PBR) system.

    PubMed

    Gulyás, Balázs; Makkai, Boglárka; Kása, Péter; Gulya, Károly; Bakota, Lidia; Várszegi, Szilvia; Beliczai, Zsuzsa; Andersson, Jan; Csiba, László; Thiele, Andrea; Dyrks, Thomas; Suhara, Tetsua; Suzuki, Kazutoshi; Higuchi, Makato; Halldin, Christer

    2009-01-01

    The binding of two radiolabelled analogues (N-(5-[125I]Iodo-2-phenoxyphenyl)-N-(2,5-dimethoxybenzyl)acetamide ([125I]desfluoro-DAA1106) and N-(5-[125I]Fluoro-2-phenoxyphenyl)-N-(2-[125I]Iodo-5-methoxybenzyl)acetamide ([125I]desmethoxy-DAA1106) of the peripheral benzodiazepine receptor (PBR) (or TSPO, 18kDa translocator protein) ligand DAA1106 was examined by in vitro autoradiography on human post mortem whole hemisphere brain slices obtained from Alzheimer's disease (AD) patients and age-matched controls. Both [(125)I]desfluoro-IDAA1106 and [(125)I]desmethoxy-IDAA1106 were effectively binding to various brain structures. The binding could be blocked by the unlabelled ligand as well as by other PBR specific ligands. With both radiolabelled compounds, the binding showed regional inhomogeneity and the specific binding values proved to be the highest in the hippocampus, temporal and parietal cortex, the basal ganglia and thalamus in the AD brains. Compared with age-matched control brains, specific binding in several brain structures (temporal and parietal lobes, thalamus and white matter) in Alzheimer brains was significantly higher, indicating that the radioligands can effectively label-activated microglia and the up-regulated PBR/TSPO system in AD. Complementary immunohistochemical studies demonstrated reactive microglia activation in the AD brain tissue and indicated that increased ligand binding coincides with increased regional microglia activation due to neuroinflammation. These investigations yield further support to the PBR/TSPO binding capacity of DAA1106 in human brain tissue, demonstrate the effective usefulness of its radio-iodinated analogues as imaging biomarkers in post mortem human studies, and indicate that its radiolabelled analogues, labelled with short half-time bioisotopes, can serve as prospective in vivo imaging biomarkers of activated microglia and the up-regulated PBR/TSPO system in the human brain. PMID:18984021

  3. Event-related brain potentials, bilateral electrodermal activity and Mangina-Test performance in learning disabled/ADHD pre-adolescents with severe behavioral disorders as compared to age-matched normal controls.

    PubMed

    Mangina, C A; Beuzeron-Mangina, J H; Grizenko, N

    2000-07-01

    The most frequently encountered developmental problems of learning disabilities/ADHD often co-exist with severe behavioral disorders. As a direct consequence, this condition opens the way to delinquency, school drop-out, depression, suicide, substance abuse, work absenteeism, and other psycho-social complications. In this paper, we are presenting a selective overview of our previous research and its clinical applications in this field as it relates to our present research data pertaining to the effects of our original Memory Workload Paradigm on the event-related brain potentials in differentiating normal and pathological pre-adolescents (learning disabled/ADHD with concomitant severe behavioral disorders such as oppositional and conduct). In addition, it provides data on the bilateral electrodermal activity during cognitive workload and Mangina-Test performance of pathological and normal pre-adolescents conducted in separate sessions. The results of our present research indicate that a significant memory load effect for the P450 latency (F(3,27)=4.98, P<0.01) and the P450 amplitude (F(3,27)=3.57, P<0.05) was present for normal pre-adolescents which was absent in pathological pre-adolescents. Moreover, enhanced N450 ERP amplitudes to our Memory Workload Paradigm in pre-frontal and frontal regions clearly differentiated normal from pathological pre-adolescents (F(1, 18)=12.21, P<0.004). Furthermore, significant differences between normal and pathological groups were found in bilateral electrodermal activity (F(1,18)=23.86, P<0.001) and on the Mangina-Test performance (F(1,18)=75.35, P<0.001). Our present research findings provide an original and valuable demonstration of an integrative and effective clinical psychophysiological application of central (ERPs), autonomic (bilateral electrodermal activity) and neuro-psychometric aspects (Mangina-Test) which characterize normal and pathological pre-adolescents and underpin the neurophysiological basis of learning

  4. Comparison of Conditioning Impairments in Children with Down Syndrome, Autistic Spectrum Disorders and Mental Age-Matched Controls

    ERIC Educational Resources Information Center

    Reed, P.; Staytom, L.; Stott, S.; Truzoli, R.

    2011-01-01

    Background: This study investigated the relative ease of learning across four tasks suggested by an adaptation of Thomas's hierarchy of learning in children with Down syndrome, autism spectrum disorders and mental age-matched controls. Methods: Learning trials were carried out to investigate observational learning, instrumental learning, reversal…

  5. Pitch Characteristics Before Ulnar Collateral Ligament Reconstruction in Major League Pitchers Compared With Age-Matched Controls

    PubMed Central

    Prodromo, John; Patel, Nimit; Kumar, Neil; Denehy, Kevin; Tabb, Loni Philip; Tom, James

    2016-01-01

    Background: Ulnar collateral ligament reconstruction (UCLR) is commonly performed in Major League Baseball (MLB) pitchers, but little is known about the preoperative pitch type and velocity characteristics of pitchers who go on to undergo UCLR. Hypothesis: Pitchers who required UCLR have thrown a greater percentage of fastballs and have greater pitch velocities compared with age-matched controls in the season before injury. Study Design: Case-control study; Level of evidence, 3. Methods: MLB pitchers active during the 2002 to 2015 seasons were included. The UCLR group consisted of MLB pitchers who received UCLR between 2003 and 2015, utilizing the season before surgery (2002-2014) for analysis. The control group comprised age-matched controls of the same season. Players who pitched less than 20 innings in the season before surgery were excluded. Pitch types were recorded as percentage of total pitches thrown. Pitch velocities were recorded for each pitch type. Pitch type and pitch velocities during preoperative seasons for UCLR pitchers were compared with age-matched controls using univariate and multivariate models. Results: A total of 114 cases that went on to UCLR and 3780 controls were included in the study. Pitchers who went on to UCLR appear to have greater fastball, slider, curveball, changeup, and split-fingered fastball velocities; there were no significant differences in pitch selection between the 2 groups. Conclusion: In the season before surgery, MLB pitchers who underwent UCLR demonstrated greater fastball, slider, curveball, changeup, and split-fingered fastball velocities, with no significant difference in pitch type. PMID:27350954

  6. Prematurely Delivered Rats Show Improved Motor Coordination During Sensory-evoked Motor Responses Compared to Age-matched Controls

    PubMed Central

    Roberto, Megan E.; Brumley, Michele R.

    2014-01-01

    The amount of postnatal experience for perinatal rats was manipulated by delivering pups one day early (postconception day 21; PC21) by cesarean delivery and comparing their motor behavior to age-matched controls on PC22 (the typical day of birth). On PC22, pups were tested on multiple measures of motor coordination: leg extension response (LER), facial wiping, contact righting, and fore- and hindlimb stepping. The LER and facial wiping provided measures of synchronous hind- and forelimb coordination, respectively, and were sensory-evoked. Contact righting also was sensory-evoked and provided a measure of axial coordination. Stepping provided a measure of alternated forelimb and hindlimb coordination and was induced with the serotonin receptor agonist quipazine. Pups that were delivered prematurely and spent an additional day in the postnatal environment showed more bilateral limb coordination during expression of the LER and facial wiping, as well as a more mature righting strategy, compared to controls. These findings suggest that experience around the time of birth shapes motor coordination and the expression of species-typical behavior in the developing rat. PMID:24680729

  7. No consistent difference in gray matter volume between individuals with fibromyalgia and age-matched healthy subjects when controlling for affective disorder.

    PubMed

    Hsu, Michael C; Harris, Richard E; Sundgren, Pia C; Welsh, Robert C; Fernandes, Carlo R; Clauw, Daniel J; Williams, David A

    2009-06-01

    Fibromyalgia (FM) is thought to involve abnormalities in central pain processing. Recent studies involving small samples have suggested alterations in gray matter volume (GMV) in brains of FM patients. Our objective was to verify these findings in a somewhat larger sample using voxel-based morphometry (VBM), while controlling for the presence of affective disorders (AD). T1-weighted magnetic resonance image (MRI) brain scans were obtained on 29 FM patients with AD, 29 FM patients without AD, and 29 age-matched healthy controls (HCs) using a 3T scanner. Segmentation, spatial normalization, and volumetric modulation were performed using an automated protocol within SPM5. Smoothed gray matter segments were entered into a voxel-wise one-way ANOVA, and a search for significant clusters was performed using thresholding methods published in previous studies (whole-brain threshold of p<.05 correcting for multiple comparisons; region-of-interest (ROI) threshold of p< or =.001 uncorrected, or p<.05 small-volume corrected). The whole-brain analysis did not reveal any significant clusters. ROI-based analysis revealed a significant difference in left anterior insula GMV among the three groups (xyz={-28, 21, 9}; p=.026, corrected). However, on post-hoc testing, FM patients without AD did not differ significantly from HC with respect to mean GMV extracted from this cluster. A significant negative correlation was found between mean cluster GMV and scores of trait anxiety (State-Trait Personality Inventory, Trait Anxiety scale; rho=-.470, p<.001). No other significant clusters were found on ROI-based analysis. Our results emphasize the importance of correcting for AD when carrying out VBM studies in chronic pain. PMID:19375224

  8. No Consistent Difference in Gray Matter Volume between Individuals with Fibromyalgia and Age-Matched Healthy Subjects when Controlling for Affective Disorder

    PubMed Central

    Hsu, Michael C.; Harris, Richard E.; Sundgren, Pia C.; Welsh, Robert C.; Fernandes, Carlo R.; Clauw, Daniel J.; Williams, David A.

    2009-01-01

    Fibromyalgia (FM) is thought to involve abnormalities in central pain processing. Recent studies involving small samples have suggested alterations in gray matter volume (GMV) in brains of FM patients. Our objective was to verify these findings in a somewhat larger sample using voxel-based morphometry (VBM), while controlling for presence of affective disorders (AD). T1-weighted magnetic resonance image (MRI) brain scans were obtained on 29 FM patients with AD, 29 FM patients without AD, and 29 age-matched healthy controls (HC) using a 3T scanner. Segmentation, spatial normalization, and volumetric modulation were performed using an automated protocol within SPM5. Smoothed gray matter segments were entered into a voxel-wise one-way ANOVA, and a search for significant clusters was performed using thresholding methods published in previous studies (whole-brain threshold of p<.05 correcting for multiple comparisons; region-of-interest (ROI) threshold of p≤.001 uncorrected, or p<.05 small-volume corrected). The whole-brain analysis did not reveal any significant clusters. ROI-based analysis revealed a significant difference in left anterior insula GMV among the three groups (xyz={−28, 21, 9}; p=.026, corrected). However, on post-hoc testing, FM patients without AD did not differ significantly from HC with respect to mean GMV extracted from this cluster. A significant negative correlation was found between mean cluster GMV and scores of trait anxiety (State-Trait Personality Inventory, Trait Anxiety scale; rho=−.470, p<.001). No other significant clusters were found on ROI-based analysis. Our results emphasize the importance of correcting for AD when carrying out VBM studies in chronic pain. PMID:19375224

  9. A Comparison of Substantia Nigra T1 Hyperintensity in Parkinson's Disease Dementia, Alzheimer's Disease and Age-Matched Controls: Volumetric Analysis of Neuromelanin Imaging

    PubMed Central

    Park, Ju-Yeon; Yun, Won-Sung; Jeon, Ji Yeong; Moon, Yeon Sil; Kim, Heejin; Kwak, Ki-Chang; Lee, Jong-Min; Han, Seol-Heui

    2016-01-01

    Objective Neuromelanin loss of substantia nigra (SN) can be visualized as a T1 signal reduction on T1-weighted high-resolution imaging. We investigated whether volumetric analysis of T1 hyperintensity for SN could be used to differentiate between Parkinson's disease dementia (PDD), Alzheimer's disease (AD) and age-matched controls. Materials and Methods This retrospective study enrolled 10 patients with PDD, 18 patients with AD, and 13 age-matched healthy elderly controls. MR imaging was performed at 3 tesla. To measure the T1 hyperintense area of SN, we obtained an axial thin section high-resolution T1-weighted fast spin echo sequence. The volumes of interest for the T1 hyperintense SN were drawn onto heavily T1-weighted FSE sequences through midbrain level, using the MIPAV software. The measurement differences were tested using the Kruskal-Wallis test followed by a post hoc comparison. Results A comparison of the three groups showed significant differences in terms of volume of T1 hyperintensity (p < 0.001, Bonferroni corrected). The volume of T1 hyperintensity was significantly lower in PDD than in AD and normal controls (p < 0.005, Bonferroni corrected). However, the volume of T1 hyperintensity was not different between AD and normal controls (p = 0.136, Bonferroni corrected). Conclusion The volumetric measurement of the T1 hyperintensity of SN can be an imaging marker for evaluating neuromelanin loss in neurodegenerative diseases and a differential in PDD and AD cases. PMID:27587951

  10. Comparative gait analysis between children with autism and age-matched controls: analysis with temporal-spatial and foot pressure variables

    PubMed Central

    Lim, Bee-Oh; O’Sullivan, David; Choi, Bum-Gwon; Kim, Mi-Young

    2016-01-01

    [Purpose] The purpose of this study was to investigate the gait pattern of children with autism by using a gait analysis system. [Subjects] Thirty children were selected for this study: 15 with autism (age, 11.2 ± 2.8 years; weight, 48.1 ± 14.1 kg; height, 1.51 ± 0.11 m) and 15 healthy age-matched controls (age, 11.0 ± 2.9 years; weight, 43.6 ± 10 kg; height, 1.51 ± 0.011 m). [Methods] All participants walked three times on the GAITRite® system while their plantar pressure was being recorded. [Results] The results showed a reduction in cadence, gait velocity, and step length, and an increase in step width in children with autism. Plantar pressure variables highlight the differences between the active pressure areas, especially in the hindfoot of children with autism. [Conclusion] The results suggest that children with autism have an abnormal gait compared with that of age-matched controls, and thus they need extra attention to correct these abnormal gait patterns. PMID:26957776

  11. Sensorimotor Control of Tracking Movements at Various Speeds for Stroke Patients as Well as Age-Matched and Young Healthy Subjects

    PubMed Central

    Ao, Di; Song, Rong; Tong, Kai-yu

    2015-01-01

    There are aging- and stroke-induced changes on sensorimotor control in daily activities, but their mechanisms have not been well investigated. This study explored speed-, aging-, and stroke-induced changes on sensorimotor control. Eleven stroke patients (affected sides and unaffected sides) and 20 control subjects (10 young and 10 age-matched individuals) were enrolled to perform elbow tracking tasks using sinusoidal trajectories, which included 6 target speeds (15.7, 31.4, 47.1, 62.8, 78.5, and 94.2 deg/s). The actual elbow angle was recorded and displayed on a screen as visual feedback, and three indicators, the root mean square error (RMSE), normalized integrated jerk (NIJ) and integral of the power spectrum density of normalized speed (IPNS), were used to investigate the strategy of sensorimotor control. Both NIJ and IPNS had significant differences among the four groups (P<0.01), and the values were ranked in the following order: young controls < age-matched controls control. The RMSE increased with the increase in the target speed and the NIJ and IPNS initially declined and then remained steady for all four groups, which indicated a shift from feedback to feedforward control as the target speed increased. The feedback-feedforward trade-off induced by stroke, aging and speed might be explained by a change in the transmission delay and neuromotor noise. The findings in this study improve our understanding of the mechanism underlying the sensorimotor control and neurological changes caused by stroke and aging. PMID:26030289

  12. Stable Schizophrenia Patients Learn Equally Well as Age-Matched Controls and Better than Elderly Controls in Two Sensorimotor Rotary Pursuit Tasks

    PubMed Central

    De Picker, Livia J.; Cornelis, Claudia; Hulstijn, Wouter; Dumont, Glenn; Fransen, Erik; Timmers, Maarten; Janssens, Luc; Morrens, Manuel; Sabbe, Bernard G. C.

    2014-01-01

    Objective: To compare sensorimotor performance and learning in stable schizophrenia patients, healthy age- and sex-matched controls and elderly controls on two variations of the rotary pursuit: circle pursuit (true motor learning) and figure pursuit (motor and sequence learning). Method: In the circle pursuit, a target circle, rotating with increasing speed along a predictable circular path on the computer screen, must be followed by a cursor controlled by a pen on a writing tablet. In the eight-trial figure pursuit, subjects learn to draw a complex figure by pursuing the target circle that moves along an invisible trajectory between and around several goals. Tasks were administered thrice (day 1, day 2, day 7) to 30 patients with stable schizophrenia (S), 30 healthy age- and sex-matched controls (C), and 30 elderly participants (>65 years; E) and recorded with a digitizing tablet and pressure-sensitive pen. The outcome measure accuracy (% of time that cursor is within the target) was used to assess performance. Results: We observed significant group differences in accuracy, both in circle and figure pursuit tasks (E < S < C, p < 0.01). Strong learning effects were found in each group. Learning curves were similar in circle pursuit but differed between groups in figure pursuit. When corrected for group differences in starting level, the learning gains over the three sessions of schizophrenia patients and age-matched controls were equal and both were larger than those of the elderly controls. Conclusion: Despite the reduced sensorimotor performance that was found in the schizophrenia patients, their sensorimotor learning seems to be preserved. The relevance of this finding for the evaluation of procedural learning in schizophrenia is discussed. The better performance and learning rate of the patients compared to the elderly controls was unexpected and deserves further study. PMID:25505425

  13. Immunity in young adult survivors of childhood leukemia is similar to the elderly rather than age-matched controls: Role of cytomegalovirus.

    PubMed

    Azanan, Mohamad Shafiq; Abdullah, Noor Kamila; Chua, Ling Ling; Lum, Su Han; Abdul Ghafar, Sayyidatul Syahirah; Kamarulzaman, Adeeba; Kamaruzzaman, Shahrul; Lewin, Sharon R; Woo, Yin Ling; Ariffin, Hany; Rajasuriar, Reena

    2016-07-01

    Many treatment complications that occur late in childhood cancer survivors resemble age-related comorbidities observed in the elderly. An immune phenotype characterized by increased immune activation, systemic inflammation, and accumulation of late-differentiated memory CD57(+) CD28(-) T cells has been associated with comorbidities in the elderly. Here, we explored if this phenotype was present in young adult leukemia survivors following an average of 19 years from chemotherapy and/or radiotherapy completion, and compared this with that in age-matched controls. We found that markers of systemic inflammation-IL-6 and human C-reactive protein and immune activation-CD38 and HLA-DR on T cells, soluble CD (sCD)163 from monocytes and macrophages-were increased in survivors compared to controls. T-cell responses specific to cytomegalovirus (CMV) were also increased in survivors compared to controls while CMV IgG levels in survivors were comparable to levels measured in the elderly (>50years) and correlated with IL-6, human C-reactive protein, sCD163, and CD57(+) CD28(-) memory T cells. Immune activation and inflammation markers correlated poorly with prior chemotherapy and radiotherapy exposure. These data suggest that CMV infection/reactivation is strongly correlated with the immunological phenotype seen in young childhood leukemia survivors and these changes may be associated with the early onset of age-related comorbidities in this group. PMID:27129782

  14. Premature infants display increased noxious-evoked neuronal activity in the brain compared to healthy age-matched term-born infants.

    PubMed

    Slater, Rebeccah; Fabrizi, Lorenzo; Worley, Alan; Meek, Judith; Boyd, Stewart; Fitzgerald, Maria

    2010-08-15

    This study demonstrates that infants who are born prematurely and who have experienced at least 40days of intensive or special care have increased brain neuronal responses to noxious stimuli compared to healthy newborns at the same postmenstrual age. We have measured evoked potentials generated by noxious clinically-essential heel lances in infants born at term (8 infants; born 37-40weeks) and in infants born prematurely (7 infants; born 24-32weeks) who had reached the same postmenstrual age (mean age at time of heel lance 39.2+/-1.2weeks). These noxious-evoked potentials are clearly distinguishable from shorter latency potentials evoked by non-noxious tactile sensory stimulation. While the shorter latency touch potentials are not dependent on the age of the infant at birth, the noxious-evoked potentials are significantly larger in prematurely-born infants. This enhancement is not associated with specific brain lesions but reflects a functional change in pain processing in the brain that is likely to underlie previously reported changes in pain sensitivity in older ex-preterm children. Our ability to quantify and measure experience-dependent changes in infant cortical pain processing will allow us to develop a more rational approach to pain management in neonatal intensive care. PMID:20438855

  15. Training understanding of reversible sentences: a study comparing language-impaired children with age-matched and grammar-matched controls

    PubMed Central

    Hsu, Hsinjen Julie

    2014-01-01

    Introduction. Many children with specific language impairment (SLI) have problems with language comprehension, and little is known about how to remediate these. We focused here on errors in interpreting sentences such as “the ball is above the cup”, where the spatial configuration depends on word order. We asked whether comprehension of such short reversible sentences could be improved by computerized training, and whether learning by children with SLI resembled that of younger, typically-developing children. Methods. We trained 28 children with SLI aged 6–11 years, 28 typically-developing children aged from 4 to 7 years who were matched to the SLI group for raw scores on a test of receptive grammar, and 20 typically-developing children who were matched to the SLI group on chronological age. A further 20 children with SLI were given pre- and post-test assessments, but did not undergo training. Those in the trained groups were given training on four days using a computer game adopting an errorless learning procedure, during which they had to select pictures to correspond to spoken sentences such as “the cup is above the drum” or “the bird is below the hat”. Half the trained children heard sentences using above/below and the other half heard sentences using before/after (with a spatial interpretation). A total of 96 sentences was presented over four sessions. Half the sentences were unique, whereas the remainder consisted of 12 repetitions of each of four sentences that became increasingly familiar as training proceeded. Results. Age-matched control children performed near ceiling (≥ 90% correct) in the first session and were excluded from the analysis. Around half the trained SLI children also performed this well. Training effects were examined in 15 SLI and 16 grammar-matched children who scored less than 90% correct on the initial training session. Overall, children’s scores improved with training. Memory span was a significant predictor of

  16. Intensively managed young children with type 1 diabetes consume high-fat, low-fiber diets similar to age-matched controls.

    PubMed

    Mehta, Sanjeev N; Volkening, Lisa K; Quinn, Nicolle; Laffel, Lori M B

    2014-05-01

    Despite significant emphasis on nutrition, older children with diabetes demonstrate poor dietary quality. We tested the hypothesis that dietary quality in young children with type 1 diabetes (T1D) would be better than age-matched children in the US population. Dietary data from children with T1D (n = 67) aged 2 to 12 years attending a pediatric diabetes clinic were compared with a nationally representative, age-matched sample from the National Health and Nutrition Examination Survey (NHANES; n = 1691). Multiple 24-hour dietary recalls were used. Recommended intakes were based on national guidelines, and dietary quality was assessed using the Healthy Eating Index-2005. More children with T1D were overweight or obese compared with children participating in NHANES (42% vs 30%, P = .04). Greater proportions of children with T1D met daily recommendations for vegetables (22% vs 13%, P = .03), whole grains (12% vs 5%, P = .005), and dairy (55% vs 36%, P = .001) compared with NHANES children, whereas similar proportions met daily fruit recommendations (40% vs 33%, P = .2). Less than one-third of all children limited total fat to recommended levels; children with T1D consumed more saturated fat than did NHANES children (14% vs 12% total energy intake, P = .0009). Fiber intakes were very low in both groups. Compared with NHANES children, children with T1D had higher Healthy Eating Index-2005 scores (59.6 vs 49.7, P = .0006) primarily because of lower intakes of added sugars. The nutritional intake of young children with T1D remains suboptimal in the contemporary era of diabetes management. Despite focused nutrition management, young children with T1D consume high-fat, low-fiber diets comparable with youth in the general population. PMID:24916556

  17. Assessment of the cardiac autonomic neuropathy among the known diabetics and age-matched controls using noninvasive cardiovascular reflex tests in a South-Indian population: A case–control study

    PubMed Central

    Sukla, Pradeep; Shrivastava, Saurabh RamBihariLal; Shrivastava, Prateek Saurabh; Rao, Nambaru Lakshmana

    2016-01-01

    Aim: Diabetes mellitus is a chronic condition characterized by hyperglycemia. The objective of the study was to estimate the prevalence of cardiac autonomic neuropathy in a rural area of South India, among the known diabetics after comparing them with the age-matched healthy controls, utilizing noninvasive cardiac autonomic neuropathy reflex tests. Materials and Methods: A case–control study was conducted for 4 months (October 2014 to January 2015) at an Urban Health and Training Center (UHTC) of a Medical College located in Kancheepuram district, Tamil Nadu. The study was conducted among 126 diagnosed Type 2 diabetes patients and in 152 age- and sex-matched healthy controls to ensure comparability between the cases and controls and, thus, reduce variability due to demographic variables. All the study subjects (cases and controls) were selected from the patients attending UHTC during the study duration, provided they satisfied the inclusion and exclusion criteria. Study participants were subjected to undergo noninvasive cardiac autonomic neuropathy reflex tests. The associations were tested using paired t-test for the continuous (mean ± standard deviation) variables. Results: The overall prevalence of cardiac autonomic neuropathy among diabetic patients was found to be as 53.2% (67/126). On further classification, positive (abnormal) results were obtained in 56 (sympathetic – 44.4%) and 51 (parasympathetic – 40.5%) diabetic cases. Overall, heart rate variation during deep breathing was found to be the most sensitive test to detect parasympathetic autonomic neuropathy while the diastolic blood pressure response to sustained handgrip exercise was the most sensitive method to detect sympathetic neuropathy dysfunction. Conclusion: The overall prevalence of cardiac autonomic neuropathy among diabetic patients was found to be as 53.2%. Even though cardiac autonomic neuropathy can be detected by various invasive tests, noninvasive tests remain a key tool to detect

  18. Brain controlled robots.

    PubMed

    Kawato, Mitsuo

    2008-06-01

    In January 2008, Duke University and the Japan Science and Technology Agency (JST) publicized their successful control of a brain-machine interface for a humanoid robot by a monkey brain across the Pacific Ocean. The activities of a few hundred neurons were recorded from a monkey's motor cortex in Miguel Nicolelis's lab at Duke University, and the kinematic features of monkey locomotion on a treadmill were decoded from neural firing rates in real time. The decoded information was sent to a humanoid robot, CB-i, in ATR Computational Neuroscience Laboratories located in Kyoto, Japan. This robot was developed by the JST International Collaborative Research Project (ICORP) as the "Computational Brain Project." CB-i's locomotion-like movement was video-recorded and projected on a screen in front of the monkey. Although the bidirectional communication used a conventional Internet connection, its delay was suppressed below one over several seconds, partly due to a video-streaming technique, and this encouraged the monkey's voluntary locomotion and influenced its brain activity. This commentary introduces the background and future directions of the brain-controlled robot. PMID:19404467

  19. Soluble BACE-1 Activity and sAβPPβ Concentrations in Alzheimer's Disease and Age-Matched Healthy Control Cerebrospinal Fluid from the Alzheimer's Disease Neuroimaging Initiative-1 Baseline Cohort.

    PubMed

    Savage, Mary J; Holder, Daniel J; Wu, Guoxin; Kaplow, June; Siuciak, Judith A; Potter, William Z

    2015-01-01

    β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) plays an important role in the development of Alzheimer's disease (AD), freeing the amyloid-β (Aβ) N-terminus from the amyloid-β protein precursor (AβPP), the first step in Aβ formation. Increased BACE1 activity in AD brain or cerebrospinal fluid (CSF) has been reported. Other studies, however, found either no change or a decrease with AD diagnosis in either BACE1 activity or sAβPPβ, the N-terminal secreted product of BACE1 (sBACE1) activity on AβPP. Here, sBACE1 enzymatic activity and secreted AβPPβ (sAβPPβ) were measured in Alzheimer's Disease Neuroimaging Initiative-1 (ADNI-1) baseline CSF samples and no statistically significant changes were found in either measure comparing healthy control, mild cognitively impaired, or AD individual samples. While CSF sBACE1 activity and sAβPPβ demonstrated a moderate yet significant degree of correlation with each other, there was no correlation of either analyte to CSF Aβ peptide ending at residue 42. Surprisingly, a stronger correlation was demonstrated between CSF sBACE1 activity and tau, which was comparable to that between CSF Aβ₄₂ and tau. Unlike for these latter two analytes, receiver-operator characteristic curves demonstrate that neither CSF sBACE1 activity nor sAβPPβ concentrations can be used to differentiate between healthy elderly and AD individuals. PMID:25790831

  20. Electrophysiological Neuroimaging using sLORETA Comparing 22 Age Matched Male and Female Schizophrenia Patients

    PubMed Central

    Eugene, Andy R.; Masiak, Jolanta; Kapica, Jacek; Masiak, Marek

    2015-01-01

    Introduction The purpose of this electrophysiological neuroimaging study was to provide a deeper mechanistic understanding of both olanzapine and risperidone pharmacodynamics relative to gender. In doing so, we age-matched 22 men and women and evaluated their resting-state EEG recordings and later used standard low resolution brain Electrotomography to visualize the differences in brain activity amongst the two patient groups. Methods In this investigation, electroencephalogram (EEG) data were analyzed from male and female schizophrenia patients treated with either olanzapine or risperidone, both atypical antipsychotics, during their in-patient stay at the Department of Psychiatry. Twenty-two males and females were age-matched and EEG recordings were analyzed from 19 Ag/AgCl electrodes. Thirty-seconds of resting EEG were spectrally transformed in standardized low resolution electromagnetic tomography (sLORETA). 3D statistical non-paramentric maps for the sLORETA Global Field Power within each band were finally computed. Results The results indicated that, relative to males patients, females schizophrenia patients had increased neuronal synchronization in delta frequency, slow-wave, EEG band located in the dorsolateral prefrontal cortex, within the middle frontal gyrus (t= -2.881, p < 0.03580). These findings suggest that females experience greater dopamine (D2) receptor and serotonin (5-HT2) receptor neuronal blockade relative to age-matched males. Further, our finding provided insight to the pharmacodynamics of second-generation antipsychotics olanzapine and risperidone. Conclusion When compared to male patients, female patients, suffering from schizophrenia, have D2 and 5-HT2 receptors that are blocked more readily than age-matched male schizophrenia patients. Clinically, this may translate into a quicker time to treatment-response in females as compared to male patients. PMID:26617679

  1. Controllability of structural brain networks

    NASA Astrophysics Data System (ADS)

    Gu, Shi; Pasqualetti, Fabio; Cieslak, Matthew; Telesford, Qawi K.; Yu, Alfred B.; Kahn, Ari E.; Medaglia, John D.; Vettel, Jean M.; Miller, Michael B.; Grafton, Scott T.; Bassett, Danielle S.

    2015-10-01

    Cognitive function is driven by dynamic interactions between large-scale neural circuits or networks, enabling behaviour. However, fundamental principles constraining these dynamic network processes have remained elusive. Here we use tools from control and network theories to offer a mechanistic explanation for how the brain moves between cognitive states drawn from the network organization of white matter microstructure. Our results suggest that densely connected areas, particularly in the default mode system, facilitate the movement of the brain to many easily reachable states. Weakly connected areas, particularly in cognitive control systems, facilitate the movement of the brain to difficult-to-reach states. Areas located on the boundary between network communities, particularly in attentional control systems, facilitate the integration or segregation of diverse cognitive systems. Our results suggest that structural network differences between cognitive circuits dictate their distinct roles in controlling trajectories of brain network function.

  2. Controllability of structural brain networks

    PubMed Central

    Gu, Shi; Pasqualetti, Fabio; Cieslak, Matthew; Telesford, Qawi K.; Yu, Alfred B.; Kahn, Ari E.; Medaglia, John D.; Vettel, Jean M.; Miller, Michael B.; Grafton, Scott T.; Bassett, Danielle S.

    2015-01-01

    Cognitive function is driven by dynamic interactions between large-scale neural circuits or networks, enabling behaviour. However, fundamental principles constraining these dynamic network processes have remained elusive. Here we use tools from control and network theories to offer a mechanistic explanation for how the brain moves between cognitive states drawn from the network organization of white matter microstructure. Our results suggest that densely connected areas, particularly in the default mode system, facilitate the movement of the brain to many easily reachable states. Weakly connected areas, particularly in cognitive control systems, facilitate the movement of the brain to difficult-to-reach states. Areas located on the boundary between network communities, particularly in attentional control systems, facilitate the integration or segregation of diverse cognitive systems. Our results suggest that structural network differences between cognitive circuits dictate their distinct roles in controlling trajectories of brain network function. PMID:26423222

  3. Brain catechol synthesis - Control by brain tyrosine concentration

    NASA Technical Reports Server (NTRS)

    Wurtman, R. J.; Larin, F.; Mostafapour, S.; Fernstrom, J. D.

    1974-01-01

    Brain catechol synthesis was estimated by measuring the rate at which brain dopa levels rose following decarboxylase inhibition. Dopa accumulation was accelerated by tyrosine administration, and decreased by treatments that lowered brain tyrosine concentrations (for example, intraperitoneal tryptophan, leucine, or parachlorophenylalanine). A low dose of phenylalanine elevated brain tyrosine without accelerating dopa synthesis. Our findings raise the possibility that nutritional and endocrine factors might influence brain catecholamine synthesis by controlling the availability of tyrosine.

  4. Analysis of abstract and concrete word processing in persons with aphasia and age-matched neurologically healthy adults using fMRI.

    PubMed

    Sandberg, Chaleece; Kiran, Swathi

    2014-08-01

    The concreteness effect occurs in both normal and language-disordered populations. Research suggests that abstract and concrete concepts elicit differing neural activation patterns in healthy young adults, but this is undocumented in persons with aphasia (PWA). Three PWA and three age-matched controls were scanned using fMRI while processing abstract and concrete words. Consistent with current theories of abstract and concrete word processing, abstract words elicited activation in verbal areas, whereas concrete words additionally activated multimodal association areas. PWA show greater differences in neural activation than age-matched controls between abstract and concrete words, possibly due to an exaggerated concreteness effect. PMID:23548150

  5. Self-Control and the Developing Brain

    ERIC Educational Resources Information Center

    Tarullo, Amanda R.; Obradovic, Jelena; Gunnar, Megan R.

    2009-01-01

    Self-control is a skill that children need to succeed academically, socially, and emotionally. Brain regions essential to self-control are immature at birth and develop slowly throughout childhood. From ages 3 to 6 years, as these brain regions become more mature, children show improved ability to control impulses, shift their attention flexibly,…

  6. Brain stimulation and inhibitory control.

    PubMed

    Juan, Chi-Hung; Muggleton, Neil G

    2012-04-01

    Inhibitory control mechanisms are important in a range of behaviours to prevent execution of motor acts which, having been planned, are no longer necessary or appropriate. Examples of this can be seen in a range of sports, such as cricket and baseball, where the choice between execution and inhibition of a bat swing must be made in a very brief time window. Deficits in inhibitory control have been associated with problems in behavioural regulation in impulsive violence as well as a range of clinical disorders. The roles of various areas, including the frontal eye fields (FEF), the pre-supplementary motor area (pre-SMA) and the inferior frontal gyrus, in inhibitory control have been investigated using an inhibitory control task and both transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). Typically effects on response inhibition but no effects on response generation have been seen. The contributions of these areas to performance seem to differ with, for example, pre-SMA being involved when the task is relatively novel whereas this is not the case for FEF. The findings from brain stimulation studies offer both insight into which areas are necessary for effective inhibitory control and recent extension of findings for the role of the inferior frontal gyrus illustrate how the specific functions by which these areas contribute may be further clarified. Future work, including making use of the temporal specificity of TMS and combination of TMS/tDCS with other neuroimaging techniques, may further clarify the nature and functions played by the network of areas involved in inhibitory control. PMID:22494830

  7. Understanding the brain by controlling neural activity

    PubMed Central

    Krug, Kristine; Salzman, C. Daniel; Waddell, Scott

    2015-01-01

    Causal methods to interrogate brain function have been employed since the advent of modern neuroscience in the nineteenth century. Initially, randomly placed electrodes and stimulation of parts of the living brain were used to localize specific functions to these areas. Recent technical developments have rejuvenated this approach by providing more precise tools to dissect the neural circuits underlying behaviour, perception and cognition. Carefully controlled behavioural experiments have been combined with electrical devices, targeted genetically encoded tools and neurochemical approaches to manipulate information processing in the brain. The ability to control brain activity in these ways not only deepens our understanding of brain function but also provides new avenues for clinical intervention, particularly in conditions where brain processing has gone awry. PMID:26240417

  8. Is reproductive ageing controlled by the brain?

    PubMed

    Gore, Andrea C

    2007-08-01

    Female reproductive function is controlled by complex interactions of the brain, pituitary gland and ovary. Each of these organs produces unique hormones, and each hormone acts upon the other organs to affect a response. Differentiating the causes and the consequences of reproductive senescence in mammals is thus a 'chicken and egg' puzzle. Surprisingly, recent evidence indicates a more important role for the brain in the initiation and transition to reproductive senescence. PMID:17620108

  9. 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…

  10. Electrical stimulation directs engineered cardiac tissue to an age-matched native phenotype

    PubMed Central

    Lasher, Richard A; Pahnke, Aric Q; Johnson, Jeffrey M; Sachse, Frank B

    2012-01-01

    Quantifying structural features of native myocardium in engineered tissue is essential for creating functional tissue that can serve as a surrogate for in vitro testing or the eventual replacement of diseased or injured myocardium. We applied three-dimensional confocal imaging and image analysis to quantitatively describe the features of native and engineered cardiac tissue. Quantitative analysis methods were developed and applied to test the hypothesis that environmental cues direct engineered tissue toward a phenotype resembling that of age-matched native myocardium. The analytical approach was applied to engineered cardiac tissue with and without the application of electrical stimulation as well as to age-matched and adult native tissue. Individual myocytes were segmented from confocal image stacks and assigned a coordinate system from which measures of cell geometry and connexin-43 spatial distribution were calculated. The data were collected from 9 nonstimulated and 12 electrically stimulated engineered tissue constructs and 5 postnatal day 12 and 7 adult hearts. The myocyte volume fraction was nearly double in stimulated engineered tissue compared to nonstimulated engineered tissue (0.34 ± 0.14 vs 0.18 ± 0.06) but less than half of the native postnatal day 12 (0.90 ± 0.06) and adult (0.91 ± 0.04) myocardium. The myocytes under electrical stimulation were more elongated compared to nonstimulated myocytes and exhibited similar lengths, widths, and heights as in age-matched myocardium. Furthermore, the percentage of connexin-43-positive membrane staining was similar in the electrically stimulated, postnatal day 12, and adult myocytes, whereas it was significantly lower in the nonstimulated myocytes. Connexin-43 was found to be primarily located at cell ends for adult myocytes and irregularly but densely clustered over the membranes of nonstimulated, stimulated, and postnatal day 12 myocytes. These findings support our hypothesis and reveal that the

  11. The Teenage Brain: Self Control

    PubMed Central

    Casey, BJ; Caudle, Kristina

    2014-01-01

    Adolescence refers to the transition from childhood to adulthood that begins with the onset of puberty and ends with successful independence from the parent. A paradox for human adolescence is why, during a time when the individual is probably faster, stronger, of higher reasoning capacity and more resistant to disease, there is such an increase in mortality relative to childhood. These untimely deaths are not due to disease, but rather to preventable forms of death (accidental fatalities, suicide and homicide) associated with adolescents putting themselves in harm’s way due, in part, to diminished self control – the ability to suppress inappropriate emotions, desires and actions. This paper highlights how self control varies as a function of age, context and the individual and delineates its neurobiological basis. PMID:25284961

  12. Controlling chaos in the brain

    NASA Astrophysics Data System (ADS)

    Schiff, Steven J.; Jerger, Kristin; Duong, Duc H.; Chang, Taeun; Spano, Mark L.; Ditto, William L.

    1994-08-01

    In a spontaneously bursting neuronal network in vitro, chaos can be demonstrated by the presence of unstable fixed-point behaviour. Chaos control techniques can increase the periodicity of such neuronal population bursting behaviour. Periodic pacing is also effective in entraining such systems, although in a qualitatively different fashion. Using a strategy of anticontrol such systems can be made less periodic. These techniques may be applicable to in vivo epileptic foci.

  13. Comparison of serum sodium and potassium levels in patients with senile cataract and age-matched individuals without cataract

    PubMed Central

    Mathur, Gaurav; Pai, Vijaya

    2016-01-01

    Aim: The study was to analyze mean serum sodium and potassium levels in cataract patients and age-matched individuals without cataract. Methods and Materials: It was a prospective case-control study. Individuals more than 50 years of age who attended our ophthalmic center in the year 2007-2010 were grouped into those having cataract and those without cataract. Mean serum sodium and potassium levels in the cataract groups were calculated and compared with the control group. Statistical software SPSS14 was used for statistical analysis. Results: Mean serum sodium levels in cataract group was 135.1 meqv/l and 133 meqv/l in the control group. Mean potassium was 3.96 meqv/l in the case study group and 3.97 meqv/l in controls. Mean sodium levels among cases were significantly higher than control group. No difference was seen in the PSC group and control. The difference in mean potassium among the two groups was statistically insignificant. Conclusion: Diets with high sodium contents are a risk factor for senile cataract formation and dietary modifications can possibly reduce the rate of progression cataract. PMID:23552357

  14. Prevalence of temporomandibular disorder pain in Chinese adolescents compared to an age-matched Swedish population.

    PubMed

    Hongxing, L; Astrøm, A N; List, T; Nilsson, I-M; Johansson, A

    2016-04-01

    This study aimed to (i) assess the prevalence and perceived need for treatment of TMD pain, and its association with socio-economic factors and gender, in adolescents in Xi᾽an, Shaanxi Province, China, and (ii) compare the prevalence and association with gender of TMD pain in Xi᾽an to an age-matched Swedish population. We surveyed Chinese adolescents aged 15 to 19 years in Xi'an, China (n = 5524), using a questionnaire with two-stage stratified sampling and the school as the sampling unit. The study included second-year students at selected high schools. It also included an age-matched Swedish population (n = 17 015) surveyed using the same diagnostic criteria for TMD pain as that used in the Chinese sample. The survey found TMD pain in 14·8% (n = 817) of the Chinese sample and 5·1% (n = 871) of the Swedish sample (P < 0·0001). Girls had significantly more TMD pain than boys in both the Chinese (P < 0·05) and Swedish (P < 0·001) samples. TMD pain increased with age in the Chinese population. Of the Chinese adolescents with TMD pain, 47% reported that they felt a need for treatment. Rural schools, low paternal education levels, poverty, living outside the home, poor general and oral health, and dissatisfaction with teeth all showed significant positive correlations with TMD pain. Prevalence of TMD pain in Chinese adolescents was significantly higher than in the Swedish sample. PMID:26538188

  15. Embryonal brain tumors and developmental control genes

    SciTech Connect

    Aguzzi, A.

    1995-12-31

    Cell proliferation in embryogenesis and neoplastic transformation is thought to be controlled by similar sets of regulatory genes. This is certainly true for tumors of embryonic origin, such as Ewing sarcoma, Wilms` tumor and retinoblastoma, in which developmental control genes are either activated as oncogenes to promote proliferation, or are inactivated to eliminate their growth suppressing function. However, to date little is known about the genetic events underlying the pathogenesis of medulloblastoma, the most common brain tumor in children, which still carries an unfavourable prognosis. None of the common genetic alterations identified in other neuroectodermal tumors, such as mutation of the p53 gene or amplification of tyrosine kinase receptor genes, could be uncovered as key events in the formation of medulloblastoma. The identification of regulatory genes which are expressed in this pediatric brain tumor may provide an alternative approach to gain insight into the molecular aspects of tumor formation.

  16. Heroin snorters versus injectors: comparison on drug use and treatment outcome in age-matched samples.

    PubMed

    Carpenter, M J; Chutuape, M A; Stitzer, M L

    1998-12-01

    Drug use histories and treatment outcomes were compared for age, race and gender-matched samples of intravenous (IV; n = 28) versus intranasal (IN; n = 28) opiate abusers entering a 3-day inpatient detoxification unit. Data were derived from the Addiction Severity Index (ASI) interview. Both groups reported daily heroin use prior to detoxification, but IV users reported more days of alcohol and multiple drug use during the past 30 days. Despite age matching, IV users also started using alcohol at an earlier age and accumulated more lifetime months of regular alcohol, cocaine and multidrug use. IV users were more likely to enter treatment following the detox, but no significant outcome differences were noted at 1 and 3 months post-detoxification. The results show that intravenous, as compared to intranasal, opiate users have both a more severe pattern and a more extensive history of the use of non-opiate drugs. PMID:10933336

  17. Neural mechanisms of verb argument structure processing in agrammatic aphasic and healthy age-matched listeners

    PubMed Central

    Thompson, C.K.; Bonakdarpour, B.; Fix, S.F.

    2010-01-01

    Processing of lexical verbs involves automatic access to argument structure entries entailed within the verb's representation. Recent neuroimaging studies with young normal listeners suggest that this involves bilateral posterior perisylvian tissue, with graded activation in these regions based on argument structure complexity. The aim of the present study was to examine the neural mechanisms of verb processing using functional magnetic resonance imaging (fMRI) in older normal volunteers and patients with stroke-induced agrammatic aphasia, a syndrome in which verb, as compared to noun, production often is selectively impaired, but verb comprehension in both on-line and off-line tasks is spared. Fourteen healthy listeners and five age-matched aphasic patients performed a lexical decision task, which examined verb processing by argument structure complexity, i.e., one-argument (i.e., intransitive (v1)); two-argument (i.e., transitive (v2)), and three-argument (v3) verbs. Results for the age-matched listeners largely replicated those for younger participants studied by Thompson et al. (2007): v3-v1 comparisons showed activation of the angular gyrus in both hemispheres and this same heteromodal region was activated in the left hemisphere in the (v2+v3)-v1 contrast. Similar results were derived for the agrammatic aphasic patients, however, activation was unilateral (in the right hemisphere for 3 participants) rather than bilateral likely because these patients' lesions extended to the left temporoparietal region. All performed the task with high accuracy and, despite differences in lesion site and extent, they recruited spared tissue in the same regions as healthy normals. Consistent with psycholinguistic models of sentence processing, these findings indicate that the posterior language network is engaged for processing verb argument structure and is crucial for semantic integration of argument structure information. PMID:19702460

  18. Flexible brain network reconfiguration supporting inhibitory control.

    PubMed

    Spielberg, Jeffrey M; Miller, Gregory A; Heller, Wendy; Banich, Marie T

    2015-08-11

    The ability to inhibit distracting stimuli from interfering with goal-directed behavior is crucial for success in most spheres of life. Despite an abundance of studies examining regional brain activation, knowledge of the brain networks involved in inhibitory control remains quite limited. To address this critical gap, we applied graph theory tools to functional magnetic resonance imaging data collected while a large sample of adults (n = 101) performed a color-word Stroop task. Higher demand for inhibitory control was associated with restructuring of the global network into a configuration that was more optimized for specialized processing (functional segregation), more efficient at communicating the output of such processing across the network (functional integration), and more resilient to potential interruption (resilience). In addition, there were regional changes with right inferior frontal sulcus and right anterior insula occupying more central positions as network hubs, and dorsal anterior cingulate cortex becoming more tightly coupled with its regional subnetwork. Given the crucial role of inhibitory control in goal-directed behavior, present findings identifying functional network organization supporting inhibitory control have the potential to provide additional insights into how inhibitory control may break down in a wide variety of individuals with neurological or psychiatric difficulties. PMID:26216985

  19. Whole-Brain Diffusion-Tensor Changes in Parkinsonian Patients with Impulse Control Disorders

    PubMed Central

    Yoo, Hye Bin; Lee, Jee-Young; Kang, Hyejin; Kim, Yu Kyeong; Song, In Chan; Lee, Dong Soo

    2015-01-01

    Background and Purpose The aim of this study was to determine the changes in diffusion-tensor images associated with medication-related impulse control disorder (ICD) in Parkinson's disease (PD) patients undergoing chronic dopamine-replacement therapy. Methods Nineteen PD patients, comprising 10 with ICD (PD-ICD) and 9 without ICD (PD-nonICD), and 18 age-matched healthy controls (HCs) with no cognitive or other psychiatric disorders were analyzed. All subjects underwent 3-T magnetic resonance diffusion-tensor imaging. For all PD patients, clinical data on PD duration, antiparkinsonian medication dosages, Unified Parkinson's Disease Rating Scale and Mini-Mental State Examination were collected. Whole-brain voxel-based measures of fractional anisotropy (FA) and mean diffusivity (MD) were analyzed. Results In comparison with HCs, the PD-nonICD subjects had low FA at the bilateral orbitofrontal areas. While the PD-ICD subjects exhibited no such difference, their FA was significantly elevated at the anterior corpus callosum. Analysis of FA between the two PD groups revealed that FA in the anterior corpus callosum, right internal capsule posterior limbs, right posterior cingulum, and right thalamic radiations were significantly higher (corrected p<0.05) in the PD-ICD than in the PD-nonICD patients. MD did not differ between the PD-ICD and PD-nonICD groups in any brain regions. Conclusions The PD-ICD patients appear to have relatively preserved white-matter integrity in the regions involved in reward-related behaviors compared to PD-nonICD patients. Further investigation is required to determine whether the difference in FA between PD-ICD and PD-nonICD patients reflects microstructural differences in the pathological progression of PD or is secondary to ICD. PMID:25628736

  20. Brain mechanisms that control sleep and waking

    NASA Astrophysics Data System (ADS)

    Siegel, Jerome

    This review paper presents a brief historical survey of the technological and early research that laid the groundwork for recent advances in sleep-waking research. A major advance in this field occurred shortly after the end of World War II with the discovery of the ascending reticular activating system (ARAS) as the neural source in the brain stem of the waking state. Subsequent research showed that the brain stem activating system produced cortical arousal via two pathways: a dorsal route through the thalamus and a ventral route through the hypothalamus and basal forebrain. The nuclei, pathways, and neurotransmitters that comprise the multiple components of these arousal systems are described. Sleep is now recognized as being composed of two very different states: rapid eye movements (REMs) sleep and non-REM sleep. The major findings on the neural mechanisms that control these two sleep states are presented. This review ends with a discussion of two current views on the function of sleep: to maintain the integrity of the immune system and to enhance memory consolidation.

  1. Sex differences in brain control of prosody.

    PubMed

    Rymarczyk, Krystyna; Grabowska, Anna

    2007-03-14

    Affective (emotional) prosody is a neuropsychological function that encompasses non-verbal aspects of language that are necessary for recognizing and conveying emotions in communication, whereas non-affective (linguistic) prosody indicates whether the sentence is a question, an order or a statement. Considerable evidence points to a dominant role for the right hemisphere in both aspects of prosodic function. However, it has yet to be established whether separate parts of the right hemisphere are involved in processing different kinds of emotional intonation. The aim of this study was to answer this question. In addition, the issue of sex differences in the ability to understand prosody was considered. Fifty-two patients with damage to frontal, temporo-parietal or subcortical (basal) parts of the right hemisphere and 26 controls were tested for their ability to assess prosody information in normal (well-formed) sentences and in pseudo-sentences. General impairment of prosody processing was seen in all patient groups but the effect of damage was more apparent for emotional rather than linguistic prosody. Interestingly, appreciation of emotional prosody appeared to depend on the type of emotional expression and the location of the brain lesion. The patients with frontal damage were mostly impaired in comprehension of happy intonations; those with temporo-parietal damage in assessment of sad intonations, while subcortical lesions mostly affected comprehension of angry intonations. Differential effects of lesion location on the performance of men and women were also observed. Frontal lesions were more detrimental to women, whereas subcortical lesions led to stronger impairment in men. This suggests sex differences in brain organization of prosodic functions. PMID:17005213

  2. Which oropharyngeal factors are significant risk factors for obstructive sleep apnea? An age-matched study and dentist perspectives

    PubMed Central

    Ruangsri, Supanigar; Jorns, Teekayu Plangkoon; Puasiri, Subin; Luecha, Thitisan; Chaithap, Chariya; Sawanyawisuth, Kittisak

    2016-01-01

    Objective Obstructive sleep apnea (OSA) is a common sleep breathing disorder. Untreated OSA may lead to a number of cardiovascular complications. Dentists may play an important role in OSA detection by conducting careful oral examinations. This study focused on the correlation of oral anatomical features in Thai patients who presented with OSA. Methods We conducted a prospective comparative study at a sleep/hypertension clinic and a dental clinic at Khon Kaen University in Thailand. Patients with OSA were enrolled in the study, along with age-matched patients with non-OSA (controls). Baseline characteristics, clinical data, and oropharyngeal data of all patients were compared between the two groups. Oropharyngeal measurements included tongue size, torus mandibularis, Mallampati classification, palatal space, and lateral pharyngeal wall area. Multivariate logistic regression analysis was used to identify the factors associated with OSA. Results During the study period, there were 156 patients who met the study criteria; 78 were patients with OSA and the other 78 were healthy control subjects. In the OSA group, there were 43 males with a mean age of 53 (standard deviation 12.29) years and a mean BMI of 30.86 kg/mm2. There were 37 males in the control group with a mean age of 50 (standard deviation 12.04) years and a mean BMI of 24.03 kg/mm2. According to multivariate logistic analysis, three factors were perfectly associated with OSA, including torus mandibularis class 6, narrow lateral pharyngeal wall, and Mallampati class 4. There were two other significant factors associated with having OSA, namely, BMI and Mallampati classification. The adjusted odds ratios (95% confidence interval) of these two factors were 1.445 (1.017, 2.052) and 5.040 (1.655, 15.358), respectively. Conclusion Dentists may play an important role in the detection of OSA in patients with high BMI through careful oropharyngeal examination in routine dental treatment. A large torus mandibularis

  3. The bilingual brain: Flexibility and control in the human cortex

    NASA Astrophysics Data System (ADS)

    Buchweitz, Augusto; Prat, Chantel

    2013-12-01

    The goal of the present review is to discuss recent cognitive neuroscientific findings concerning bilingualism. Three interrelated questions about the bilingual brain are addressed: How are multiple languages represented in the brain? how are languages controlled in the brain? and what are the real-world implications of experience with multiple languages? The review is based on neuroimaging research findings about the nature of bilingual processing, namely, how the brain adapts to accommodate multiple languages in the bilingual brain and to control which language should be used, and when. We also address how this adaptation results in differences observed in the general cognition of bilingual individuals. General implications for models of human learning, plasticity, and cognitive control are discussed.

  4. Evaluation of visual stress symptoms in age-matched dyslexic, Meares-Irlen syndrome and normal adults

    PubMed Central

    Alanazi, Mana A.; Alanazi, Saud A.; Osuagwu, Uchechukwu L.

    2016-01-01

    AIM To examine the prevalence of dyslexia and Meares-Irlen syndrome (MIS) among female students and determine their level of visual stress in comparison with normal subjects. METHODS A random sample of 450 female medical students of King Saud University Riyadh (age range, 18-30y) responded to a wide range of questions designed to accomplish the aims of this study. The detailed questionnaire consisted of 54 questions with 12 questions enquiring on ocular history and demography of participants while 42 questions were on visual symptoms. Items were categorized into critical and non-critical questions (CQ and NCQ) and were rated on four point Likert scale. Based on the responses obtained, the subjects were grouped into normal (control), dyslexic with or without MIS (Group 1) and subjects with MIS only (Group 2). Responses were analysed as averages and mean scores were calculated and compared between groups using one way analysis of variance to evaluate total visual stress score (TVSS=NCQ+CQ), critical and non-critical visual stress scores. The relationship between categorical variables such as age, handedness and condition were assessed with Chi-square test. RESULTS The completion rate was 97.6% and majority of the respondents (92%) were normal readers, 2% dyslexic and 6% had MIS. They were age-matched. More than half of the participants had visited an eye care practitioner in the last 2y. About 13% were recommended eye exercises and one participant experienced pattern glare. Hand preference was not associated with any condition but Group 1 subjects (3/9, 33%) were significantly more likely to be diagnosed of lazy eye than Group 2 (2/27, 7%) and control (27/414, 7%) subjects. The mean±SD of TVSS responses were 63±14 and it was 44±9 for CQ and 19±5 for NCQ. Responses from all three variables were normally distributed but the CQ responses were on the average more positive (82%) in Group 2 and less positive (46%) in Group 1 than control. With NCQ, the responses were

  5. Secreted proteome profiling in human RPE cell cultures derived from donors with age related macular degeneration and age matched healthy donors.

    PubMed

    An, Eunkyung; Lu, Xiaoning; Flippin, Jessica; Devaney, Joseph M; Halligan, Brian; Hoffman, Eric P; Hoffman, Eric; Strunnikova, Nataly; Csaky, Karl; Hathout, Yetrib

    2006-10-01

    Age-related macular degeneration (AMD) is characterized by progressive loss of central vision, which is attributed to abnormal accumulation of macular deposits called "drusen" at the interface between the basal surface of the retinal pigment epithelium (RPE) and Bruch's membrane. In the most severe cases, drusen deposits are accompanied by the growth of new blood vessels that breach the RPE layer and invade photoreceptors. In this study, we hypothesized that RPE secreted proteins are responsible for drusen formation and choroidal neovascularization. We used stable isotope labeling by amino acids in cell culture (SILAC) in combination with LC-MS/MS analysis and ZoomQuant quantification to assess differential protein secretion by RPE cell cultures prepared from human autopsy eyes of AMD donors (diagnosed by histological examinations of the macula and genotyped for the Y402H-complement factor H variant) and age-matched healthy control donors. In general, RPE cells were found to secrete a variety of extracellular matrix proteins, complement factors, and protease inhibitors that have been reported to be major constituents of drusen (hallmark deposits in AMD). Interestingly, RPE cells from AMD donors secreted 2 to 3-fold more galectin 3 binding protein, fibronectin, clusterin, matrix metalloproteinase-2 and pigment epithelium derived factor than RPE cells from age-matched healthy donors. Conversely, secreted protein acidic and rich in cysteine (SPARC) was found to be down regulated by 2-fold in AMD RPE cells versus healthy RPE cells. Ingenuity pathway analysis grouped these differentially secreted proteins into two groups; those involved in tissue development and angiogenesis and those involved in complement regulation and protein aggregation such as clusterin. Overall, these data strongly suggest that RPE cells are involved in the biogenesis of drusen and the pathology of AMD. PMID:17022631

  6. Prefrontal and limbic resting state brain network functional connectivity differs between nicotine-dependent smokers and non-smoking controls

    PubMed Central

    Janes, Amy C.; Nickerson, Lisa; Frederick, Blaise deB.; Kaufman, Marc J.

    2012-01-01

    Background Brain dysfunction in prefrontal cortex (PFC) and dorsal striatum (DS) contributes to habitual drug use. These regions are constituents of brain networks thought to be involved in drug addiction. To investigate whether networks containing these regions differ between nicotine dependent female smokers and age-matched female non-smokers, we employed functional MRI (fMRI) at rest. Methods Data were processed with independent component analysis (ICA) to identify resting state networks (RSNs). We identified a subcortical limbic network and three discrete PFC networks: a medial prefrontal cortex (mPFC) network and right and left lateralized fronto-parietal networks common to all subjects. We then compared these RSNs between smokers and non-smokers using a dual regression approach. Results Smokers had greater coupling versus non-smokers between left fronto-parietal and mPFC networks. Smokers with the greatest mPFC-left fronto-parietal coupling had the most DS smoking cue reactivity as measured during an fMRI smoking cue reactivity paradigm. This may be important because the DS plays a critical role in maintaining drug-cue associations. Furthermore, subcortical limbic network amplitude was greater in smokers. Conclusions Our results suggest that prefrontal brain networks are more strongly coupled in smokers, which could facilitate drug-cue responding. Our data also are the first to document greater reward-related network fMRI amplitude in smokers. Our findings suggest that resting state PFC network interactions and limbic network amplitude can differentiate nicotine-dependent smokers from controls, and may serve as biomarkers for nicotine dependence severity and treatment efficacy. PMID:22459914

  7. Wireless brain-machine interface using EEG and EOG: brain wave classification and robot control

    NASA Astrophysics Data System (ADS)

    Oh, Sechang; Kumar, Prashanth S.; Kwon, Hyeokjun; Varadan, Vijay K.

    2012-04-01

    A brain-machine interface (BMI) links a user's brain activity directly to an external device. It enables a person to control devices using only thought. Hence, it has gained significant interest in the design of assistive devices and systems for people with disabilities. In addition, BMI has also been proposed to replace humans with robots in the performance of dangerous tasks like explosives handling/diffusing, hazardous materials handling, fire fighting etc. There are mainly two types of BMI based on the measurement method of brain activity; invasive and non-invasive. Invasive BMI can provide pristine signals but it is expensive and surgery may lead to undesirable side effects. Recent advances in non-invasive BMI have opened the possibility of generating robust control signals from noisy brain activity signals like EEG and EOG. A practical implementation of a non-invasive BMI such as robot control requires: acquisition of brain signals with a robust wearable unit, noise filtering and signal processing, identification and extraction of relevant brain wave features and finally, an algorithm to determine control signals based on the wave features. In this work, we developed a wireless brain-machine interface with a small platform and established a BMI that can be used to control the movement of a robot by using the extracted features of the EEG and EOG signals. The system records and classifies EEG as alpha, beta, delta, and theta waves. The classified brain waves are then used to define the level of attention. The acceleration and deceleration or stopping of the robot is controlled based on the attention level of the wearer. In addition, the left and right movements of eye ball control the direction of the robot.

  8. Brain-Computer Interface Controlled Cyborg: Establishing a Functional Information Transfer Pathway from Human Brain to Cockroach Brain.

    PubMed

    Li, Guangye; Zhang, Dingguo

    2016-01-01

    An all-chain-wireless brain-to-brain system (BTBS), which enabled motion control of a cyborg cockroach via human brain, was developed in this work. Steady-state visual evoked potential (SSVEP) based brain-computer interface (BCI) was used in this system for recognizing human motion intention and an optimization algorithm was proposed in SSVEP to improve online performance of the BCI. The cyborg cockroach was developed by surgically integrating a portable microstimulator that could generate invasive electrical nerve stimulation. Through Bluetooth communication, specific electrical pulse trains could be triggered from the microstimulator by BCI commands and were sent through the antenna nerve to stimulate the brain of cockroach. Serial experiments were designed and conducted to test overall performance of the BTBS with six human subjects and three cockroaches. The experimental results showed that the online classification accuracy of three-mode BCI increased from 72.86% to 78.56% by 5.70% using the optimization algorithm and the mean response accuracy of the cyborgs using this system reached 89.5%. Moreover, the results also showed that the cyborg could be navigated by the human brain to complete walking along an S-shape track with the success rate of about 20%, suggesting the proposed BTBS established a feasible functional information transfer pathway from the human brain to the cockroach brain. PMID:26982717

  9. Brain-Computer Interface Controlled Cyborg: Establishing a Functional Information Transfer Pathway from Human Brain to Cockroach Brain

    PubMed Central

    2016-01-01

    An all-chain-wireless brain-to-brain system (BTBS), which enabled motion control of a cyborg cockroach via human brain, was developed in this work. Steady-state visual evoked potential (SSVEP) based brain-computer interface (BCI) was used in this system for recognizing human motion intention and an optimization algorithm was proposed in SSVEP to improve online performance of the BCI. The cyborg cockroach was developed by surgically integrating a portable microstimulator that could generate invasive electrical nerve stimulation. Through Bluetooth communication, specific electrical pulse trains could be triggered from the microstimulator by BCI commands and were sent through the antenna nerve to stimulate the brain of cockroach. Serial experiments were designed and conducted to test overall performance of the BTBS with six human subjects and three cockroaches. The experimental results showed that the online classification accuracy of three-mode BCI increased from 72.86% to 78.56% by 5.70% using the optimization algorithm and the mean response accuracy of the cyborgs using this system reached 89.5%. Moreover, the results also showed that the cyborg could be navigated by the human brain to complete walking along an S-shape track with the success rate of about 20%, suggesting the proposed BTBS established a feasible functional information transfer pathway from the human brain to the cockroach brain. PMID:26982717

  10. Multilayer PDMS microfluidic chamber for controlling brain slice microenvironment

    PubMed Central

    Blake, A. J.; Pearce, T. M.; Rao, N. S.; Johnson, S. M.; Williams, J. C.

    2008-01-01

    A novel three-layer microfluidic polydimethylsiloxane (PDMS) device was constructed with two fluid chambers that holds a brain slice in place with microposts while maintaining laminar perfusate flow above and below the slice. Our fabrication technique permits rapid production of PDMS layers that can be applied to brain slices of different shapes and sizes. In this study, the device was designed to fit the shape and thickness (530-700 μm) of a medullary brain slice taken from P0-P4 neonatal rats. Medullary slices in this chamber spontaneously produced rhythmic, respiratory-related motor output for up to 3 h, thereby demonstrating that brain slice viability was maintained for prolonged periods. This design is unique in that it achieves independent control of fluids through multiple channels in two separate fluid chambers. The laminar flow exhibited by the microfluidic chamber allows controlled solutions to target specific areas of the brain slice based on the input flow rates. To demonstrate this capability, a stream of Na+-free solution was focused on one half of a medullary slice to abolish spontaneous neural activity in only that half of the brain slice, while the other half remained active. We also demonstrated that flow of different solutions can be focused over the midline of the brain slice. The multilayer brain slice chamber design can integrate several traditional types of electrophysiology tools that are commonly used to measure neurophysiological properties of brain slices. Thus, this new microfluidic chamber is advantageous for experiments that involve controlled drug or solution delivery at high spatiotemporal resolution. PMID:17594002

  11. Stimulation-Based Control of Dynamic Brain Networks.

    PubMed

    Muldoon, Sarah Feldt; Pasqualetti, Fabio; Gu, Shi; Cieslak, Matthew; Grafton, Scott T; Vettel, Jean M; Bassett, Danielle S

    2016-09-01

    The ability to modulate brain states using targeted stimulation is increasingly being employed to treat neurological disorders and to enhance human performance. Despite the growing interest in brain stimulation as a form of neuromodulation, much remains unknown about the network-level impact of these focal perturbations. To study the system wide impact of regional stimulation, we employ a data-driven computational model of nonlinear brain dynamics to systematically explore the effects of targeted stimulation. Validating predictions from network control theory, we uncover the relationship between regional controllability and the focal versus global impact of stimulation, and we relate these findings to differences in the underlying network architecture. Finally, by mapping brain regions to cognitive systems, we observe that the default mode system imparts large global change despite being highly constrained by structural connectivity. This work forms an important step towards the development of personalized stimulation protocols for medical treatment or performance enhancement. PMID:27611328

  12. Theory of feedback controlled brain stimulations for Parkinson's disease

    NASA Astrophysics Data System (ADS)

    Sanzeni, A.; Celani, A.; Tiana, G.; Vergassola, M.

    2016-01-01

    Limb tremor and other debilitating symptoms caused by the neurodegenerative Parkinson's disease are currently treated by administering drugs and by fixed-frequency deep brain stimulation. The latter interferes directly with the brain dynamics by delivering electrical impulses to neurons in the subthalamic nucleus. While deep brain stimulation has shown therapeutic benefits in many instances, its mechanism is still unclear. Since its understanding could lead to improved protocols of stimulation and feedback control, we have studied a mathematical model of the many-body neural network dynamics controlling the dynamics of the basal ganglia. On the basis of the results obtained from the model, we propose a new procedure of active stimulation, that depends on the feedback of the network and that respects the constraints imposed by existing technology. We show by numerical simulations that the new protocol outperforms the standard ones for deep brain stimulation and we suggest future experiments that could further improve the feedback procedure.

  13. Optogenetic control of human neurons in organotypic brain cultures.

    PubMed

    Andersson, My; Avaliani, Natalia; Svensson, Andreas; Wickham, Jenny; Pinborg, Lars H; Jespersen, Bo; Christiansen, Søren H; Bengzon, Johan; Woldbye, David P D; Kokaia, Merab

    2016-01-01

    Optogenetics is one of the most powerful tools in neuroscience, allowing for selective control of specific neuronal populations in the brain of experimental animals, including mammals. We report, for the first time, the application of optogenetic tools to human brain tissue providing a proof-of-concept for the use of optogenetics in neuromodulation of human cortical and hippocampal neurons as a possible tool to explore network mechanisms and develop future therapeutic strategies. PMID:27098488

  14. Optogenetic control of human neurons in organotypic brain cultures

    PubMed Central

    Andersson, My; Avaliani, Natalia; Svensson, Andreas; Wickham, Jenny; Pinborg, Lars H.; Jespersen, Bo; Christiansen, Søren H.; Bengzon, Johan; Woldbye, David P.D.; Kokaia, Merab

    2016-01-01

    Optogenetics is one of the most powerful tools in neuroscience, allowing for selective control of specific neuronal populations in the brain of experimental animals, including mammals. We report, for the first time, the application of optogenetic tools to human brain tissue providing a proof-of-concept for the use of optogenetics in neuromodulation of human cortical and hippocampal neurons as a possible tool to explore network mechanisms and develop future therapeutic strategies. PMID:27098488

  15. Genetic control over the resting brain

    PubMed Central

    Glahn, D. C.; Winkler, A. M.; Kochunov, P.; Almasy, L.; Duggirala, R.; Carless, M. A.; Curran, J. C.; Olvera, R. L.; Laird, A. R.; Smith, S. M.; Beckmann, C. F.; Fox, P. T.; Blangero, J.

    2010-01-01

    The default-mode network, a coherent resting-state brain network, is thought to characterize basal neural activity. Aberrant default-mode connectivity has been reported in a host of neurological and psychiatric illnesses and in persons at genetic risk for such illnesses. Whereas the neurophysiologic mechanisms that regulate default-mode connectivity are unclear, there is growing evidence that genetic factors play a role. In this report, we estimate the importance of genetic effects on the default-mode network by examining covariation patterns in functional connectivity among 333 individuals from 29 randomly selected extended pedigrees. Heritability for default-mode functional connectivity was 0.424 ± 0.17 (P = 0.0046). Although neuroanatomic variation in this network was also heritable, the genetic factors that influence default-mode functional connectivity and gray-matter density seem to be distinct, suggesting that unique genes influence the structure and function of the network. In contrast, significant genetic correlations between regions within the network provide evidence that the same genetic factors contribute to variation in functional connectivity throughout the default mode. Specifically, the left parahippocampal region was genetically correlated with all other network regions. In addition, the posterior cingulate/precuneus region, medial prefrontal cortex, and right cerebellum seem to form a subnetwork. Default-mode functional connectivity is influenced by genetic factors that cannot be attributed to anatomic variation or a single region within the network. By establishing the heritability of default-mode functional connectivity, this experiment provides the obligatory evidence required before these measures can be considered as endophenotypes for psychiatric or neurological illnesses or to identify genes influencing intrinsic brain function. PMID:20133824

  16. 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.

  17. Robot Control Through Brain Computer Interface For Patterns Generation

    NASA Astrophysics Data System (ADS)

    Belluomo, P.; Bucolo, M.; Fortuna, L.; Frasca, M.

    2011-09-01

    A Brain Computer Interface (BCI) system processes and translates neuronal signals, that mainly comes from EEG instruments, into commands for controlling electronic devices. This system can allow people with motor disabilities to control external devices through the real-time modulation of their brain waves. In this context an EEG-based BCI system that allows creative luminous artistic representations is here presented. The system that has been designed and realized in our laboratory interfaces the BCI2000 platform performing real-time analysis of EEG signals with a couple of moving luminescent twin robots. Experiments are also presented.

  18. Effects of Controlled Cortical Impact on the Mouse Brain Vasculome.

    PubMed

    Guo, Shuzhen; Lok, Josephine; Zhao, Song; Leung, Wendy; Som, Angel T; Hayakawa, Kazuhide; Wang, Qingzhi; Xing, Changhong; Wang, Xiaoying; Ji, Xunming; Zhou, Yiming; Lo, Eng H

    2016-07-15

    Perturbations in blood vessels play a critical role in the pathophysiology of brain injury and neurodegeneration. Here, we use a systematic genome-wide transcriptome screening approach to investigate the vasculome after brain trauma in mice. Mice were subjected to controlled cortical impact and brains were extracted for analysis at 24 h post-injury. The core of the traumatic lesion was removed and then cortical microvesels were isolated from nondirectly damaged ipsilateral cortex. Compared to contralateral cortex and normal cortex from sham-operated mice, we identified a wide spectrum of responses in the vasculome after trauma. Up-regulated pathways included those involved in regulation of inflammation and extracellular matrix processes. Decreased pathways included those involved in regulation of metabolism, mitochondrial function, and transport systems. These findings suggest that microvascular perturbations can be widespread and not necessarily localized to core areas of direct injury per se and may further provide a broader gene network context for existing knowledge regarding inflammation, metabolism, and blood-brain barrier alterations after brain trauma. Further efforts are warranted to map the vasculome with higher spatial and temporal resolution from acute to delayed phase post-trauma. Investigating the widespread network responses in the vasculome may reveal potential mechanisms, therapeutic targets, and biomarkers for traumatic brain injury. PMID:26528928

  19. Brain-machine interface: Can thoughts control machines?

    NASA Astrophysics Data System (ADS)

    Rudolph, Alan

    2002-03-01

    Recent advances in the fabrication and implantation of high density wireless interfaces in the brain have driven new programmatic thrusts at DARPA aimed at creating cortical prosthetics that could extract and utilize motor and sensory executive commands. These commands have already been shown to drive a peripheral devices in the control of a robotic arm. New efforts will be aimed at examining the ability to humans to control peripheral devices replacing lost peripheral function or augmenting human performance.

  20. Enhancing Hebbian Learning to Control Brain Oscillatory Activity.

    PubMed

    Soekadar, Surjo R; Witkowski, Matthias; Birbaumer, Niels; Cohen, Leonardo G

    2015-09-01

    Sensorimotor rhythms (SMR, 8-15 Hz) are brain oscillations associated with successful motor performance, imagery, and imitation. Voluntary modulation of SMR can be used to control brain-machine interfaces (BMI) in the absence of any physical movements. The mechanisms underlying acquisition of such skill are unknown. Here, we provide evidence for a causal link between function of the primary motor cortex (M1), active during motor skill learning and retention, and successful acquisition of abstract skills such as control over SMR. Thirty healthy participants were trained on 5 consecutive days to control SMR oscillations. Each participant was randomly assigned to one of 3 groups that received either 20 min of anodal, cathodal, or sham transcranial direct current stimulation (tDCS) over M1. Learning SMR control across training days was superior in the anodal tDCS group relative to the other 2. Cathodal tDCS blocked the beneficial effects of training, as evidenced with sham tDCS. One month later, the newly acquired skill remained superior in the anodal tDCS group. Thus, application of weak electric currents of opposite polarities over M1 differentially modulates learning SMR control, pointing to this primary cortical region as a common substrate for acquisition of physical motor skills and learning to control brain oscillatory activity. PMID:24626608

  1. Towards a brain controlled assistive technology for powered mobility.

    PubMed

    Kaneswaran, Kelly; Arshak, Khalil; Burke, Edward; Condron, James

    2010-01-01

    For individuals with mobility limitations, powered wheelchair systems provide improved functionality, increased access to healthcare, education and social activities. Input devices such as joystick and switches can provide the necessary input required for efficient control of the powered wheelchair. For persons with limited dexterity, or fine control of the fingers, access to mechanical hardware such as buttons and joysticks can be quite difficult and sometimes painful. For individuals with conditions such as Traumatic Brain Injury (TBI), Multiple Sclerosis (MS) or Amyotrophic lateral sclerosis (ALS) voluntary control of limb movement maybe substantially limited or completely absent. Brain Computer Interfaces (BCI) are emerging as a possible method to replace the brains normal output pathways of peripheral nerves and muscles, allowing individuals with paralysis a method of communication and computer control. This study involves the analysis of non-invasive electroencephalograms (EEG) arising from the use of a newly developed Human Machine Interface (HMI) for powered wheelchair control. Using a delayed response task, binary classification of left and right movement intentions were classified with a best classification rate of 81.63% from single trial EEG. Results suggest that this method may be used to enhance control of HMI's for individuals with severe mobility limitations. PMID:21096887

  2. A natural basis for efficient brain-actuated control

    NASA Technical Reports Server (NTRS)

    Makeig, S.; Enghoff, S.; Jung, T. P.; Sejnowski, T. J.

    2000-01-01

    The prospect of noninvasive brain-actuated control of computerized screen displays or locomotive devices is of interest to many and of crucial importance to a few 'locked-in' subjects who experience near total motor paralysis while retaining sensory and mental faculties. Currently several groups are attempting to achieve brain-actuated control of screen displays using operant conditioning of particular features of the spontaneous scalp electroencephalogram (EEG) including central mu-rhythms (9-12 Hz). A new EEG decomposition technique, independent component analysis (ICA), appears to be a foundation for new research in the design of systems for detection and operant control of endogenous EEG rhythms to achieve flexible EEG-based communication. ICA separates multichannel EEG data into spatially static and temporally independent components including separate components accounting for posterior alpha rhythms and central mu activities. We demonstrate using data from a visual selective attention task that ICA-derived mu-components can show much stronger spectral reactivity to motor events than activity measures for single scalp channels. ICA decompositions of spontaneous EEG would thus appear to form a natural basis for operant conditioning to achieve efficient and multidimensional brain-actuated control in motor-limited and locked-in subjects.

  3. Brain and behavioral inhibitory control of kindergartners facing negative emotions.

    PubMed

    Farbiash, Tali; Berger, Andrea

    2016-09-01

    Inhibitory control (IC) - one of the most critical functions underlying a child's ability to self-regulate - develops significantly throughout the kindergarten years. Experiencing negative emotions imposes challenges on executive functioning and may specifically affect IC. In this study, we examined kindergartners' IC and its related brain activity during a negative emotional situation: 58 children (aged 5.5-6.5 years) performed an emotion-induction Go/NoGo task. During this task, we recorded children's performance and brain activity, focusing on the fronto-central N2 component in the event-related potential (ERP) and the power of its underlying theta frequency. Compared to Go trials, inhibition of NoGo trials was associated with larger N2 amplitudes and theta power. The negative emotional experience resulted in better IC performance and, at the brain level, in larger theta power. Source localization of this effect showed that the brain activity related to IC during the negative emotional experience was principally generated in the posterior frontal regions. Furthermore, the band power measure was found to be a more sensitive index for children's inhibitory processes than N2 amplitudes. This is the first study to focus on kindergartners' IC while manipulating their emotional experience to induce negative emotions. Our findings suggest that a kindergartner's experience of negative emotion can result in improved IC and increases in associated aspects of brain activity. Our results also suggest the utility of time-frequency analyses in the study of brain processes associated with response inhibition in young children. PMID:26287125

  4. Prospects of brain-machine interfaces for space system control

    NASA Astrophysics Data System (ADS)

    Menon, Carlo; de Negueruela, Cristina; Millán, José del R.; Tonet, Oliver; Carpi, Federico; Broschart, Michael; Ferrez, Pierre; Buttfield, Anna; Tecchio, Franca; Sepulveda, Francisco; Citi, Luca; Laschi, Cecilia; Tombini, Mario; Dario, Paolo; Maria Rossini, Paolo; De Rossi, Danilo

    2009-02-01

    The dream of controlling and guiding computer-based systems using human brain signals has slowly but steadily become a reality. The available technology allows real-time implementation of systems that measure neuronal activity, convert their signals, and translate their output for the purpose of controlling mechanical and electronic systems. This paper describes the state of the art of non-invasive brain-machine interfaces (BMIs) and critically investigates both the current technological limits and the future potential that BMIs have for space applications. We present an assessment of the advantages that BMIs can provide and justify the preferred candidate concepts for space applications together with a vision of future directions for their implementation.

  5. Inhibitory Control after Traumatic Brain Injury in Children

    PubMed Central

    Sinopoli, Katia J.; Dennis, Maureen

    2011-01-01

    Inhibitory control describes a number of distinct processes. Effortless inhibition refers to acts of control that are automatic and reflexive. Effortful inhibition refers to voluntary, goal-directed acts of control such as response flexibility, interference control, cancellation inhibition, and restraint inhibition. Disruptions to a number of inhibitory control processes occur as a consequence of childhood traumatic brain injury (TBI). This paper reviews the current knowledge of inhibition deficits following childhood TBI, and includes an overview of the inhibition construct and a discussion of the specific deficits shown by children and adolescents with TBI and the factors that mediate the expression of these deficits, including injury-related variables and the expression of pre- and post-injury attention-deficit/hyperactivity disorder. The review illustrates that inhibitory control processes differ in terms of measurement, assessment, and neurological underpinnings, and also that childhood TBI may selectively disrupt particular forms of inhibition. PMID:22100363

  6. Brain

    MedlinePlus

    ... will return after updating. Resources Archived Modules Updates Brain Cerebrum The cerebrum is the part of the ... the outside of the brain and spinal cord. Brain Stem The brain stem is the part of ...

  7. THE EFFECTS OF BRAIN LATERALIZATION ON MOTOR CONTROL AND ADAPTATION

    PubMed Central

    Mutha, Pratik K.; Haaland, Kathleen Y.; Sainburg, Robert L.

    2012-01-01

    Lateralization of mechanisms mediating functions such as language and perception is widely accepted as a fundamental feature of neural organization. Recent research has revealed that a similar organization exists for the control of motor actions, in that each brain hemisphere contributes unique control mechanisms to the movements of each arm. We now review current research that addresses the nature of the control mechanisms that are lateralized to each hemisphere and how they impact motor adaptation and learning. In general, the studies reviewed here suggest an enhanced role for the left hemisphere during adaptation, and the learning of new sequences and skills. We suggest that this specialization emerges from a left hemisphere specialization for predictive control – the ability to effectively plan and coordinate motor actions, possibly by optimizing certain cost functions. In contrast, right hemisphere circuits appear to be important for updating ongoing actions and stopping at a goal position, through modulation of sensorimotor stabilization mechanisms such as reflexes. We also propose that each brain hemisphere contributes its mechanism to the control of both arms. We conclude by examining the potential advantages of such a lateralized control system. PMID:23237468

  8. Training-induced behavioral and brain plasticity in inhibitory control

    PubMed Central

    Spierer, Lucas; Chavan, Camille F.; Manuel, Aurelie L.

    2013-01-01

    Deficits in inhibitory control, the ability to suppress ongoing or planned motor or cognitive processes, contribute to many psychiatric and neurological disorders. The rehabilitation of inhibition-related disorders may therefore benefit from neuroplasticity-based training protocols aiming at normalizing inhibitory control proficiency and the underlying brain networks. Current literature on training-induced behavioral and brain plasticity in inhibitory control suggests that improvements may follow either from the development of automatic forms of inhibition or from the strengthening of top-down, controlled inhibition. Automatic inhibition develops in conditions of consistent and repeated associations between inhibition-triggering stimuli and stopping goals. Once established, the stop signals directly elicit inhibition, thereby bypassing slow, top-down executive control and accelerating stopping processes. In contrast, training regimens involving varying stimulus-response associations or frequent inhibition failures prevent the development of automatic inhibition and thus strengthen top-down inhibitory processes rather than bottom-up ones. We discuss these findings in terms of developing optimal inhibitory control training regimens for rehabilitation purposes. PMID:23914169

  9. Single-port laparoscopic cholecystectomy vs standard laparoscopic cholecystectomy: A non-randomized, age-matched single center trial

    PubMed Central

    van der Linden, Yoen TK; Bosscha, Koop; Prins, Hubert A; Lips, Daniel J

    2015-01-01

    AIM: To compare the safety of single-port laparoscopic cholecystectomies with standard four-port cholecystectomies. METHODS: Between January 2011 and December 2012 datas were gathered from 100 consecutive patients who received a single-port cholecystectomy. Patient baseline characteristics of all 100 single-port cholecystectomies were collected (body mass index, age, etc.) in a database. This group was compared with 100 age-matched patients who underwent a conventional laparoscopic cholecystectomy in the same period. Retrospectively, per- and postoperative data were added. The two groups were compared to each other using independent t-tests and χ2-tests, P values below 0.05 were considered significantly different. RESULTS: No differences were found between both groups regarding baseline characteristics. Operating time was significantly shorter in the total single-port group (42 min vs 62 min, P < 0.05); in procedures performed by surgeons the same trend was seen (45 min vs 59 min, P < 0.05). Peroperative complications between both groups were equal (3 in the single-port group vs 5 in the multiport group; P = 0.42). Although not significant less postoperative complications were seen in the single-port group compared with the multiport group (3 vs 9; P = 0.07). No statistically significant differences were found between both groups with regard to length of hospital stay, readmissions and mortality. CONCLUSION: Single-port laparoscopic cholecystectomy has the potential to be a safe technique with a low complication rate, short in-hospital stay and comparable operating time. Single-port cholecystectomy provides the patient an almost non-visible scar while preserving optimal quality of surgery. Further prospective studies are needed to prove the safety of the single-port technique. PMID:26328034

  10. Dopamine treatment during acute hypoxia is neuroprotective in the developing sheep brain.

    PubMed

    Brew, N; Azhan, A; den Heijer, I; Boomgardt, M; Davies, G I; Nitsos, I; Miller, S L; Walker, A M; Walker, D W; Wong, F Y

    2016-03-01

    Dopamine is often used to treat hypotension in preterm infants; these infants are at risk of developing brain injury due to impaired autoregulation and cerebral hypoperfusion. However the effects of dopamine on the immature brain under conditions of cerebral hypoxia are not known. We hypothesized that pretreatment with dopamine would protect the immature brain from injury caused by cerebral hypoxia. Preterm fetal sheep were used to determine the effects of intravenous dopamine on hypoxia-induced brain injury. In 16 pregnant sheep at 90days of gestation (0.6 of term, term=147days) catheters were implanted aseptically into the fetal carotid artery and jugular vein; an inflatable occluder was placed loosely around the umbilical cord for later induction of fetal hypoxemia. At 5days after surgery, dopamine (10μg/kg/min, n=7 fetuses) or saline (n=9 fetuses) was infused for 74h. Two hours after commencing the dopamine/saline infusion, we induced umbilical cord occlusion (UCO) for up to 25min to produce fetal asphyxia. Fetuses were allowed to recover, and brains were collected 72h later for assessment of neuropathology. Un-operated twin fetuses were used as age-matched non-UCO controls (n=8). In UCO+saline fetuses, microglial and apoptotic cell density in the subcortical and periventricular white matter, caudate nucleus and hippocampus was greater than that in age-matched controls; oxidative stress was elevated in the subcortical and periventricular white matter and caudate nucleus compared to that in age-matched controls. In UCO+dopamine fetuses microglial density and oxidative stress in the cerebral white matter and caudate nucleus were not different to that of age-matched controls. Apoptotic cell death was decreased in the cerebral white matter of UCO+dopamine brains, relative to UCO+saline brains. We conclude that pretreatment with dopamine does not exacerbate hypoxia-induced injury in the immature brain and may be neuroprotective because it led to decreased apoptosis

  11. Brain-controlled telepresence robot by motor-disabled people.

    PubMed

    Tonin, Luca; Carlson, Tom; Leeb, Robert; del R Millán, José

    2011-01-01

    In this paper we present the first results of users with disabilities in mentally controlling a telepresence robot, a rather complex task as the robot is continuously moving and the user must control it for a long period of time (over 6 minutes) to go along the whole path. These two users drove the telepresence robot from their clinic more than 100 km away. Remarkably, although the patients had never visited the location where the telepresence robot was operating, they achieve similar performances to a group of four healthy users who were familiar with the environment. In particular, the experimental results reported in this paper demonstrate the benefits of shared control for brain-controlled telepresence robots. It allows all subjects (including novel BMI subjects as our users with disabilities) to complete a complex task in similar time and with similar number of commands to those required by manual control. PMID:22255272

  12. Region based Brain Computer Interface for a home control application.

    PubMed

    Akman Aydin, Eda; Bay, Omer Faruk; Guler, Inan

    2015-08-01

    Environment control is one of the important challenges for disabled people who suffer from neuromuscular diseases. Brain Computer Interface (BCI) provides a communication channel between the human brain and the environment without requiring any muscular activation. The most important expectation for a home control application is high accuracy and reliable control. Region-based paradigm is a stimulus paradigm based on oddball principle and requires selection of a target at two levels. This paper presents an application of region based paradigm for a smart home control application for people with neuromuscular diseases. In this study, a region based stimulus interface containing 49 commands was designed. Five non-disabled subjects were attended to the experiments. Offline analysis results of the experiments yielded 95% accuracy for five flashes. This result showed that region based paradigm can be used to select commands of a smart home control application with high accuracy in the low number of repetitions successfully. Furthermore, a statistically significant difference was not observed between the level accuracies. PMID:26736451

  13. Controlled Cortical Impact Model for Traumatic Brain Injury

    PubMed Central

    Romine, Jennifer; Gao, Xiang; Chen, Jinhui

    2014-01-01

    Every year over a million Americans suffer a traumatic brain injury (TBI). Combined with the incidence of TBIs worldwide, the physical, emotional, social, and economical effects are staggering. Therefore, further research into the effects of TBI and effective treatments is necessary. The controlled cortical impact (CCI) model induces traumatic brain injuries ranging from mild to severe. This method uses a rigid impactor to deliver mechanical energy to an intact dura exposed following a craniectomy. Impact is made under precise parameters at a set velocity to achieve a pre-determined deformation depth. Although other TBI models, such as weight drop and fluid percussion, exist, CCI is more accurate, easier to control, and most importantly, produces traumatic brain injuries similar to those seen in humans. However, no TBI model is currently able to reproduce pathological changes identical to those seen in human patients. The CCI model allows investigation into the short-term and long-term effects of TBI, such as neuronal death, memory deficits, and cerebral edema, as well as potential therapeutic treatments for TBI. PMID:25145417

  14. Controlled cortical impact model for traumatic brain injury.

    PubMed

    Romine, Jennifer; Gao, Xiang; Chen, Jinhui

    2014-01-01

    Every year over a million Americans suffer a traumatic brain injury (TBI). Combined with the incidence of TBIs worldwide, the physical, emotional, social, and economical effects are staggering. Therefore, further research into the effects of TBI and effective treatments is necessary. The controlled cortical impact (CCI) model induces traumatic brain injuries ranging from mild to severe. This method uses a rigid impactor to deliver mechanical energy to an intact dura exposed following a craniectomy. Impact is made under precise parameters at a set velocity to achieve a pre-determined deformation depth. Although other TBI models, such as weight drop and fluid percussion, exist, CCI is more accurate, easier to control, and most importantly, produces traumatic brain injuries similar to those seen in humans. However, no TBI model is currently able to reproduce pathological changes identical to those seen in human patients. The CCI model allows investigation into the short-term and long-term effects of TBI, such as neuronal death, memory deficits, and cerebral edema, as well as potential therapeutic treatments for TBI. PMID:25145417

  15. Simulation of spread and control of lesions in brain.

    PubMed

    Thamattoor Raman, Krishna Mohan

    2012-01-01

    A simulation model for the spread and control of lesions in the brain is constructed using a planar network (graph) representation for the central nervous system (CNS). The model is inspired by the lesion structures observed in the case of multiple sclerosis (MS), a chronic disease of the CNS. The initial lesion site is at the center of a unit square and spreads outwards based on the success rate in damaging edges (axons) of the network. The damaged edges send out alarm signals which, at appropriate intensity levels, generate programmed cell death. Depending on the extent and timing of the programmed cell death, the lesion may get controlled or aggravated akin to the control of wild fires by burning of peripheral vegetation. The parameter phase space of the model shows smooth transition from uncontrolled situation to controlled situation. The simulations show that the model is capable of generating a wide variety of lesion growth and arrest scenarios. PMID:22319549

  16. Lactate: Brain Fuel in Human Traumatic Brain Injury: A Comparison with Normal Healthy Control Subjects

    PubMed Central

    Martin, Neil A.; Horning, Michael A.; McArthur, David L.; Hovda, David A.; Vespa, Paul; Brooks, George A.

    2015-01-01

    Abstract We evaluated the hypothesis that lactate shuttling helps support the nutritive needs of injured brains. To that end, we utilized dual isotope tracer [6,6-2H2]glucose, that is, D2-glucose, and [3-13C]lactate techniques involving arm vein tracer infusion along with simultaneous cerebral (arterial [art] and jugular bulb [JB]) blood sampling. Traumatic brain injury (TBI) patients with nonpenetrating brain injuries (n=12) were entered into the study following consent of patients' legal representatives. Written and informed consent was obtained from control volunteers (n=6). Patients were studied 5.7±2.2 (mean±SD) days post-injury; during periods when arterial glucose concentration tended to be higher in TBI patients. As in previous investigations, the cerebral metabolic rate for glucose (CMRgluc, i.e., net glucose uptake) was significantly suppressed following TBI (p<0.001). However, lactate fractional extraction, an index of cerebral lactate uptake related to systemic lactate supply, approximated 11% in both healthy control subjects and TBI patients. Further, neither the CMR for lactate (CMRlac, i.e., net lactate release), nor the tracer-measured cerebral lactate uptake differed between healthy controls and TBI patients. The percentages of lactate tracer taken up and released as 13CO2 into the JB accounted for 92% and 91% for control and TBI conditions, respectively, suggesting that most cerebral lactate uptake was oxidized following TBI. Comparisons of isotopic enrichments of lactate oxidation from infused [3-13C]lactate tracer and 13C-glucose produced during hepatic and renal gluconeogenesis (GNG) showed that 75–80% of 13CO2 released into the JB was from lactate and that the remainder was from the oxidation of glucose secondarily labeled from lactate. Hence, either directly as lactate uptake, or indirectly via GNG, peripheral lactate production accounted for ∼70% of carbohydrate (direct lactate uptake+uptake of glucose from lactate) consumed by the

  17. Effects of the FITKids Randomized Controlled Trial on Executive Control and Brain Function

    PubMed Central

    Pontifex, Matthew B.; Castelli, Darla M.; Khan, Naiman A.; Raine, Lauren B.; Scudder, Mark R.; Drollette, Eric S.; Moore, Robert D.; Wu, Chien-Ting; Kamijo, Keita

    2014-01-01

    OBJECTIVE: To assess the effect of a physical activity (PA) intervention on brain and behavioral indices of executive control in preadolescent children. METHODS: Two hundred twenty-one children (7–9 years) were randomly assigned to a 9-month afterschool PA program or a wait-list control. In addition to changes in fitness (maximal oxygen consumption), electrical activity in the brain (P3-ERP) and behavioral measures (accuracy, reaction time) of executive control were collected by using tasks that modulated attentional inhibition and cognitive flexibility. RESULTS: Fitness improved more among intervention participants from pretest to posttest compared with the wait-list control (1.3 mL/kg per minute, 95% confidence interval [CI]: 0.3 to 2.4; d = 0.34 for group difference in pre-to-post change score). Intervention participants exhibited greater improvements from pretest to posttest in inhibition (3.2%, 95% CI: 0.0 to 6.5; d = 0.27) and cognitive flexibility (4.8%, 95% CI: 1.1 to 8.4; d = 0.35 for group difference in pre-to-post change score) compared with control. Only the intervention group increased attentional resources from pretest to posttest during tasks requiring increased inhibition (1.4 µV, 95% CI: 0.3 to 2.6; d = 0.34) and cognitive flexibility (1.5 µV, 95% CI: 0.6 to 2.5; d = 0.43). Finally, improvements in brain function on the inhibition task (r = 0.22) and performance on the flexibility task correlated with intervention attendance (r = 0.24). CONCLUSIONS: The intervention enhanced cognitive performance and brain function during tasks requiring greater executive control. These findings demonstrate a causal effect of a PA program on executive control, and provide support for PA for improving childhood cognition and brain health. PMID:25266425

  18. Brain-specific transcriptional regulator T-brain-1 controls brain wiring and neuronal activity in autism spectrum disorders

    PubMed Central

    Huang, Tzyy-Nan; Hsueh, Yi-Ping

    2015-01-01

    T-brain-1 (TBR1) is a brain-specific T-box transcription factor. In 1995, Tbr1 was first identified from a subtractive hybridization that compared mouse embryonic and adult telencephalons. Previous studies of Tbr1−∕− mice have indicated critical roles for TBR1 in the development of the cerebral cortex, amygdala, and olfactory bulb. Neuronal migration and axonal projection are two important developmental features controlled by TBR1. Recently, recurrent de novo disruptive mutations in the TBR1 gene have been found in patients with autism spectrum disorders (ASDs). Human genetic studies have identified TBR1 as a high-confidence risk factor for ASDs. Because only one allele of the TBR1 gene is mutated in these patients, Tbr1+∕− mice serve as a good genetic mouse model to explore the mechanism by which de novo TBR1 mutation leads to ASDs. Although neuronal migration and axonal projection defects of cerebral cortex are the most prominent phenotypes in Tbr1−∕− mice, these features are not found in Tbr1+∕− mice. Instead, inter- and intra-amygdalar axonal projections and NMDAR expression and activity in amygdala are particularly susceptible to Tbr1 haploinsufficiency. The studies indicated that both abnormal brain wiring (abnormal amygdalar connections) and excitation/inhibition imbalance (NMDAR hypoactivity), two prominent models for ASD etiology, are present in Tbr1+∕− mice. Moreover, calcium/calmodulin-dependent serine protein kinase (CASK) was found to interact with TBR1. The CASK–TBR1 complex had been shown to directly bind the promoter of the Grin2b gene, which is also known as Nmdar2b, and upregulate Grin2b expression. This molecular function of TBR1 provides an explanation for NMDAR hypoactivity in Tbr1+∕− mice. In addition to Grin2b, cell adhesion molecules—including Ntng1, Cdh8, and Cntn2—are also regulated by TBR1 to control axonal projections of amygdala. Taken together, the studies of Tbr1 provide an integrated picture of ASD

  19. Controllable permeability of blood-brain barrier and reduced brain injury through low-intensity pulsed ultrasound stimulation

    PubMed Central

    Huang, Sin-Luo; Liu, Shing-Hwa; Yang, Feng-Yi

    2015-01-01

    It has been shown that the blood-brain barrier (BBB) can be locally disrupted by focused ultrasound (FUS) in the presence of microbubbles (MB) while sustaining little damage to the brain tissue. Thus, the safety issue associated with FUS-induced BBB disruption (BBBD) needs to be investigated for future clinical applications. This study demonstrated the neuroprotective effects induced by low-intensity pulsed ultrasound (LIPUS) against brain injury in the sonicated brain. Rats subjected to a BBB disruption injury received LIPUS exposure for 5 min after FUS/MB application. Measurements of BBB permeability, brain water content, and histological analysis were then carried out to evaluate the effects of LIPUS. The permeability and time window of FUS-induced BBBD can be effectively modulated with LIPUS. LIPUS also significantly reduced brain edema, neuronal death, and apoptosis in the sonicated brain. Our results show that brain injury in the FUS-induced BBBD model could be ameliorated by LIPUS and that LIPUS may be proposed as a novel treatment modality for controllable release of drugs into the brain. PMID:26517350

  20. Learning to control brain rhythms: making a brain-computer interface possible.

    PubMed

    Pineda, Jaime A; Silverman, David S; Vankov, Andrey; Hestenes, John

    2003-06-01

    The ability to control electroencephalographic rhythms and to map those changes to the actuation of mechanical devices provides the basis for an assistive brain-computer interface (BCI). In this study, we investigate the ability of subjects to manipulate the sensorimotor mu rhythm (8-12-Hz oscillations recorded over the motor cortex) in the context of a rich visual representation of the feedback signal. Four subjects were trained for approximately 10 h over the course of five weeks to produce similar or differential mu activity over the two hemispheres in order to control left or right movement in a three-dimensional video game. Analysis of the data showed a steep learning curve for producing differential mu activity during the first six training sessions and leveling off during the final four sessions. In contrast, similar mu activity was easily obtained and maintained throughout all the training sessions. The results suggest that an intentional BCI based on a binary signal is possible. During a realistic, interactive, and motivationally engaging task, subjects learned to control levels of mu activity faster when it involves similar activity in both hemispheres. This suggests that while individual control of each hemisphere is possible, it requires more learning time. PMID:12899268

  1. Brain metabolism in autism. Resting cerebral glucose utilization rates as measured with positron emission tomography

    SciTech Connect

    Rumsey, J.M.; Duara, R.; Grady, C.; Rapoport, J.L.; Margolin, R.A.; Rapoport, S.I.; Cutler, N.R.

    1985-05-01

    The cerebral metabolic rate for glucose was studied in ten men (mean age = 26 years) with well-documented histories of infantile autism and in 15 age-matched normal male controls using positron emission tomography and (F-18) 2-fluoro-2-deoxy-D-glucose. Positron emission tomography was completed during rest, with reduced visual and auditory stimulation. While the autistic group as a whole showed significantly elevated glucose utilization in widespread regions of the brain, there was considerable overlap between the two groups. No brain region showed a reduced metabolic rate in the autistic group. Significantly more autistic, as compared with control, subjects showed extreme relative metabolic rates (ratios of regional metabolic rates to whole brain rates and asymmetries) in one or more brain regions.

  2. Exploratory case-control study of brain tumors in adults

    SciTech Connect

    Burch, J.D.; Craib, K.J.; Choi, B.C.; Miller, A.B.; Risch, H.A.; Howe, G.R.

    1987-04-01

    An exploratory study of brain tumors in adults was carried out using 215 cases diagnosed in Southern Ontario between 1979 and 1982, with an individually matched, hospital control series. Significantly elevated risks were observed for reported use of spring water, drinking of wine, and consumption of pickled fish, together with a significant protective effect for the regular consumption of any of several types of fruit. While these factors are consistent with a role for N-nitroso compounds in the etiology of these tumors, for several other factors related to this hypothesis, no association was observed. Occupation in the rubber industry was associated with a significant relative risk of 9.0, though no other occupational associations were seen. Two previously unreported associations were with smoking nonfilter cigarettes with a significant trend and with the use of hair dyes or sprays. The data do not support an association between physical head trauma requiring medical attention and risk of brain tumors and indicate that exposure to ionizing radiation and vinyl chloride monomer does not contribute any appreciable fraction of attributable risk in the population studied. The findings warrant further detailed investigation in future epidemiologic studies.

  3. Executive and Language Control in the Multilingual Brain

    PubMed Central

    Kong, Anthony Pak-Hin; Abutalebi, Jubin; Lam, Karen Sze-Yan; Weekes, Brendan

    2014-01-01

    Neuroimaging studies suggest that the neural network involved in language control may not be specific to bi-/multilingualism but is part of a domain-general executive control system. We report a trilingual case of a Cantonese (L1), English (L2), and Mandarin (L3) speaker, Dr. T, who sustained a brain injury at the age of 77 causing lesions in the left frontal lobe and in the left temporo-parietal areas resulting in fluent aphasia. Dr. T's executive functions were impaired according to a modified version of the Stroop color-word test and the Wisconsin Card Sorting Test performance was characterized by frequent perseveration errors. Dr. T demonstrated pathological language switching and mixing across her three languages. Code switching in Cantonese was more prominent in discourse production than confrontation naming. Our case suggests that voluntary control of spoken word production in trilingual speakers shares neural substrata in the frontobasal ganglia system with domain-general executive control mechanisms. One prediction is that lesions to such a system would give rise to both pathological switching and impairments of executive functions in trilingual speakers. PMID:24868121

  4. Executive and language control in the multilingual brain.

    PubMed

    Kong, Anthony Pak-Hin; Abutalebi, Jubin; Lam, Karen Sze-Yan; Weekes, Brendan

    2014-01-01

    Neuroimaging studies suggest that the neural network involved in language control may not be specific to bi-/multilingualism but is part of a domain-general executive control system. We report a trilingual case of a Cantonese (L1), English (L2), and Mandarin (L3) speaker, Dr. T, who sustained a brain injury at the age of 77 causing lesions in the left frontal lobe and in the left temporo-parietal areas resulting in fluent aphasia. Dr. T's executive functions were impaired according to a modified version of the Stroop color-word test and the Wisconsin Card Sorting Test performance was characterized by frequent perseveration errors. Dr. T demonstrated pathological language switching and mixing across her three languages. Code switching in Cantonese was more prominent in discourse production than confrontation naming. Our case suggests that voluntary control of spoken word production in trilingual speakers shares neural substrata in the frontobasal ganglia system with domain-general executive control mechanisms. One prediction is that lesions to such a system would give rise to both pathological switching and impairments of executive functions in trilingual speakers. PMID:24868121

  5. Intelligence and Regional Brain Volumes in Normal Controls.

    ERIC Educational Resources Information Center

    Flashman, Laura A.; Andreasen, Nancy C.; Flaum, Michael; Swayze, Victor W., II

    1998-01-01

    The relationship between brain size and intelligence was examined in 90 normal volunteers. Results support the notion of a modest relationship between brain size and measures of global intelligence and suggest diffuse brain involvement on performance tasks that require integration and use of multiple cognitive domains. (Author/SLD)

  6. Role of brain hemispheric dominance in anticipatory postural control strategies.

    PubMed

    Cioncoloni, David; Rosignoli, Deborah; Feurra, Matteo; Rossi, Simone; Bonifazi, Marco; Rossi, Alessandro; Mazzocchio, Riccardo

    2016-07-01

    Most of the cerebral functions are asymmetrically represented in the two hemispheres. Moreover, dexterity and coordination of the distal segment of the dominant limbs depend on cortico-motor lateralization. In this study, we investigated whether postural control may be also considered a lateralized hemispheric brain function. To this aim, 15 young subjects were tested in standing position by measuring center of pressure (COP) shifts along the anteroposterior axis (COP-Y) during dynamic posturography before and after continuous Theta Burst Stimulation (cTBS) intervention applied to the dominant or non-dominant M1 hand area as well as to the vertex. We show that when subjects were expecting a forward platform translation, the COP-Y was positioned significantly backward or forward after dominant or non-dominant M1 stimulation, respectively. We postulate that cTBS applied on M1 may have disrupted the functional connectivity between intra- and interhemispheric areas implicated in the anticipatory control of postural stability. This study suggests a functional asymmetry between the two homologous primary motor areas, with the dominant hemisphere playing a critical role in the selection of the appropriate postural control strategy. PMID:26952051

  7. Noninvasive brain-actuated control of a mobile robot by human EEG.

    PubMed

    Millán, José del R; Renkens, Frédéric; Mouriño, Josep; Gerstner, Wulfram

    2004-06-01

    Brain activity recorded noninvasively is sufficient to control a mobile robot if advanced robotics is used in combination with asynchronous electroencephalogram (EEG) analysis and machine learning techniques. Until now brain-actuated control has mainly relied on implanted electrodes, since EEG-based systems have been considered too slow for controlling rapid and complex sequences of movements. We show that two human subjects successfully moved a robot between several rooms by mental control only, using an EEG-based brain-machine interface that recognized three mental states. Mental control was comparable to manual control on the same task with a performance ratio of 0.74. PMID:15188874

  8. Brain-computer interface control along instructed paths

    NASA Astrophysics Data System (ADS)

    Sadtler, P. T.; Ryu, S. I.; Tyler-Kabara, E. C.; Yu, B. M.; Batista, A. P.

    2015-02-01

    Objective. Brain-computer interfaces (BCIs) are being developed to assist paralyzed people and amputees by translating neural activity into movements of a computer cursor or prosthetic limb. Here we introduce a novel BCI task paradigm, intended to help accelerate improvements to BCI systems. Through this task, we can push the performance limits of BCI systems, we can quantify more accurately how well a BCI system captures the user’s intent, and we can increase the richness of the BCI movement repertoire. Approach. We have implemented an instructed path task, wherein the user must drive a cursor along a visible path. The instructed path task provides a versatile framework to increase the difficulty of the task and thereby push the limits of performance. Relative to traditional point-to-point tasks, the instructed path task allows more thorough analysis of decoding performance and greater richness of movement kinematics. Main results. We demonstrate that monkeys are able to perform the instructed path task in a closed-loop BCI setting. We further investigate how the performance under BCI control compares to native arm control, whether users can decrease their movement variability in the face of a more demanding task, and how the kinematic richness is enhanced in this task. Significance. The use of the instructed path task has the potential to accelerate the development of BCI systems and their clinical translation.

  9. Brain-computer interface control along instructed paths

    PubMed Central

    Sadtler, P T; Ryu, S I; Tyler-Kabara, E C; Yu, B M; Batista, A P

    2015-01-01

    Objective Brain-computer interfaces (BCIs) are being developed to assist paralyzed people and amputees by translating neural activity into movements of a computer cursor or prosthetic limb. Here we introduce a novel BCI task paradigm, intended to help accelerate improvements to BCI systems. Through this task, we can push the performance limits of BCI systems, we can quantify more accurately how well a BCI system captures the user’s intent, and we can increase the richness of the BCI movement repertoire. Approach We have implemented an instructed path task, wherein the user must drive a cursor along a visible path. The instructed path task provides a versatile framework to increase the difficulty of the task and thereby push the limits of performance. Relative to traditional point-to-point tasks, the instructed path task allows more thorough analysis of decoding performance and greater richness of movement kinematics. Main results We demonstrate that monkeys are able to perform the instructed path task in a closed-loop BCI setting. We further investigate how the performance under BCI control compares to native arm control, whether users can decrease their movement variability in the face of a more demanding task, and how the kinematic richness is enhanced in this task. Significance The use of the instructed path task has the potential to accelerate the development of BCI systems and their clinical translation. PMID:25605498

  10. Modeling Pediatric Brain Trauma: Piglet Model of Controlled Cortical Impact.

    PubMed

    Pareja, Jennifer C Munoz; Keeley, Kristen; Duhaime, Ann-Christine; Dodge, Carter P

    2016-01-01

    The brain has different responses to traumatic injury as a function of its developmental stage. As a model of injury to the immature brain, the piglet shares numerous similarities in regards to morphology and neurodevelopmental sequence compared to humans. This chapter describes a piglet scaled focal contusion model of traumatic brain injury that accounts for the changes in mass and morphology of the brain as it matures, facilitating the study of age-dependent differences in response to a comparable mechanical trauma. PMID:27604727

  11. Graph Analysis of Functional Brain Networks for Cognitive Control of Action in Traumatic Brain Injury

    ERIC Educational Resources Information Center

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

    2012-01-01

    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…

  12. A fuzzy-based shared controller for brain-actuated simulated robotic system.

    PubMed

    Liu, Rong; Xue, Kuang-Zheng; Wang, Yong-Xuan; Yang, Le

    2011-01-01

    The primary problems of brain-computer interface (BCI) are the low channel capacity and high error rate. Therefore, an assistive motion control method is important for the brain-actuated robot to realize real-time and reliable control. To make the brain-actuated robot respond to the external environments with more flexibility, a shared control method based on fuzzy logic is proposed. Experimental results obtained with ten healthy voluntary subjects show that the proposed fuzzy-based shared controller has improved performance compared with direct control approach. PMID:22256045

  13. Controlling ferrofluid permeability across the blood-brain barrier model

    NASA Astrophysics Data System (ADS)

    Shi, Di; Sun, Linlin; Mi, Gujie; Sheikh, Lubna; Bhattacharya, Soumya; Nayar, Suprabha; Webster, Thomas J.

    2014-02-01

    In the present study, an in vitro blood-brain barrier model was developed using murine brain endothelioma cells (b.End3 cells). Confirmation of the blood-brain barrier model was completed by examining the permeability of FITC-Dextran at increasing exposure times up to 96 h in serum-free medium and comparing such values with values from the literature. After such confirmation, the permeability of five novel ferrofluid (FF) nanoparticle samples, GGB (ferrofluids synthesized using glycine, glutamic acid and BSA), GGC (glycine, glutamic acid and collagen), GGP (glycine, glutamic acid and PVA), BPC (BSA, PEG and collagen) and CPB (collagen, PVA and BSA), was determined using this blood-brain barrier model. All of the five FF samples were characterized by zeta potential to determine their charge as well as TEM and dynamic light scattering for determining their hydrodynamic diameter. Results showed that FF coated with collagen passed more easily through the blood-brain barrier than FF coated with glycine and glutamic acid based on an increase of 4.5% in permeability. Through such experiments, diverse magnetic nanomaterials (such as FF) were identified for: (1) MRI use since they were less permeable to penetrate the blood-brain barrier to avoid neural tissue toxicity (e.g. GGB) or (2) brain drug delivery since they were more permeable to the blood-brain barrier (e.g. CPB).

  14. Controlling ferrofluid permeability across the blood–brain barrier model.

    PubMed

    Shi, Di; Sun, Linlin; Mi, Gujie; Sheikh, Lubna; Bhattacharya, Soumya; Nayar, Suprabha; Webster, Thomas J

    2014-02-21

    In the present study, an in vitro blood–brain barrier model was developed using murine brain endothelioma cells (b.End3 cells). Confirmation of the blood–brain barrier model was completed by examining the permeability of FITCDextran at increasing exposure times up to 96 h in serum-free medium and comparing such values with values from the literature. After such confirmation, the permeability of five novel ferrofluid (FF) nanoparticle samples, GGB (ferrofluids synthesized using glycine, glutamic acid and BSA), GGC (glycine, glutamic acid and collagen), GGP (glycine, glutamic acid and PVA), BPC (BSA, PEG and collagen) and CPB (collagen, PVA and BSA), was determined using this blood–brain barrier model. All of the five FF samples were characterized by zeta potential to determine their charge as well as TEM and dynamic light scattering for determining their hydrodynamic diameter. Results showed that FF coated with collagen passed more easily through the blood–brain barrier than FF coated with glycine and glutamic acid based on an increase of 4.5% in permeability. Through such experiments, diverse magnetic nanomaterials (such as FF) were identified for: (1) MRI use since they were less permeable to penetrate the blood–brain barrier to avoid neural tissue toxicity (e.g. GGB) or (2) brain drug delivery since they were more permeable to the blood–brain barrier (e.g. CPB). PMID:24457539

  15. Brain lipid sensing and the neural control of energy balance.

    PubMed

    Magnan, Christophe; Levin, Barry E; Luquet, Serge

    2015-12-15

    Fatty acid (FA) -sensitive neurons are present in the brain, especially the hypothalamus, and play a key role in the neural control of energy and glucose homeostasis including feeding behavior, secretion insulin and action. Subpopulations of neurons in the arcuate and ventromedial hypothalamic nuclei are selectively either activated or inhibited by FA. Molecular effectors of these FA effects include ion channels such as chloride, potassium or calcium. In addition, at least half of the responses in the hypothalamic ventromedial FA neurons are mediated through interaction with the FA translocator/receptor, FAT/CD36, that does not require metabolism to activate intracellular signaling downstream. Recently, an important role of lipoprotein lipase in FA detection has also been demonstrated not only in the hypothalamus, but also in the hippocampus and striatum. Finally, FA could overload energy homeostasis via increased hypothalamic ceramide synthesis which could, in turn, contribute to the pathogenesis of diabetes of obesity and/or type 2 in predisposed individuals by disrupting the endocrine signaling pathways of insulin and/or leptin. PMID:26415589

  16. High Toxoplasma gondii Seropositivity among Brain Tumor Patients in Korea.

    PubMed

    Jung, Bong-Kwang; Song, Hyemi; Kim, Min-Jae; Cho, Jaeeun; Shin, Eun-Hee; Chai, Jong-Yil

    2016-04-01

    Toxoplasma gondii is an intracellular protozoan that can modulate the environment of the infected host. An unfavorable environment modulated by T. gondii in the brain includes tumor microenvironment. Literature has suggested that T. gondii infection is associated with development of brain tumors. However, in Korea, epidemiological data regarding this correlation have been scarce. In this study, in order to investigate the relationship between T. gondii infection and brain tumor development, we investigated the seroprevalence of T. gondii among 93 confirmed brain tumor patients (various histological types, including meningioma and astrocytoma) in Korea using ELISA. The results revealed that T. gondii seropositivity among brain tumor patients (18.3%) was significantly (P<0.05) higher compared with that of healthy controls (8.6%). The seropositivity of brain tumor patients showed a significant age-tendency, i.e., higher in younger age group, compared with age-matched healthy controls (P<0.05). In conclusion, this study supports the close relationship between T. gondii infection and incidence of brain tumors. PMID:27180580

  17. High Toxoplasma gondii Seropositivity among Brain Tumor Patients in Korea

    PubMed Central

    Jung, Bong-Kwang; Song, Hyemi; Kim, Min-Jae; Cho, Jaeeun; Shin, Eun-Hee; Chai, Jong-Yil

    2016-01-01

    Toxoplasma gondii is an intracellular protozoan that can modulate the environment of the infected host. An unfavorable environment modulated by T. gondii in the brain includes tumor microenvironment. Literature has suggested that T. gondii infection is associated with development of brain tumors. However, in Korea, epidemiological data regarding this correlation have been scarce. In this study, in order to investigate the relationship between T. gondii infection and brain tumor development, we investigated the seroprevalence of T. gondii among 93 confirmed brain tumor patients (various histological types, including meningioma and astrocytoma) in Korea using ELISA. The results revealed that T. gondii seropositivity among brain tumor patients (18.3%) was significantly (P<0.05) higher compared with that of healthy controls (8.6%). The seropositivity of brain tumor patients showed a significant age-tendency, i.e., higher in younger age group, compared with age-matched healthy controls (P<0.05). In conclusion, this study supports the close relationship between T. gondii infection and incidence of brain tumors. PMID:27180580

  18. Caloric restriction increases ketone bodies metabolism and preserves blood flow in aging brain

    PubMed Central

    Lin, Ai-Ling; Zhang, Wei; Gao, Xiaoli; Watts, Lora

    2015-01-01

    Caloric restriction (CR) has been shown to increase the life span and health span of a broad range of species. However, CR effects on in vivo brain functions are far from explored. In this study, we used multimetric neuroimaging methods to characterize the CR-induced changes of brain metabolic and vascular functions in aging rats. We found that old rats (24 months of age) with CR diet had reduced glucose uptake and lactate concentration, but increased ketone bodies level, compared with the age-matched and young (5 months of age) controls. The shifted metabolism was associated with preserved vascular function: old CR rats also had maintained cerebral blood flow relative to the age-matched controls. When investigating the metabolites in mitochondrial tricarboxylic acid cycle, we found that citrate and α-ketoglutarate were preserved in the old CR rats. We suggest that CR is neuroprotective; ketone bodies, cerebral blood flow, and α-ketoglutarate may play important roles in preserving brain physiology in aging. PMID:25896951

  19. The inner CSF–brain barrier: developmentally controlled access to the brain via intercellular junctions

    PubMed Central

    Whish, Sophie; Dziegielewska, Katarzyna M.; Møllgård, Kjeld; Noor, Natassya M.; Liddelow, Shane A.; Habgood, Mark D.; Richardson, Samantha J.; Saunders, Norman R.

    2015-01-01

    In the adult the interface between the cerebrospinal fluid and the brain is lined by the ependymal cells, which are joined by gap junctions. These intercellular connections do not provide a diffusional restrain between the two compartments. However, during development this interface, initially consisting of neuroepithelial cells and later radial glial cells, is characterized by “strap” junctions, which limit the exchange of different sized molecules between cerebrospinal fluid and the brain parenchyma. Here we provide a systematic study of permeability properties of this inner cerebrospinal fluid-brain barrier during mouse development from embryonic day, E17 until adult. Results show that at fetal stages exchange across this barrier is restricted to the smallest molecules (286Da) and the diffusional restraint is progressively removed as the brain develops. By postnatal day P20, molecules the size of plasma proteins (70 kDa) diffuse freely. Transcriptomic analysis of junctional proteins present in the cerebrospinal fluid-brain interface showed expression of adherens junctional proteins, actins, cadherins and catenins changing in a development manner consistent with the observed changes in the permeability studies. Gap junction proteins were only identified in the adult as was claudin-11. Immunohistochemistry was used to localize at the cellular level some of the adherens junctional proteins of genes identified from transcriptomic analysis. N-cadherin, β - and α-catenin immunoreactivity was detected outlining the inner CSF-brain interface from E16; most of these markers were not present in the adult ependyma. Claudin-5 was present in the apical-most part of radial glial cells and in endothelial cells in embryos, but only in endothelial cells including plexus endothelial cells in adults. Claudin-11 was only immunopositive in the adult, consistent with results obtained from transcriptomic analysis. These results provide information about physiological, molecular

  20. Quantitative autoradiography of angiotensin II receptors in the SHR brain

    SciTech Connect

    Gehlert, D.R.; Speth, R.C.; Wamsley, J.K.

    1986-11-01

    Several lines of evidence indicate brain angiotensin II is associated with the elevation of blood pressure seen in the spontaneously hypertensive rat (SHR). These include an increased pressor response to intracerebroventricularly administered angiotensin II and a reduction of blood pressure in response to centrally administered angiotensin II receptor antagonists. Using quantitative receptor autoradiography, we have detected greater angiotensin II receptor binding in a number of discrete brain nuclei of the 6-week-old SHR when compared to age-matched Wistar-Kyoto controls. Tissue sections from various brain regions were labeled with (/sup 125/I)-angiotensin II according to a previously described method. Autoradiograms were generated by apposing the labeled tissue sections to LKB Ultrofilm along with brain paste standards which contained known amounts of (/sup 125/I). Quantitation of the binding, utilizing computer-assisted microdensitometry, indicated greater (/sup 125/I)-angiotensin II binding in several brain areas implicated in cardiovascular control including the subfornical organ, nucleus of the solitary tract, dorsal motor nucleus of the vagus, locus coeruleus, supraoptic nucleus and the organum vasculosum of the lamina terminalis. Scatchard analysis of the binding in the nucleus of the solitary tract indicated an increased receptor number (Bmax) was responsible for the change while binding in two forebrain structures, the subfornical organ and supraoptic nucleus, showed alterations in receptor number and affinity (Kd). Several other brain regions, unrelated to cardiovascular control, exhibited no change in (/sup 125/I)-angiotensin II binding.

  1. Neurophotonics: optical methods to study and control the brain

    NASA Astrophysics Data System (ADS)

    Doronina-Amitonova, L. V.; Fedotov, I. V.; Fedotov, A. B.; Anokhin, K. V.; Zheltikov, A. M.

    2015-04-01

    Methods of optical physics offer unique opportunities for the investigation of brain and higher nervous activity. The integration of cutting-edge laser technologies and advanced neurobiology opens a new cross-disciplinary area of natural sciences - neurophotonics - focusing on the development of a vast arsenal of tools for functional brain diagnostics, stimulation of individual neurons and neural networks, and the molecular engineering of brain cells aimed at the diagnosis and therapy of neurodegenerative and psychic diseases. Optical fibers help to confront the most challenging problems in brain research, including the analysis of molecular-cellular mechanisms of the formation of memory and behavior. New generation optical fibers provide new solutions for the development of fundamentally new, unique tools for neurophotonics and laser neuroengineering - fiber-optic neuroendoscopes and neurointerfaces. These instruments broaden research horizons when investigating the most complex brain functions, enabling a long-term multiplex detection of fluorescent protein markers, as well as photostimulation of neuronal activity in deep brain areas in living, freely moving animals with an unprecedented spatial resolution and minimal invasiveness. This emerging technology opens new horizons for understanding learning and long-term memory through experiments with living, freely moving mammals. Here, we present a brief review of this rapidly growing field of research.

  2. Mitochondria-controlled signaling mechanisms of brain protection in hypoxia

    PubMed Central

    Lukyanova, Ludmila D.; Kirova, Yulia I.

    2015-01-01

    The article is focused on the role of the cell bioenergetic apparatus, mitochondria, involved in development of immediate and delayed molecular mechanisms for adaptation to hypoxic stress in brain cortex. Hypoxia induces reprogramming of respiratory chain function and switching from oxidation of NAD-related substrates (complex I) to succinate oxidation (complex II). Transient, reversible, compensatory activation of respiratory chain complex II is a major mechanism of immediate adaptation to hypoxia necessary for (1) succinate-related energy synthesis in the conditions of oxygen deficiency and formation of urgent resistance in the body; (2) succinate-related stabilization of HIF-1α and initiation of its transcriptional activity related with formation of long-term adaptation; (3) succinate-related activation of the succinate-specific receptor, GPR91. This mechanism participates in at least four critical regulatory functions: (1) sensor function related with changes in kinetic properties of complex I and complex II in response to a gradual decrease in ambient oxygen concentration; this function is designed for selection of the most efficient pathway for energy substrate oxidation in hypoxia; (2) compensatory function focused on formation of immediate adaptive responses to hypoxia and hypoxic resistance of the body; (3) transcriptional function focused on activated synthesis of HIF-1 and the genes providing long-term adaptation to low pO2; (4) receptor function, which reflects participation of mitochondria in the intercellular signaling system via the succinate-dependent receptor, GPR91. In all cases, the desired result is achieved by activation of the succinate-dependent oxidation pathway, which allows considering succinate as a signaling molecule. Patterns of mitochondria-controlled activation of GPR-91- and HIF-1-dependent reaction were considered, and a possibility of their participation in cellular-intercellular-systemic interactions in hypoxia and adaptation was

  3. Reorganization and Preservation of Motor Control of the Brain in Spinal Cord Injury: A Systematic Review

    PubMed Central

    Kokotilo, Kristen J; Eng, Janice J; Curt, Armin

    2011-01-01

    Reorganization of brain function in people with CNS damage has been identified as one of the fundamental mechanisms involved in the recovery of sensori-motor function. Spinal cord injury (SCI) brain mapping studies during motor tasks aim for assessing the reorganization and preservation of brain networks involved in motor control. Revealing the activation of cortical and sub-cortical brain areas in people with SCI can indicate principal patterns of brain reorganization when the neurotrauma is distal to the brain. This review assessed brain activation after SCI in terms of intensity, volume, and somatotopic localization, as well as preservation of activation during attempted and/or imagined movements. Twenty-five studies meeting the inclusion criteria could be identified in MEDLINE (1980 to January 2008). Relevant characteristics of studies (level of lesion, time after injury, motor task) and mapping techniques varied widely. Changes in brain activation were found in both cortical and subcortical areas of individuals with SCI. In addition, several studies described a shift in the region of brain activation. These patterns appeared to be dynamic and influenced by the level, completeness and time after injury, as well as extent of clinical recovery. In addition, several aspects of reorganization of brain function following SCI resembled those reported in stroke. This review demonstrates that brain networks involved in different demands of motor control remain responsive even in chronic paralysis. These findings imply that therapeutic strategies aiming for restoring spinal cord function even in people with chronic SCI can build on a preserved competent brain control. PMID:19604097

  4. Structural Dissociation of Attentional Control and Memory in Adults with and without Mild Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Niogi, Sumit N.; Mukherjee, Pratik; Ghajar, Jamshid; Johnson, Carl E.; Kolster, Rachel; Lee, Hana; Suh, Minah; Zimmerman, Robert D.; Manley, Geoffrey T.; McCandliss, Bruce D.

    2008-01-01

    Memory and attentional control impairments are the two most common forms of dysfunction following mild traumatic brain injury (TBI) and lead to significant morbidity in patients, yet these functions are thought to be supported by different brain networks. This 3 T magnetic resonance diffusion tensor imaging (DTI) study investigates whether…

  5. The Autism Brain Imaging Data Exchange: Towards Large-Scale Evaluation of the Intrinsic Brain Architecture in Autism

    PubMed Central

    Di Martino, Adriana; Yan, Chao-Gan; Li, Qingyang; Denio, Erin; Castellanos, Francisco X.; Alaerts, Kaat; Anderson, Jeffrey S.; Assaf, Michal; Bookheimer, Susan Y.; Dapretto, Mirella; Deen, Ben; Delmonte, Sonja; Dinstein, Ilan; Ertl-Wagner, Birgit; Fair, Damien A.; Gallagher, Louise; Kennedy, Daniel P.; Keown, Christopher L.; Keysers, Christian; Lainhart, Janet E.; Lord, Catherine; Luna, Beatriz; Menon, Vinod; Minshew, Nancy; Monk, Christopher S.; Mueller, Sophia; Müller, Ralph-Axel; Nebel, Mary Beth; Nigg, Joel T.; O’Hearn, Kirsten; Pelphrey, Kevin A.; Peltier, Scott J.; Rudie, Jeffrey D.; Sunaert, Stefan; Thioux, Marc; Tyszka, J. Michael; Uddin, Lucina Q.; Verhoeven, Judith S.; Wenderoth, Nicole; Wiggins, Jillian L.; Mostofsky, Stewart H.; Milham, Michael P.

    2014-01-01

    Autism spectrum disorders (ASD) represent a formidable challenge for psychiatry and neuroscience because of their high prevalence, life-long nature, complexity and substantial heterogeneity. Facing these obstacles requires large-scale multidisciplinary efforts. While the field of genetics has pioneered data sharing for these reasons, neuroimaging had not kept pace. In response, we introduce the Autism Brain Imaging Data Exchange (ABIDE) – a grassroots consortium aggregating and openly sharing 1112 existing resting-state functional magnetic resonance imaging (R-fMRI) datasets with corresponding structural MRI and phenotypic information from 539 individuals with ASD and 573 age-matched typical controls (TC; 7–64 years) (http://fcon_1000.projects.nitrc.org/indi/abide/). Here, we present this resource and demonstrate its suitability for advancing knowledge of ASD neurobiology based on analyses of 360 males with ASD and 403 male age-matched TC. We focused on whole-brain intrinsic functional connectivity and also survey a range of voxel-wise measures of intrinsic functional brain architecture. Whole-brain analyses reconciled seemingly disparate themes of both hypo and hyperconnectivity in the ASD literature; both were detected, though hypoconnectivity dominated, particularly for cortico-cortical and interhemispheric functional connectivity. Exploratory analyses using an array of regional metrics of intrinsic brain function converged on common loci of dysfunction in ASD (mid and posterior insula, posterior cingulate cortex), and highlighted less commonly explored regions such as thalamus. The survey of the ABIDE R-fMRI datasets provides unprecedented demonstrations of both replication and novel discovery. By pooling multiple international datasets, ABIDE is expected to accelerate the pace of discovery setting the stage for the next generation of ASD studies. PMID:23774715

  6. The autism brain imaging data exchange: towards a large-scale evaluation of the intrinsic brain architecture in autism.

    PubMed

    Di Martino, A; Yan, C-G; Li, Q; Denio, E; Castellanos, F X; Alaerts, K; Anderson, J S; Assaf, M; Bookheimer, S Y; Dapretto, M; Deen, B; Delmonte, S; Dinstein, I; Ertl-Wagner, B; Fair, D A; Gallagher, L; Kennedy, D P; Keown, C L; Keysers, C; Lainhart, J E; Lord, C; Luna, B; Menon, V; Minshew, N J; Monk, C S; Mueller, S; Müller, R-A; Nebel, M B; Nigg, J T; O'Hearn, K; Pelphrey, K A; Peltier, S J; Rudie, J D; Sunaert, S; Thioux, M; Tyszka, J M; Uddin, L Q; Verhoeven, J S; Wenderoth, N; Wiggins, J L; Mostofsky, S H; Milham, M P

    2014-06-01

    Autism spectrum disorders (ASDs) represent a formidable challenge for psychiatry and neuroscience because of their high prevalence, lifelong nature, complexity and substantial heterogeneity. Facing these obstacles requires large-scale multidisciplinary efforts. Although the field of genetics has pioneered data sharing for these reasons, neuroimaging had not kept pace. In response, we introduce the Autism Brain Imaging Data Exchange (ABIDE)-a grassroots consortium aggregating and openly sharing 1112 existing resting-state functional magnetic resonance imaging (R-fMRI) data sets with corresponding structural MRI and phenotypic information from 539 individuals with ASDs and 573 age-matched typical controls (TCs; 7-64 years) (http://fcon_1000.projects.nitrc.org/indi/abide/). Here, we present this resource and demonstrate its suitability for advancing knowledge of ASD neurobiology based on analyses of 360 male subjects with ASDs and 403 male age-matched TCs. We focused on whole-brain intrinsic functional connectivity and also survey a range of voxel-wise measures of intrinsic functional brain architecture. Whole-brain analyses reconciled seemingly disparate themes of both hypo- and hyperconnectivity in the ASD literature; both were detected, although hypoconnectivity dominated, particularly for corticocortical and interhemispheric functional connectivity. Exploratory analyses using an array of regional metrics of intrinsic brain function converged on common loci of dysfunction in ASDs (mid- and posterior insula and posterior cingulate cortex), and highlighted less commonly explored regions such as the thalamus. The survey of the ABIDE R-fMRI data sets provides unprecedented demonstrations of both replication and novel discovery. By pooling multiple international data sets, ABIDE is expected to accelerate the pace of discovery setting the stage for the next generation of ASD studies. PMID:23774715

  7. A brain sexual dimorphism controlled by adult circulating androgens.

    PubMed

    Cooke, B M; Tabibnia, G; Breedlove, S M

    1999-06-22

    Reports of structural differences between the brains of men and women, heterosexual and homosexual men, and male-to-female transsexuals and other men have been offered as evidence that the behavioral differences between these groups are likely caused by differences in the early development of the brain. However, a possible confounding variable is the concentration of circulating hormones seen in these groups in adulthood. Evaluation of this possibility hinges on the extent to which circulating hormones can alter the size of mammalian brain regions as revealed by Nissl stains. We now report a sexual dimorphism in the volume of a brain nucleus in rats that can be completely accounted for by adult sex differences in circulating androgen. The posterodorsal nucleus of the medial amygdala (MePD) has a greater volume in male rats than in females, but adult castration of males causes the volume to shrink to female values within four weeks, whereas androgen treatment of adult females for that period enlarges the MePD to levels equivalent to normal males. This report demonstrates that adult hormone manipulations can completely reverse a sexual dimorphism in brain regional volume in a mammalian species. The sex difference and androgen responsiveness of MePD volume is reflected in the soma size of neurons there. PMID:10377450

  8. QT Is Longer in Drug-Free Patients with Schizophrenia Compared with Age-Matched Healthy Subjects

    PubMed Central

    Fujii, Kumiko; Ozeki, Yuji; Okayasu, Hiroaki; Takano, Yumiko; Shinozaki, Takahiro; Hori, Hiroaki; Orui, Masami; Horie, Minoru; Kunugi, Hiroshi; Shimoda, Kazutaka

    2014-01-01

    The potassium voltage-gated channel KCNH2 is a well-known gene in which mutations induce familial QT interval prolongation. KCNH2 is suggested to be a risk gene for schizophrenia. Additionally, the disturbance of autonomic control, which affects the QT interval, is known in schizophrenia. Therefore, we speculate that schizophrenic patients have characteristic features in terms of the QT interval in addition to the effect of antipsychotic medication. The QT interval of patients with schizophrenia not receiving antipsychotics (n = 85) was compared with that of patients with schizophrenia receiving relatively large doses of antipsychotics (n = 85) and healthy volunteers (n = 85). The QT interval was corrected using four methods (Bazett, Fridericia, Framingham or Hodges method). In ANCOVA with age and heart rate as covariates, patients not receiving antipsychotic treatment had longer QT intervals than did the healthy volunteers, but antipsychotics prolonged the QT interval regardless of the correction method used (P<0.01). Schizophrenic patients with and without medication had a significantly higher mean heart rate than did the healthy volunteers, with no obvious sex-related differences in the QT interval. The QT interval prolongation may be manifestation of a certain biological feature of schizophrenia. PMID:24887423

  9. Brain Endothelial Cells Synthesize Neurotoxic Thrombin in Alzheimer’s Disease

    PubMed Central

    Yin, Xiangling; Wright, Jill; Wall, Trevor; Grammas, Paula

    2010-01-01

    Alzheimer’s disease (AD) is characterized by neuronal death; thus, identifying neurotoxic proteins and their source is central to understanding and treating AD. The multifunctional protease thrombin is neurotoxic and found in AD senile plaques. The objective of this study was to determine whether brain endothelial cells can synthesize thrombin and thus be a source of this neurotoxin in AD brains. Microvessels were isolated from AD patient brains and from age-matched controls. Reverse transcription-PCR demonstrated that thrombin message was highly expressed in microvessels from AD brains but was not detectable in control vessels. Similarly, Western blot analysis of microvessels showed that the thrombin protein was highly expressed in AD- but not control-derived microvessels. In addition, high levels of thrombin were detected in cerebrospinal fluid obtained from AD but not control patients, and sections from AD brains showed reactivity to thrombin antibody in blood vessel walls but not in vessels from controls. Finally, we examined the ability of brain endothelial cells in culture to synthesize thrombin and showed that oxidative stress or cell signaling perturbations led to increased expression of thrombin mRNA in these cells. The results demonstrate, for the first time, that brain endothelial cells can synthesize thrombin, and suggest that novel therapeutics targeting vascular stabilization that prevent or decrease release of thrombin could prove useful in treating this neurodegenerative disease. PMID:20150433

  10. Study Reveals Brain Biology behind Self-Control

    ERIC Educational Resources Information Center

    Sparks, Sarah D.

    2011-01-01

    A new neuroscience twist on a classic psychology study offers some clues to what makes one student able to buckle down for hours of homework before a test while his classmates party. The study published in the September 2011 edition of "Proceedings of the National Academy of Science," suggests environmental cues may "hijack" the brain's mechanisms…

  11. Immediate processing of erotic stimuli in paedophilia and controls: a case control study

    PubMed Central

    2013-01-01

    Background Most neuroimaging studies investigating sexual arousal in paedophilia used erotic pictures together with a blocked fMRI design and long stimulus presentation time. While this approach allows the detection of sexual arousal, it does not enable the assessment of the immediate processing of erotically salient stimuli. Our study aimed to identify neuronal networks related to the immediate processing of erotic stimuli in heterosexual male paedophiles and healthy age-matched controls. Methods We presented erotic pictures of prepubescent children and adults in an event related fMRI-design to eight paedophilic subjects and age-matched controls. Results Erotic pictures of females elicited more activation in the right temporal lobe, the right parietal lobe and both occipital lobes and erotic pictures of children activated the right dorsomedial prefrontal cortex in both groups. An interaction of sex, age and group was present in the right anteriolateral oribitofrontal cortex. Conclusions Our event related study design confirmed that erotic pictures activate some of the brain regions already known to be involved in the processing of erotic pictures when these are presented in blocks. In addition, it revealed that erotic pictures of prepubescent children activate brain regions critical for choosing response strategies in both groups, and that erotically salient stimuli selectively activate a brain region in paedophilic subjects that had previously been attributed to reward and punishment, and that had been shown to be implicated in the suppression of erotic response and deception. PMID:23510246

  12. Redox control of brain calcium in health and disease.

    PubMed

    Hidalgo, Cecilia; Carrasco, M Angélica

    2011-04-01

    Calcium ion is a highly versatile cellular messenger. Calcium signals-defined as transient increments in intracellular-free calcium concentration-elicit a multiplicity of responses that depend on cell type and signal properties such as their intensity, duration, cellular localization, and frequency. The vast literature available on the role of calcium signals in brain cells, chiefly centered on neuronal cells, indicates that calcium signals regulate essential neuronal functions, including synaptic transmission, gene expression, synaptic plasticity processes underlying learning and memory, and survival or death. The eight articles comprising this forum issue address different and novel aspects of calcium signaling in normal neuronal function, including how calcium signals interact with the generation of reactive species of oxygen/nitrogen with various functional consequences, and focus also on how abnormal calcium homeostasis and signaling, plus oxidative stress, affect overall brain physiology during aging and in neurodegenerative conditions such as Alzheimer's or Parkinson's disease. PMID:21050143

  13. Control of Brain Development, Function, and Behavior by the Microbiome

    PubMed Central

    Sampson, Timothy R.; Mazmanian, Sarkis K.

    2015-01-01

    Animals share an intimate and life-long partnership with a myriad of resident microbial species, collectively referred to as the microbiota. Symbiotic microbes have been shown to regulate nutrition and metabolism, and are critical for the development and function of the immune system. More recently, studies have suggested that gut bacteria can impact neurological outcomes – altering behavior and potentially affecting the onset and/or severity of nervous system disorders. In this review, we highlight emerging evidence that the microbiome extends its influence to the brain via various pathways connecting the gut to the central nervous system. While understanding and appreciation of a gut microbial impact on neurological function is nascent, unraveling gut-microbiome-brain connections holds the promise of transforming the neurosciences and revealing potentially novel etiologies for psychiatric and neurodegenerative disorders. PMID:25974299

  14. Mitochondrial DNA Rearrangement Spectrum in Brain Tissue of Alzheimer’s Disease: Analysis of 13 Cases

    PubMed Central

    Chen, Yucai; Liu, Changsheng; Parker, William Davis; Chen, Hongyi; Beach, Thomas G.; Liu, Xinhua; Serrano, Geidy E.; Lu, Yanfen; Huang, Jianjun; Yang, Kunfang; Wang, Chunmei

    2016-01-01

    Background Mitochondrial dysfunction may play a central role in the pathologic process of Alzheimer’s disease (AD), but there is still a scarcity of data that directly links the pathology of AD with the alteration of mitochondrial DNA. This study aimed to provide a comprehensive assessment of mtDNA rearrangement events in AD brain tissue. Patients and Methods Postmortem frozen human brain cerebral cortex samples were obtained from the Banner Sun Health Research Institute Brain and Body Donation Program, Sun City, AZ. Mitochondria were isolated and direct sequence by using MiSeq®, and analyzed by relative software. Results Three types of mitochondrial DNA (mtDNA) rearrangements have been seen in post mortem human brain tissue from patients with AD and age matched control. These observed rearrangements include a deletion, F-type rearrangement, and R-type rearrangement. We detected a high level of mtDNA rearrangement in brain tissue from cognitively normal subjects, as well as the patients with Alzheimer's disease (AD). The rate of rearrangements was calculated by dividing the number of positive rearrangements by the coverage depth. The rearrangement rate was significantly higher in AD brain tissue than in control brain tissue (17.9%versus 6.7%; p = 0.0052). Of specific types of rearrangement, deletions were markedly increased in AD (9.2% versus 2.3%; p = 0.0005). Conclusions Our data showed that failure of mitochondrial DNA in AD brain might be important etiology of AD pathology. PMID:27299301

  15. The Left Hand Second to Fourth Digit Ratio (2D:4D) Does Not Discriminate World-Class Female Gymnasts from Age Matched Sedentary Girls

    PubMed Central

    Peeters, Maarten W.; Claessens, Albrecht L.

    2012-01-01

    Introduction The second to fourth-digit-ratio (2D:4D), a putative marker of prenatal androgen action and a sexually dimorphic trait, has been suggested to be related with sports performance, although results are not univocal. If this relation exists, it is most likely to be detected by comparing extreme groups on the continuum of sports performance. Methods In this study the 2D:4D ratio of world-class elite female artistic gymnasts (n = 129), competing at the 1987 Rotterdam World-Championships was compared to the 2D:4D ratio of sedentary age-matched sedentary girls (n = 129), alongside with other anthropometric characteristics including other sexually dimorphic traits such as an androgyny index (Bayer & Bayley) and Heath-Carter somatotype components (endomorphy, mesomorphy, ectomorphy) using AN(C)OVA. 2D:4D was measured on X-rays of the left hand. Results Left hand 2D:4D digit ratio in world class elite female gymnasts (0.921±0.020) did not differ significantly from 2D:4D in age-matched sedentary girls (0.924±0.018), either with or without inclusion of potentially confounding covariates such as skeletal age, height, weight, somatotype components or androgyny index. Height (161.9±6.4 cm vs 155.4±6.6 cm p<0.01), weight (53.9±7.6 kg vs 46.2 6.3 kg p<0.01), BMI (20.51±2.41 kg/m2 vs 19.05±1.56 kg/m2), skeletal age (15.2±1.1 y vs 14.5±1.2 y p>0.01), somatotype components (4.0/3.0/2.9 vs 1.7/3.7/3.2 for endomorphy (p<0.01), mesomorphy (p<0.01) and ectomorphy (p<0.05) respectively) all differed significantly between sedentary girls and elite gymnasts. As expressed by the androgyny index, gymnasts have, on average, broader shoulders relative to their hips, compared to the reference sample. Correlations between the 2D:4D ratio and chronological age, skeletal age, and the anthropometric characteristics are low and not significant. Conclusion Although other anthropometric characteristics of sexual dimorphism were significantly different between the two samples

  16. Persistent Angiogenesis in the Autism Brain: An Immunocytochemical Study of Postmortem Cortex, Brainstem and Cerebellum

    PubMed Central

    Saccomano, Z. T.; Alzoobaee, M. F.; Boldrini, M.; Whitaker-Azmitia, P. M.

    2016-01-01

    In the current work, we conducted an immunocytochemical search for markers of ongoing neurogenesis (e.g. nestin) in auditory cortex from postmortem sections of autism spectrum disorder (ASD) and age-matched control donors. We found nestin labeling in cells of the vascular system, indicating blood vessels plasticity. Evidence of angiogenesis was seen throughout superior temporal cortex (primary auditory cortex), fusiform cortex (face recognition center), pons/midbrain and cerebellum in postmortem brains from ASD patients but not control brains. We found significant increases in both nestin and CD34, which are markers of angiogenesis localized to pericyte cells and endothelial cells, respectively. This labeling profile is indicative of splitting (intussusceptive), rather than sprouting, angiogenesis indicating the blood vessels are in constant flux rather than continually expanding. PMID:26667147

  17. Altered Brain Microstate Dynamics in Adolescents with Narcolepsy.

    PubMed

    Drissi, Natasha M; Szakács, Attila; Witt, Suzanne T; Wretman, Anna; Ulander, Martin; Ståhlbrandt, Henriettae; Darin, Niklas; Hallböök, Tove; Landtblom, Anne-Marie; Engström, Maria

    2016-01-01

    Narcolepsy is a chronic sleep disorder caused by a loss of hypocretin-1 producing neurons in the hypothalamus. Previous neuroimaging studies have investigated brain function in narcolepsy during rest using positron emission tomography (PET) and single photon emission computed tomography (SPECT). In addition to hypothalamic and thalamic dysfunction they showed aberrant prefrontal perfusion and glucose metabolism in narcolepsy. Given these findings in brain structure and metabolism in narcolepsy, we anticipated that changes in functional magnetic resonance imaging (fMRI) resting state network (RSN) dynamics might also be apparent in patients with narcolepsy. The objective of this study was to investigate and describe brain microstate activity in adolescents with narcolepsy and correlate these to RSNs using simultaneous fMRI and electroencephalography (EEG). Sixteen adolescents (ages 13-20) with a confirmed diagnosis of narcolepsy were recruited and compared to age-matched healthy controls. Simultaneous EEG and fMRI data were collected during 10 min of wakeful rest. EEG data were analyzed for microstates, which are discrete epochs of stable global brain states obtained from topographical EEG analysis. Functional MRI data were analyzed for RSNs. Data showed that narcolepsy patients were less likely than controls to spend time in a microstate which we found to be related to the default mode network and may suggest a disruption of this network that is disease specific. We concluded that adolescents with narcolepsy have altered resting state brain dynamics. PMID:27536225

  18. Altered Brain Microstate Dynamics in Adolescents with Narcolepsy

    PubMed Central

    Drissi, Natasha M.; Szakács, Attila; Witt, Suzanne T.; Wretman, Anna; Ulander, Martin; Ståhlbrandt, Henriettae; Darin, Niklas; Hallböök, Tove; Landtblom, Anne-Marie; Engström, Maria

    2016-01-01

    Narcolepsy is a chronic sleep disorder caused by a loss of hypocretin-1 producing neurons in the hypothalamus. Previous neuroimaging studies have investigated brain function in narcolepsy during rest using positron emission tomography (PET) and single photon emission computed tomography (SPECT). In addition to hypothalamic and thalamic dysfunction they showed aberrant prefrontal perfusion and glucose metabolism in narcolepsy. Given these findings in brain structure and metabolism in narcolepsy, we anticipated that changes in functional magnetic resonance imaging (fMRI) resting state network (RSN) dynamics might also be apparent in patients with narcolepsy. The objective of this study was to investigate and describe brain microstate activity in adolescents with narcolepsy and correlate these to RSNs using simultaneous fMRI and electroencephalography (EEG). Sixteen adolescents (ages 13–20) with a confirmed diagnosis of narcolepsy were recruited and compared to age-matched healthy controls. Simultaneous EEG and fMRI data were collected during 10 min of wakeful rest. EEG data were analyzed for microstates, which are discrete epochs of stable global brain states obtained from topographical EEG analysis. Functional MRI data were analyzed for RSNs. Data showed that narcolepsy patients were less likely than controls to spend time in a microstate which we found to be related to the default mode network and may suggest a disruption of this network that is disease specific. We concluded that adolescents with narcolepsy have altered resting state brain dynamics. PMID:27536225

  19. Evidence for an inhibitory-control theory of the reasoning brain

    PubMed Central

    Houdé, Olivier; Borst, Grégoire

    2015-01-01

    In this article, we first describe our general inhibitory-control theory and, then, we describe how we have tested its specific hypotheses on reasoning with brain imaging techniques in adults and children. The innovative part of this perspective lies in its attempt to come up with a brain-based synthesis of Jean Piaget’s theory on logical algorithms and Daniel Kahneman’s theory on intuitive heuristics. PMID:25852528

  20. Evidence for an inhibitory-control theory of the reasoning brain.

    PubMed

    Houdé, Olivier; Borst, Grégoire

    2015-01-01

    In this article, we first describe our general inhibitory-control theory and, then, we describe how we have tested its specific hypotheses on reasoning with brain imaging techniques in adults and children. The innovative part of this perspective lies in its attempt to come up with a brain-based synthesis of Jean Piaget's theory on logical algorithms and Daniel Kahneman's theory on intuitive heuristics. PMID:25852528

  1. A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size.

    PubMed

    Bond, Jacquelyn; Roberts, Emma; Springell, Kelly; Lizarraga, Sofia B; Lizarraga, Sophia; Scott, Sheila; Higgins, Julie; Hampshire, Daniel J; Morrison, Ewan E; Leal, Gabriella F; Silva, Elias O; Costa, Suzana M R; Baralle, Diana; Raponi, Michela; Karbani, Gulshan; Rashid, Yasmin; Jafri, Hussain; Bennett, Christopher; Corry, Peter; Walsh, Christopher A; Woods, C Geoffrey

    2005-04-01

    Autosomal recessive primary microcephaly is a potential model in which to research genes involved in human brain growth. We show that two forms of the disorder result from homozygous mutations in the genes CDK5RAP2 and CENPJ. We found neuroepithelial expression of the genes during prenatal neurogenesis and protein localization to the spindle poles of mitotic cells, suggesting that a centrosomal mechanism controls neuron number in the developing mammalian brain. PMID:15793586

  2. GABAergic control of depression-related brain states

    PubMed Central

    Luscher, Bernhard; Fuchs, Thomas

    2016-01-01

    The GABAergic deficit hypothesis of major depressive disorders posits that reduced GABA concentration in brain, impaired function of GABAergic interneurons, altered expression and function of GABAA receptors, and changes in GABAergic transmission dictated by altered chloride homeostasis can contribute to the etiology of Major Depressive Disorder (MDD). Conversely, the hypothesis posits that the efficacy of currently used antidepressants is determined by their ability to enhance GABAergic neurotransmission. We here provide an update for corresponding evidence from studies of patients and preclinical animal models of depression. In addition, we propose an explanation for the continued lack of genetic evidence that explains the considerable heritability of MDD. Lastly, we discuss how alterations in GABAergic transmission are integral to other hypotheses of MDD that emphasize (i) the role of monoaminergic deficits, (ii) stress-based etiologies, (iii) neurotrophic deficits, and (iv) the neurotoxic and neural circuit-impairing consequences of chronic excesses of glutamate. We propose that altered GABAergic transmission serves as a common denominator of MDD that can account for all these other hypotheses and that plays a causal and common role in diverse mechanistic etiologies of depressive brain states and in the mechanism of action of current antidepressant drug therapies. PMID:25637439

  3. Mitochondrial Control by DRP1 in Brain Tumor Initiating Cells

    PubMed Central

    Xie, Qi; Wu, Qiulian; Horbinski, Craig M.; Flavahan, William A.; Yang, Kailin; Zhou, Wenchao; Dombrowski, Stephen M.; Huang, Zhi; Fang, Xiaoguang; Shi, Yu; Ferguson, Ashley N.; Kashatus, David F.; Bao, Shideng; Rich, Jeremy N.

    2015-01-01

    Brain tumor initiating cells (BTICs) coopt the neuronal high affinity GLUT3 glucose transporter to withstand metabolic stress. Here, we investigated another mechanism critical to brain metabolism, mitochondrial morphology. BTICs displayed mitochondrial fragmentation relative to non-BTICs, suggesting that BTICs have increased mitochondrial fission. The essential mediator of mitochondrial fission, dynamin-related protein 1 (DRP1), was activated in BTICs and inhibited in non-BTICs. Targeting DRP1 using RNA interference or pharmacologic inhibition induced BTIC apoptosis and inhibited tumor growth. Downstream, DRP1 activity regulated the essential metabolic stress sensor, AMP-activated protein kinase (AMPK), and AMPK targeting rescued the effects of DRP1 disruption. Cyclin-dependent kinase 5 (CDK5) phosphorylated DRP1 to increase its activity in BTICs, whereas Ca2+–calmodulin-dependent protein kinase 2 (CAMK2) inhibited DRP1 in non-BTICs, suggesting tumor cell differentiation induces a regulatory switch in mitochondrial morphology. DRP1 activation correlates with poor prognosis in glioblastoma, suggesting mitochondrial dynamics may represent a therapeutic target for BTICs. PMID:25730670

  4. GABAergic control of depression-related brain states.

    PubMed

    Luscher, Bernhard; Fuchs, Thomas

    2015-01-01

    The GABAergic deficit hypothesis of major depressive disorders (MDDs) posits that reduced γ-aminobutyric acid (GABA) concentration in brain, impaired function of GABAergic interneurons, altered expression and function of GABA(A) receptors, and changes in GABAergic transmission dictated by altered chloride homeostasis can contribute to the etiology of MDD. Conversely, the hypothesis posits that the efficacy of currently used antidepressants is determined by their ability to enhance GABAergic neurotransmission. We here provide an update for corresponding evidence from studies of patients and preclinical animal models of depression. In addition, we propose an explanation for the continued lack of genetic evidence that explains the considerable heritability of MDD. Lastly, we discuss how alterations in GABAergic transmission are integral to other hypotheses of MDD that emphasize (i) the role of monoaminergic deficits, (ii) stress-based etiologies, (iii) neurotrophic deficits, and (iv) the neurotoxic and neural circuit-impairing consequences of chronic excesses of glutamate. We propose that altered GABAergic transmission serves as a common denominator of MDD that can account for all these other hypotheses and that plays a causal and common role in diverse mechanistic etiologies of depressive brain states and in the mechanism of action of current antidepressant drug therapies. PMID:25637439

  5. Executive Control of Language in the Bilingual Brain: Integrating the Evidence from Neuroimaging to Neuropsychology

    PubMed Central

    Hervais-Adelman, Alexis Georges; Moser-Mercer, Barbara; Golestani, Narly

    2011-01-01

    In this review we will focus on delineating the neural substrates of the executive control of language in the bilingual brain, based on the existing neuroimaging, intracranial, transcranial magnetic stimulation, and neuropsychological evidence. We will also offer insights from ongoing brain-imaging studies into the development of expertise in multilingual language control. We will concentrate specifically on evidence regarding how the brain selects and controls languages for comprehension and production. This question has been addressed in a number of ways and using various tasks, including language switching during production or perception, translation, and interpretation. We will attempt to synthesize existing evidence in order to bring to light the neural substrates that are crucial to executive control of language. PMID:21954391

  6. Regional homogeneity of resting-state brain abnormalities in violent juvenile offenders: a biomarker of brain immaturity?

    PubMed

    Chen, Chen; Zhou, Jiansong; Liu, Chunhong; Witt, Katrina; Zhang, Yingdong; Jing, Bin; Li, Chun; Wang, Xiaoping; Li, Lingjiang

    2015-01-01

    The authors investigated whether male violent juvenile offenders demonstrate any differences in local functional connectivity indicative of delayed maturation of the brain that may serve as a biomarker of violence. Twenty-nine violent juvenile offenders and 28 age-matched controls were recruited. Regional homogeneity (ReHo) method was used to analyze resting-state magnetic resonance images. Violent offenders showed significantly lower ReHo values in the right caudate, right medial prefrontal cortex, and left precuneus, and higher values in the right supramarginal gyrus than the controls. These regions had both high sensitivity and specificity in distinguishing between the two groups suggesting that dysfunction in these regions can be used to correctly classify those individuals who are violent. Dysfunction in the right medial prefrontal-caudate circuit may, therefore, represent an important biomarker of violence juvenile males. PMID:25716485

  7. Network Analysis of Intrinsic Functional Brain Connectivity in Alzheimer's Disease

    PubMed Central

    Supekar, Kaustubh; Menon, Vinod; Rubin, Daniel; Musen, Mark; Greicius, Michael D.

    2008-01-01

    Functional brain networks detected in task-free (“resting-state”) functional magnetic resonance imaging (fMRI) have a small-world architecture that reflects a robust functional organization of the brain. Here, we examined whether this functional organization is disrupted in Alzheimer's disease (AD). Task-free fMRI data from 21 AD subjects and 18 age-matched controls were obtained. Wavelet analysis was applied to the fMRI data to compute frequency-dependent correlation matrices. Correlation matrices were thresholded to create 90-node undirected-graphs of functional brain networks. Small-world metrics (characteristic path length and clustering coefficient) were computed using graph analytical methods. In the low frequency interval 0.01 to 0.05 Hz, functional brain networks in controls showed small-world organization of brain activity, characterized by a high clustering coefficient and a low characteristic path length. In contrast, functional brain networks in AD showed loss of small-world properties, characterized by a significantly lower clustering coefficient (p<0.01), indicative of disrupted local connectivity. Clustering coefficients for the left and right hippocampus were significantly lower (p<0.01) in the AD group compared to the control group. Furthermore, the clustering coefficient distinguished AD participants from the controls with a sensitivity of 72% and specificity of 78%. Our study provides new evidence that there is disrupted organization of functional brain networks in AD. Small-world metrics can characterize the functional organization of the brain in AD, and our findings further suggest that these network measures may be useful as an imaging-based biomarker to distinguish AD from healthy aging. PMID:18584043

  8. Subthalamic Nucleus Deep Brain Stimulation Changes Velopharyngeal Control in Parkinson's Disease

    ERIC Educational Resources Information Center

    Hammer, Michael J.; Barlow, Steven M.; Lyons, Kelly E.; Pahwa, Rajesh

    2011-01-01

    Purpose: Adequate velopharyngeal control is essential for speech, but may be impaired in Parkinson's disease (PD). Bilateral subthalamic nucleus deep brain stimulation (STN DBS) improves limb function in PD, but the effects on velopharyngeal control remain unknown. We tested whether STN DBS would change aerodynamic measures of velopharyngeal…

  9. Glypican-1 controls brain size through regulation of fibroblast growth factor signaling in early neurogenesis

    PubMed Central

    Jen, Yi-Huei Linda; Musacchio, Michele; Lander, Arthur D

    2009-01-01

    Background Cell surface heparan sulfate proteoglycans (HSPGs) act as co-receptors for multiple families of growth factors that regulate animal cell proliferation, differentiation and patterning. Elimination of heparan sulfate during brain development is known to produce severe structural abnormalities. Here we investigate the developmental role played by one particular HSPG, glypican-1 (Gpc1), which is especially abundant on neuronal cell membranes, and is the major HSPG of the adult rodent brain. Results Mice with a null mutation in Gpc1 were generated and found to be viable and fertile. The major phenotype associated with Gpc1 loss is a highly significant reduction in brain size, with only subtle effects on brain patterning (confined to the anterior cerebellum). The brain size difference emerges very early during neurogenesis (between embryonic days 8.5 and 9.5), and remains roughly constant throughout development and adulthood. By examining markers of different signaling pathways, and the differentiation behaviors of cells in the early embryonic brain, we infer that Gpc1-/- phenotypes most likely result from a transient reduction in fibroblast growth factor (FGF) signaling. Through the analysis of compound mutants, we provide strong evidence that Fgf17 is the FGF family member through which Gpc1 controls brain size. Conclusion These data add to a growing literature that implicates the glypican family of HSPGs in organ size control. They also argue that, among heparan sulfate-dependent signaling molecules, FGFs are disproportionately sensitive to loss of HSPGs. Finally, because heterozygous Gpc1 mutant mice were found to have brain sizes half-way between homozygous and wild type, the data imply that endogenous HSPG levels quantitatively control growth factor signaling, a finding that is both novel and relevant to the general question of how the activities of co-receptors are exploited during development. PMID:19732411

  10. The Resting Brain of Alcoholics.

    PubMed

    Müller-Oehring, Eva M; Jung, Young-Chul; Pfefferbaum, Adolf; Sullivan, Edith V; Schulte, Tilman

    2015-11-01

    Chronic alcohol consumption affects multiple cognitive processes supported by far-reaching cerebral networks. To identify neurofunctional mechanisms underlying selective deficits, 27 sober alcoholics and 26 age-matched controls underwent resting-state functional magnetic resonance imaging and neuropsychological testing. Functional connectivity analysis assessed the default mode network (DMN); integrative executive control (EC), salience (SA), and attention (AT) networks; primary somatosensory, auditory, and visual (VI) input networks; and subcortical reward (RW) and emotion (EM) networks. The groups showed an extensive overlap of intrinsic connectivity in all brain networks examined, suggesting overall integrity of large-scale functional networks. Despite these similar patterns, connectivity analyses identified network-specific differences of weaker within-network connectivity and expanded connectivity to regions outside the main networks in alcoholics compared with controls. For AT and VI networks, better task performance was related to expanded connectivity in alcoholism, supporting the concept of network expansion as a neural mechanism for functional compensation. For default mode, SA, RW, and EC networks, both weaker within-network and expanded outside-network connectivity correlated with poorer performance and mood. Current smoking contributed to some of these abnormalities in connectivity. The observed pattern of resting-state connectivity might reflect neural vulnerability of intrinsic networking in alcoholics and suggests a mechanism to explain signature impairments in EM, RW evaluation, and EC ability. PMID:24935777

  11. Human Brain Expansion during Evolution Is Independent of Fire Control and Cooking.

    PubMed

    Cornélio, Alianda M; de Bittencourt-Navarrete, Ruben E; de Bittencourt Brum, Ricardo; Queiroz, Claudio M; Costa, Marcos R

    2016-01-01

    What makes humans unique? This question has fascinated scientists and philosophers for centuries and it is still a matter of intense debate. Nowadays, human brain expansion during evolution has been acknowledged to explain our empowered cognitive capabilities. The drivers for such accelerated expansion remain, however, largely unknown. In this sense, studies have suggested that the cooking of food could be a pre-requisite for the expansion of brain size in early hominins. However, this appealing hypothesis is only supported by a mathematical model suggesting that the increasing number of neurons in the brain would constrain body size among primates due to a limited amount of calories obtained from diets. Here, we show, by using a similar mathematical model, that a tradeoff between body mass and the number of brain neurons imposed by dietary constraints during hominin evolution is unlikely. Instead, the predictable number of neurons in the hominin brain varies much more in function of foraging efficiency than body mass. We also review archeological data to show that the expansion of the brain volume in the hominin lineage is described by a linear function independent of evidence of fire control, and therefore, thermal processing of food does not account for this phenomenon. Finally, we report experiments in mice showing that thermal processing of meat does not increase its caloric availability in mice. Altogether, our data indicate that cooking is neither sufficient nor necessary to explain hominin brain expansion. PMID:27199631

  12. Human Brain Expansion during Evolution Is Independent of Fire Control and Cooking

    PubMed Central

    Cornélio, Alianda M.; de Bittencourt-Navarrete, Ruben E.; de Bittencourt Brum, Ricardo; Queiroz, Claudio M.; Costa, Marcos R.

    2016-01-01

    What makes humans unique? This question has fascinated scientists and philosophers for centuries and it is still a matter of intense debate. Nowadays, human brain expansion during evolution has been acknowledged to explain our empowered cognitive capabilities. The drivers for such accelerated expansion remain, however, largely unknown. In this sense, studies have suggested that the cooking of food could be a pre-requisite for the expansion of brain size in early hominins. However, this appealing hypothesis is only supported by a mathematical model suggesting that the increasing number of neurons in the brain would constrain body size among primates due to a limited amount of calories obtained from diets. Here, we show, by using a similar mathematical model, that a tradeoff between body mass and the number of brain neurons imposed by dietary constraints during hominin evolution is unlikely. Instead, the predictable number of neurons in the hominin brain varies much more in function of foraging efficiency than body mass. We also review archeological data to show that the expansion of the brain volume in the hominin lineage is described by a linear function independent of evidence of fire control, and therefore, thermal processing of food does not account for this phenomenon. Finally, we report experiments in mice showing that thermal processing of meat does not increase its caloric availability in mice. Altogether, our data indicate that cooking is neither sufficient nor necessary to explain hominin brain expansion. PMID:27199631

  13. Vascular Basis for Brain Degeneration: Faltering Controls and Risk Factors for Dementia

    PubMed Central

    Kalaria, Raj N.

    2010-01-01

    The integrity of the vascular system is essential for the efficient functioning of the brain. Ageing related structural and functional disturbances in the macro- or microcirculation of the brain make it vulnerable to cognitive dysfunction leading to brain degeneration and dementing illness. Several faltering controls including impairment in autoregulation, neurovascular coupling, blood-brain barrier leakage, decreased cerebrospinal fluid and reduced vascular tone appear responsible for variable degrees of neurodegeneration in old age. There is ample evidence that vascular risk factors are also linked to neurodegenerative processes preceding cognitive decline and dementia. Age is the strongest risk factor for brain degeneration whether it results from vascular or neurodegenerative mechanisms or both. However, several modifiable risks such as cardiovascular disease, hypertension, dyslipidaemia, diabetes and obesity enhance the rate of cognitive decline and increase the risk of Alzheimer’s disease in particular. The ultimate accumulation of brain pathological lesions may be modified by genetic influences such as apoliopoprotein E ε4 allele and the environment. Lifestyle measures that maintain or improve cardiovascular health including consumption of healthy diets, moderate use of alcohol and implementing regular physical exercise are important factors for brain protection. PMID:21091952

  14. Brain-region–specific alterations of the trajectories of neuronal volume growth throughout the lifespan in autism

    PubMed Central

    2014-01-01

    Several morphometric studies have revealed smaller than normal neurons in the neocortex of autistic subjects. To test the hypothesis that abnormal neuronal growth is a marker of an autism-associated global encephalopathy, neuronal volumes were estimated in 16 brain regions, including various subcortical structures, Ammon’s horn, archicortex, cerebellum, and brainstem in 14 brains from individuals with autism 4 to 60 years of age and 14 age-matched control brains. This stereological study showed a significantly smaller volume of neuronal soma in 14 of 16 regions in the 4- to 8-year-old autistic brains than in the controls. Arbitrary classification revealed a very severe neuronal volume deficit in 14.3% of significantly altered structures, severe in 50%, moderate in 21.4%, and mild in 14.3% structures. This pattern suggests desynchronized neuronal growth in the interacting neuronal networks involved in the autistic phenotype. The comparative study of the autistic and control subject brains revealed that the number of structures with a significant volume deficit decreased from 14 in the 4- to 8-year-old autistic subjects to 4 in the 36- to 60-year-old. Neuronal volumes in 75% of the structures examined in the older adults with autism are comparable to neuronal volume in age-matched controls. This pattern suggests defects of neuronal growth in early childhood and delayed up-regulation of neuronal growth during adolescence and adulthood reducing neuron soma volume deficit in majority of examined regions. However, significant correction of neuron size but limited clinical improvements suggests that delayed correction does not restore functional deficits. PMID:24612906

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

    PubMed

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

    2013-11-01

    Synthetic biology has significantly advanced the design of synthetic trigger-controlled devices that can reprogram mammalian cells to interface with complex metabolic activities. In the brain, the neurotransmitter dopamine coordinates communication with target neurons via a set of dopamine receptors that control behavior associated with reward-driven learning. This dopamine transmission has recently been suggested to increase central sympathetic outflow, resulting in plasma dopamine levels that correlate with corresponding brain activities. By functionally rewiring the human dopamine receptor D1 (DRD1) via the second messenger cyclic adenosine monophosphate (cAMP) to synthetic promoters containing cAMP response element-binding protein 1(CREB1)-specific cAMP-responsive operator modules, we have designed a synthetic dopamine-sensitive transcription controller that reversibly fine-tunes specific target gene expression at physiologically relevant brain-derived plasma dopamine levels. Following implantation of circuit-transgenic human cell lines insulated by semipermeable immunoprotective microcontainers into mice, the designer device interfaced with dopamine-specific brain activities and produced a systemic expression response when the animal's reward system was stimulated by food, sexual arousal, or addictive drugs. Reward-triggered brain activities were able to remotely program peripheral therapeutic implants to produce sufficient amounts of the atrial natriuretic peptide, which reduced the blood pressure of hypertensive mice to the normal physiologic range. Seamless control of therapeutic transgenes by subconscious behavior may provide opportunities for treatment strategies of the future. PMID:24127594

  16. Brain-bladder control network: the unsolved 21st century urological mystery.

    PubMed

    Kitta, Takeya; Mitsui, Takahiko; Kanno, Yukiko; Chiba, Hiroki; Moriya, Kimihiko; Shinohara, Nobuo

    2015-04-01

    A review of functional brain imaging studies of bladder control in participants with normal control and pathological conditions. In the normal condition, bladder and urethral afferents received in the periaqueductal gray relay the information to the insula, the anterior cingulate cortex and the prefrontal cortex. During the storage phase, these superior regions control the pontine micturition center to inhibit voiding. In overactive bladder patients, brain responses are different. Cortical responses become exaggerated, especially in the anterior cingulate cortex and the supplementary motor area. That is what presumably evokes the "urgency". The supplementary motor area is activated during contraction of the pelvic floor muscles, and provides protection against incontinence. We believe that functional brain imaging studies are promising not only for the understanding of bladder dysfunction, but also as an aid to the development of therapeutic options for chronic disorders. PMID:25693685

  17. Wide-ranging alterations in the brain fatty acid complement of subjects with late Alzheimer’s disease as detected by GC-MS

    PubMed Central

    Nasaruddin, Muhammad Luqman; Hölscher, Christian; Kehoe, Patrick; Graham, Stewart Francis; Green, Brian Desmond

    2016-01-01

    Disturbed lipid metabolism is a well-established feature of human Alzheimer’s disease (AD). The present study used gas chromatography-mass spectrometry (GC-MS) analysis of fatty acid methyl esters (FAMES) to profile all detectable fatty acid (FA) species present in post-mortem neocortical tissue (Brodmann 7 region). Quantitative targeted analysis was undertaken from 29 subjects (n=15 age-matched controls; n=14 late-stage AD). GC-MS analysis of FAMES detected a total of 24 FAs and of these, 20 were fully quantifiable. The results showed significant and wide ranging elevations in AD brain FA concentrations. A total of 9 FAs were elevated in AD with cis-13,16-docosenoic acid increased most (170%; P=0.033). Intriguingly, docosahexanoic acid (DHA; C22:6) concentrations were elevated (47%; P=0.018) which conflicts with the findings of others (unaltered or decreased) in some brain regions after the onset of AD. Furthermore, our results appear to indicate that subject gender influences brain FA levels in AD subjects (but not in age-matched control subjects). Among AD subjects 7 FA species were significantly higher in males than in females. These preliminary findings pinpoint FA disturbances as potentially important in the pathology of AD. Further work is required to determine if such changes are influenced by disease severity or different types of dementia. PMID:27069549

  18. Wide-ranging alterations in the brain fatty acid complement of subjects with late Alzheimer's disease as detected by GC-MS.

    PubMed

    Nasaruddin, Muhammad Luqman; Hölscher, Christian; Kehoe, Patrick; Graham, Stewart Francis; Green, Brian Desmond

    2016-01-01

    Disturbed lipid metabolism is a well-established feature of human Alzheimer's disease (AD). The present study used gas chromatography-mass spectrometry (GC-MS) analysis of fatty acid methyl esters (FAMES) to profile all detectable fatty acid (FA) species present in post-mortem neocortical tissue (Brodmann 7 region). Quantitative targeted analysis was undertaken from 29 subjects (n=15 age-matched controls; n=14 late-stage AD). GC-MS analysis of FAMES detected a total of 24 FAs and of these, 20 were fully quantifiable. The results showed significant and wide ranging elevations in AD brain FA concentrations. A total of 9 FAs were elevated in AD with cis-13,16-docosenoic acid increased most (170%; P=0.033). Intriguingly, docosahexanoic acid (DHA; C22:6) concentrations were elevated (47%; P=0.018) which conflicts with the findings of others (unaltered or decreased) in some brain regions after the onset of AD. Furthermore, our results appear to indicate that subject gender influences brain FA levels in AD subjects (but not in age-matched control subjects). Among AD subjects 7 FA species were significantly higher in males than in females. These preliminary findings pinpoint FA disturbances as potentially important in the pathology of AD. Further work is required to determine if such changes are influenced by disease severity or different types of dementia. PMID:27069549

  19. Rewiring the Brain: Potential Role of the Premotor Cortex in Motor Control, Learning, and Recovery of Function Following Brain Injury

    PubMed Central

    Kantak, Shailesh S.; Stinear, James W.; Buch, Ethan R.; Cohen, Leonardo G.

    2016-01-01

    The brain is a plastic organ with a capability to reorganize in response to behavior and/or injury. Following injury to the motor cortex or emergent corticospinal pathways, recovery of function depends on the capacity of surviving anatomical resources to recover and repair in response to task-specific training. One such area implicated in poststroke reorganization to promote recovery of upper extremity recovery is the premotor cortex (PMC). This study reviews the role of distinct subdivisions of PMC: dorsal (PMd) and ventral (PMv) premotor cortices as critical anatomical and physiological nodes within the neural networks for the control and learning of goal-oriented reach and grasp actions in healthy individuals and individuals with stroke. Based on evidence emerging from studies of intrinsic and extrinsic connectivity, transcranial magnetic stimulation, functional neuroimaging, and experimental studies in animals and humans, the authors propose 2 distinct patterns of reorganization that differentially engage ipsilesional and contralesional PMC. Research directions that may offer further insights into the role of PMC in motor control, learning, and poststroke recovery are also proposed. This research may facilitate neuroplasticity for maximal recovery of function following brain injury. PMID:21926382

  20. Brain locations controlling the behavioral effects of chronic amphetamine intoxication.

    PubMed

    Hitzemann, R; Wu, J; Hom, D; Loh, H

    1980-01-01

    Rats were administered D-amphetamine repeatedly for 4 days. After day 1 of treatment, the amphetamine-induced increases in ambulation, rearing, and stereotyped activity were augmented. However, after 4 days treatment, the rearing and ambulatory responses became attenuated while the stereotyped activities remained augmented. Micro-injection studies revealed that both the augmentation and attenuation of nonstereotyped ambulation were generated from the nucleus accumbens. The augmentation of stereotyped behaviors was generated from the caudate nucleus. Chronically treated animals who were administered 0.7 but not 1.0 mg/kg apomorphine showed augmented behavioral response. Chronic amphetamine treatment significantly decreased (3H) spiroperidol binding in both the nucleus accumbens and caudate nucleus. However, no effect on the DA-stimulated adenyl cyclase activity was observed in either brain region. It is concluded that repeated D-amphetamine administration selectively augments and attenuates D-amphetamine-induced behaviors and that these selective effects are mediated by different dopamine systems. PMID:6162168

  1. Embryonic cerebrospinal fluid in brain development: neural progenitor control.

    PubMed

    Gato, Angel; Alonso, M Isabel; Martín, Cristina; Carnicero, Estela; Moro, José Antonio; De la Mano, Aníbal; Fernández, José M F; Lamus, Francisco; Desmond, Mary E

    2014-08-28

    Due to the effort of several research teams across the world, today we have a solid base of knowledge on the liquid contained in the brain cavities, its composition, and biological roles. Although the cerebrospinal fluid (CSF) is among the most relevant parts of the central nervous system from the physiological point of view, it seems that it is not a permanent and stable entity because its composition and biological properties evolve across life. So, we can talk about different CSFs during the vertebrate life span. In this review, we focus on the CSF in an interesting period, early in vertebrate development before the formation of the choroid plexus. This specific entity is called "embryonic CSF." Based on the structure of the compartment, CSF composition, origin and circulation, and its interaction with neuroepithelial precursor cells (the target cells) we can conclude that embryonic CSF is different from the CSF in later developmental stages and from the adult CSF. This article presents arguments that support the singularity of the embryonic CSF, mainly focusing on its influence on neural precursor behavior during development and in adult life. PMID:25165044

  2. Embryonic cerebrospinal fluid in brain development: neural progenitor control

    PubMed Central

    Gato, Angel; Alonso, M. Isabel; Martín, Cristina; Carnicero, Estela; Moro, José Antonio; De la Mano, Aníbal; Fernández, José M. F.; Lamus, Francisco; Desmond, Mary E.

    2014-01-01

    Due to the effort of several research teams across the world, today we have a solid base of knowledge on the liquid contained in the brain cavities, its composition, and biological roles. Although the cerebrospinal fluid (CSF) is among the most relevant parts of the central nervous system from the physiological point of view, it seems that it is not a permanent and stable entity because its composition and biological properties evolve across life. So, we can talk about different CSFs during the vertebrate life span. In this review, we focus on the CSF in an interesting period, early in vertebrate development before the formation of the choroid plexus. This specific entity is called “embryonic CSF.” Based on the structure of the compartment, CSF composition, origin and circulation, and its interaction with neuroepithelial precursor cells (the target cells) we can conclude that embryonic CSF is different from the CSF in later developmental stages and from the adult CSF. This article presents arguments that support the singularity of the embryonic CSF, mainly focusing on its influence on neural precursor behavior during development and in adult life. PMID:25165044

  3. Investigating Neuromagnetic Brain Responses against Chromatic Flickering Stimuli by Wavelet Entropies

    PubMed Central

    Bhagat, Mayank; Bhushan, Chitresh; Saha, Goutam; Shimjo, Shinsuke; Watanabe, Katsumi; Bhattacharya, Joydeep

    2009-01-01

    Background Photosensitive epilepsy is a type of reflexive epilepsy triggered by various visual stimuli including colourful ones. Despite the ubiquitous presence of colorful displays, brain responses against different colour combinations are not properly studied. Methodology/Principal Findings Here, we studied the photosensitivity of the human brain against three types of chromatic flickering stimuli by recording neuromagnetic brain responses (magnetoencephalogram, MEG) from nine adult controls, an unmedicated patient, a medicated patient, and two controls age-matched with patients. Dynamical complexities of MEG signals were investigated by a family of wavelet entropies. Wavelet entropy is a newly proposed measure to characterize large scale brain responses, which quantifies the degree of order/disorder associated with a multi-frequency signal response. In particular, we found that as compared to the unmedicated patient, controls showed significantly larger wavelet entropy values. We also found that Renyi entropy is the most powerful feature for the participant classification. Finally, we also demonstrated the effect of combinational chromatic sensitivity on the underlying order/disorder in MEG signals. Conclusions/Significance Our results suggest that when perturbed by potentially epileptic-triggering stimulus, healthy human brain manages to maintain a non-deterministic, possibly nonlinear state, with high degree of disorder, but an epileptic brain represents a highly ordered state which making it prone to hyper-excitation. Further, certain colour combination was found to be more threatening than other combinations. PMID:19779630

  4. The costs and benefits of brain dopamine for cognitive control.

    PubMed

    Cools, Roshan

    2016-09-01

    Cognitive control helps us attain our goals by resisting distraction and temptations. Dopaminergic drugs are well known to enhance cognitive control. However, there is great variability in the effects of dopaminergic drugs across different contexts, with beneficial effects on some tasks but detrimental effects on other tasks. The mechanisms underlying this variability across cognitive task demands remain unclear. I aim to elucidate this across-task variability in dopaminergic drug efficacy by going beyond classic models that emphasize the importance of dopamine in the prefrontal cortex for cognitive control and working memory. To this end, I build on recent advances in cognitive neuroscience that highlight a role for dopamine in cost-benefit decision making. Specifically, I reconceptualize cognitive control as involving not just prefrontal dopamine but also modulation of cost-benefit decision making by striatal dopamine. This approach will help us understand why we sometimes fail to (choose to) exert cognitive control while also identifying mechanistic factors that predict dopaminergic drug effects on cognitive control. WIREs Cogn Sci 2016, 7:317-329. doi: 10.1002/wcs.1401 For further resources related to this article, please visit the WIREs website. PMID:27507774

  5. Continuous shared control for stabilizing reaching and grasping with brain-machine interfaces.

    PubMed

    Kim, Hyun K; Biggs, S James; Schloerb, David W; Carmena, Jose M; Lebedev, Mikhail A; Nicolelis, Miguel A L; Srinivasan, Mandayam A

    2006-06-01

    Research on brain-machine interfaces (BMI's) is directed toward enabling paralyzed individuals to manipulate their environment through slave robots. Even for able-bodied individuals, using a robot to reach and grasp objects in unstructured environments can be a difficult telemanipulation task. Controlling the slave directly with neural signals instead of a hand-master adds further challenges, such as uncertainty about the intended trajectory coupled with a low update rate for the command signal. To address these challenges, a continuous shared control (CSC) paradigm is introduced for BMI where robot sensors produce reflex-like reactions to augment brain-controlled trajectories. To test the merits of this approach, CSC was implemented on a 3-degree-of-freedom robot with a gripper bearing three co-located range sensors. The robot was commanded to follow eighty-three reach-and-grasp trajectories estimated previously from the outputs of a population of neurons recorded from the brain of a monkey. Five different levels of sensor-based reflexes were tested. Weighting brain commands 70% and sensor commands 30% produced the best task performance, better than brain signals alone by more than seven-fold. Such a marked performance improvement in this test case suggests that some level of machine autonomy will be an important component of successful BMI systems in general. PMID:16761843

  6. Motor cortical control of movement speed with implications for brain-machine interface control

    PubMed Central

    Golub, Matthew D.; Yu, Byron M.; Schwartz, Andrew B.

    2014-01-01

    Motor cortex plays a substantial role in driving movement, yet the details underlying this control remain unresolved. We analyzed the extent to which movement-related information could be extracted from single-trial motor cortical activity recorded while monkeys performed center-out reaching. Using information theoretic techniques, we found that single units carry relatively little speed-related information compared with direction-related information. This result is not mitigated at the population level: simultaneously recorded population activity predicted speed with significantly lower accuracy relative to direction predictions. Furthermore, a unit-dropping analysis revealed that speed accuracy would likely remain lower than direction accuracy, even given larger populations. These results suggest that the instantaneous details of single-trial movement speed are difficult to extract using commonly assumed coding schemes. This apparent paucity of speed information takes particular importance in the context of brain-machine interfaces (BMIs), which rely on extracting kinematic information from motor cortex. Previous studies have highlighted subjects' difficulties in holding a BMI cursor stable at targets. These studies, along with our finding of relatively little speed information in motor cortex, inspired a speed-dampening Kalman filter (SDKF) that automatically slows the cursor upon detecting changes in decoded movement direction. Effectively, SDKF enhances speed control by using prevalent directional signals, rather than requiring speed to be directly decoded from neural activity. SDKF improved success rates by a factor of 1.7 relative to a standard Kalman filter in a closed-loop BMI task requiring stable stops at targets. BMI systems enabling stable stops will be more effective and user-friendly when translated into clinical applications. PMID:24717350

  7. An FDES-Based Shared Control Method for Asynchronous Brain-Actuated Robot.

    PubMed

    Liu, Rong; Wang, Yong-Xuan; Zhang, Lin

    2016-06-01

    The asynchronous brain-computer interface (BCI) offers more natural human-machine interaction. However, it is still considered insufficient to control rapid and complex sequences of movements for a robot without any advanced control method. This paper proposes a new shared controller based on the supervisory theory of fuzzy discrete event system (FDES) for brain-actuated robot control. The developed supervisory theory allows the more reliable control mode to play a dominant role in the robot control which is beneficial to reduce misoperation and improve the robustness of the system. The experimental procedures consist of real-time direct manual control and BCI control tests from ten volunteers. Both tests have shown that the proposed method significantly improves the performance and robustness of the robotic control. In an online BCI experiment, eight of the participants successfully controlled the robot to circumnavigate obstacles and reached the target with a three mental states asynchronous BCI while the other two participants failed in all the BCI control sessions. Furthermore, the FDES-based shared control method also helps to reduce the workload. It can be stated that the asynchronous BCI, in combination with FDES-based shared controller, is feasible for the real-time and robust control of robotics. PMID:26357416

  8. Effects of Parkinson's disease on brain-wave phase synchronisation and cross-modulation

    NASA Astrophysics Data System (ADS)

    Stumpf, K.; Schumann, A. Y.; Plotnik, M.; Gans, F.; Penzel, T.; Fietze, I.; Hausdorff, J. M.; Kantelhardt, J. W.

    2010-02-01

    We study the effects of Parkinson's disease (PD) on phase synchronisation and cross-modulation of instantaneous amplitudes and frequencies for brain waves during sleep. Analysing data from 40 full-night EEGs (electro-encephalograms) of ten patients with PD and ten age-matched healthy controls we find that phase synchronisation between the left and right hemisphere of the brain is characteristically reduced in patients with PD. Since there is no such difference in phase synchronisation for EEGs from the same hemisphere, our results suggest the possibility of a relation with problems in coordinated motion of left and right limbs in some patients with PD. Using the novel technique of amplitude and frequency cross-modulation analysis, relating oscillations in different EEG bands and distinguishing both positive and negative modulation, we observe an even more significant decrease in patients for several band combinations.

  9. Control of a brain-computer interface without spike sorting

    NASA Astrophysics Data System (ADS)

    Fraser, George W.; Chase, Steven M.; Whitford, Andrew; Schwartz, Andrew B.

    2009-10-01

    Two rhesus monkeys were trained to move a cursor using neural activity recorded with silicon arrays of 96 microelectrodes implanted in the primary motor cortex. We have developed a method to extract movement information from the recorded single and multi-unit activity in the absence of spike sorting. By setting a single threshold across all channels and fitting the resultant events with a spline tuning function, a control signal was extracted from this population using a Bayesian particle-filter extraction algorithm. The animals achieved high-quality control comparable to the performance of decoding schemes based on sorted spikes. Our results suggest that even the simplest signal processing is sufficient for high-quality neuroprosthetic control.

  10. Processing Words Varying in Personal Familiarity (Based on Reading and Spelling) by Poor Readers and Age-Matched and Reading-Matched Controls

    ERIC Educational Resources Information Center

    Corcos, Evelyne; Willows, Dale M.

    2009-01-01

    To evaluate whether performance differences between good and poor readers relate to reading-specific cognitive factors that result from engaging in reading activities and other experiential factors, the authors gave students in Grades 4 and 6 a perceptual identification test of words not only drawn from their personal lexicon but also varying in…

  11. Deep-brain stimulator and control of Parkinson's disease

    NASA Astrophysics Data System (ADS)

    Varadan, Vijay K.; Harbaugh, Robert; Abraham, Jose K.

    2004-07-01

    The design of a novel feedback sensor system with wireless implantable polymer MEMS sensors for detecting and wirelessly transmitting physiological data that can be used for the diagnosis and treatment of various neurological disorders, such as Parkinson's disease, epilepsy, head injury, stroke, hydrocephalus, changes in pressure, patient movements, and tremors is presented in this paper. The sensor system includes MEMS gyroscopes, accelerometers, and pressure sensors. This feedback sensor system focuses on the development and integration of implantable systems with various wireless sensors for medical applications, particularly for the Parkinson's disease. It is easy to integrate and modify the sensor network feed back system for other neurological disorders mentioned above. The monitoring and control of tremor in Parkinson's disease can be simulated on a skeleton via wireless telemetry system communicating with electroactive polymer actuator, and microsensors attached to the skeleton hand and legs. Upon sensing any abnormal motor activity which represent the characteristic rhythmic motion of a typical Parkinson's (PD) patient, these sensors will generate necessary control pulses which will be transmitted to a hat sensor system on the skeleton head. Tiny inductively coupled antennas attached to the hat sensor system can receive these control pulses, demodulate and deliver it to actuate the parts of the skeleton to control the abnormal motor activity. This feedback sensor system can further monitor and control depending on the amplitude of the abnormal motor activity. This microsystem offers cost effective means of monitoring and controlling of neurological disorders in real PD patients. Also, this network system offers a remote monitoring of the patients conditions without visiting doctors office or hospitals. The data can be monitored using PDA and can be accessed using internet (or cell phone). Cellular phone technology will allow a health care worker to be

  12. 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. PMID:24815947

  13. Brain-machine interfacing control of whole-body humanoid motion.

    PubMed

    Bouyarmane, Karim; Vaillant, Joris; Sugimoto, Norikazu; Keith, François; Furukawa, Jun-Ichiro; Morimoto, Jun

    2014-01-01

    We propose to tackle in this paper the problem of controlling whole-body humanoid robot behavior through non-invasive brain-machine interfacing (BMI), motivated by the perspective of mapping human motor control strategies to human-like mechanical avatar. Our solution is based on the adequate reduction of the controllable dimensionality of a high-DOF humanoid motion in line with the state-of-the-art possibilities of non-invasive BMI technologies, leaving the complement subspace part of the motion to be planned and executed by an autonomous humanoid whole-body motion planning and control framework. The results are shown in full physics-based simulation of a 36-degree-of-freedom humanoid motion controlled by a user through EEG-extracted brain signals generated with motor imagery task. PMID:25140134

  14. Brain-machine interfacing control of whole-body humanoid motion

    PubMed Central

    Bouyarmane, Karim; Vaillant, Joris; Sugimoto, Norikazu; Keith, François; Furukawa, Jun-ichiro; Morimoto, Jun

    2014-01-01

    We propose to tackle in this paper the problem of controlling whole-body humanoid robot behavior through non-invasive brain-machine interfacing (BMI), motivated by the perspective of mapping human motor control strategies to human-like mechanical avatar. Our solution is based on the adequate reduction of the controllable dimensionality of a high-DOF humanoid motion in line with the state-of-the-art possibilities of non-invasive BMI technologies, leaving the complement subspace part of the motion to be planned and executed by an autonomous humanoid whole-body motion planning and control framework. The results are shown in full physics-based simulation of a 36-degree-of-freedom humanoid motion controlled by a user through EEG-extracted brain signals generated with motor imagery task. PMID:25140134

  15. The norepinephrine transporter (NET) radioligand (S,S)-[18F]FMeNER-D2 shows significant decreases in NET density in the human brain in Alzheimer's disease: a post-mortem autoradiographic study.

    PubMed

    Gulyás, Balázs; Brockschnieder, Damian; Nag, Sangram; Pavlova, Elena; Kása, Péter; Beliczai, Zsuzsa; Légrádi, Adám; Gulya, Károly; Thiele, Andrea; Dyrks, Thomas; Halldin, Christer

    2010-01-01

    Earlier post-mortem histological and autoradiographic studies have indicated a reduction of cell numbers in the locus coeruleus (LC) and a corresponding decrease in norepinephrine transporter (NET) in brains obtained from Alzheimer's disease (AD) patients as compared to age-matched healthy controls. In order to test the hypothesis that the regional decrease of NET is a disease specific biomarker in AD and as such, it can be used in PET imaging studies for diagnostic considerations, regional differences in the density of NET in various anatomical structures were measured in whole hemisphere human brain slices obtained from AD patients and age-matched control subjects in a series of autoradiographic experiments using the novel selective PET radioligand for NET (S,S)-[(18)F]FMeNER-D(2). (S,S)-[(18)F]FMeNER-D(2) appears to be a useful imaging biomarker for quantifying the density of NET in various brain structures, including the LC and the thalamus wherein the highest densities are found in physiological conditions. In AD significant decreases of NET densities can be demonstrated with the radioligand in both structures as compared to age-matched controls. The decreases in AD correlate with the progress of the disease as indicated by Braak grades. As the size of the LC is below the spatial resolution of the PET scanners, but the size of the thalamus can be detected with appropriate spatial accuracy in advanced scanners, the present findings confirm our earlier observations with PET that the in vivo imaging of NET with (S,S)-[(18)F]FMeNER-D(2) in the thalamus is viable. Nevertheless, further studies are warranted to assess the usefulness of such an imaging approach for the early detection of changes in thalamic NET densities as a disease-specific biomarker and the possible use of (S,S)-[(18)F]FMeNER-D(2) as a molecular imaging biomarker in AD. PMID:20211213

  16. Development of Automatic Controller of Brain Temperature Based on the Conditions of Clinical Use

    NASA Astrophysics Data System (ADS)

    Utsuki, Tomohiko; Wakamatsu, Hidetoshi

    A new automatic controller of brain temperature was developed based on the inevitable conditions of its clinical use from the viewpoint of various kinds of feasibility, in particular, electric power consumption of less than 1,500W in ICU. The adaptive algorithm was employed to cope with individual time-varying characteristic change of patients. The controller under water-surface cooling hypothermia requires much power for the frequent regulation of the water temperature of cooling blankets. Thus, in this study, the power consumption of the controller was checked by several kinds of examinations involving the control simulation of brain temperature using a mannequin with thermal characteristics similar to that of adult patients. The required accuracy of therapeutic brain hypothermia, i.e. control deviation within ±0.1C was experimentally confirmed using “root mean square of the control error”, despite the present controller consumes less energy comparing with the one in the case of our conventional controller, where it can still keeps remaining power margin more than 300W even in the full operation. Thereby, the clinically required water temperature was also confirmed within the limit of power supply, thus its practical application is highly expected with less physical burden of medical staff inclusive of more usability and more medical cost performance.

  17. A pilot case-cohort study of brain cancer in poultry and control workers.

    PubMed

    Gandhi, S; Felini, M J; Ndetan, H; Cardarelli, K; Jadhav, S; Faramawi, M; Johnson, E S

    2014-01-01

    We conducted an exploratory study to investigate which exposures (including poultry oncogenic viruses) are associated with brain cancer in poultry workers. A total of 46,819 workers in poultry and nonpoultry plants from the same union were initially followed for mortality. Brain cancer was observed to be in excess among poultry workers. Here we report on a pilot case-cohort study with cases consisting of 26 (55%) of the 47 brain cancer deaths recorded in the cohort, and controls consisting of a random sample of the cohort (n = 124). Exposure information was obtained from telephone interviews, and brain cancer mortality risk estimated by odds ratios. Increased risk of brain cancer was associated with killing chickens, odds ratio (OR) = 5.8 (95% confidence interval, 1.2-28.3); working in a shell-fish farm, OR = 13.0 (95% CI, 1.9-84.2); and eating uncooked fish, OR = 8.2 (95% CI, 1.8-37.0). Decreased risks were observed for chicken pox illness, OR = 0.2 (95% CI, 0.1-0.6), and measles vaccination, OR = 0.2 (95% CI, 0.1-0.6). Killing chickens, an activity associated with the highest occupational exposure to poultry oncogenic viruses, was associated with brain cancer mortality, as were occupational and dietary shellfish exposures. These findings are novel. PMID:24564367

  18. Age-associated changes of brain copper, iron, and zinc in Alzheimer's disease and dementia with Lewy bodies.

    PubMed

    Graham, Stewart F; Nasaruddin, Muhammad Bin; Carey, Manus; Holscher, Christian; McGuinness, Bernadette; Kehoe, Patrick G; Love, Seth; Passmore, Peter; Elliott, Christopher T; Meharg, Andrew A; Green, Brian D

    2014-01-01

    Disease-, age-, and gender-associated changes in brain copper, iron, and zinc were assessed in postmortem neocortical tissue (Brodmann area 7) from patients with moderate Alzheimer's disease (AD) (n = 14), severe AD (n = 28), dementia with Lewy bodies (n = 15), and normal age-matched control subjects (n = 26). Copper was lower (20%; p < 0.001) and iron higher (10-16%; p < 0.001) in severe AD compared with controls. Intriguingly significant Group*Age interactions were observed for both copper and iron, suggesting gradual age-associated decline of these metals in healthy non-cognitively impaired individuals. Zinc was unaffected in any disease pathologies and no age-associated changes were apparent. Age-associated changes in brain elements warrant further investigation. PMID:25024342

  19. Effects of specific carotid body and brain hypoxia on respiratory muscle control in the awake goat.

    PubMed Central

    Smith, C A; Engwall, M J; Dempsey, J A; Bisgard, G E

    1993-01-01

    1. We assessed the effects of specific brain hypoxia on the control of inspiratory and expiratory muscle electromyographic (EMG) activities in response to specific carotid body hypoxia in seven awake goats. We used an isolated carotid body perfusion technique that permitted specific, physiological, steady-state stimulation of the carotid bodies or maintenance of normoxia and normocapnia at the carotid bodies while varying the level of systemic, and therefore, brain oxygenation. 2. Isolated brain normocapnic hypoxia of up to 1.5 h duration increased inspired minute ventilation (VI) by means of increases in both tidal volume (VT) and respiratory frequency (fR). Electromyographic activities of both inspiratory and expiratory muscles were augmented as well. These responses were similar to those produced by low levels of whole-body normoxic hypercapnia. We conclude that moderate levels of brain hypoxia (Pa,O2 approximately 40 mmHg) in awake goats caused a net stimulation of ventilatory motor output. 3. Hypoxic stimulation of the carotid bodies alone caused comparable increases in VT and fR, and EMG augmentation of both inspiratory and expiratory muscles whether the brain was hypoxic or normoxic. These responses were quite similar to those obtained over a wide range of whole-body normoxic hypercapnia. We conclude that the integration of carotid body afferent information is not affected by moderate brain hypoxia in awake goats. 4. We found no evidence for an asymmetrical recruitment pattern of inspiratory vs. expiratory muscles in response to carotid body hypoxia or in response to brain hypoxia alone. 5. Our data support the concept that moderate brain hypoxia results in a net stimulation of respiratory motor output. These findings question the significance of 'central hypoxic depression' to the regulation of breathing under physiological levels of hypoxaemia in the awake animal. PMID:8487210

  20. Assessing brain structural associations with working-memory related brain patterns in schizophrenia and healthy controls using linked independent component analysis.

    PubMed

    Brandt, Christine Lycke; Doan, Nhat Trung; Tønnesen, Siren; Agartz, Ingrid; Hugdahl, Kenneth; Melle, Ingrid; Andreassen, Ole A; Westlye, Lars T

    2015-01-01

    Schizophrenia (SZ) is a psychotic disorder with significant cognitive dysfunction. Abnormal brain activation during cognitive processing has been reported, both in task-positive and task-negative networks. Further, structural cortical and subcortical brain abnormalities have been documented, but little is known about how task-related brain activation is associated with brain anatomy in SZ compared to healthy controls (HC). Utilizing linked independent component analysis (LICA), a data-driven multimodal analysis approach, we investigated structure-function associations in a large sample of SZ (n = 96) and HC (n = 142). We tested for associations between task-positive (fronto-parietal) and task-negative (default-mode) brain networks derived from fMRI activation during an n-back working memory task, and brain structural measures of surface area, cortical thickness, and gray matter volume, and to what extent these associations differed in SZ compared to HC. A significant association (p < .05, corrected for multiple comparisons) was found between a component reflecting the task-positive fronto-parietal network and another component reflecting cortical thickness in fronto-temporal brain regions in SZ, indicating increased activation with increased thickness. Other structure-function associations across, between and within groups were generally moderate and significant at a nominal p-level only, with more numerous and stronger associations in SZ compared to HC. These results indicate a complex pattern of moderate associations between brain activation during cognitive processing and brain morphometry, and extend previous findings of fronto-temporal brain abnormalities in SZ by suggesting a coupling between cortical thickness of these brain regions and working memory-related brain activation. PMID:26509112

  1. Control of adult neurogenesis by programmed cell death in the mammalian brain.

    PubMed

    Ryu, Jae Ryun; Hong, Caroline Jeeyeon; Kim, Joo Yeon; Kim, Eun-Kyoung; Sun, Woong; Yu, Seong-Woon

    2016-01-01

    The presence of neural stem cells (NSCs) and the production of new neurons in the adult brain have received great attention from scientists and the public because of implications to brain plasticity and their potential use for treating currently incurable brain diseases. Adult neurogenesis is controlled at multiple levels, including proliferation, differentiation, migration, and programmed cell death (PCD). Among these, PCD is the last and most prominent process for regulating the final number of mature neurons integrated into neural circuits. PCD can be classified into apoptosis, necrosis, and autophagic cell death and emerging evidence suggests that all three may be important modes of cell death in neural stem/progenitor cells. However, the molecular mechanisms that regulate PCD and thereby impact the intricate balance between self-renewal, proliferation, and differentiation during adult neurogenesis are not well understood. In this comprehensive review, we focus on the extent, mechanism, and biological significance of PCD for the control of adult neurogenesis in the mammalian brain. The role of intrinsic and extrinsic factors in the regulation of PCD at the molecular and systems levels is also discussed. Adult neurogenesis is a dynamic process, and the signals for differentiation, proliferation, and death of neural progenitor/stem cells are closely interrelated. A better understanding of how adult neurogenesis is influenced by PCD will help lead to important insights relevant to brain health and diseases. PMID:27098178

  2. Teaching brain-machine interfaces as an alternative paradigm to neuroprosthetics control.

    PubMed

    Iturrate, Iñaki; Chavarriaga, Ricardo; Montesano, Luis; Minguez, Javier; Millán, José del R

    2015-01-01

    Brain-machine interfaces (BMI) usually decode movement parameters from cortical activity to control neuroprostheses. This requires subjects to learn to modulate their brain activity to convey all necessary information, thus imposing natural limits on the complexity of tasks that can be performed. Here we demonstrate an alternative and complementary BMI paradigm that overcomes that limitation by decoding cognitive brain signals associated with monitoring processes relevant for achieving goals. In our approach the neuroprosthesis executes actions that the subject evaluates as erroneous or correct, and exploits the brain correlates of this assessment to learn suitable motor behaviours. Results show that, after a short user's training period, this teaching BMI paradigm operated three different neuroprostheses and generalized across several targets. Our results further support that these error-related signals reflect a task-independent monitoring mechanism in the brain, making this teaching paradigm scalable. We anticipate this BMI approach to become a key component of any neuroprosthesis that mimics natural motor control as it enables continuous adaptation in the absence of explicit information about goals. Furthermore, our paradigm can seamlessly incorporate other cognitive signals and conventional neuroprosthetic approaches, invasive or non-invasive, to enlarge the range and complexity of tasks that can be accomplished. PMID:26354145

  3. Teaching brain-machine interfaces as an alternative paradigm to neuroprosthetics control

    PubMed Central

    Iturrate, Iñaki; Chavarriaga, Ricardo; Montesano, Luis; Minguez, Javier; Millán, José del R.

    2015-01-01

    Brain-machine interfaces (BMI) usually decode movement parameters from cortical activity to control neuroprostheses. This requires subjects to learn to modulate their brain activity to convey all necessary information, thus imposing natural limits on the complexity of tasks that can be performed. Here we demonstrate an alternative and complementary BMI paradigm that overcomes that limitation by decoding cognitive brain signals associated with monitoring processes relevant for achieving goals. In our approach the neuroprosthesis executes actions that the subject evaluates as erroneous or correct, and exploits the brain correlates of this assessment to learn suitable motor behaviours. Results show that, after a short user’s training period, this teaching BMI paradigm operated three different neuroprostheses and generalized across several targets. Our results further support that these error-related signals reflect a task-independent monitoring mechanism in the brain, making this teaching paradigm scalable. We anticipate this BMI approach to become a key component of any neuroprosthesis that mimics natural motor control as it enables continuous adaptation in the absence of explicit information about goals. Furthermore, our paradigm can seamlessly incorporate other cognitive signals and conventional neuroprosthetic approaches, invasive or non-invasive, to enlarge the range and complexity of tasks that can be accomplished. PMID:26354145

  4. The Association between Mild Traumatic Brain Injury History and Cognitive Control

    ERIC Educational Resources Information Center

    Pontifex, Matthew B.; O'Connor, Phillip M.; Broglio, Steven P.; Hillman, Charles H.

    2009-01-01

    The influence of multiple mild traumatic brain injuries (mTBIs) on neuroelectric and task performance indices of the cognitive control of action monitoring was assessed in individuals with and without a history of concussion. Participants completed a standard clinical neurocognitive assessment and the error-related negativity of the…

  5. Dysfunctional whole brain networks in mild cognitive impairment patients: an fMRI study

    NASA Astrophysics Data System (ADS)

    Liu, Zhenyu; Bai, Lijun; Dai, Ruwei; Zhong, Chongguang; Xue, Ting; You, Youbo; Tian, Jie

    2012-03-01

    Mild cognitive impairment (MCI) was recognized as the prodromal stage of Alzheimer's disease (AD). Recent researches have shown that cognitive and memory decline in AD patients is coupled with losses of small-world attributes. However, few studies pay attention to the characteristics of the whole brain networks in MCI patients. In the present study, we investigated the topological properties of the whole brain networks utilizing graph theoretical approaches in 16 MCI patients, compared with 18 age-matched healthy subjects as a control. Both MCI patients and normal controls showed small-world architectures, with large clustering coefficients and short characteristic path lengths. We detected significantly longer characteristic path length in MCI patients compared with normal controls at the low sparsity. The longer characteristic path lengths in MCI indicated disrupted information processing among distant brain regions. Compared with normal controls, MCI patients showed decreased nodal centrality in the brain areas of the angular gyrus, heschl gyrus, hippocampus and superior parietal gyrus, while increased nodal centrality in the calcarine, inferior occipital gyrus and superior frontal gyrus. These changes in nodal centrality suggested a widespread rewiring in MCI patients, which may be an integrated reflection of reorganization of the brain networks accompanied with the cognitive decline. Our findings may be helpful for further understanding the pathological mechanisms of MCI.

  6. Cognitive control of drug craving inhibits brain reward regions in cocaine abusers

    SciTech Connect

    Volkow, N.D.; Fowler, J.; Wang, G.J.; Telang, F.; Logan, J.; Jayne, M.; Ma, Y.; Pradhan, K.; Wong, C.T.; Swanson, J.M.

    2010-01-01

    Loss of control over drug taking is considered a hallmark of addiction and is critical in relapse. Dysfunction of frontal brain regions involved with inhibitory control may underlie this behavior. We evaluated whether addicted subjects when instructed to purposefully control their craving responses to drug-conditioned stimuli can inhibit limbic brain regions implicated in drug craving. We used PET and 2-deoxy-2[18F]fluoro-D-glucose to measure brain glucose metabolism (marker of brain function) in 24 cocaine abusers who watched a cocaine-cue video and compared brain activation with and without instructions to cognitively inhibit craving. A third scan was obtained at baseline (without video). Statistical parametric mapping was used for analysis and corroborated with regions of interest. The cocaine-cue video increased craving during the no-inhibition condition (pre 3 {+-} 3, post 6 {+-} 3; p < 0.001) but not when subjects were instructed to inhibit craving (pre 3 {+-} 2, post 3 {+-} 3). Comparisons with baseline showed visual activation for both cocaine-cue conditions and limbic inhibition (accumbens, orbitofrontal, insula, cingulate) when subjects purposefully inhibited craving (p < 0.001). Comparison between cocaine-cue conditions showed lower metabolism with cognitive inhibition in right orbitofrontal cortex and right accumbens (p < 0.005), which was associated with right inferior frontal activation (r = -0.62, p < 0.005). Decreases in metabolism in brain regions that process the predictive (nucleus accumbens) and motivational value (orbitofrontal cortex) of drug-conditioned stimuli were elicited by instruction to inhibit cue-induced craving. This suggests that cocaine abusers may retain some ability to inhibit craving and that strengthening fronto-accumbal regulation may be therapeutically beneficial in addiction.

  7. Ghrelin action in the brain controls adipocyte metabolism

    PubMed Central

    Theander-Carrillo, Claudia; Wiedmer, Petra; Cettour-Rose, Philippe; Nogueiras, Ruben; Perez-Tilve, Diego; Pfluger, Paul; Castaneda, Tamara R.; Muzzin, Patrick; Schürmann, Annette; Szanto, Ildiko; Tschöp, Matthias H.; Rohner-Jeanrenaud, Françoise

    2006-01-01

    Many homeostatic processes, including appetite and food intake, are controlled by neuroendocrine circuits involving the CNS. The CNS also directly regulates adipocyte metabolism, as we have shown here by examining central action of the orexigenic hormone ghrelin. Chronic central ghrelin infusion resulted in increases in the glucose utilization rate of white and brown adipose tissue without affecting skeletal muscle. In white adipocytes, mRNA expression of various fat storage–promoting enzymes such as lipoprotein lipase, acetyl-CoA carboxylase α, fatty acid synthase, and stearoyl-CoA desaturase–1 was markedly increased, while that of the rate-limiting step in fat oxidation, carnitine palmitoyl transferase–1α, was decreased. In brown adipocytes, central ghrelin infusion resulted in lowered expression of the thermogenesis-related mitochondrial uncoupling proteins 1 and 3. These ghrelin effects were dose dependent, occurred independently from ghrelin-induced hyperphagia, and seemed to be mediated by the sympathetic nervous system. Additionally, the expression of some fat storage enzymes was decreased in ghrelin-deficient mice, which led us to conclude that central ghrelin is of physiological relevance in the control of cell metabolism in adipose tissue. These results unravel the existence of what we believe to be a new CNS-based neuroendocrine circuit regulating metabolic homeostasis of adipose tissue. PMID:16767221

  8. Brain Diseases

    MedlinePlus

    The brain is the control center of the body. It controls thoughts, memory, speech, and movement. It regulates the function of many organs. When the brain is healthy, it works quickly and automatically. However, ...

  9. Recasting brain-machine interface design from a physical control system perspective.

    PubMed

    Zhang, Yin; Chase, Steven M

    2015-10-01

    With the goal of improving the quality of life for people suffering from various motor control disorders, brain-machine interfaces provide direct neural control of prosthetic devices by translating neural signals into control signals. These systems act by reading motor intent signals directly from the brain and using them to control, for example, the movement of a cursor on a computer screen. Over the past two decades, much attention has been devoted to the decoding problem: how should recorded neural activity be translated into the movement of the cursor? Most approaches have focused on this problem from an estimation standpoint, i.e., decoders are designed to return the best estimate of motor intent possible, under various sets of assumptions about how the recorded neural signals represent motor intent. Here we recast the decoder design problem from a physical control system perspective, and investigate how various classes of decoders lead to different types of physical systems for the subject to control. This framework leads to new interpretations of why certain types of decoders have been shown to perform better than others. These results have implications for understanding how motor neurons are recruited to perform various tasks, and may lend insight into the brain's ability to conceptualize artificial systems. PMID:26142906

  10. Does deep brain stimulation of the nucleus ventralis intermedius affect postural control and locomotion in Parkinson's disease?

    PubMed

    Pinter, M M; Murg, M; Alesch, F; Freundl, B; Helscher, R J; Binder, H

    1999-11-01

    The purpose of this study was to evaluate the effect of unilateral stimulation of the nucleus ventralis intermedius (VIM) on parkinsonian signs like postural stability and locomotion with respect to the severity of Parkinson's disease (PD). Seven patients with idiopathic PD were included in the study. Changes in visual cues on postural stability and step initiation were assessed on a fixed platform system with VIM stimulation switched either on (VIM ON) or off (VIM OFF), and compared with a control group of seven age-matched normal individuals. Sway scores (area and path) were significantly (p <0.05) higher in the parkinsonian patients with VIM OFF than with VIM ON as well as compared with the control subjects. No correlation was obtained between extent of sway scores and severity of contralateral tremor after cessation of VIM stimulation. Locomotion parameters, by contrast, were not influenced by VIM stimulation: latency until step initiation and walking-cycle time were the same among parkinsonian patients as among normal individuals, both in the presence and in the absence of VIM stimulation. In conclusion, our results indicate that tremor suppression by VIM stimulation improves postural stability. PMID:10584670

  11. Brain-machine interface control of a manipulator using small-world neural network and shared control strategy.

    PubMed

    Li, Ting; Hong, Jun; Zhang, Jinhua; Guo, Feng

    2014-03-15

    The improvement of the resolution of brain signal and the ability to control external device has been the most important goal in BMI research field. This paper describes a non-invasive brain-actuated manipulator experiment, which defined a paradigm for the motion control of a serial manipulator based on motor imagery and shared control. The techniques of component selection, spatial filtering and classification of motor imagery were involved. Small-world neural network (SWNN) was used to classify five brain states. To verify the effectiveness of the proposed classifier, we replace the SWNN classifier by a radial basis function (RBF) networks neural network, a standard multi-layered feed-forward backpropagation network (SMN) and a multi-SVM classifier, with the same features for the classification. The results also indicate that the proposed classifier achieves a 3.83% improvement over the best results of other classifiers. We proposed a shared control method consisting of two control patterns to expand the control of BMI from the software angle. The job of path building for reaching the 'end' point was designated as an assessment task. We recorded all paths contributed by subjects and picked up relevant parameters as evaluation coefficients. With the assistance of two control patterns and series of machine learning algorithms, the proposed BMI originally achieved the motion control of a manipulator in the whole workspace. According to experimental results, we confirmed the feasibility of the proposed BMI method for 3D motion control of a manipulator using EEG during motor imagery. PMID:24333753

  12. Goal selection versus process control in a brain-computer interface based on sensorimotor rhythms

    NASA Astrophysics Data System (ADS)

    Royer, Audrey S.; He, Bin

    2009-02-01

    In a brain-computer interface (BCI) utilizing a process control strategy, the signal from the cortex is used to control the fine motor details normally handled by other parts of the brain. In a BCI utilizing a goal selection strategy, the signal from the cortex is used to determine the overall end goal of the user, and the BCI controls the fine motor details. A BCI based on goal selection may be an easier and more natural system than one based on process control. Although goal selection in theory may surpass process control, the two have never been directly compared, as we are reporting here. Eight young healthy human subjects participated in the present study, three trained and five naïve in BCI usage. Scalp-recorded electroencephalograms (EEG) were used to control a computer cursor during five different paradigms. The paradigms were similar in their underlying signal processing and used the same control signal. However, three were based on goal selection, and two on process control. For both the trained and naïve populations, goal selection had more hits per run, was faster, more accurate (for seven out of eight subjects) and had a higher information transfer rate than process control. Goal selection outperformed process control in every measure studied in the present investigation.

  13. Brain Circuit for Cognitive Control is Shared by Task and Language Switching.

    PubMed

    De Baene, Wouter; Duyck, Wouter; Brass, Marcel; Carreiras, Manuel

    2015-09-01

    Controlling multiple languages during speech production is believed to rely on functional mechanisms that are (at least partly) shared with domain-general cognitive control in early, highly proficient bilinguals. Recent neuroimaging results have indeed suggested a certain degree of neural overlap between language control and nonverbal cognitive control in bilinguals. However, this evidence is only indirect. Direct evidence for neural overlap between language control and nonverbal cognitive control can only be provided if two prerequisites are met: Language control and nonverbal cognitive control should be compared within the same participants, and the task requirements of both conditions should be closely matched. To provide such direct evidence for the first time, we used fMRI to examine the overlap in brain activation between switch-specific activity in a linguistic switching task and a closely matched nonlinguistic switching task, within participants, in early, highly proficient Spanish-Basque bilinguals. The current findings provide direct evidence that, in these bilinguals, highly similar brain circuits are involved in language control and domain-general cognitive control. PMID:25901448

  14. Control of abdominal muscles by brain stem respiratory neurons in the cat

    NASA Technical Reports Server (NTRS)

    Miller, Alan D.; Ezure, Kazuhisa; Suzuki, Ichiro

    1985-01-01

    The nature of the control of abdominal muscles by the brain stem respiratory neurons was investigated in decerebrate unanesthetized cats. First, it was determined which of the brain stem respiratory neurons project to the lumbar cord (from which the abdominal muscles receive part of their innervation), by stimulating the neurons monopolarly. In a second part of the study, it was determined if lumbar-projecting respiratory neurons make monosynaptic connections with abdominal motoneurons; in these experiments, discriminate spontaneous spikes of antidromically acivated expiratory (E) neurons were used to trigger activity from both L1 and L2 nerves. A large projection was observed from E neurons in the caudal ventral respiratory group to the contralateral upper lumber cord. However, cross-correlation experiments found only two (out of 47 neuron pairs tested) strong monosynaptic connections between brain stem neurons and abdominal motoneurons.

  15. Responses to Vocalizations and Auditory Controls in the Human Newborn Brain

    PubMed Central

    Cristia, Alejandrina; Minagawa, Yasuyo; Dupoux, Emmanuel

    2014-01-01

    In the adult brain, speech can recruit a brain network that is overlapping with, but not identical to, that involved in perceiving non-linguistic vocalizations. Using the same stimuli that had been presented to human 4-month-olds and adults, as well as adult macaques, we sought to shed light on the cortical networks engaged when human newborns process diverse vocalization types. Near infrared spectroscopy was used to register the response of 40 newborns' perisylvian regions when stimulated with speech, human and macaque emotional vocalizations, as well as auditory controls where the formant structure was destroyed but the long-term spectrum was retained. Left fronto-temporal and parietal regions were significantly activated in the comparison of stimulation versus rest, with unclear selectivity in cortical activation. These results for the newborn brain are qualitatively and quantitatively compared with previous work on newborns, older human infants, adult humans, and adult macaques reported in previous work. PMID:25517997

  16. Brain networks governing the golf swing in professional golfers.

    PubMed

    Kim, Jin Hyun; Han, Joung Kyue; Kim, Bung-Nyun; Han, Doug Hyun

    2015-01-01

    Golf, as with most complex motor skills, requires multiple different brain functions, including attention, motor planning, coordination, calculation of timing, and emotional control. In this study we assessed the correlation between swing components and brain connectivity from the cerebellum to the cerebrum. Ten female golf players and 10 age-matched female controls were recruited. In order to determine swing consistency among participants, the standard deviation (SD) of the mean swing speed time and the SD of the mean swing angle were assessed over 30 swings. Functional brain connectivity was assessed by resting state functional MRI. Pro-golfers showed greater positive left cerebellum connectivity to the occipital lobe, temporal lobe, parietal lobe and both frontal lobes compared to controls. The SD of play scores was positively correlated with the SD of the impact angle. Constant swing speed and back swing angle in professional golfers were associated with functional connectivity (FC) between the cerebellum and parietal and frontal lobes. In addition, the constant impact angle in professional golfers was associated with improved golf scores and additional FC of the thalamus. PMID:25761601

  17. Brain tumours and exposure to pesticides: a case–control study in southwestern France

    PubMed Central

    Provost, Dorothée; Cantagrel, Anne; Lebailly, Pierre; Jaffré, Anne; Loyant, Véronique; Loiseau, Hugues; Vital, Anne; Brochard, Patrick; Baldi, Isabelle

    2007-01-01

    Background Brain tumours are often disabling and rapidly lethal; their aetiology is largely unknown. Among potential risk factors, pesticides are suspected. Objective To examine the relationship between exposure to pesticides and brain tumours in adults in a population‐based case–control study in southwestern France. Methods Between May 1999 and April 2001, 221 incident cases of brain tumours and 442 individually matched controls selected from the general population were enrolled. Histories of occupational and environmental exposures, medical and lifestyle information were collected. A cumulative index of occupational exposure to pesticides was created, based on expert review of lifelong jobs and tasks. Separate analyses were performed for gliomas and meningiomas. Results A non‐statistically significant increase in risk was found for brain tumours when all types of occupational exposure to pesticides were considered (OR = 1.29, 95% CI 0.87 to 1.91) and slightly higher but still non‐statistically significant when gliomas were considered separately (OR = 1.47, 95% CI 0.81 to 2.66). In the highest quartile of the cumulative index, a significant association was found for brain tumours (OR = 2.16, 95% CI 1.10 to 4.23) and for gliomas (OR = 3.21, 95% CI 1.13 to 9.11), but not for meningiomas. A significant increase in risk was also seen for the treatment of home plants (OR = 2.24, 95% CI 1.16 to 4.30) owing to environmental exposure to pesticides. Conclusions These data suggest that a high level of occupational exposure to pesticides might be associated with an excess risk of brain tumours, and especially of gliomas. PMID:17537748

  18. A history of optogenetics: the development of tools for controlling brain circuits with light

    PubMed Central

    2011-01-01

    Understanding how different kinds of neuron in the brain work together to implement sensations, feelings, thoughts, and movements, and how deficits in specific kinds of neuron result in brain diseases, has long been a priority in basic and clinical neuroscience. “Optogenetic” tools are genetically encoded molecules that, when targeted to specific neurons in the brain, enable their activity to be driven or silenced by light. These molecules are microbial opsins, seven-transmembrane proteins adapted from organisms found throughout the world, which react to light by transporting ions across the lipid membranes of cells in which they are genetically expressed. These tools are enabling the causal assessment of the roles that different sets of neurons play within neural circuits, and are accordingly being used to reveal how different sets of neurons contribute to the emergent computational and behavioral functions of the brain. These tools are also being explored as components of prototype neural control prosthetics capable of correcting neural circuit computations that have gone awry in brain disorders. This review gives an account of the birth of optogenetics and discusses the technology and its applications. PMID:21876722

  19. Relaxed genetic control of cortical organization in human brains compared with chimpanzees

    PubMed Central

    Gómez-Robles, Aida; Hopkins, William D.; Schapiro, Steven J.; Sherwood, Chet C.

    2015-01-01

    The study of hominin brain evolution has focused largely on the neocortical expansion and reorganization undergone by humans as inferred from the endocranial fossil record. Comparisons of modern human brains with those of chimpanzees provide an additional line of evidence to define key neural traits that have emerged in human evolution and that underlie our unique behavioral specializations. In an attempt to identify fundamental developmental differences, we have estimated the genetic bases of brain size and cortical organization in chimpanzees and humans by studying phenotypic similarities between individuals with known kinship relationships. We show that, although heritability for brain size and cortical organization is high in chimpanzees, cerebral cortical anatomy is substantially less genetically heritable than brain size in humans, indicating greater plasticity and increased environmental influence on neurodevelopment in our species. This relaxed genetic control on cortical organization is especially marked in association areas and likely is related to underlying microstructural changes in neural circuitry. A major result of increased plasticity is that the development of neural circuits that underlie behavior is shaped by the environmental, social, and cultural context more intensively in humans than in other primate species, thus providing an anatomical basis for behavioral and cognitive evolution. PMID:26627234

  20. Relaxed genetic control of cortical organization in human brains compared with chimpanzees.

    PubMed

    Gómez-Robles, Aida; Hopkins, William D; Schapiro, Steven J; Sherwood, Chet C

    2015-12-01

    The study of hominin brain evolution has focused largely on the neocortical expansion and reorganization undergone by humans as inferred from the endocranial fossil record. Comparisons of modern human brains with those of chimpanzees provide an additional line of evidence to define key neural traits that have emerged in human evolution and that underlie our unique behavioral specializations. In an attempt to identify fundamental developmental differences, we have estimated the genetic bases of brain size and cortical organization in chimpanzees and humans by studying phenotypic similarities between individuals with known kinship relationships. We show that, although heritability for brain size and cortical organization is high in chimpanzees, cerebral cortical anatomy is substantially less genetically heritable than brain size in humans, indicating greater plasticity and increased environmental influence on neurodevelopment in our species. This relaxed genetic control on cortical organization is especially marked in association areas and likely is related to underlying microstructural changes in neural circuitry. A major result of increased plasticity is that the development of neural circuits that underlie behavior is shaped by the environmental, social, and cultural context more intensively in humans than in other primate species, thus providing an anatomical basis for behavioral and cognitive evolution. PMID:26627234

  1. Development of Visual Motion Perception for Prospective Control: Brain and Behavioral Studies in Infants

    PubMed Central

    Agyei, Seth B.; van der Weel, F. R. (Ruud); van der Meer, Audrey L. H.

    2016-01-01

    During infancy, smart perceptual mechanisms develop allowing infants to judge time-space motion dynamics more efficiently with age and locomotor experience. This emerging capacity may be vital to enable preparedness for upcoming events and to be able to navigate in a changing environment. Little is known about brain changes that support the development of prospective control and about processes, such as preterm birth, that may compromise it. As a function of perception of visual motion, this paper will describe behavioral and brain studies with young infants investigating the development of visual perception for prospective control. By means of the three visual motion paradigms of occlusion, looming, and optic flow, our research shows the importance of including behavioral data when studying the neural correlates of prospective control. PMID:26903908

  2. Brain functional plasticity associated with the emergence of expertise in extreme language control.

    PubMed

    Hervais-Adelman, Alexis; Moser-Mercer, Barbara; Golestani, Narly

    2015-07-01

    We used functional magnetic resonance imaging (fMRI) to longitudinally examine brain plasticity arising from long-term, intensive simultaneous interpretation training. Simultaneous interpretation is a bilingual task with heavy executive control demands. We compared brain responses observed during simultaneous interpretation with those observed during simultaneous speech repetition (shadowing) in a group of trainee simultaneous interpreters, at the beginning and at the end of their professional training program. Age, sex and language-proficiency matched controls were scanned at similar intervals. Using multivariate pattern classification, we found distributed patterns of changes in functional responses from the first to second scan that distinguished the interpreters from the controls. We also found reduced recruitment of the right caudate nucleus during simultaneous interpretation as a result of training. Such practice-related change is consistent with decreased demands on multilingual language control as the task becomes more automatized with practice. These results demonstrate the impact of simultaneous interpretation training on the brain functional response in a cerebral structure that is not specifically linguistic, but that is known to be involved in learning, in motor control, and in a variety of domain-general executive functions. Along with results of recent studies showing functional and structural adaptations in the caudate nuclei of experts in a broad range of domains, our results underline the importance of this structure as a central node in expertise-related networks. PMID:25869858

  3. Restoration of grasp following paralysis through brain-controlled stimulation of muscles.

    PubMed

    Ethier, C; Oby, E R; Bauman, M J; Miller, L E

    2012-05-17

    Patients with spinal cord injury lack the connections between brain and spinal cord circuits that are essential for voluntary movement. Clinical systems that achieve muscle contraction through functional electrical stimulation (FES) have proven to be effective in allowing patients with tetraplegia to regain control of hand movements and to achieve a greater measure of independence in daily activities. In existing clinical systems, the patient uses residual proximal limb movements to trigger pre-programmed stimulation that causes the paralysed muscles to contract, allowing use of one or two basic grasps. Instead, we have developed an FES system in primates that is controlled by recordings made from microelectrodes permanently implanted in the brain. We simulated some of the effects of the paralysis caused by C5 or C6 spinal cord injury by injecting rhesus monkeys with a local anaesthetic to block the median and ulnar nerves at the elbow. Then, using recordings from approximately 100 neurons in the motor cortex, we predicted the intended activity of several of the paralysed muscles, and used these predictions to control the intensity of stimulation of the same muscles. This process essentially bypassed the spinal cord, restoring to the monkeys voluntary control of their paralysed muscles. This achievement is a major advance towards similar restoration of hand function in human patients through brain-controlled FES. We anticipate that in human patients, this neuroprosthesis would allow much more flexible and dexterous use of the hand than is possible with existing FES systems. PMID:22522928

  4. Restoration of grasp following paralysis through brain-controlled stimulation of muscles

    PubMed Central

    Ethier, C.; Oby, E.R.; Bauman, M.J.; Miller, L.E.

    2012-01-01

    Patients with spinal cord injury lack the connections between brain and spinal cord circuits essential for voluntary movement. Clinical systems that achieve muscle contraction through functional electrical stimulation (FES) have proven to be effective in allowing patients with tetraplegia to regain control of hand movement and to achieve a greater measure of independence in activities of daily living 1,2. In typical systems, the patient uses residual proximal limb movements to trigger pre-programmed stimulation that causes the paralyzed muscles to contract, allowing use of one or two basic grasps. Instead, we have developed, in primates, an FES system that is controlled by recordings made from microelectrodes permanently implanted in the brain. We simulated some of the effects of the paralysis caused by C5-C6 spinal cord injury 3 by injecting a local anesthetic to block the median and ulnar nerves at the elbow. Then, using recordings from approximately 100 neurons in the motor cortex, we predicted the intended activity of several of the paralyzed muscles, and used these predictions to control the intensity of stimulation of the same muscles. This process essentially bypassed the spinal cord, restoring to the monkeys voluntary control of their paralyzed muscles. This achievement represents a major advance toward similar restoration of hand function in human patients through brain-controlled FES. We anticipate that in human patients, this neuroprosthesis would allow much more flexible and dexterous use of the hand than is possible with existing FES systems. PMID:22522928

  5. Disrupted Brain Networks in the Aging HIV+ Population

    PubMed Central

    Jahanshad, Neda; Valcour, Victor G.; Nir, Talia M.; Kohannim, Omid; Busovaca, Edgar; Nicolas, Krista

    2012-01-01

    Abstract Antiretroviral therapies have become widely available, and as a result, individuals infected with the human immunodeficiency virus (HIV) are living longer, and becoming integrated into the geriatric population. Around half of the HIV+ population shows some degree of cognitive impairment, but it is unknown how their neural networks and brain connectivity compare to those of noninfected people. Here we combined magnetic resonance imaging-based cortical parcellations with high angular resolution diffusion tensor imaging tractography in 55 HIV-seropositive patients and 30 age-matched controls, to map white matter connections between cortical regions. We set out to determine selective virus-associated disruptions in the brain's structural network. All individuals in this study were aged 60–80, with full access to antiretroviral therapy. Frontal and motor connections were compromised in HIV+ individuals. HIV+ people who carried the apolipoprotein E4 allele (ApoE4) genotype—which puts them at even greater risk for neurodegeneration—showed additional network structure deficits in temporal and parietal connections. The ApoE4 genotype interacted with duration of illness. Carriers showed greater brain network inefficiencies the longer they were infected. Neural network deficiencies in HIV+ populations exceed those typical of normal aging, and are worse in those genetically predisposed to brain degeneration. This work isolates neuropathological alterations in HIV+ elders, even when treated with antiretroviral therapy. Network impairments may contribute to the neuropsychological abnormalities in elderly HIV patients, who will soon account for around half of all HIV+ adults. PMID:23240599

  6. 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

  7. Histamine Induces Alzheimer's Disease-Like Blood Brain Barrier Breach and Local Cellular Responses in Mouse Brain Organotypic Cultures.

    PubMed

    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

  8. Autonomous control for mechanically stable navigation of microscale implants in brain tissue to record neural activity.

    PubMed

    Anand, Sindhu; Kumar, Swathy Sampath; Muthuswamy, Jit

    2016-08-01

    Emerging neural prosthetics require precise positional tuning and stable interfaces with single neurons for optimal function over a lifetime. In this study, we report an autonomous control to precisely navigate microscale electrodes in soft, viscoelastic brain tissue without visual feedback. The autonomous control optimizes signal-to-noise ratio (SNR) of single neuronal recordings in viscoelastic brain tissue while maintaining quasi-static mechanical stress conditions to improve stability of the implant-tissue interface. Force-displacement curves from microelectrodes in in vivo rodent experiments are used to estimate viscoelastic parameters of the brain. Using a combination of computational models and experiments, we determined an optimal movement for the microelectrodes with bidirectional displacements of 3:2 ratio between forward and backward displacements and a inter-movement interval of 40 s for minimizing mechanical stress in the surrounding brain tissue. A regulator with the above optimal bidirectional motion for the microelectrodes in in vivo experiments resulted in significant reduction in the number of microelectrode movements (0.23 movements/min) and longer periods of stable SNR (53 % of the time) compared to a regulator using a conventional linear, unidirectional microelectrode movement (with 1.48 movements/min and stable SNR 23 % of the time). PMID:27457752

  9. Emulation of computer mouse control with a noninvasive brain-computer interface

    PubMed Central

    McFarland, Dennis J.; Krusienski, Dean J.; Sarnacki, William A.; Wolpaw, Jonathan R.

    2009-01-01

    Brain-computer interface (BCI) technology can provide nonmuscular communication and control to people who are severely paralyzed. BCIs can use noninvasive or invasive techniques for recording the brain signals that convey the user’s commands. Although noninvasive BCIs are used for simple applications, it has frequently been assumed that only invasive BCIs, which use electrodes implanted in the brain, will be able to provide multidimensional sequential control of a robotic arm or a neuroprosthesis. The present study shows that a noninvasive BCI using scalp-recorded EEG activity and an adaptive algorithm can provide people, including people with spinal cord injuries, with two-dimensional cursor movement and target selection. Multiple targets were presented around the periphery of a computer screen, with one designated as the correct target. The user’s task was to use EEG to move a cursor from the center the screen to the correct target and then to use an additional EEG feature to select the target. If the cursor reached an incorrect target, the user was instructed not to select it. Thus, this task emulated the key features of mouse operation. The results indicate that people with severe motor disabilities could use brain signals for sequential multidimensional movement and selection. PMID:18367779

  10. Traumatic Brain Injury Increases Cortical Glutamate Network Activity by Compromising GABAergic Control

    PubMed Central

    Cantu, David; Walker, Kendall; Andresen, Lauren; Taylor-Weiner, Amaro; Hampton, David; Tesco, Giuseppina; Dulla, Chris G.

    2015-01-01

    Traumatic brain injury (TBI) is a major risk factor for developing pharmaco-resistant epilepsy. Although disruptions in brain circuitry are associated with TBI, the precise mechanisms by which brain injury leads to epileptiform network activity is unknown. Using controlled cortical impact (CCI) as a model of TBI, we examined how cortical excitability and glutamatergic signaling was altered following injury. We optically mapped cortical glutamate signaling using FRET-based glutamate biosensors, while simultaneously recording cortical field potentials in acute brain slices 2–4 weeks following CCI. Cortical electrical stimulation evoked polyphasic, epileptiform field potentials and disrupted the input–output relationship in deep layers of CCI-injured cortex. High-speed glutamate biosensor imaging showed that glutamate signaling was significantly increased in the injured cortex. Elevated glutamate responses correlated with epileptiform activity, were highest directly adjacent to the injury, and spread via deep cortical layers. Immunoreactivity for markers of GABAergic interneurons were significantly decreased throughout CCI cortex. Lastly, spontaneous inhibitory postsynaptic current frequency decreased and spontaneous excitatory postsynaptic current increased after CCI injury. Our results suggest that specific cortical neuronal microcircuits may initiate and facilitate the spread of epileptiform activity following TBI. Increased glutamatergic signaling due to loss of GABAergic control may provide a mechanism by which TBI can give rise to post-traumatic epilepsy. PMID:24610117

  11. Brain Regions Affected by Impaired Control Modulate Responses to Alcohol and Smoking Cues

    PubMed Central

    Liu, Jingyu; Claus, Eric D; Calhoun, Vince D; Hutchison, Kent E

    2014-01-01

    Objective: Despite the commonly observed comorbidity of alcohol and tobacco use disorders and years of research, the mechanism underlying concurrent use of alcohol and tobacco is not yet clear. In this study, we used functional magnetic resonance imaging (fMRI) to investigate the relationship between brain responses to alcohol and smoking cues in 45 subjects with episodic drinking and regular smoking. Method: fMRI data were collected from two studies performing an alcohol-craving task and a smoking-craving task. First, we identified brain voxels significantly activated for both substance cues and then associated the activation of these voxels with various alcohol- and nicotine-dependence measures. Significant clusters (cluster-wise p < .05) correlated with behavioral assessments were extracted, and clusters identified from both cues were compared. Results: The association tests with various dependence scores showed that the loss of behavioral control subcategory in the Alcohol Dependence Scale was significantly correlated with brain activation of the posterior cingulate cortex (PCC) and right posterior insula regardless of cue types. Conclusions: Our findings suggest that the PCC and right posterior insula, each playing a role in the salience network, are affected significantly by impaired control for alcohol and in turn influence brain responses to not only alcohol but also smoking cues, providing insight to neuronal mechanisms for concurrent use or comorbidity of alcohol and nicotine dependence. PMID:25208199

  12. Cerebrospinal fluid control of neurogenesis induced by retinoic acid during early brain development.

    PubMed

    Alonso, M I; Martín, C; Carnicero, E; Bueno, D; Gato, A

    2011-07-01

    Embryonic-cerebrospinal fluid (E-CSF) plays crucial roles in early brain development including the control of neurogenesis. Although FGF2 and lipoproteins present in the E-CSF have previously been shown to be involved in neurogenesis, the main factor triggering this process remains unknown. E-CSF contains all-trans-retinol and retinol-binding protein involved in the synthesis of retinoic acid (RA), a neurogenesis inducer. In early chick embryo brain, only the mesencephalic-rombencephalic isthmus (IsO) is able to synthesize RA. Here we show that in chick embryo brain development: (1) E-CSF helps to control RA synthesis in the IsO by means of the RBP and all-trans-retinol it contains; (2) E-CSF has retinoic acid activity, which suggests it may act as a diffusion pathway for RA; and (3) the influence of E-CSF on embryonic brain neurogenesis is to a large extent due to its involvement in RA synthesis. These data help to understand neurogenesis from neural progenitor cells. PMID:21594951

  13. [Research of controlling of smart home system based on P300 brain-computer interface].

    PubMed

    Wang, Jinjia; Yang, Chengjie

    2014-08-01

    Using electroencephalogram (EEG) signal to control external devices has always been the research focus in the field of brain-computer interface (BCI). This is especially significant for those disabilities who have lost capacity of movements. In this paper, the P300-based BCI and the microcontroller-based wireless radio frequency (RF) technology are utilized to design a smart home control system, which can be used to control household appliances, lighting system, and security devices directly. Experiment results showed that the system was simple, reliable and easy to be populirised. PMID:25464783

  14. [Research of controlling of smart home system based on P300 brain-computer interface].

    PubMed

    Wang, Jinjia; Yang, Chengjie

    2014-08-01

    Using electroencephalogram (EEG) signal to control external devices has always been the research focus in the field of brain-computer interface (BCI). This is especially significant for those disabilities who have lost capacity of movements. In this paper, the P300-based BCI and the microcontroller-based wireless radio frequency (RF) technology are utilized to design a smart home control system, which can be used to control household appliances, lighting system, and security devices directly. Experiment results showed that the system was simple, reliable and easy to be populirised. PMID:25508414

  15. Multidimensional morphometric 3D MRI analyses for detecting brain abnormalities in children: impact of control population.

    PubMed

    Wilke, Marko; Rose, Douglas F; Holland, Scott K; Leach, James L

    2014-07-01

    Automated morphometric approaches are used to detect epileptogenic structural abnormalities in 3D MR images in adults, using the variance of a control population to obtain z-score maps in an individual patient. Due to the substantial changes the developing human brain undergoes, performing such analyses in children is challenging. This study investigated six features derived from high-resolution T1 datasets in four groups: normal children (1.5T or 3T data), normal clinical scans (3T data), and patients with structural brain lesions (3T data), with each n = 10. Normative control data were obtained from the NIH study on normal brain development (n = 401). We show that control group size substantially influences the captured variance, directly impacting the patient's z-scores. Interestingly, matching on gender does not seem to be beneficial, which was unexpected. Using data obtained at higher field scanners produces slightly different base rates of suprathreshold voxels, as does using clinically derived normal studies, suggesting a subtle but systematic effect of both factors. Two approaches for controlling suprathreshold voxels in a multidimensional approach (combining features and requiring a minimum cluster size) were shown to be substantial and effective in reducing this number. Finally, specific strengths and limitations of such an approach could be demonstrated in individual cases. PMID:25050423

  16. Brain MR spectroscopy in autism spectrum disorder—the GABA excitatory/inhibitory imbalance theory revisited”

    PubMed Central

    Brix, Maiken K.; Ersland, Lars; Hugdahl, Kenneth; Grüner, Renate; Posserud, Maj-Britt; Hammar, Åsa; Craven, Alexander R.; Noeske, Ralph; Evans, C. John; Walker, Hanne B.; Midtvedt, Tore; Beyer, Mona K.

    2015-01-01

    Magnetic resonance spectroscopy (MRS) from voxels placed in the left anterior cingulate cortex (ACC) was measured from 14 boys with Autism Spectrum Disorder (ASD) and 24 gender and age-matched typically developing (TD) control group. Our main aims were to compare the concentration of γ-aminobutyric acid (GABA) between the two groups, and to investigate the relationship between brain metabolites and autism symptom severity in the ASD group. We did find a significant negative correlation in the ASD group between Autism Spectrum Screening Questionnaire (ASSQ) and GABA+/Cr, which may imply that severity of symptoms in ASD is associated with differences in the level of GABA in the brain, supporting the excitatory/inhibitory (E/I) imbalance theory. However we did not find a significant difference between the two groups in GABA levels. PMID:26157380

  17. Positron Emission Tomography Reveals Abnormal Topological Organization in Functional Brain Network in Diabetic Patients

    PubMed Central

    Qiu, Xiangzhe; Zhang, Yanjun; Feng, Hongbo; Jiang, Donglang

    2016-01-01

    Recent studies have demonstrated alterations in the topological organization of structural brain networks in diabetes mellitus (DM). However, the DM-related changes in the topological properties in functional brain networks are unexplored so far. We therefore used fluoro-D-glucose positron emission tomography (FDG-PET) data to construct functional brain networks of 73 DM patients and 91 sex- and age-matched normal controls (NCs), followed by a graph theoretical analysis. We found that both DM patients and NCs had a small-world topology in functional brain network. In comparison to the NC group, the DM group was found to have significantly lower small-world index, lower normalized clustering coefficients and higher normalized characteristic path length. Moreover, for diabetic patients, the nodal centrality was significantly reduced in the right rectus, the right cuneus, the left middle occipital gyrus, and the left postcentral gyrus, and it was significantly increased in the orbitofrontal region of the left middle frontal gyrus, the left olfactory region, and the right paracentral lobule. Our results demonstrated that the diabetic brain was associated with disrupted topological organization in the functional PET network, thus providing functional evidence for the abnormalities of brain networks in DM. PMID:27303259

  18. Positron Emission Tomography Reveals Abnormal Topological Organization in Functional Brain Network in Diabetic Patients.

    PubMed

    Qiu, Xiangzhe; Zhang, Yanjun; Feng, Hongbo; Jiang, Donglang

    2016-01-01

    Recent studies have demonstrated alterations in the topological organization of structural brain networks in diabetes mellitus (DM). However, the DM-related changes in the topological properties in functional brain networks are unexplored so far. We therefore used fluoro-D-glucose positron emission tomography (FDG-PET) data to construct functional brain networks of 73 DM patients and 91 sex- and age-matched normal controls (NCs), followed by a graph theoretical analysis. We found that both DM patients and NCs had a small-world topology in functional brain network. In comparison to the NC group, the DM group was found to have significantly lower small-world index, lower normalized clustering coefficients and higher normalized characteristic path length. Moreover, for diabetic patients, the nodal centrality was significantly reduced in the right rectus, the right cuneus, the left middle occipital gyrus, and the left postcentral gyrus, and it was significantly increased in the orbitofrontal region of the left middle frontal gyrus, the left olfactory region, and the right paracentral lobule. Our results demonstrated that the diabetic brain was associated with disrupted topological organization in the functional PET network, thus providing functional evidence for the abnormalities of brain networks in DM. PMID:27303259

  19. Abnormal brain aging as a radical-related disease: A new target for nuclear medicine

    SciTech Connect

    Fujibayashi, Y.; Yamamoto, S.; Waki, A. |

    1996-05-01

    DNA damages caused by endogenously produced radicals are closely correlated with aging. Among them, mitochondrial DNA (mtDNA) deletions have been reported as a memory of DNA damage by oxygen radicals. In fact, clinical as well as experimental studies indicated the accumulation of deleted mtDNA in the brain, myocardium and son on, in aged subjects. In our previous work, radioiodinated radical trapping agent, p-iodophenyl-N-t-butylnitrone, and hypoxia imaging agent, Cu-62 diacetyl-bis-N-4-methyl-thiosemicarbazone have been developed for the diagnosis of radical-related diseases, such as ischemic, inflammation, cancer or aging. The aim of the present work was to evaluate these agents for brain aging studies. In our university, an unique animal model, a senescence accelerated model mouse (SAM), has been established. Among the various substrains, SAMP8 showing memory deterioration in its young age ({approximately}3 month) was basically evaluated as an abnormal brain aging model with mtDNA deletion. As controls, SAMR1 showing normal aging and ddY mice were used. MtDNA deletion n the brain was analyzed with polymerase-chain reaction (PCR) method, and relationship between mtDNA deletion and brain uptake of IPBN or Cu-62-ATSM was studied. In 1-3 month old SAMP8 brain, multiple mtDNa deletions were already found and their content was significantly higher than that of SAMR1 or age-matched ddY control. Thus, it was cleared that SAMP8 brain has high tendency to be attacked by endogenously produced oxygen radicals, possibly from its birth. Both IPBN and Cu-ATSM showed significantly higher accumulation in the SAMP8 brain than in the SAMR1 brain, indicating that these agents have high possibility for the early detection of abnormal brain aging as a radical-related disease.

  20. Development of Demand-Controlled Deep Brain Stimulation Techniques Based on Stochastic Phase Resetting

    NASA Astrophysics Data System (ADS)

    Tass, Peter A.

    2003-05-01

    Stimulation techniques are discussed here which make it possible to effectively desynchronize a synchronized cluster of globally coupled phase oscillators in the presence of noise. To this end composite stimuli are used which consist of a first, stronger stimulus followed by a second, weaker stimulus after a constant time delay. The first stimulus controls the dynamics of the cluster by resetting it, whereas the second stimulus desynchronizes the cluster by hitting it in a vulnerable state. The first, resetting stimulus can be a strong single pulse, a high-frequency pulse train or a low-frequency pulse train. The cluster's resynchronization can effectively be blocked by repeated administration of a composite stimulus. Demand controlled deep brain stimulation with these desynchronizing stimulation techniques is suggested for the therapy of patients suffering from tremor-dominant Parkinson's disease or essential tremor as a milder and more efficient therapy compared to the standard permanent high-frequency deep brain stimulation.

  1. Exercise therapy, cardiorespiratory fitness and their effect on brain volumes: a randomised controlled trial in patients with schizophrenia and healthy controls.

    PubMed

    Scheewe, Thomas W; van Haren, Neeltje E M; Sarkisyan, Gayane; Schnack, Hugo G; Brouwer, Rachel M; de Glint, Maria; Hulshoff Pol, Hilleke E; Backx, Frank J G; Kahn, René S; Cahn, Wiepke

    2013-07-01

    The objective of this study was to examine exercise effects on global brain volume, hippocampal volume, and cortical thickness in schizophrenia patients and healthy controls. Irrespective of diagnosis and intervention, associations between brain changes and cardiorespiratory fitness improvement were examined. Sixty-three schizophrenia patients and fifty-five healthy controls participated in this randomised controlled trial. Global brain volumes, hippocampal volume, and cortical thickness were estimated from 3-Tesla MRI scans. Cardiorespiratory fitness was assessed with a cardiopulmonary ergometer test. Subjects were assigned exercise therapy or occupational therapy (patients) and exercise therapy or life-as-usual (healthy controls) for six months 2h weekly. Exercise therapy effects were analysed for subjects who were compliant at least 50% of sessions offered. Significantly smaller baseline cerebral (grey) matter, and larger third ventricle volumes, and thinner cortex in most areas of the brain were found in patients versus controls. Exercise therapy did not affect global brain and hippocampal volume or cortical thickness in patients and controls. Cardiorespiratory fitness improvement was related to increased cerebral matter volume and lateral and third ventricle volume decrease in patients and to thickening in the left hemisphere in large areas of the frontal, temporal and cingulate cortex irrespective of diagnosis. One to 2h of exercise therapy did not elicit significant brain volume changes in patients or controls. However, cardiorespiratory fitness improvement attenuated brain volume changes in schizophrenia patients and increased thickness in large areas of the left cortex in both schizophrenia patients and healthy controls. PMID:22981376

  2. Prenatal Origins of Temperament: Fetal Growth, Brain Structure, and Inhibitory Control in Adolescence

    PubMed Central

    Schlotz, Wolff; Godfrey, Keith M.; Phillips, David I.

    2014-01-01

    Objective Individual differences in the temperamental dimension of effortful control are constitutionally based and have been associated with an adverse prenatal developmental environment, with structural brain alterations presenting a potential mechanism. We investigated this hypothesis for anatomically defined brain regions implicated in cognitive and inhibitory motor control. Methods Twenty-seven 15–16 year old participants with low, medium, or high fetal growth were selected from a longitudinal birth cohort to maximize variation and represent the full normal spectrum of fetal growth. Outcome measures were parent ratings of attention and inhibitory control, thickness and surface area of the orbitofrontal cortex (lateral (LOFC) and medial (MOFC)) and right inferior frontal gyrus (rIFG), and volumetric measures of the striatum and amygdala. Results Lower birth weight was associated with lower inhibitory control, smaller surface area of LOFC, MOFC and rIFG, lower caudate volume, and thicker MOFC. A mediation model found a significant indirect effect of birth weight on inhibitory control via caudate volume. Conclusions Our findings support a neuroanatomical mechanism underlying potential long-term consequences of an adverse fetal developmental environment for behavioral inhibitory control in adolescence and have implications for understanding putative prenatal developmental origins of externalizing behavioral problems and self-control. PMID:24802625

  3. Apoptotic markers in cultured fibroblasts correlate with brain metabolites and regional brain volume in antipsychotic-naive first-episode schizophrenia and healthy controls.

    PubMed

    Batalla, A; Bargalló, N; Gassó, P; Molina, O; Pareto, D; Mas, S; Roca, J M; Bernardo, M; Lafuente, A; Parellada, E

    2015-01-01

    Cultured fibroblasts from first-episode schizophrenia patients (FES) have shown increased susceptibility to apoptosis, which may be related to glutamate dysfunction and progressive neuroanatomical changes. Here we determine whether apoptotic markers obtained from cultured fibroblasts in FES and controls correlate with changes in brain glutamate and N-acetylaspartate (NAA) and regional brain volumes. Eleven antipsychotic-naive FES and seven age- and gender-matched controls underwent 3-Tesla magnetic resonance imaging scanning. Glutamate plus glutamine (Glx) and NAA levels were measured in the anterior cingulate (AC) and the left thalamus (LT). Hallmarks of apoptotic susceptibility (caspase-3-baseline activity, phosphatidylserine externalization and chromatin condensation) were measured in fibroblast cultures obtained from skin biopsies after inducing apoptosis with staurosporine (STS) at doses of 0.25 and 0.5 μM. Apoptotic biomarkers were correlated to brain metabolites and regional brain volume. FES and controls showed a negative correlation in the AC between Glx levels and percentages of cells with condensed chromatin (CC) after both apoptosis inductions (STS 0.5 μM: r = -0.90; P = 0.001; STS 0.25 μM: r = -0.73; P = 0.003), and between NAA and cells with CC (STS 0.5 μM induction r = -0.76; P = 0.002; STS 0.25 μM r = -0.62; P = 0.01). In addition, we found a negative correlation between percentages of cells with CC and regional brain volume in the right supratemporal cortex and post-central region (STS 0.25 and 0.5 μM; P < 0.05 family-wise error corrected (FWEc)). We reveal for the first time that peripheral markers of apoptotic susceptibility may correlate with brain metabolites, Glx and NAA, and regional brain volume in FES and controls, which is consistent with the neuroprogressive theories around the onset of the schizophrenia illness. PMID:26305477

  4. Studies on the control of 4-aminobutyrate metabolism in 'synaptosomal' and free rat brain mitochondria.

    PubMed Central

    Walsh, J M; Clark, J B

    1976-01-01

    1. The specific activities of 4-aminobutyrate aminotransferase (EC 2.6.1.19) and succinate semialdehyde dehydrogenase (EC 1.2.1.16) were significantly higher in brain mitochondria of non-synaptic origin (fraction M) than those derived from the lysis of synaptosomes (fraction SM2). 2. The metabolisms of 4-aminobutyrate in both 'free' (non-synaptic, fraction M) and 'synaptic' (fraction SM2) rat brain mitochondria was studied under various conditions. 3. It is proposed that 4-aminobutyrate enters both types of brain mitochondria by a non-carrier-mediated process. 4. The rate of 4-aminobutyrate metabolism was in all cases higher in the 'free' (fraction M) brain mitochondria than in the synaptic (fraction SM2) mitochondria, paralleling the differences in the specific activities of the 4-aminobutyrate-shunt enzymes. 5. The intramitochondrial concentration of 2-oxoglutarate appears to be an important controlling parameter in the rate of 4-aminobutyrate metabolism, since, although 2-oxoglutarate is required, high concentrations (2.5 mM) of extramitochondrial 2-oxoglutarate inhibit the formation of aspartate via the glutamate-oxaloacetate transaminase. 6. The redox state of the intramitochondrial NAD pool is also important in the control of 4-aminobutyrate metabolism; NADH exhibits competitive inhibition of 4-aminobutyrate metabolism by both mitochondrial populations with an apparent Ki of 102 muM. 7. Increased potassium concentrations stimulate 4-aminobutyrate metabolsim in the synaptic mitochondria but not in 'free' brain mitochondria. This is discussed with respect to the putative transmitter role of 4-aminobutyrate. PMID:188415

  5. Speech networks at rest and in action: interactions between functional brain networks controlling speech production

    PubMed Central

    Fuertinger, Stefan

    2015-01-01

    Speech production is one of the most complex human behaviors. Although brain activation during speaking has been well investigated, our understanding of interactions between the brain regions and neural networks remains scarce. We combined seed-based interregional correlation analysis with graph theoretical analysis of functional MRI data during the resting state and sentence production in healthy subjects to investigate the interface and topology of functional networks originating from the key brain regions controlling speech, i.e., the laryngeal/orofacial motor cortex, inferior frontal and superior temporal gyri, supplementary motor area, cingulate cortex, putamen, and thalamus. During both resting and speaking, the interactions between these networks were bilaterally distributed and centered on the sensorimotor brain regions. However, speech production preferentially recruited the inferior parietal lobule (IPL) and cerebellum into the large-scale network, suggesting the importance of these regions in facilitation of the transition from the resting state to speaking. Furthermore, the cerebellum (lobule VI) was the most prominent region showing functional influences on speech-network integration and segregation. Although networks were bilaterally distributed, interregional connectivity during speaking was stronger in the left vs. right hemisphere, which may have underlined a more homogeneous overlap between the examined networks in the left hemisphere. Among these, the laryngeal motor cortex (LMC) established a core network that fully overlapped with all other speech-related networks, determining the extent of network interactions. Our data demonstrate complex interactions of large-scale brain networks controlling speech production and point to the critical role of the LMC, IPL, and cerebellum in the formation of speech production network. PMID:25673742

  6. Speech networks at rest and in action: interactions between functional brain networks controlling speech production.

    PubMed

    Simonyan, Kristina; Fuertinger, Stefan

    2015-04-01

    Speech production is one of the most complex human behaviors. Although brain activation during speaking has been well investigated, our understanding of interactions between the brain regions and neural networks remains scarce. We combined seed-based interregional correlation analysis with graph theoretical analysis of functional MRI data during the resting state and sentence production in healthy subjects to investigate the interface and topology of functional networks originating from the key brain regions controlling speech, i.e., the laryngeal/orofacial motor cortex, inferior frontal and superior temporal gyri, supplementary motor area, cingulate cortex, putamen, and thalamus. During both resting and speaking, the interactions between these networks were bilaterally distributed and centered on the sensorimotor brain regions. However, speech production preferentially recruited the inferior parietal lobule (IPL) and cerebellum into the large-scale network, suggesting the importance of these regions in facilitation of the transition from the resting state to speaking. Furthermore, the cerebellum (lobule VI) was the most prominent region showing functional influences on speech-network integration and segregation. Although networks were bilaterally distributed, interregional connectivity during speaking was stronger in the left vs. right hemisphere, which may have underlined a more homogeneous overlap between the examined networks in the left hemisphere. Among these, the laryngeal motor cortex (LMC) established a core network that fully overlapped with all other speech-related networks, determining the extent of network interactions. Our data demonstrate complex interactions of large-scale brain networks controlling speech production and point to the critical role of the LMC, IPL, and cerebellum in the formation of speech production network. PMID:25673742

  7. Traumatic brain injury impairs small-world topology

    PubMed Central

    Pandit, Anand S.; Expert, Paul; Lambiotte, Renaud; Bonnelle, Valerie; Leech, Robert; Turkheimer, Federico E.

    2013-01-01

    Objective: We test the hypothesis that brain networks associated with cognitive function shift away from a “small-world” organization following traumatic brain injury (TBI). Methods: We investigated 20 TBI patients and 21 age-matched controls. Resting-state functional MRI was used to study functional connectivity. Graph theoretical analysis was then applied to partial correlation matrices derived from these data. The presence of white matter damage was quantified using diffusion tensor imaging. Results: Patients showed characteristic cognitive impairments as well as evidence of damage to white matter tracts. Compared to controls, the graph analysis showed reduced overall connectivity, longer average path lengths, and reduced network efficiency. A particular impact of TBI is seen on a major network hub, the posterior cingulate cortex. Taken together, these results confirm that a network critical to cognitive function shows a shift away from small-world characteristics. Conclusions: We provide evidence that key brain networks involved in supporting cognitive function become less small-world in their organization after TBI. This is likely to be the result of diffuse white matter damage, and may be an important factor in producing cognitive impairment after TBI. PMID:23596068

  8. A generalizable adaptive brain-machine interface design for control of anesthesia.

    PubMed

    Yuxiao Yang; Shanechi, Maryam M

    2015-08-01

    Brain-machine interfaces (BMIs) for closed-loop control of anesthesia have the potential to automatically monitor and control brain states under anesthesia. Since a variety of anesthetic states are needed in different clinical scenarios, designing a generalizable BMI architecture that can control a wide range of anesthetic states is essential. In addition, drug dynamics are non-stationary over time and could change with the depth of anesthesia. Hence for precise control, a BMI needs to track these non-stationarities online. Here we design a BMI architecture that generalizes to control of various anesthetic states and their associated neural signatures, and is adaptive to time-varying drug dynamics. We provide a systematic approach to build general parametric models that quantify the anesthetic state and describe the drug dynamics. Based on these models, we develop an adaptive closed-loop controller within the framework of stochastic optimal feedback control. This controller tracks the non-stationarities in drug dynamics, achieves tight control in a time-varying environment, and removes the need for an offline system identification session. For robustness, the BMI also ensures small drug infusion rate variations at steady state. We test the BMI architecture for control of two common anesthetic states, i.e., burst suppression in medically-induced coma and unconsciousness in general anesthesia. Using numerical experiments, we find that the BMI generalizes to control of both these anesthetic states; in a time-varying environment, even without initial knowledge of model parameters, the BMI accurately controls these two different anesthetic states, reducing bias and error more than 70 times and 9 times, respectively, compared with a non-adaptive system. PMID:26736457

  9. Examination of blood-brain barrier permeability in dementia of the Alzheimer type with (68Ga)EDTA and positron emission tomography

    SciTech Connect

    Schlageter, N.L.; Carson, R.E.; Rapoport, S.I.

    1987-02-01

    Positron emission tomography with (/sup 68/Ga)ethylenediaminetetraacetic acid ((/sup 68/Ga)EDTA) was used to examine the integrity of the blood-brain barrier (BBB) in five patients with dementia of the Alzheimer type and in five healthy age-matched controls. Within a scanning time of 90 min, there was no evidence that measurable intravascular tracer entered the brain in either the dementia or the control group. An upper limit for the cerebrovascular permeability-surface area product of (68Ga)EDTA was estimated as 2 X 10(-6) s-1 in both groups. The results provide no evidence for breakdown of the BBB in patients with dementia of the Alzheimer type.

  10. Can ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer's disease.

    PubMed

    Cunnane, Stephen C; Courchesne-Loyer, Alexandre; St-Pierre, Valérie; Vandenberghe, Camille; Pierotti, Tyler; Fortier, Mélanie; Croteau, Etienne; Castellano, Christian-Alexandre

    2016-03-01

    Brain glucose uptake is impaired in Alzheimer's disease (AD). A key question is whether cognitive decline can be delayed if this brain energy defect is at least partly corrected or bypassed early in the disease. The principal ketones (also called ketone bodies), β-hydroxybutyrate and acetoacetate, are the brain's main physiological alternative fuel to glucose. Three studies in mild-to-moderate AD have shown that, unlike with glucose, brain ketone uptake is not different from that in healthy age-matched controls. Published clinical trials demonstrate that increasing ketone availability to the brain via moderate nutritional ketosis has a modest beneficial effect on cognitive outcomes in mild-to-moderate AD and in mild cognitive impairment. Nutritional ketosis can be safely achieved by a high-fat ketogenic diet, by supplements providing 20-70 g/day of medium-chain triglycerides containing the eight- and ten-carbon fatty acids octanoate and decanoate, or by ketone esters. Given the acute dependence of the brain on its energy supply, it seems reasonable that the development of therapeutic strategies aimed at AD mandates consideration of how the underlying problem of deteriorating brain fuel supply can be corrected or delayed. PMID:26766547

  11. Control of a humanoid robot by a noninvasive brain-computer interface in humans.

    PubMed

    Bell, Christian J; Shenoy, Pradeep; Chalodhorn, Rawichote; Rao, Rajesh P N

    2008-06-01

    We describe a brain-computer interface for controlling a humanoid robot directly using brain signals obtained non-invasively from the scalp through electroencephalography (EEG). EEG has previously been used for tasks such as controlling a cursor and spelling a word, but it has been regarded as an unlikely candidate for more complex forms of control owing to its low signal-to-noise ratio. Here we show that by leveraging advances in robotics, an interface based on EEG can be used to command a partially autonomous humanoid robot to perform complex tasks such as walking to specific locations and picking up desired objects. Visual feedback from the robot's cameras allows the user to select arbitrary objects in the environment for pick-up and transport to chosen locations. Results from a study involving nine users indicate that a command for the robot can be selected from four possible choices in 5 s with 95% accuracy. Our results demonstrate that an EEG-based brain-computer interface can be used for sophisticated robotic interaction with the environment, involving not only navigation as in previous applications but also manipulation and transport of objects. PMID:18483450

  12. 3D Data Mapping and Real-Time Experiment Control and Visualization in Brain Slices.

    PubMed

    Navarro, Marco A; Hibbard, Jaime V K; Miller, Michael E; Nivin, Tyler W; Milescu, Lorin S

    2015-10-20

    Here, we propose two basic concepts that can streamline electrophysiology and imaging experiments in brain slices and enhance data collection and analysis. The first idea is to interface the experiment with a software environment that provides a 3D scene viewer in which the experimental rig, the brain slice, and the recorded data are represented to scale. Within the 3D scene viewer, the user can visualize a live image of the sample and 3D renderings of the recording electrodes with real-time position feedback. Furthermore, the user can control the instruments and visualize their status in real time. The second idea is to integrate multiple types of experimental data into a spatial and temporal map of the brain slice. These data may include low-magnification maps of the entire brain slice, for spatial context, or any other type of high-resolution structural and functional image, together with time-resolved electrical and optical signals. The entire data collection can be visualized within the 3D scene viewer. These concepts can be applied to any other type of experiment in which high-resolution data are recorded within a larger sample at different spatial and temporal coordinates. PMID:26488641

  13. Brain-derived neurotrophic factor reduces amyloidogenic processing through control of SORLA gene expression.

    PubMed

    Rohe, Michael; Synowitz, Michael; Glass, Rainer; Paul, Steven M; Nykjaer, Anders; Willnow, Thomas E

    2009-12-01

    Sorting protein-related receptor with A-type repeats (SORLA) is a major risk factor in cellular processes leading to Alzheimer's disease (AD). It acts as sorting receptor for the amyloid precursor protein (APP) that regulates intracellular trafficking and processing into amyloidogenic-beta peptides (A beta). Overexpression of SORLA in neurons reduces while inactivation of gene expression (as in knock-out mouse models) accelerates amyloidogenic processing and senile plaque formation. The current study aimed at identifying molecular pathways that control SORLA gene transcription in vivo and that may contribute to low levels of receptor expression in the brain of patients with AD. Using screening approaches in primary neurons, we identified brain-derived neurotrophic factor (BDNF) as a major inducer of Sorla that activates receptor gene transcription through the ERK (extracellular regulated kinase) pathway. In line with a physiological role as regulator of Sorla, expression of the receptor is significantly impaired in mouse models with genetic (Bdnf(-/-)) or disease-related loss of BDNF activity in the brain (Huntington's disease). Intriguingly, exogenous application of BDNF reduced A beta production in primary neurons and in the brain of wild-type mice in vivo, but not in animals genetically deficient for Sorla. These findings demonstrate that the beneficial effects ascribed to BDNF in APP metabolism act through induction of Sorla that encodes a negative regulator of neuronal APP processing. PMID:20007471

  14. 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

  15. Homeostasis of Brain Dynamics in Epilepsy: A Feedback Control Systems Perspective of Seizures

    PubMed Central

    Chakravarthy, Niranjan; Tsakalis, Kostas; Sabesan, Shivkumar; Iasemidis, Leon

    2010-01-01

    In an effort to understand basic functional mechanisms that can produce epileptic seizures, some key features are introduced in coupled lumped-parameter neural population models that produce “seizure”-like events and dynamics similar to the ones during the route of the epileptic brain towards seizures. In these models, modified from existing ones in the literature, internal feedback mechanisms are incorporated to maintain the normal low level of synchronous behavior in the presence of coupling variations. While the internal feedback is developed using basic feedback systems principles, it is also functionally equivalent to actual neurophysiological mechanisms such as homeostasis that act to maintain normal activity in neural systems that are subject to extrinsic and intrinsic perturbations. Here it is hypothesized that a plausible cause of seizures is a pathology in the internal feedback action; normal internal feedback quickly regulates an abnormally high coupling between the neural populations, whereas pathological internal feedback can lead to “seizure”-like high amplitude oscillations. Several external seizure-control paradigms, that act to achieve the operational objective of maintaining normal levels of synchronous behavior, are also developed and tested in this paper. In particular, closed-loop “modulating” control with predefined stimuli, and closed-loop feedback decoupling control are considered. Among these, feedback decoupling control is the consistently successful and robust seizure-control strategy. The proposed model and remedies are consistent with a variety of recent observations in the human and animal epileptic brain, and with theories from nonlinear systems, adaptive systems, optimization, and neurophysiology. The results from the analysis of these models have two key implications, namely, developing a basic theory for epilepsy and other brain disorders, and the development of a robust seizure-control device through electrical

  16. Brain limbic system-based intelligent controller application to lane change manoeuvre

    NASA Astrophysics Data System (ADS)

    Kim, Changwon; Langari, Reza

    2011-12-01

    This paper presents the application of a novel neuromorphic control strategy for lane change manoeuvres in the highway environment. The lateral dynamics of a vehicle with and without wind disturbance are derived and utilised to implement a control strategy based on the brain limbic system. To show the robustness of the proposed controller, several disturbance conditions including wind, uncertainty in the cornering stiffness, and changes in the vehicle mass are investigated. To demonstrate the performance of the suggested strategy, simulation results of the proposed method are compared with the human driver model-based control scheme, which has been discussed in the literature. The simulation results demonstrate the superiority of the proposed controller in energy efficiency, driving comfort, and robustness.

  17. Simultaneous interpreters vs. professional multilingual controls: Group differences in cognitive control as well as brain structure and function.

    PubMed

    Becker, Maxi; Schubert, Torsten; Strobach, Tilo; Gallinat, Jürgen; Kühn, Simone

    2016-07-01

    There is a vast amount of literature indicating that multiple language expertise leads to positive transfer effects onto other non-language cognitive domains possibly due to enhanced cognitive control. However, there is hardly any evidence about underlying mechanisms on how complex behavior like simultaneous interpreting benefits cognitive functioning in other non-language domains. Therefore, we investigated whether simultaneous interpreters (SIs) exhibit cognitive benefits in tasks measuring aspects of cognitive control compared to a professional multilingual control group. We furthermore investigated in how far potential cognitive benefits are related to brain structure (using voxel-based morphometry) and function (using regions-of-interest-based functional connectivity and graph-analytical measures on low-frequency BOLD signals in resting-state brain data). Concerning cognitive control, the results reveal that SIs exhibit less mixing costs in a task switching paradigm and a dual-task advantage compared to professional multilingual controls. In addition, SIs show more gray matter volume in the left frontal pole (BA 10) compared to controls. Graph theoretical analyses revealed that this region exhibits higher network values for global efficiency and degree and is functionally more strongly connected to the left inferior frontal gyrus and middle temporal gyrus in SIs compared to controls. Thus, the data provide evidence that SIs possess cognitive benefits in tasks measuring cognitive control. It is discussed in how far the central role of the left frontal pole and its stronger functional connectivity to the left inferior frontal gyrus represents a correlate of the neural mechanisms for the observed behavioral effects. PMID:27085505

  18. APOE-by-sex interactions on brain structure and metabolism in healthy elderly controls

    PubMed Central

    de Leon, Mony J; Alcolea, Daniel; Pegueroles, Jordi; Montal, Victor; Carmona-Iragui, María; Sala, Isabel; Sánchez-Saudinos, María-Belén; Antón-Aguirre, Sofía; Morenas-Rodríguez, Estrella; Camacho, Valle; Falcón, Carles; Pavía, Javier; Ros, Domènec; Clarimón, Jordi; Blesa, Rafael; Lleó, Alberto; Fortea, Juan

    2015-01-01

    Background The APOE effect on Alzheimer Disease (AD) risk is stronger in women than in men but its mechanisms have not been established. We assessed the APOE-by-sex interaction on core CSF biomarkers, brain metabolism and structure in healthy elderly control individuals (HC). Methods Cross-sectional study. HC from the Alzheimer’s Disease Neuroimaging Initiative with available CSF (n = 274) and/or 3T-MRI (n = 168) and/or a FDG-PET analyses (n = 328) were selected. CSF amyloid-β1–42 (Aβ1–42), total-tau (t-tau) and phospho-tau (p-tau181p) levels were measured by Luminex assays. We analyzed the APOE-by-sex interaction on the CSF biomarkers in an analysis of covariance (ANCOVA). FDG uptake was analyzed by SPM8 and cortical thickness (CTh) was measured by FreeSurfer. FDG and CTh difference maps were derived from interaction and group analyses. Results APOE4 carriers had lower CSF Aβ1–42 and higher CSF p-tau181p values than non-carriers, but there was no APOE-by-sex interaction on CSF biomarkers. The APOE-by-sex interaction on brain metabolism and brain structure was significant. Sex stratification showed that female APOE4 carriers presented widespread brain hypometabolism and cortical thinning compared to female non-carriers whereas male APOE4 carriers showed only a small cluster of hypometabolism and regions of cortical thickening compared to male non-carriers. Conclusions The impact of APOE4 on brain metabolism and structure is modified by sex. Female APOE4 carriers show greater hypometabolism and atrophy than male carriers. This APOE-by-sex interaction should be considered in clinical trials in preclinical AD where APOE4 status is a selection criterion. PMID:26397226

  19. Occupational risk factors for brain cancer: a population-based case-control study in Iowa.

    PubMed

    Zheng, T; Cantor, K P; Zhang, Y; Keim, S; Lynch, C F

    2001-04-01

    A number of occupations and industries have been inconsistently associated with the risk of brain cancer. To further explore possible relationships, we conducted a population-based case-control study of brain glioma in the state of Iowa, involving 375 histologically confirmed incident cases and 2434 population-based controls. Among men, the industries and/or occupations that had a significantly increased risk for employment of more than 10 years included roofing, siding, and sheet metalworking; newspaper work; rubber and plastics products, particularly tires and inner tubes; miscellaneous manufacturing industries; wholesale trade of durable goods, grain, and field beans; cleaning and building service occupations; miscellaneous mechanics and repairers; and janitors and cleaners. Subjects who worked in plumbing, heating, and air conditioning; electrical services; gasoline service stations; and military occupations also experienced a significantly increased risk. Among women, significant excess risk was observed for occupations in agricultural services and farming, apparel and textile products, electrical and electronic equipment manufacturing, various retail sales, record-keeping, and restaurant service. Workers in industries with a potential for gasoline or motor exhaust exposures experienced a non-significant excess risk of brain glioma. PMID:11322092

  20. Reconfiguration of brain network architecture to support executive control in aging.

    PubMed

    Gallen, Courtney L; Turner, Gary R; Adnan, Areeba; D'Esposito, Mark

    2016-08-01

    Aging is accompanied by declines in executive control abilities and changes in underlying brain network architecture. Here, we examined brain networks in young and older adults during a task-free resting state and an N-back task and investigated age-related changes in the modular network organization of the brain. Compared with young adults, older adults showed larger changes in network organization between resting state and task. Although young adults exhibited increased connectivity between lateral frontal regions and other network modules during the most difficult task condition, older adults also exhibited this pattern of increased connectivity during less-demanding task conditions. Moreover, the increase in between-module connectivity in older adults was related to faster task performance and greater fractional anisotropy of the superior longitudinal fasciculus. These results demonstrate that older adults who exhibit more pronounced network changes between a resting state and task have better executive control performance and greater structural connectivity of a core frontal-posterior white matter pathway. PMID:27318132

  1. Empathic control through coordinated interaction of amygdala, theory of mind and extended pain matrix brain regions.

    PubMed

    Bruneau, Emile G; Jacoby, Nir; Saxe, Rebecca

    2015-07-01

    Brain regions in the "pain matrix", can be activated by observing or reading about others in physical pain. In previous research, we found that reading stories about others' emotional suffering, by contrast, recruits a different group of brain regions mostly associated with thinking about others' minds. In the current study, we examined the neural circuits responsible for deliberately regulating empathic responses to others' pain and suffering. In Study 1, a sample of college-aged participants (n=18) read stories about physically painful and emotionally distressing events during functional magnetic resonance imaging (fMRI), while either actively empathizing with the main character or trying to remain objective. In Study 2, the same experiment was performed with professional social workers, who are chronically exposed to human suffering (n=21). Across both studies activity in the amygdala was associated with empathic regulation towards others' emotional pain, but not their physical pain. In addition, psychophysiological interaction (PPI) analysis and Granger causal modeling (GCM) showed that amygdala activity while reading about others' emotional pain was preceded by and positively coupled with activity in the theory of mind brain regions, and followed by and negatively coupled with activity in regions associated with physical pain and bodily sensations. Previous work has shown that the amygdala is critically involved in the deliberate control of self-focused distress - the current results extend the central importance of amygdala activity to the control of other-focused empathy, but only when considering others' emotional pain. PMID:25913703

  2. An exploratory case-control study of brain tumors in children.

    PubMed

    Howe, G R; Burch, J D; Chiarelli, A M; Risch, H A; Choi, B C

    1989-08-01

    An exploratory case-control study of childhood brain tumors was conducted in southern Ontario between 1977 and 1983, on 74 cases and 138 age- and sex-matched population controls. A significantly elevated risk (perhaps due to early case symptoms) was seen for skull X-rays at least 5 years prior to diagnosis, and for head or neck injuries which required medical attention. However, no evidence of an increased risk appeared for exposure to sick pets or to pesticides, maternal or paternal history of smoking, and various birth characteristics or antenatal exposure of the child, though these have previously been reported to be associated with childhood brain tumors. With respect to the hypothesis that N-nitroso compounds may be involved in the etiology of childhood brain tumors, most exposures of this type were not associated with risk, though a significant positive association was seen for consumption of beer by the mother during pregnancy, and a significant negative association was seen with consumption of fruit juice by the child. Other findings in the present study include an association with developmental problems relating to height and weight and with certain socioeconomic characteristics of the mother. Further investigation of these results in future studies is warranted. PMID:2743324

  3. Candidate Agtr2 influenced genes and pathways identified by expression profiling in the developing brain of Agtr2−/y mice

    PubMed Central

    Pawlowski, Traci L.; Heringer-Walther, Silvia; Cheng, Chun-Huai; Archie, John G.; Chen, Chin-Fu; Walther, Thomas; Srivastava, Anand K.

    2009-01-01

    Intellectual disability (ID) is a common developmental disability observed in one to three percent of the human population. A possible role for the Angiotensin II type 2 receptor (AGTR2) in brain function, affecting learning, memory, and behavior, has been suggested in humans and rodents. Mice lacking the Agtr2 gene (Agtr2−/y) showed significant impairment in their spatial memory and exhibited abnormal dendritic spine morphology. To identify Agtr2 influenced genes and pathways, we performed whole genome microarray analysis on RNA isolated from brains of Agtr2−/y and control male mice at embryonic day 15 (E15) and postnatal day one (P1). The gene expression profiles of the Agtr2−/y brain samples were significantly different when compared to profiles of the age-matched control brains. We identified 62 differently expressed genes (p ≤ 0.005) at E15 and in P1 brains of the Agtr2−/y mice. We verified the differential expression of several of these genes in brain samples using quantitative RT-PCR. Differentially expressed genes encode molecules involved in multiple cellular processes including microtubule functions associated with dendritic spine morphology. This study provides insight into Agtr2 influenced candidate genes and suggests that expression dysregulation of these genes may modulate Agtr2 actions in the brain that influences learning and memory. PMID:19501643

  4. Enhanced regional brain metabolic responses to benzodiazepines in cocaine abusers

    SciTech Connect

    Volkow, N.D.; Wang, G.J.; Fowler, J.S.

    1997-05-01

    While dopamine (DA) appears to be crucial for cocaine reinforcement, its involvement in cocaine addiction is much less clear. Using PET we have shown persistent reductions in striatal DA D2 receptors (which arc predominantly located on GABA cells) in cocaine abusers. This finding coupled to GABA`s role as an effector for DA led us to investigate if there were GABAergic abnormalities in cocaine abusers. In this study we measured regional brain metabolic responses to lorazepam, to indirectly assess GABA function (benzodiazepines facilitate GABAergic neurotransmission). Methods: The experimental subjects consisted of 12 active cocaine abusers and 32 age matched controls. Each subject underwent two PET FDG scans obtained within 1 week of each other. The first FDG scan was obtained after administration of placebo (3 cc of saline solution) given 40-50 minutes prior to FDG; and the second after administration of lorazepam (30 {mu}g/kg) given 40-50 minutes prior to FDG. The subjects were blind to the drugs received. Results: Lorazepam-induced sleepiness was significantly greater in abusers than in controls (p<0.001). Lorazepam-induced decreases in brain glucose metabolism were significantly larger in cocaine abusers than in controls. Whereas in controls whole brain metabolism decreased 13{+-}7 %, in cocaine abusers it decreased 21{+-}13 % (p < 0.05). Lorazepam-induced decrements in regional metabolism were significantly larger in striatum (p < 0.0 1), thalamus (p < 0.01) and cerebellum (p < 0.005) of cocaine abusers than of controls (ANOVA diagnosis by condition (placebo versus lorazepam) interaction effect). The only brain region for which the absolute metabolic changes-induced by lorazepam in cocaine abusers were equivalent to those in controls was the orbitofrontal cortex. These results document an accentuated sensitivity to benzodiazepines in cocaine abusers which is compatible with disrupted GABAergic function in these patients.

  5. Brain response to visual sexual stimuli in homosexual pedophiles

    PubMed Central

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

    2008-01-01

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

  6. MRI-controlled interstitial ultrasound brain therapy: An initial in-vivo study

    NASA Astrophysics Data System (ADS)

    N'Djin, W. Apoutou; Burtnyk, Mathieu; Lipsman, Nir; Bronskill, Michael; Schwartz, Michael; Kucharczyk, Walter; Chopra, Rajiv

    2012-11-01

    The recent emergence at the clinical level of minimally-invasive focal therapy such as laser-induced thermal therapy (LITT) has demonstrated promise in the management of brain metastasis [1], although control over the spatial pattern of heating is limited. Delivery of HIFU from minimally-invasive applicators enables high spatial control of the heat deposition in biological tissues, large treatment volumes and high treatment rate in well chosen conditions [2,3]. In this study, the feasibility of MRI-guided interstitial ultrasound therapy in brain was studies in-vivo in a porcine model. A prototype system originally developed for transurethral ultrasound therapy [4,5,6] was used in this study. Two burr holes of 12 mm in diameter were created in the animal's skull to allow the insertion of the therapeutic ultrasound applicator (probe) into the brain at two locations (right and left frontal lobe). A 4-element linear ultrasound transducer (f = 8 MHz) was mounted at the tip of a 25-cm linear probe (6 mm in diameter). The target boundary was traced to cover in 2D a surface compatible with the treatment of a 2 cm brain tumor. Acoustic power of each element and rotation rate of the device were adjusted in real-time based on MR-thermometry feedback control to optimize heat deposition at the target boundary [2,4,5]. Two MRT-controlled ultrasound brain treatments per animal have been performed using a maximal surface acoustic power of 10W.cm-2. In all cases, it was possible to increase accurately the temperature of the brain tissues in the targeted region over the 55°C threshold necessary for the creation of irreversible thermal lesion. Tissue changes were visible on T1w contrast-enhanced images immediately after treatment. These changes were also evident on T2w FSE images taken 2 hours after the 1st treatment and correlated well with the temperature image. On average, the targeted volume was 4.7 ± 2.3 cm3 and the 55°C treated volume was 6.7 ± 4.4 cm3. The volumetric

  7. Control of a 2 DoF robot using a brain-machine interface.

    PubMed

    Hortal, Enrique; Ubeda, Andrés; Iáñez, Eduardo; Azorín, José M

    2014-09-01

    In this paper, a non-invasive spontaneous Brain-Machine Interface (BMI) is used to control the movement of a planar robot. To that end, two mental tasks are used to manage the visual interface that controls the robot. The robot used is a PupArm, a force-controlled planar robot designed by the nBio research group at the Miguel Hernández University of Elche (Spain). Two control strategies are compared: hierarchical and directional control. The experimental test (performed by four users) consists of reaching four targets. The errors and time used during the performance of the tests are compared in both control strategies (hierarchical and directional control). The advantages and disadvantages of each method are shown after the analysis of the results. The hierarchical control allows an accurate approaching to the goals but it is slower than using the directional control which, on the contrary, is less precise. The results show both strategies are useful to control this planar robot. In the future, by adding an extra device like a gripper, this BMI could be used in assistive applications such as grasping daily objects in a realistic environment. In order to compare the behavior of the system taking into account the opinion of the users, a NASA Tasks Load Index (TLX) questionnaire is filled out after two sessions are completed. PMID:24694722

  8. Brain-Emulating Cognition and Control Architecture (BECCA) v. 0.2 beta

    2009-06-16

    BECCA is a learning and control method based on the function of the human brain. The goal behind its creation is to learn to control robots in unfamiliar environments in a way that is very robust, similar to the way that an infant learns to interact with her environment by trial and error. As of this release, this software contains an application for controlling robot hardware through a socket. The code was created so asmore » to make it extensible to new applications. It is modular, object-oriented code in which the portions of the code that are specific to one robot are easily separable from those portions that are the constant between implementations. BECCA makes very few assumptions about the robot and environment it is learning, and so is applicable to a wide range of learning and control problems.« less

  9. Cognitive control, cognitive reserve, and memory in the aging bilingual brain

    PubMed Central

    Grant, Angela; Dennis, Nancy A.; Li, Ping

    2014-01-01

    In recent years bilingualism has been linked to both advantages in executive control and positive impacts on aging. Such positive cognitive effects of bilingualism have been attributed to the increased need for language control during bilingual processing and increased cognitive reserve, respectively. However, a mechanistic explanation of how bilingual experience contributes to cognitive reserve is still lacking. The current paper proposes a new focus on bilingual memory as an avenue to explore the relationship between executive control and cognitive reserve. We argue that this focus will enhance our understanding of the functional and structural neural mechanisms underlying bilingualism-induced cognitive effects. With this perspective we discuss and integrate recent cognitive and neuroimaging work on bilingual advantage, and suggest an account that links cognitive control, cognitive reserve, and brain reserve in bilingual aging and memory. PMID:25520695

  10. Brain-computer interfaces for dissecting cognitive processes underlying sensorimotor control.

    PubMed

    Golub, Matthew D; Chase, Steven M; Batista, Aaron P; Yu, Byron M

    2016-04-01

    Sensorimotor control engages cognitive processes such as prediction, learning, and multisensory integration. Understanding the neural mechanisms underlying these cognitive processes with arm reaching is challenging because we currently record only a fraction of the relevant neurons, the arm has nonlinear dynamics, and multiple modalities of sensory feedback contribute to control. A brain-computer interface (BCI) is a well-defined sensorimotor loop with key simplifying advantages that address each of these challenges, while engaging similar cognitive processes. As a result, BCI is becoming recognized as a powerful tool for basic scientific studies of sensorimotor control. Here, we describe the benefits of BCI for basic scientific inquiries and review recent BCI studies that have uncovered new insights into the neural mechanisms underlying sensorimotor control. PMID:26796293

  11. Brain-Emulating Cognition and Control Architecture (BECCA) v. 0.2 beta

    SciTech Connect

    ROHRER, BRANDON; & MORROW, JAMES

    2009-06-16

    BECCA is a learning and control method based on the function of the human brain. The goal behind its creation is to learn to control robots in unfamiliar environments in a way that is very robust, similar to the way that an infant learns to interact with her environment by trial and error. As of this release, this software contains an application for controlling robot hardware through a socket. The code was created so as to make it extensible to new applications. It is modular, object-oriented code in which the portions of the code that are specific to one robot are easily separable from those portions that are the constant between implementations. BECCA makes very few assumptions about the robot and environment it is learning, and so is applicable to a wide range of learning and control problems.

  12. A Modified Controlled Cortical Impact Technique to Model Mild Traumatic Brain Injury Mechanics in Mice

    PubMed Central

    Chen, YungChia; Mao, Haojie; Yang, King H.; Abel, Ted; Meaney, David F.

    2014-01-01

    For the past 25 years, controlled cortical impact (CCI) has been a useful tool in traumatic brain injury (TBI) research, creating injury patterns that includes primary contusion, neuronal loss, and traumatic axonal damage. However, when CCI was first developed, very little was known on the underlying biomechanics of mild TBI. This paper uses information generated from recent computational models of mild TBI in humans to alter CCI and better reflect the biomechanical conditions of mild TBI. Using a finite element model of CCI in the mouse, we adjusted three primary features of CCI: the speed of the impact to achieve strain rates within the range associated with mild TBI, the shape, and material of the impounder to minimize strain concentrations in the brain, and the impact depth to control the peak deformation that occurred in the cortex and hippocampus. For these modified cortical impact conditions, we observed peak strains and strain rates throughout the brain were significantly reduced and consistent with estimated strains and strain rates observed in human mild TBI. We saw breakdown of the blood–brain barrier but no primary hemorrhage. Moreover, neuronal degeneration, axonal injury, and both astrocytic and microglia reactivity were observed up to 8 days after injury. Significant deficits in rotarod performance appeared early after injury, but we observed no impairment in spatial object recognition or contextual fear conditioning response 5 and 8 days after injury, respectively. Together, these data show that simulating the biomechanical conditions of mild TBI with a modified cortical impact technique produces regions of cellular reactivity and neuronal loss that coincide with only a transient behavioral impairment. PMID:24994996

  13. A combination strategy based brain-computer interface for two-dimensional movement control

    NASA Astrophysics Data System (ADS)

    Xia, Bin; Maysam, Oladazimi; Veser, Sandra; Cao, Lei; Li, Jie; Jia, Jie; Xie, Hong; Birbaumer, Niels

    2015-08-01

    Objective. Two-dimensional (2D) movement control is an important issue in brain-computer interfaces (BCIs) research because being able to move, for example, a cursor with the brain will enable patients with motor disabilities to control their environment. However, it is still a challenge to continuously control 2D movement with a non-invasive BCI system. In this paper, we developed a 2D cursor control with motor imagery BCI tasks allowing users to move a cursor to any position by using a combination strategy. With this strategy, a user can combine multiple motor imagery tasks, alternatively or simultaneously, to control 2D movements. Approach. After a training session, six participants took part in the first control strategy experiment (the center-out experiment) to verify the effectiveness of the cursor control. Three of the six participants performed an additional experiment, in which they were required to move the cursor to hit five targets in a given sequence. Main results. The average hit rate was more than 95.6% and the trajectories were close to the shortest path. The average hit rate was more than 95.6% and the trajectories were close to the shortest path in the center-out experiment. In the additional experiment, three participants achieved a 100% hit rate with a short trajectory. Significance. The results demonstrated that users were able to effectively control the 2D movement using the proposed strategy. The present system may be used as a tool to interact with the external world.

  14. A state-space framework for movement control to dynamic goals through brain-driven interfaces.

    PubMed

    Srinivasan, Lakshminarayan; Brown, Emery N

    2007-03-01

    State-space estimation is a convenient framework for the design of brain-driven interfaces, where neural activity is used to control assistive devices for individuals with severe motor deficits. Recently, state-space approaches were developed to combine goal planning and trajectory-guiding neural activity in the control of reaching movements of an assistive device to static goals. In this paper, we extend these algorithms to allow for goals that may change over the course of the reach. Performance between static and dynamic goal state equations and a standard free movement state equation is compared in simulation. Simulated trials are also used to explore the possibility of incorporating activity from parietal areas that have previously been associated with dynamic goal position. Performance is quantified using mean-square error (MSE) of trajectory estimates. We also demonstrate the use of goal estimate MSE in evaluating algorithms for the control of goal-directed movements. Finally, we propose a framework to combine sensor data and control algorithms along with neural activity and state equations, to coordinate goal-directed movements through brain-driven interfaces. PMID:17355066

  15. Using the electrocorticographic speech network to control a brain-computer interface in humans

    NASA Astrophysics Data System (ADS)

    Leuthardt, Eric C.; Gaona, Charles; Sharma, Mohit; Szrama, Nicholas; Roland, Jarod; Freudenberg, Zac; Solis, Jamie; Breshears, Jonathan; Schalk, Gerwin

    2011-06-01

    Electrocorticography (ECoG) has emerged as a new signal platform for brain-computer interface (BCI) systems. Classically, the cortical physiology that has been commonly investigated and utilized for device control in humans has been brain signals from the sensorimotor cortex. Hence, it was unknown whether other neurophysiological substrates, such as the speech network, could be used to further improve on or complement existing motor-based control paradigms. We demonstrate here for the first time that ECoG signals associated with different overt and imagined phoneme articulation can enable invasively monitored human patients to control a one-dimensional computer cursor rapidly and accurately. This phonetic content was distinguishable within higher gamma frequency oscillations and enabled users to achieve final target accuracies between 68% and 91% within 15 min. Additionally, one of the patients achieved robust control using recordings from a microarray consisting of 1 mm spaced microwires. These findings suggest that the cortical network associated with speech could provide an additional cognitive and physiologic substrate for BCI operation and that these signals can be acquired from a cortical array that is small and minimally invasive.

  16. Using the Electrocorticographic Speech Network to Control a Brain-Computer Interface in Humans

    PubMed Central

    Leuthardt, Eric C.; Gaona, Charles; Sharma, Mohit; Szrama, Nicholas; Roland, Jarod; Freudenberg, Zac; Solis, Jamie; Breshears, Jonathan; Schalk, Gerwin

    2013-01-01

    Electrocorticography (ECoG) has emerged as a new signal platform for brain-computer interface (BCI) systems. Classically, the cortical physiology that has been commonly investigated and utilized for device control in humans has been brain signals from sensorimotor cortex. Hence, it was unknown whether other neurophysiological substrates, such as the speech network, could be used to further improve on or complement existing motor-based control paradigms. We demonstrate here for the first time that ECoG signals associated with different overt and imagined phoneme articulation can enable invasively monitored human patients to control a one-dimensional computer cursor rapidly and accurately. This phonetic content was distinguishable within higher gamma frequency oscillations and enabled users to achieve final target accuracies between 68 and 91% within 15 minutes. Additionally, one of the patients achieved robust control using recordings from a microarray consisting of 1 mm spaced microwires. These findings suggest that the cortical network associated with speech could provide an additional cognitive and physiologic substrate for BCI operation and that these signals can be acquired from a cortical array that is small and minimally invasive. PMID:21471638

  17. Brain regions essential for improved lexical access in an aged aphasic patient: a case report

    PubMed Central

    Meinzer, Marcus; Flaisch, Tobias; Obleser, Jonas; Assadollahi, Ramin; Djundja, Daniela; Barthel, Gabriela; Rockstroh, Brigitte

    2006-01-01

    Background The relationship between functional recovery after brain injury and concomitant neuroplastic changes is emphasized in recent research. In the present study we aimed to delineate brain regions essential for language performance in aphasia using functional magnetic resonance imaging and acquisition in a temporal sparse sampling procedure, which allows monitoring of overt verbal responses during scanning. Case presentation An 80-year old patient with chronic aphasia (2 years post-onset) was investigated before and after intensive language training using an overt picture naming task. Differential brain activation in the right inferior frontal gyrus for correct word retrieval and errors was found. Improved language performance following therapy was mirrored by increased fronto-thalamic activation while stability in more general measures of attention/concentration and working memory was assured. Three healthy age-matched control subjects did not show behavioral changes or increased activation when tested repeatedly within the same 2-week time interval. Conclusion The results bear significance in that the changes in brain activation reported can unequivocally be attributed to the short-term training program and a language domain-specific plasticity process. Moreover, it further challenges the claim of a limited recovery potential in chronic aphasia, even at very old age. Delineation of brain regions essential for performance on a single case basis might have major implications for treatment using transcranial magnetic stimulation. PMID:16916464

  18. Brain capillaries in Alzheimer's disease.

    PubMed

    Baloyannis, Stavros J

    2015-01-01

    , silver impregnation techniques revealed a marked tortuosity of the capillaries in early cases of AD. In addition, the distance between two branch points is longer in capillaries of AD brains, whereas the branch point density as well as the ratio of the branch point density to astrocytic density is substantially decreased in AD in comparison with age matched normal controls. EM revealed, that the most frequent morphological alterations of the brain capillaries in AD consist of thickness, splitting and duplication of the basement membrane, reduction of the length of tight junctions, decrease of the number of tight junctions per vessel length, associated as a rule, with morphological alterations of the mitochondria of the endothelial cells, the pericytes and the perivascular astrocytic processes. The number of the pinocytotic vesicles is substantially increase in the endothelium of the brain capillaries in AD in comparison with age matched normal controls. Endothelial cells play a very important role in the transport systems in the brain. Subsequently, the dysfunction of the endothelial cells and the disruption of the BBB may induce serious impairment in the transport system. The dysfunction of the brain capillaries may result in releasing neurotoxic factors, such as thrombin, pro-inflammatory cytokines, nitric oxide and leukocyte adhesion molecules, and in abnormal regulation of Aβ-peptide homeostasis in the brain. The impairment of the brain capillaries in structures of the brain, which are crucial for the homeostatic equilibrium, such as the hypothalamic nuclei, may induce autonomic dysfunction, which usually occur in the advanced stages of AD, affecting dramatically the viability of the patients. Degeneration of the pericytes is also observed emphasizing even more the importance of the vascular factor in AD. Pericytes may serve as integrators, coordinators and effectors of blood-brain barrier structure and maintenance, and play a key role in microvascular stability

  19. Wnt/Notum spatial feedback inhibition controls neoblast differentiation to regulate reversible growth of the planarian brain.

    PubMed

    Hill, Eric M; Petersen, Christian P

    2015-12-15

    Mechanisms determining final organ size are poorly understood. Animals undergoing regeneration or ongoing adult growth are likely to require sustained and robust mechanisms to achieve and maintain appropriate sizes. Planarians, well known for their ability to undergo whole-body regeneration using pluripotent adult stem cells of the neoblast population, can reversibly scale body size over an order of magnitude by controlling cell number. Using quantitative analysis, we showed that after injury planarians perfectly restored brain:body proportion by increasing brain cell number through epimorphosis or decreasing brain cell number through tissue remodeling (morphallaxis), as appropriate. We identified a pathway controlling a brain size set-point that involves feedback inhibition between wnt11-6/wntA/wnt4a and notum, encoding conserved antagonistic signaling factors expressed at opposite brain poles. wnt11-6/wntA/wnt4a undergoes feedback inhibition through canonical Wnt signaling but is likely to regulate brain size in a non-canonical pathway independently of beta-catenin-1 and APC. Wnt/Notum signaling tunes numbers of differentiated brain cells in regenerative growth and tissue remodeling by influencing the abundance of brain progenitors descended from pluripotent stem cells, as opposed to regulating cell death. These results suggest that the attainment of final organ size might be accomplished by achieving a balance of positional signaling inputs that regulate the rates of tissue production. PMID:26525673

  20. Using reinforcement learning to provide stable brain-machine interface control despite neural input reorganization.

    PubMed

    Pohlmeyer, Eric A; Mahmoudi, Babak; Geng, Shijia; Prins, Noeline W; Sanchez, Justin C

    2014-01-01

    Brain-machine interface (BMI) systems give users direct neural control of robotic, communication, or functional electrical stimulation systems. As BMI systems begin transitioning from laboratory settings into activities of daily living, an important goal is to develop neural decoding algorithms that can be calibrated with a minimal burden on the user, provide stable control for long periods of time, and can be responsive to fluctuations in the decoder's neural input space (e.g. neurons appearing or being lost amongst electrode recordings). These are significant challenges for static neural decoding algorithms that assume stationary input/output relationships. Here we use an actor-critic reinforcement learning architecture to provide an adaptive BMI controller that can successfully adapt to dramatic neural reorganizations, can maintain its performance over long time periods, and which does not require the user to produce specific kinetic or kinematic activities to calibrate the BMI. Two marmoset monkeys used the Reinforcement Learning BMI (RLBMI) to successfully control a robotic arm during a two-target reaching task. The RLBMI was initialized using random initial conditions, and it quickly learned to control the robot from brain states using only a binary evaluative feedback regarding whether previously chosen robot actions were good or bad. The RLBMI was able to maintain control over the system throughout sessions spanning multiple weeks. Furthermore, the RLBMI was able to quickly adapt and maintain control of the robot despite dramatic perturbations to the neural inputs, including a series of tests in which the neuron input space was deliberately halved or doubled. PMID:24498055

  1. Using Reinforcement Learning to Provide Stable Brain-Machine Interface Control Despite Neural Input Reorganization

    PubMed Central

    Pohlmeyer, Eric A.; Mahmoudi, Babak; Geng, Shijia; Prins, Noeline W.; Sanchez, Justin C.

    2014-01-01

    Brain-machine interface (BMI) systems give users direct neural control of robotic, communication, or functional electrical stimulation systems. As BMI systems begin transitioning from laboratory settings into activities of daily living, an important goal is to develop neural decoding algorithms that can be calibrated with a minimal burden on the user, provide stable control for long periods of time, and can be responsive to fluctuations in the decoder’s neural input space (e.g. neurons appearing or being lost amongst electrode recordings). These are significant challenges for static neural decoding algorithms that assume stationary input/output relationships. Here we use an actor-critic reinforcement learning architecture to provide an adaptive BMI controller that can successfully adapt to dramatic neural reorganizations, can maintain its performance over long time periods, and which does not require the user to produce specific kinetic or kinematic activities to calibrate the BMI. Two marmoset monkeys used the Reinforcement Learning BMI (RLBMI) to successfully control a robotic arm during a two-target reaching task. The RLBMI was initialized using random initial conditions, and it quickly learned to control the robot from brain states using only a binary evaluative feedback regarding whether previously chosen robot actions were good or bad. The RLBMI was able to maintain control over the system throughout sessions spanning multiple weeks. Furthermore, the RLBMI was able to quickly adapt and maintain control of the robot despite dramatic perturbations to the neural inputs, including a series of tests in which the neuron input space was deliberately halved or doubled. PMID:24498055

  2. The Current Status of Somatostatin-Interneurons in Inhibitory Control of Brain Function and Plasticity.

    PubMed

    Scheyltjens, Isabelle; Arckens, Lutgarde

    2016-01-01

    The mammalian neocortex contains many distinct inhibitory neuronal populations to balance excitatory neurotransmission. A correct excitation/inhibition equilibrium is crucial for normal brain development, functioning, and controlling lifelong cortical plasticity. Knowledge about how the inhibitory network contributes to brain plasticity however remains incomplete. Somatostatin- (SST-) interneurons constitute a large neocortical subpopulation of interneurons, next to parvalbumin- (PV-) and vasoactive intestinal peptide- (VIP-) interneurons. Unlike the extensively studied PV-interneurons, acknowledged as key components in guiding ocular dominance plasticity, the contribution of SST-interneurons is less understood. Nevertheless, SST-interneurons are ideally situated within cortical networks to integrate unimodal or cross-modal sensory information processing and therefore likely to be important mediators of experience-dependent plasticity. The lack of knowledge on SST-interneurons partially relates to the wide variety of distinct subpopulations present in the sensory neocortex. This review informs on those SST-subpopulations hitherto described based on anatomical, molecular, or electrophysiological characteristics and whose functional roles can be attributed based on specific cortical wiring patterns. A possible role for these subpopulations in experience-dependent plasticity will be discussed, emphasizing on learning-induced plasticity and on unimodal and cross-modal plasticity upon sensory loss. This knowledge will ultimately contribute to guide brain plasticity into well-defined directions to restore sensory function and promote lifelong learning. PMID:27403348

  3. Creative thinking as orchestrated by semantic processing vs. cognitive control brain networks

    PubMed Central

    Abraham, Anna

    2014-01-01

    Creativity is primarily investigated within the neuroscientific perspective as a unitary construct. While such an approach is beneficial when trying to infer the general picture regarding creativity and brain function, it is insufficient if the objective is to uncover the information processing brain mechanisms by which creativity occurs. As creative thinking emerges through the dynamic interplay between several cognitive processes, assessing the neural correlates of these operations would enable the development and characterization of an information processing framework from which to better understand this complex ability. This article focuses on two aspects of creative cognition that are central to generating original ideas. “Conceptual expansion” refers to the ability to widen one’s conceptual structures to include unusual or novel associations, while “overcoming knowledge constraints” refers to our ability to override the constraining influence imposed by salient or pertinent knowledge when trying to be creative. Neuroimaging and neuropsychological evidence is presented to illustrate how semantic processing and cognitive control networks in the brain differentially modulate these critical facets of creative cognition. PMID:24605098

  4. Motor Control and Aging: Links to Age-Related Brain Structural, Functional, and Biochemical Effects

    PubMed Central

    Seidler, Rachael D.; Bernard, Jessica A.; Burutolu, Taritonye B.; Fling, Brett W.; Gordon, Mark T.; Gwin, Joseph T.; Kwak, Youngbin; Lipps, David B.

    2009-01-01

    Although connections between cognitive deficits and age-associated brain differences have been elucidated, relationships with motor performance are less well understood. Here, we broadly review age-related brain differences and motor deficits in older adults in addition to cognition-action theories. Age-related atrophy of the motor cortical regions and corpus callosum may precipitate or coincide with motor declines such as balance and gait deficits, coordination deficits, and movement slowing. Correspondingly, degeneration of neurotransmitter systems—primarily the dopaminergic system—may contribute to age-related gross and fine motor declines, as well as to higher cognitive deficits. In general, older adults exhibit involvement of more widespread brain regions for motor control than young adults, particularly the prefrontal cortex and basal ganglia networks. Unfortunately these same regions are the most vulnerable to age-related effects, resulting in an imbalance of “supply and demand”. Existing exercise, pharmaceutical, and motor training interventions may ameliorate motor deficits in older adults. PMID:19850077

  5. The Current Status of Somatostatin-Interneurons in Inhibitory Control of Brain Function and Plasticity

    PubMed Central

    2016-01-01

    The mammalian neocortex contains many distinct inhibitory neuronal populations to balance excitatory neurotransmission. A correct excitation/inhibition equilibrium is crucial for normal brain development, functioning, and controlling lifelong cortical plasticity. Knowledge about how the inhibitory network contributes to brain plasticity however remains incomplete. Somatostatin- (SST-) interneurons constitute a large neocortical subpopulation of interneurons, next to parvalbumin- (PV-) and vasoactive intestinal peptide- (VIP-) interneurons. Unlike the extensively studied PV-interneurons, acknowledged as key components in guiding ocular dominance plasticity, the contribution of SST-interneurons is less understood. Nevertheless, SST-interneurons are ideally situated within cortical networks to integrate unimodal or cross-modal sensory information processing and therefore likely to be important mediators of experience-dependent plasticity. The lack of knowledge on SST-interneurons partially relates to the wide variety of distinct subpopulations present in the sensory neocortex. This review informs on those SST-subpopulations hitherto described based on anatomical, molecular, or electrophysiological characteristics and whose functional roles can be attributed based on specific cortical wiring patterns. A possible role for these subpopulations in experience-dependent plasticity will be discussed, emphasizing on learning-induced plasticity and on unimodal and cross-modal plasticity upon sensory loss. This knowledge will ultimately contribute to guide brain plasticity into well-defined directions to restore sensory function and promote lifelong learning. PMID:27403348

  6. Reinforcement learning for adaptive threshold control of restorative brain-computer interfaces: a Bayesian simulation.

    PubMed

    Bauer, Robert; Gharabaghi, Alireza

    2015-01-01

    Restorative brain-computer interfaces (BCI) are increasingly used to provide feedback of neuronal states in a bid to normalize pathological brain activity and achieve behavioral gains. However, patients and healthy subjects alike often show a large variability, or even inability, of brain self-regulation for BCI control, known as BCI illiteracy. Although current co-adaptive algorithms are powerful for assistive BCIs, their inherent class switching clashes with the operant conditioning goal of restorative BCIs. Moreover, due to the treatment rationale, the classifier of restorative BCIs usually has a constrained feature space, thus limiting the possibility of classifier adaptation. In this context, we applied a Bayesian model of neurofeedback and reinforcement learning for different threshold selection strategies to study the impact of threshold adaptation of a linear classifier on optimizing restorative BCIs. For each feedback iteration, we first determined the thresholds that result in minimal action entropy and maximal instructional efficiency. We then used the resulting vector for the simulation of continuous threshold adaptation. We could thus show that threshold adaptation can improve reinforcement learning, particularly in cases of BCI illiteracy. Finally, on the basis of information-theory, we provided an explanation for the achieved benefits of adaptive threshold setting. PMID:25729347

  7. Reinforcement learning for adaptive threshold control of restorative brain-computer interfaces: a Bayesian simulation

    PubMed Central

    Bauer, Robert; Gharabaghi, Alireza

    2015-01-01

    Restorative brain-computer interfaces (BCI) are increasingly used to provide feedback of neuronal states in a bid to normalize pathological brain activity and achieve behavioral gains. However, patients and healthy subjects alike often show a large variability, or even inability, of brain self-regulation for BCI control, known as BCI illiteracy. Although current co-adaptive algorithms are powerful for assistive BCIs, their inherent class switching clashes with the operant conditioning goal of restorative BCIs. Moreover, due to the treatment rationale, the classifier of restorative BCIs usually has a constrained feature space, thus limiting the possibility of classifier adaptation. In this context, we applied a Bayesian model of neurofeedback and reinforcement learning for different threshold selection strategies to study the impact of threshold adaptation of a linear classifier on optimizing restorative BCIs. For each feedback iteration, we first determined the thresholds that result in minimal action entropy and maximal instructional efficiency. We then used the resulting vector for the simulation of continuous threshold adaptation. We could thus show that threshold adaptation can improve reinforcement learning, particularly in cases of BCI illiteracy. Finally, on the basis of information-theory, we provided an explanation for the achieved benefits of adaptive threshold setting. PMID:25729347

  8. A case-control study of brain structure and behavioral characteristics in 47,XXX syndrome.

    PubMed

    Lenroot, R K; Blumenthal, J D; Wallace, G L; Clasen, L S; Lee, N R; Giedd, J N

    2014-11-01

    Trisomy X, the presence of an extra X chromosome in females (47,XXX), is a relatively common but under-recognized chromosomal disorder associated with characteristic cognitive and behavioral features of varying severity. The objective of this study was to determine whether there were neuroanatomical differences in girls with Trisomy X that could relate to cognitive and behavioral differences characteristic of the disorder during childhood and adolescence. MRI scans were obtained on 35 girls with Trisomy X (mean age 11.4, SD 5.5) and 70 age- and sex-matched healthy controls. Cognitive and behavioral testing was also performed. Trisomy X girls underwent a semi-structured psychiatric interview. Regional brain volumes and cortical thickness were compared between the two groups. Total brain volume was significantly decreased in subjects with Trisomy X, as were all regional volumes with the exception of parietal gray matter. Differences in cortical thickness had a mixed pattern. The subjects with Trisomy X had thicker cortex in bilateral medial prefrontal cortex and right medial temporal lobe, but decreased cortical thickness in both lateral temporal lobes. The most common psychiatric disorders present in this sample of Trisomy X girls included anxiety disorders (40%), attention-deficit disorder (17%) and depressive disorders (11%). The most strongly affected brain regions are consistent with phenotypic characteristics such as language delay, poor executive function and heightened anxiety previously described in population-based studies of Trisomy X and also found in our sample. PMID:25287572

  9. A case-control study of brain structure and behavioral characteristics in 47,XXX Syndrome

    PubMed Central

    Lenroot, Rhoshel K.; Blumenthal, Jonathan D.; Wallace, Gregory L.; Clasen, Liv S.; Lee, Nancy Raitano; Giedd, Jay N.

    2014-01-01

    Trisomy X, the presence of an extra X chromosome in females (47,XXX), is a relatively common but under-recognized chromosomal disorder associated with characteristic cognitive and behavioral features of varying severity. The objective of this study was to determine whether there were neuroanatomical differences in girls with Trisomy X that could relate to cognitive and behavioral differences characteristic of the disorder during childhood and adolescence. MRI scans were obtained on 35 girls with Trisomy X (mean age 11.4, s.d. 5.5) and 70 age- and sex- matched healthy controls. Cognitive and behavioral testing was also performed. Trisomy X girls underwent a semi-structured psychiatric interview. Regional brain volumes and cortical thickness were compared between the two groups. Total brain volume was significantly decreased in subjects with Trisomy X, as were all regional volumes with the exception of parietal gray matter. Differences in cortical thickness had a mixed pattern. The subjects with Trisomy X had thicker cortex in bilateral medial prefrontal cortex and right medial temporal lobe, but decreased cortical thickness in both lateral temporal lobes. The most common psychiatric disorders present in this sample of Trisomy X girls included anxiety disorders, (40%), Attention-Deficit Disorder (17%), and depressive disorders (11%). The most strongly affected brain regions are consistent with phenotypic characteristics such as language delay, poor executive function, and heightened anxiety previously described in population-based studies of Trisomy X and also found in our sample. PMID:25287572

  10. Goal selection versus process control while learning to use a brain-computer interface

    NASA Astrophysics Data System (ADS)

    Royer, Audrey S.; Rose, Minn L.; He, Bin

    2011-06-01

    A brain-computer interface (BCI) can be used to accomplish a task without requiring motor output. Two major control strategies used by BCIs during task completion are process control and goal selection. In process control, the user exerts continuous control and independently executes the given task. In goal selection, the user communicates their goal to the BCI and then receives assistance executing the task. A previous study has shown that goal selection is more accurate and faster in use. An unanswered question is, which control strategy is easier to learn? This study directly compares goal selection and process control while learning to use a sensorimotor rhythm-based BCI. Twenty young healthy human subjects were randomly assigned either to a goal selection or a process control-based paradigm for eight sessions. At the end of the study, the best user from each paradigm completed two additional sessions using all paradigms randomly mixed. The results of this study were that goal selection required a shorter training period for increased speed, accuracy, and information transfer over process control. These results held for the best subjects as well as in the general subject population. The demonstrated characteristics of goal selection make it a promising option to increase the utility of BCIs intended for both disabled and able-bodied users.

  11. Goal Selection vs. Process Control while Learning to Use a Brain-Computer Interface

    PubMed Central

    Royer, Audrey S; Rose, Minn L; He, Bin

    2012-01-01

    A brain-computer interface (BCI) can be used to accomplish a task without requiring motor output. Two major control strategies used by BCIs during task completion are process control and goal selection. In process control, the user exerts continuous control and independently executes the given task. In goal selection, the user communicates their goal to the BCI and then receives assistance executing the task. A previous study has shown that goal selection is more accurate and faster in use. An unanswered question is, which control strategy is easier to learn? This study directly compares goal selection and process control while learning to use a sensorimotor rhythm based BCI. Twenty young healthy human subjects were randomly assigned either to a goal selection or a process control based paradigm for 8 sessions. At the end of the study, the best user from each paradigm completed 2 additional sessions using all paradigms randomly mixed. The results of this study were that goal selection required a shorter training period for increased speed, accuracy, and information transfer over process control. These results held for the best subjects as well as in the general subject population. The demonstrated characteristics of goal selection make it a promising option to increase the utility of BCIs intended for both disabled and able bodied users. PMID:21508492

  12. Cooking breakfast after a brain injury

    PubMed Central

    Tanguay, Annick N.; Davidson, Patrick S. R.; Guerrero Nuñez, Karla V.; Ferland, Mark B.

    2014-01-01

    Acquired brain injury (ABI) often compromises the ability to carry out instrumental activities of daily living such as cooking. ABI patients' difficulties with executive functions and memory result in less independent and efficient meal preparation. Accurately assessing safety and proficiency in cooking is essential for successful community reintegration following ABI, but in vivo assessment of cooking by clinicians is time-consuming, costly, and difficult to standardize. Accordingly, we examined the usefulness of a computerized meal preparation task (the Breakfast Task; Craik and Bialystok, 2006) as an indicator of real life meal preparation skills. Twenty-two ABI patients and 22 age-matched controls completed the Breakfast Task. Patients also completed the Rehabilitation Activities of Daily Living Survey (RADLS; Salmon, 2003) and prepared actual meals that were rated by members of the clinical team. As expected, the ABI patients had significant difficulty on all aspects of the Breakfast Task (failing to have all their foods ready at the same time, over- and under-cooking foods, setting fewer places at the table, and so on) relative to controls. Surprisingly, however, patients' Breakfast Task performance was not correlated with their in vivo meal preparation. These results indicate caution when endeavoring to replace traditional evaluation methods with computerized tasks for the sake of expediency. PMID:25228863

  13. Cooking breakfast after a brain injury.

    PubMed

    Tanguay, Annick N; Davidson, Patrick S R; Guerrero Nuñez, Karla V; Ferland, Mark B

    2014-01-01

    Acquired brain injury (ABI) often compromises the ability to carry out instrumental activities of daily living such as cooking. ABI patients' difficulties with executive functions and memory result in less independent and efficient meal preparation. Accurately assessing safety and proficiency in cooking is essential for successful community reintegration following ABI, but in vivo assessment of cooking by clinicians is time-consuming, costly, and difficult to standardize. Accordingly, we examined the usefulness of a computerized meal preparation task (the Breakfast Task; Craik and Bialystok, 2006) as an indicator of real life meal preparation skills. Twenty-two ABI patients and 22 age-matched controls completed the Breakfast Task. Patients also completed the Rehabilitation Activities of Daily Living Survey (RADLS; Salmon, 2003) and prepared actual meals that were rated by members of the clinical team. As expected, the ABI patients had significant difficulty on all aspects of the Breakfast Task (failing to have all their foods ready at the same time, over- and under-cooking foods, setting fewer places at the table, and so on) relative to controls. Surprisingly, however, patients' Breakfast Task performance was not correlated with their in vivo meal preparation. These results indicate caution when endeavoring to replace traditional evaluation methods with computerized tasks for the sake of expediency. PMID:25228863

  14. The Controlled Cortical Impact Model of Experimental Brain Trauma: Overview, Research Applications, and Protocol.

    PubMed

    Osier, Nicole; Dixon, C Edward

    2016-01-01

    Controlled cortical impact (CCI) is a commonly used and highly regarded model of brain trauma that uses a pneumatically or electromagnetically controlled piston to induce reproducible and well-controlled injury. The CCI model was originally used in ferrets and it has since been scaled for use in many other species. This chapter will describe the historical development of the CCI model, compare and contrast the pneumatic and electromagnetic models, and summarize key short- and long-term consequences of TBI that have been gleaned using this model. In accordance with the recent efforts to promote high-quality evidence through the reporting of common data elements (CDEs), relevant study details-that should be reported in CCI studies-will be noted. PMID:27604719

  15. Patterns of Brain Activation in Foster Children and Nonmaltreated Children During an Inhibitory Control Task

    PubMed Central

    Bruce, Jacqueline; Fisher, Philip A.; Graham, Alice M.; Moore, William E.; Peake, Shannon J.; Mannering, Anne M.

    2012-01-01

    Children in foster care have often encountered a range of adverse experiences, including neglectful and/or abusive care and multiple caregiver transitions. Prior research findings suggest that such experiences negatively affect inhibitory control and the underlying neural circuitry. In the current study, event-related functional magnetic resonance imaging (fMRI) was employed during a go/no go task that assesses inhibitory control to compare the behavioral performance and brain activation of foster children and nonmaltreated children. The sample included two groups of 9- to 12-year-old children: 11 maltreated foster children and 11 nonmaltreated children living with their biological parents. There were no significant group differences on behavioral performance on the task. In contrast, patterns of brain activation differed by group. The nonmaltreated children demonstrated stronger activation than the foster children across several regions including the right anterior cingulate cortex, middle frontal gyrus, and right lingual gyrus during correct no go trials, whereas the foster children displayed stronger activation than the nonmaltreated children in the left inferior parietal lobule and right superior occipital cortex including the lingual gyrus and cuneus during incorrect no go trials. These results provide preliminary evidence that the early adversity experienced by foster children impacts the neural substrates of inhibitory control. PMID:24229540

  16. Fast attainment of computer cursor control with noninvasively acquired brain signals

    NASA Astrophysics Data System (ADS)

    Bradberry, Trent J.; Gentili, Rodolphe J.; Contreras-Vidal, José L.

    2011-06-01

    Brain-computer interface (BCI) systems are allowing humans and non-human primates to drive prosthetic devices such as computer cursors and artificial arms with just their thoughts. Invasive BCI systems acquire neural signals with intracranial or subdural electrodes, while noninvasive BCI systems typically acquire neural signals with scalp electroencephalography (EEG). Some drawbacks of invasive BCI systems are the inherent risks of surgery and gradual degradation of signal integrity. A limitation of noninvasive BCI systems for two-dimensional control of a cursor, in particular those based on sensorimotor rhythms, is the lengthy training time required by users to achieve satisfactory performance. Here we describe a novel approach to continuously decoding imagined movements from EEG signals in a BCI experiment with reduced training time. We demonstrate that, using our noninvasive BCI system and observational learning, subjects were able to accomplish two-dimensional control of a cursor with performance levels comparable to those of invasive BCI systems. Compared to other studies of noninvasive BCI systems, training time was substantially reduced, requiring only a single session of decoder calibration (~20 min) and subject practice (~20 min). In addition, we used standardized low-resolution brain electromagnetic tomography to reveal that the neural sources that encoded observed cursor movement may implicate a human mirror neuron system. These findings offer the potential to continuously control complex devices such as robotic arms with one's mind without lengthy training or surgery.

  17. Occludin controls HIV transcription in brain pericytes via regulation of SIRT-1 activation.

    PubMed

    Castro, Victor; Bertrand, Luc; Luethen, Mareen; Dabrowski, Sebastian; Lombardi, Jorge; Morgan, Laura; Sharova, Natalia; Stevenson, Mario; Blasig, Ingolf E; Toborek, Michal

    2016-03-01

    HIV invades the brain early after infection; however, its interactions with the cells of the blood-brain barrier (BBB) remain poorly understood. Our goal was to evaluate the role of occludin, one of the tight junction proteins that regulate BBB functions in HIV infection of BBB pericytes. We provide evidence that occludin levels largely control the metabolic responses of human pericytes to HIV. Occludin in BBB pericytes decreased by 10% during the first 48 h after HIV infection, correlating with increased nuclear translocation of the gene repressor C-terminal-binding protein (CtBP)-1 and NFκB-p65 activation. These changes were associated with decreased expression and activation of the class III histone deacetylase sirtuin (SIRT)-1. Occludin levels recovered 96 h after infection, restoring SIRT-1 and reducing HIV transcription to 20% of its highest values. We characterized occludin biochemically as a novel NADH oxidase that controls the expression and activation of SIRT-1. The inverse correlation between occludin and HIV transcription was then replicated in human primary macrophages and differentiated monocytic U937 cells, in which occludin silencing resulted in 75 and 250% increased viral transcription, respectively. Our work shows that occludin has previously unsuspected metabolic properties and is a target of HIV infection, opening the possibility of designing novel pharmacological approaches to control HIV transcription. PMID:26601824

  18. Patterns of brain activation in foster children and nonmaltreated children during an inhibitory control task.

    PubMed

    Bruce, Jacqueline; Fisher, Philip A; Graham, Alice M; Moore, William E; Peake, Shannon J; Mannering, Anne M

    2013-11-01

    Children in foster care have often encountered a range of adverse experiences, including neglectful and/or abusive care and multiple caregiver transitions. Prior research findings suggest that such experiences negatively affect inhibitory control and the underlying neural circuitry. In the current study, event-related functional magnetic resonance imaging was employed during a go/no go task that assesses inhibitory control to compare the behavioral performance and brain activation of foster children and nonmaltreated children. The sample included two groups of 9- to 12-year-old children: 11 maltreated foster children and 11 nonmaltreated children living with their biological parents. There were no significant group differences on behavioral performance on the task. In contrast, patterns of brain activation differed by group. The nonmaltreated children demonstrated stronger activation than did the foster children across several regions, including the right anterior cingulate cortex, the middle frontal gyrus, and the right lingual gyrus, during correct no go trials, whereas the foster children displayed stronger activation than the nonmaltreated children in the left inferior parietal lobule and the right superior occipital cortex, including the lingual gyrus and cuneus, during incorrect no go trials. These results provide preliminary evidence that the early adversity experienced by foster children impacts the neural substrates of inhibitory control. PMID:24229540

  19. Reduced Metabolsim in Brain 'Control Networks' Following Cocaine-Cues Exposure in Female Cocaine Abusers

    SciTech Connect

    Volkow, N.D.; Wang, G.; Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Fowler, J.S.; Telang, F.; Goldstein, R.Z.; Alia-Klein, N.; Wong, C.T.

    2011-03-01

    Gender differences in vulnerability for cocaine addiction have been reported. Though the mechanisms are not understood, here we hypothesize that gender differences in reactivity to conditioned-cues, which contributes to relapse, are involved. To test this we compared brain metabolism (using PET and {sup 18}FDG) between female (n = 10) and male (n = 16) active cocaine abusers when they watched a neutral video (nature scenes) versus a cocaine-cues video. Self-reports of craving increased with the cocaine-cue video but responses did not differ between genders. In contrast, changes in whole brain metabolism with cocaine-cues differed by gender (p<0.05); females significantly decreased metabolism (-8.6% {+-} 10) whereas males tended to increase it (+5.5% {+-} 18). SPM analysis (Cocaine-cues vs Neutral) in females revealed decreases in frontal, cingulate and parietal cortices, thalamus and midbrain (p<0.001) whereas males showed increases in right inferior frontal gyrus (BA 44/45) (only at p<0.005). The gender-cue interaction showed greater decrements with Cocaine-cues in females than males (p<0.001) in frontal (BA 8, 9, 10), anterior cingulate (BA 24, 32), posterior cingulate (BA 23, 31), inferior parietal (BA 40) and thalamus (dorsomedial nucleus). Females showed greater brain reactivity to cocaine-cues than males but no differences in craving, suggesting that there may be gender differences in response to cues that are not linked with craving but could affect subsequent drug use. Specifically deactivation of brain regions from 'control networks' (prefrontal, cingulate, inferior parietal, thalamus) in females could increase their vulnerability to relapse since it would interfere with executive function (cognitive inhibition). This highlights the importance of gender tailored interventions for cocaine addiction.

  20. Brain State-Dependent Closed-Loop Modulation of Paired Associative Stimulation Controlled by Sensorimotor Desynchronization

    PubMed Central

    Royter, Vladislav; Gharabaghi, Alireza

    2016-01-01

    Background: Pairing peripheral electrical stimulation (ES) and transcranial magnetic stimulation (TMS) increases corticospinal excitability when applied with a specific temporal pattern. When the two stimulation techniques are applied separately, motor imagery (MI)-related oscillatory modulation amplifies both ES-related cortical effects—sensorimotor event-related desynchronization (ERD), and TMS-induced peripheral responses—motor-evoked potentials (MEP). However, the influence of brain self-regulation on the associative pairing of these stimulation techniques is still unclear. Objective: The aim of this pilot study was to investigate the effects of MI-related ERD during associative ES and TMS on subsequent corticospinal excitability. Method: The paired application of functional electrical stimulation (FES) of the extensor digitorum communis (EDC) muscle and subsequent single-pulse TMS (110% resting motor threshold (RMT)) of the contralateral primary motor cortex (M1) was controlled by beta-band (16–22 Hz) ERD during MI of finger extension and applied within a brain-machine interface environment in six healthy subjects. Neural correlates were probed by acquiring the stimulus-response curve (SRC) of both MEP peak-to-peak amplitude and area under the curve (AUC) before and after the intervention. Result: The application of approximately 150 pairs of associative FES and TMS resulted in a significant increase of MEP amplitudes and AUC, indicating that the induced increase of corticospinal excitability was mediated by the recruitment of additional neuronal pools. MEP increases were brain state-dependent and correlated with beta-band ERD, but not with the background EDC muscle activity; this finding was independent of the FES intensity applied. Conclusion: These results could be relevant for developing closed-loop therapeutic approaches such as the application of brain state-dependent, paired associative stimulation (PAS) in the context of neurorehabilitation. PMID

  1. Mapping brain networks in awake mice using combined optical neural control and fMRI.

    PubMed

    Desai, M; Kahn, I; Knoblich, U; Bernstein, J; Atallah, H; Yang, A; Kopell, N; Buckner, R L; Graybiel, A M; Moore, C I; Boyden, E S

    2011-03-01

    Behaviors and brain disorders involve neural circuits that are widely distributed in the brain. The ability to map the functional connectivity of distributed circuits, and to assess how this connectivity evolves over time, will be facilitated by methods for characterizing the network impact of activating a specific subcircuit, cell type, or projection pathway. We describe here an approach using high-resolution blood oxygenation level-dependent (BOLD) functional MRI (fMRI) of the awake mouse brain-to measure the distributed BOLD response evoked by optical activation of a local, defined cell class expressing the light-gated ion channel channelrhodopsin-2 (ChR2). The utility of this opto-fMRI approach was explored by identifying known cortical and subcortical targets of pyramidal cells of the primary somatosensory cortex (SI) and by analyzing how the set of regions recruited by optogenetically driven SI activity differs between the awake and anesthetized states. Results showed positive BOLD responses in a distributed network that included secondary somatosensory cortex (SII), primary motor cortex (MI), caudoputamen (CP), and contralateral SI (c-SI). Measures in awake compared with anesthetized mice (0.7% isoflurane) showed significantly increased BOLD response in the local region (SI) and indirectly stimulated regions (SII, MI, CP, and c-SI), as well as increased BOLD signal temporal correlations between pairs of regions. These collective results suggest opto-fMRI can provide a controlled means for characterizing the distributed network downstream of a defined cell class in the awake brain. Opto-fMRI may find use in examining causal links between defined circuit elements in diverse behaviors and pathologies. PMID:21160013

  2. Beyond the brain: Optogenetic control in the spinal cord and peripheral nervous system.

    PubMed

    Montgomery, Kate L; Iyer, Shrivats M; Christensen, Amelia J; Deisseroth, Karl; Delp, Scott L

    2016-05-01

    Optogenetics offers promise for dissecting the complex neural circuits of the spinal cord and peripheral nervous system and has therapeutic potential for addressing unmet clinical needs. Much progress has been made to enable optogenetic control in normal and disease states, both in proof-of-concept and mechanistic studies in rodent models. In this Review, we discuss challenges in using optogenetics to study the mammalian spinal cord and peripheral nervous system, synthesize common features that unite the work done thus far, and describe a route forward for the successful application of optogenetics to translational research beyond the brain. PMID:27147590

  3. Optimal feedback control successfully explains changes in neural modulations during experiments with brain-machine interfaces

    PubMed Central

    Benyamini, Miri; Zacksenhouse, Miriam

    2015-01-01

    Recent experiments with brain-machine-interfaces (BMIs) indicate that the extent of neural modulations increased abruptly upon starting to operate the interface, and especially after the monkey stopped moving its hand. In contrast, neural modulations that are correlated with the kinematics of the movement remained relatively unchanged. Here we demonstrate that similar changes are produced by simulated neurons that encode the relevant signals generated by an optimal feedback controller during simulated BMI experiments. The optimal feedback controller relies on state estimation that integrates both visual and proprioceptive feedback with prior estimations from an internal model. The processing required for optimal state estimation and control were conducted in the state-space, and neural recording was simulated by modeling two populations of neurons that encode either only the estimated state or also the control signal. Spike counts were generated as realizations of doubly stochastic Poisson processes with linear tuning curves. The model successfully reconstructs the main features of the kinematics and neural activity during regular reaching movements. Most importantly, the activity of the simulated neurons successfully reproduces the observed changes in neural modulations upon switching to brain control. Further theoretical analysis and simulations indicate that increasing the process noise during normal reaching movement results in similar changes in neural modulations. Thus, we conclude that the observed changes in neural modulations during BMI experiments can be attributed to increasing process noise associated with the imperfect BMI filter, and, more directly, to the resulting increase in the variance of the encoded signals associated with state estimation and the required control signal. PMID:26042002

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2012-08-01

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

  6. [Arm Motor Function Recovery during Rehabilitation with the Use of Hand Exoskeleton Controlled by Brain-Computer Interface: a Patient with Severe Brain Damage].

    PubMed

    Biryukova, E V; Pavlova, O G; Kurganskaya, M E; Bobrov, P D; Turbina, L G; Frolov, A A; Davydov, V I; Sil'tchenko, A V; Mokienko, O A

    2016-01-01

    We studied the dynamics of motor function recovery in a patient with severe brain damage in the course of neurorehabilitation using hand exoskeleton controlled by brain-computer interface. For estimating the motor function of paretic arm, we used the biomechanical analysis of movements registered during the course of rehabilitation. After 15 weekly sessions of hand exoskeleton control, the following results were obtained: a) the velocity profile of goal-directed movements of paretic hand became bell-shaped, b) the patient began to extend and abduct the hand which was flexed and adducted in the beginning of rehabilitation, and c) the patient began to supinate the forearm which was pronated in the beginning of rehabilitation. The first result is an evidence of the general improvement of the quality of motor control, while the second and third results prove that the spasticity of paretic arm has decreased. PMID:27188144

  7. Aneuploidy in the normal, Alzheimer's disease and ataxia-telangiectasia brain: differential expression and pathological meaning.

    PubMed

    Iourov, Ivan Y; Vorsanova, Svetlana G; Liehr, Thomas; Yurov, Yuri B

    2009-05-01

    Recently it has been suggested that the human brain contains aneuploid cells; however the nature and magnitude of neural aneuploidy in health and disease remain obscure. Here, we have monitored aneuploidy in the cerebral cortex of the normal, Alzheimer's disease (AD) and ataxia telangiectasia (AT) brain by molecular cytogenetic approaches scoring more than 480,000 neural cells. Using arbitrarily selected set of DNA probes for chromosomes 1, 7, 11, 13, 14, 17, 18, 21, X and Y we have determined the mean rate of stochastic aneuploidy per chromosome as 0.5% in the normal human brain (95%CI 0.2-0.7%; SD 0.2%). The overall proportion of aneuploid cells in the normal brain has been estimated at approximately 10%. In the AT brain, we observed a 2-to-5 fold increase of stochastic aneuploidy randomly affecting different chromosomes (mean 2.1%; 95%CI - 1.5-2.6%; SD 0.8%). The overall proportion of aneuploid cells in the brain of AT individuals was estimated at approximately 20-50%. Compared with sex- and age-matched controls, the level of stochastic aneuploidy in the AD brain was not significantly increased. However, a dramatic 10-fold increase of chromosome 21-specific aneuploidy (both hypoploidy and hyperploidy) was detected in the AD cerebral cortex (6-15% versus 0.8-1.8% in control). We conclude that somatic mosaic aneuploidy differentially contributes to intercellular genomic variation in the normal, AD and AT brain. Neural aneuploidy leading to altered cellular physiology may significantly contribute to the pathogenesis of neurodegenerative diseases. These data indicate neural aneuploidy to be a newly identified feature of neurodegenerative diseases, similar to other devastative disorders hallmarked by aneuploidy such as chromosome syndromes and cancer. PMID:19344645

  8. A Hyper-connected but Less Efficient Small-world Network in the Substance-Dependent Brain

    PubMed Central

    Wang, Ze; Suh, Jesse; Li, Zhengjun; Li, Yin; Franklin, Teresa; O’Brien, Charles; Childress, Anna Rose

    2015-01-01

    Background The functional interconnections of the addicted brain may differ from the non-addicted population in important ways, but prior analytic approaches were usually limited to the study of connections between a few number of selected brain regions. Recent approaches enable examination of the vast functional interactions within the entire brain, the functional connectome (FCM). The purpose of this study was to characterize FCM alterations in addiction using resting state functional Magnetic Resonance Imaging (rsfMRI) and to assess their relations to addiction-related symptoms. Methods rsfMRI data were acquired from 20 chronic polydrug users whose primary diagnosis was cocaine dependence (DRUG) and 19 age-matched non-drug using healthy controls (CTL). FCM was assessed using graph theoretical analysis. Results Among the assessed 90 brain subdivisions, DRUG showed stronger functional connectivity. After controlling functional connectivity difference and the resultant network density, DRUG showed reduced communication efficiency and reduced small-worldness. Conclusions The increased connection strength in drug users’ brain suggests an elevated dynamic resting state that may enable a rapid, semi-automatic, execution of behaviors directed toward drug-related goals. The reduced FCM communication efficiency and reduced small-worldness suggest a loss of normal inter-regional communications and topology features that makes it difficult to inhibit the drug seeking behavior. PMID:25957794

  9. Resting-State Brain Activity in Adult Males Who Stutter

    PubMed Central

    Zhu, Chaozhe; Wang, Liang; Yan, Qian; Lin, Chunlan; Yu, Chunshui

    2012-01-01

    Although developmental stuttering has been extensively studied with structural and task-based functional magnetic resonance imaging (fMRI), few studies have focused on resting-state brain activity in this disorder. We investigated resting-state brain activity of stuttering subjects by analyzing the amplitude of low-frequency fluctuation (ALFF), region of interest (ROI)-based functional connectivity (FC) and independent component analysis (ICA)-based FC. Forty-four adult males with developmental stuttering and 46 age-matched fluent male controls were scanned using resting-state fMRI. ALFF, ROI-based FCs and ICA-based FCs were compared between male stuttering subjects and fluent controls in a voxel-wise manner. Compared with fluent controls, stuttering subjects showed increased ALFF in left brain areas related to speech motor and auditory functions and bilateral prefrontal cortices related to cognitive control. However, stuttering subjects showed decreased ALFF in the left posterior language reception area and bilateral non-speech motor areas. ROI-based FC analysis revealed decreased FC between the posterior language area involved in the perception and decoding of sensory information and anterior brain area involved in the initiation of speech motor function, as well as increased FC within anterior or posterior speech- and language-associated areas and between the prefrontal areas and default-mode network (DMN) in stuttering subjects. ICA showed that stuttering subjects had decreased FC in the DMN and increased FC in the sensorimotor network. Our findings support the concept that stuttering subjects have deficits in multiple functional systems (motor, language, auditory and DMN) and in the connections between them. PMID:22276215

  10. Identification of Novel Tau Interactions with Endoplasmic Reticulum Proteins in Alzheimer’s Disease Brain

    PubMed Central

    Meier, Shelby; Bell, Michelle; Lyons, Danielle N.; Ingram, Alexandria; Chen, Jing; Gensel, John C.; Zhu, Haining; Nelson, Peter T.; Abisambra, Jose F.

    2016-01-01

    Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is pathologically characterized by the formation of extracellular amyloid plaques and intraneuronal tau tangles. We recently identified that tau associates with proteins known to participate in endoplasmic reticulum (ER)-associated degradation (ERAD); consequently, ERAD becomes dysfunctional and causes neurotoxicity. We hypothesized that tau associates with other ER proteins, and that this association could also lead to cellular dysfunction in AD. Portions of human AD and non-demented age matched control brains were fractionated to obtain microsomes, from which tau was co-immunoprecipitated. Samples from both conditions containing tau and its associated proteins were analyzed by mass spectrometry. In total, we identified 91 ER proteins that co-immunoprecipitated with tau; 15.4% were common between AD and control brains, and 42.9% only in the AD samples. The remainder, 41.8% of the proteins, was only seen in the control brain samples. We identified a variety of previously unreported interactions between tau and ER proteins. These proteins participate in over sixteen functional categories, the most abundant being involved in RNA translation. We then determined that association of tau with these ER proteins was different between the AD and control samples. We found that tau associated equally with the ribosomal protein L28 but more robustly with the ribosomal protein P0. These data suggest that the differential association between tau and ER proteins in disease could reveal the pathogenic processes by which tau induces cellular dysfunction. PMID:26402096

  11. Pallidal Deep Brain Stimulation Improves Higher Control of the Oculomotor System in Parkinson's Disease.

    PubMed

    Antoniades, Chrystalina A; Rebelo, Pedro; Kennard, Christopher; Aziz, Tipu Z; Green, Alexander L; FitzGerald, James J

    2015-09-23

    The frontal cortex and basal ganglia form a set of parallel but mostly segregated circuits called cortico-basal ganglia loops. The oculomotor loop controls eye movements and can direct relatively simple movements, such as reflexive prosaccades, without external help but needs input from "higher" loops for more complex behaviors. The antisaccade task requires the dorsolateral prefrontal cortex, which is part of the prefrontal loop. Information flows from prefrontal to oculomotor circuits in the striatum, and directional errors in this task can be considered a measure of failure of prefrontal control over the oculomotor loop. The antisaccadic error rate (AER) is increased in Parkinson's disease (PD). Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has no effect on the AER, but a previous case suggested that DBS of the globus pallidus interna (GPi) might. Our aim was to compare the effects of STN DBS and GPi DBS on the AER. We tested eye movements in 14 human DBS patients and 10 controls. GPi DBS substantially reduced the AER, restoring lost higher control over oculomotor function. Interloop information flow involves striatal neurons that receive cortical input and project to pallidum. They are normally silent when quiescent, but in PD they fire randomly, creating noise that may account for the degradation in interloop control. The reduced AER with GPi DBS could be explained by retrograde stimulation of striatopallidal axons with consequent activation of inhibitory collaterals and reduction in background striatal firing rates. This study may help explain aspects of PD pathophysiology and the mechanism of action of GPi DBS. Significance statement: Parkinson's disease causes symptoms including stiffness, slowness of movement, and tremor. Electrical stimulation of specific areas deep in the brain can effectively treat these symptoms, but exactly how is not fully understood. Part of the cause of such symptoms may be impairments in the way information flows

  12. Pallidal Deep Brain Stimulation Improves Higher Control of the Oculomotor System in Parkinson's Disease

    PubMed Central

    Rebelo, Pedro; Kennard, Christopher; Aziz, Tipu Z.; Green, Alexander L.

    2015-01-01

    The frontal cortex and basal ganglia form a set of parallel but mostly segregated circuits called cortico-basal ganglia loops. The oculomotor loop controls eye movements and can direct relatively simple movements, such as reflexive prosaccades, without external help but needs input from “higher” loops for more complex behaviors. The antisaccade task requires the dorsolateral prefrontal cortex, which is part of the prefrontal loop. Information flows from prefrontal to oculomotor circuits in the striatum, and directional errors in this task can be considered a measure of failure of prefrontal control over the oculomotor loop. The antisaccadic error rate (AER) is increased in Parkinson's disease (PD). Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has no effect on the AER, but a previous case suggested that DBS of the globus pallidus interna (GPi) might. Our aim was to compare the effects of STN DBS and GPi DBS on the AER. We tested eye movements in 14 human DBS patients and 10 controls. GPi DBS substantially reduced the AER, restoring lost higher control over oculomotor function. Interloop information flow involves striatal neurons that receive cortical input and project to pallidum. They are normally silent when quiescent, but in PD they fire randomly, creating noise that may account for the degradation in interloop control. The reduced AER with GPi DBS could be explained by retrograde stimulation of striatopallidal axons with consequent activation of inhibitory collaterals and reduction in background striatal firing rates. This study may help explain aspects of PD pathophysiology and the mechanism of action of GPi DBS. SIGNIFICANCE STATEMENT Parkinson's disease causes symptoms including stiffness, slowness of movement, and tremor. Electrical stimulation of specific areas deep in the brain can effectively treat these symptoms, but exactly how is not fully understood. Part of the cause of such symptoms may be impairments in the way information

  13. Apoptotic markers in cultured fibroblasts correlate with brain metabolites and regional brain volume in antipsychotic-naive first-episode schizophrenia and healthy controls

    PubMed Central

    Batalla, A; Bargalló, N; Gassó, P; Molina, O; Pareto, D; Mas, S; Roca, J M; Bernardo, M; Lafuente, A; Parellada, E

    2015-01-01

    Cultured fibroblasts from first-episode schizophrenia patients (FES) have shown increased susceptibility to apoptosis, which may be related to glutamate dysfunction and progressive neuroanatomical changes. Here we determine whether apoptotic markers obtained from cultured fibroblasts in FES and controls correlate with changes in brain glutamate and N-acetylaspartate (NAA) and regional brain volumes. Eleven antipsychotic-naive FES and seven age- and gender-matched controls underwent 3-Tesla magnetic resonance imaging scanning. Glutamate plus glutamine (Glx) and NAA levels were measured in the anterior cingulate (AC) and the left thalamus (LT). Hallmarks of apoptotic susceptibility (caspase-3-baseline activity, phosphatidylserine externalization and chromatin condensation) were measured in fibroblast cultures obtained from skin biopsies after inducing apoptosis with staurosporine (STS) at doses of 0.25 and 0.5 μM. Apoptotic biomarkers were correlated to brain metabolites and regional brain volume. FES and controls showed a negative correlation in the AC between Glx levels and percentages of cells with condensed chromatin (CC) after both apoptosis inductions (STS 0.5 μM: r=−0.90; P=0.001; STS 0.25 μM: r=−0.73; P=0.003), and between NAA and cells with CC (STS 0.5 μM induction r=−0.76; P=0.002; STS 0.25 μM r=−0.62; P=0.01). In addition, we found a negative correlation between percentages of cells with CC and regional brain volume in the right supratemporal cortex and post-central region (STS 0.25 and 0.5 μM; P<0.05 family-wise error corrected (FWEc)). We reveal for the first time that peripheral markers of apoptotic susceptibility may correlate with brain metabolites, Glx and NAA, and regional brain volume in FES and controls, which is consistent with the neuroprogressive theories around the onset of the schizophrenia illness. PMID:26305477

  14. Quantitative MRI analysis of brain volume changes due to controlled cortical impact.

    PubMed

    Colgan, Niall C; Cronin, Michelle M; Gobbo, Oliviero L; O'Mara, Shane M; O'Connor, William T; Gilchrist, Michael D

    2010-07-01

    More than 85% of reported brain traumas are classified clinically as "mild" using the Glasgow Coma Scale (GCS); qualitative MRI findings are scarce and provide little correspondence to clinical symptoms. Our goal, therefore, was to establish in vivo sequelae of traumatic brain injury (TBI) following lower and higher levels of impact to the frontal lobe using quantitative MRI analysis and a mechanical model of penetrating impact injury. To investigate time-based morphological and physiological changes of living tissue requires a surrogate for the human central nervous system. The present model for TBI was a systematically varied and controlled cortical impact on deeply-anaesthetized Sprague-Dawley rats, that was designed to mimic different injury severities. Whole-brain MRI scans were performed on each rat prior to either a lower- or a higher-level of impact, and then at hourly intervals for 5 h post-impact. Both brain volume and specific anatomical structures were segmented from MR images for inter-subject comparisons post-registration. Animals subjected to lower and higher impact levels exhibited elevated intracranial pressure (ICP) in the low compensatory reserve (i.e., nearly exhausted), and terminal disturbance (i.e., exhausted) ranges, respectively. There was a statistically significant drop in cerebrospinal fluid (CSF) of 35% in the lower impacts, and 65% in the higher impacts, at 5 h compared to sham controls. There was a corresponding increase in corpus callosum volume starting at 1 h, of 60-110% and 30-40% following the lower- and higher-impact levels, respectively. A statistically significant change in the abnormal tissue from 2 h to 5 h was observed for both impact levels, with greater significance for higher impacts. Furthermore, a statistically significant difference between the lower impacts and the sham controls occurred at 3 h. These results are statistically substantiated by a fluctuation in the physical size of the corpus callosum, a decrease in

  15. Reappraisal generation after acquired brain damage: The role of laterality and cognitive control

    PubMed Central

    Salas, Christian E.; Gross, James J.; Turnbull, Oliver H.

    2014-01-01

    In the past decade, there has been growing interest in the neuroanatomical and neuropsychological bases of reappraisal. Findings suggest that reappraisal activates a set of areas in the left hemisphere (LH), which are commonly associated with language abilities and verbally mediated cognitive control. The main goal of this study was to investigate whether individuals with focal damage to the LH (n = 8) were more markedly impaired on a reappraisal generation task than individuals with right hemisphere lesions (RH, n = 8), and healthy controls (HC, n = 14). The reappraisal generation task consisted of a set of ten pictures from the IAPS, depicting negative events of different sorts. Participants were asked to quickly generate as many positive reinterpretations as possible for each picture. Two scores were derived from this task, namely difficulty and productivity. A second goal of this study was to explore which cognitive control processes were associated with performance on the reappraisal task. For this purpose, participants were assessed on several measures of cognitive control. Findings indicated that reappraisal difficulty – defined as the time taken to generate a first reappraisal – did not differ between LH and RH groups. However, differences were found between patients with brain injury (LH + RH) and HC, suggesting that brain damage in either hemisphere influences reappraisal difficulty. No differences in reappraisal productivity were found across groups, suggesting that neurological groups and HC are equally productive when time constraints are not considered. Finally, only two cognitive control processes inhibition and verbal fluency- were inversely associated with reappraisal difficulty. Implications for the neuroanatomical and neuropsychological bases of reappraisal generation are discussed, and implications for neuro-rehabilitation are considered. PMID:24711799

  16. Developmental Changes in Brain Function Underlying Inhibitory Control in Autism Spectrum Disorders

    PubMed Central

    Padmanabhan, Aarthi; Garver, Krista; O’Hearn, Kirsten; Nawarawong, Natalie; Liu, Ran; Minshew, Nancy; Sweeney, John; Luna, Beatriz

    2016-01-01

    The development of inhibitory control—the ability to suppress inappropriate actions in order to make goal-directed responses—is often impaired in autism spectrum disorders (ASD). In the present study, we examined whether the impairments in inhibitory control evident in ASD reflect—in part—differences in the development of the neural substrates of inhibitory control from adolescence into adulthood. We conducted a functional magnetic resonance imaging (fMRI) study on the anti-saccade task, a probe of inhibitory control, in high-functioning adolescents and adults with ASD compared to a matched group of typically developing (TD) individuals. The ASD group did not show the age-related improvements in behavioral performance from adolescence to adulthood evident in the typical group, consistent with previous behavioral work. The fMRI results indicated that much of the circuitry recruited by the ASD group was similar to the TD group. However, the ASD group demonstrated some unique patterns, including: (a) a failure to recruit the frontal eye field during response preparation in adolescence but comparable recruitment in adulthood; (b) greater recruitment of putamen in adolescence and precuneus in adolescence and adulthood than the TD group; and (c) decreased recruitment in the inferior parietal lobule relative to TD groups. Taken together, these results suggest that brain circuitry underlying inhibitory control develops differently from adolescence to adulthood in ASD. Specifically, there may be relative underdevelopment of brain processes underlying inhibitory control in ASD, which may lead to engagement of subcortical compensatory processes. PMID:25382787

  17. Corticosteroids in acute traumatic brain injury: systematic review of randomised controlled trials.

    PubMed Central

    Alderson, P.; Roberts, I.

    1997-01-01

    OBJECTIVE: To quantify the effectiveness and safety of corticosteroids in the treatment of acute traumatic brain injury. DESIGN: Systematic review of randomised controlled trials of corticosteroids in acute traumatic brain injury. Summary odds ratios were estimated as an inverse variance weighted average of the odds ratios for each study. SETTING: Randomised trials available by March 1996. SUBJECTS: The included trials with outcome data comprised 2073 randomised participants. RESULTS: The effect of corticosteroids on the risk of death was reported in 13 included trials. The pooled odds ratio for the 13 trials was 0.91 (95% confidence interval 0.74 to 1.12). Pooled absolute risk reduction was 1.8% (-2.5% to 5.7%). For the 10 trials that reported death or disability the pooled odds ratio was 0.90 (0.72 to 1.11). For infections of any type the pooled odds ratio was 0.92 (0.69 to 1.23) and for the seven trials reporting gastrointestinal bleeding it was 1.05 (0.44 to 2.52). With only those trials with the best quality of concealment of allocation, the pooled odds ratio estimates for death and death or disability became closer to unity. CONCLUSIONS: This systematic review of randomised controlled trials of corticosteroids in acute traumatic brain injury shows that there remains considerable uncertainty over their effects. Neither moderate benefits nor moderate harmful effects can be excluded. The widely practicable nature of the drugs and the importance of the health problem suggest that large simple trials are feasible and worth while to establish whether there are any benefits from use of corticosteroids in this setting. PMID:9224126

  18. Long-Term Upregulation of Inflammation and Suppression of Cell Proliferation in the Brain of Adult Rats Exposed to Traumatic Brain Injury Using the Controlled Cortical Impact Model

    PubMed Central

    Acosta, Sandra A.; Tajiri, Naoki; Shinozuka, Kazutaka; Ishikawa, Hiroto; Grimmig, Bethany; Diamond, David; Sanberg, Paul R.; Bickford, Paula C.; Kaneko, Yuji; Borlongan, Cesar V.

    2013-01-01

    The long-term consequences of traumatic brain injury (TBI), specifically the detrimental effects of inflammation on the neurogenic niches, are not very well understood. In the present in vivo study, we examined the prolonged pathological outcomes of experimental TBI in different parts of the rat brain with special emphasis on inflammation and neurogenesis. Sixty days after moderate controlled cortical impact injury, adult Sprague-Dawley male rats were euthanized and brain tissues harvested. Antibodies against the activated microglial marker, OX6, the cell cycle-regulating protein marker, Ki67, and the immature neuronal marker, doublecortin, DCX, were used to estimate microglial activation, cell proliferation, and neuronal differentiation, respectively, in the subventricular zone (SVZ), subgranular zone (SGZ), striatum, thalamus, and cerebral peduncle. Stereology-based analyses revealed significant exacerbation of OX6-positive activated microglial cells in the striatum, thalamus, and cerebral peduncle. In parallel, significant decrements in Ki67-positive proliferating cells in SVZ and SGZ, but only trends of reduced DCX-positive immature neuronal cells in SVZ and SGZ were detected relative to sham control group. These results indicate a progressive deterioration of the TBI brain over time characterized by elevated inflammation and suppressed neurogenesis. Therapeutic intervention at the chronic stage of TBI may confer abrogation of these deleterious cell death processes. PMID:23301065

  19. Optical monitoring of cardiac and respiratory rhythms in the skin perfusion near the brain under controlled conditions

    NASA Astrophysics Data System (ADS)

    Mukunda Rao, M.; Blazek, Vladimir; Schmitt, Hans J.

    1998-06-01

    In this investigation an attempt is made to find the effects of controlled breathing on brain with the help of optical sensors mounted on the left and right temples of a subject. It has already been established that the brain activity can be monitored in terms of arterial blood volumetric changes to the left and right hemispheres of the brain recorded with the help of optical sensors. To investigate the influence of controlled breathing, an expert in controlled breathing (pranayama) is chosen as the subject. Pranayama is believed to be the controlled intake and outflow of breath in a firmly established posture. Some types of pranayama are believed to relive mental stress. While the subject is practicing one such type of breath control, arterial blood volume changes in the brain are recorded using optical sensors mounted on the left and right temples of the subject. From these measurements at the beginning and end of the pranayama exercise, it could be noticed that the subject could induce changes in the cardiac and respiratory rhythms by controlled breathing. Rhythmic phenomena in the skin perfusion in the vicinity of the brian are also studied when the subject is holding his breath. The arterial blood volume changes to the left and right hemispheres of the brain, as monitored by the optical sensors during this period, exhibit asymmetric reaction when the subject is holding his breath. An attempt is made to understand whether these changes induced by stoppage of breathing are 'chaotic' or 'adaptive' in nature.

  20. Cutting Edge: IFN-γ Produced by Brain-Resident Cells Is Crucial To Control Cerebral Infection with Toxoplasma gondii.

    PubMed

    Sa, Qila; Ochiai, Eri; Tiwari, Ashish; Perkins, Sara; Mullins, Jeremi; Gehman, Marie; Huckle, William; Eyestone, Willard H; Saunders, Thomas L; Shelton, Brent J; Suzuki, Yasuhiro

    2015-08-01

    In vitro studies demonstrated that microglia and astrocytes produce IFN-γ in response to various stimulations, including LPS. However, the physiological role of IFN-γ production by brain-resident cells, including glial cells, in resistance against cerebral infections remains unknown. We analyzed the role of IFN-γ production by brain-resident cells in resistance to reactivation of cerebral infection with Toxoplasma gondii using a murine model. Our study using bone marrow chimeric mice revealed that IFN-γ production by brain-resident cells is essential for upregulating IFN-γ-mediated protective innate immune responses to restrict cerebral T. gondii growth. Studies using a transgenic strain that expresses IFN-γ only in CD11b(+) cells suggested that IFN-γ production by microglia, which is the only CD11b(+) cell population among brain-resident cells, is able to suppress the parasite growth. Furthermore, IFN-γ produced by brain-resident cells is pivotal for recruiting T cells into the brain to control the infection. These results indicate that IFN-γ produced by brain-resident cells is crucial for facilitating both the protective innate and T cell-mediated immune responses to control cerebral infection with T. gondii. PMID:26091720

  1. Brain tumours and cigarette smoking: analysis of the INTERPHONE Canada case–control study

    PubMed Central

    2014-01-01

    Background There is conflicting evidence regarding the associations between cigarette smoking and glioma or meningioma. Our purpose is to provide further evidence on these possible associations. Methods We conducted a set of case–control studies in three Canadian cities, Montreal, Ottawa and Vancouver. The study included 166 subjects with glioma, 93 subjects with meningioma, and 648 population-based controls. A lifetime history of cigarette smoking was collected and various smoking indices were computed. Multivariable logistic regression was used to estimate odds ratios (ORs) between smoking and each of the two types of brain tumours. Results Adjusted ORs between smoking and each type of brain tumour were not significantly elevated for all smokers combined or for smokers with over 15 pack-years ((packs / day) x years) accumulated. We tested for interactions between smoking and several sociodemographic variables; the interaction between smoking and education on glioma risk was significant, with smoking showing an elevated OR among subjects with lower education and an OR below unity among subjects with higher education. Conclusion Except for an unexplained and possibly artefactual excess risk in one population subgroup, we found little or no evidence of an association between smoking and either glioma or meningioma. PMID:24972852

  2. Intervention for infants with brain injury: Results of a randomized controlled study

    PubMed Central

    Badr, Lina Kurdahi; Garg, Meena; Kamath, Meghna

    2009-01-01

    A randomized clinical trail (RCT) employed a 12-month individualized cognitive/sensorimotor stimulation program to look at the efficacy of the intervention on 62 infants with suspected brain injury. The control group infants received the State-funded follow-up program provided by the Los Angeles (LA) Regional Centers while the intervention group received intensive stimulation using the Curriculum and Monitoring System (CAMS) taught by public health nurses (PHNs). The developmental assessments and outcome measures were performed at 6, 12 and 18 months corrected age and included the Bayley motor and mental development, the Home, mother–infant interaction (Nursing Child Assessment Feeding Scale (NCAFS) and Nursing Child Assessment Teaching Scale (NCATS)), parental stress and social support. At 18 months, 43 infants remained in the study. The results indicate that the intervention had minimal positive effects on the Bayley mental and motor development scores of infants in the intervention group. Likewise, the intervention did not contribute to less stress or better mother–infant interaction at 12 or 18 months although there were significant differences in the NCAFS scores favoring the intervention group at 6 months. There was a significant trend, however, for the control group to have a significant decrease over time on the Bayley mental scores. Although the sample was not large and attrition was at 31%, this study provides further support to the minimal effects of stimulation and home intervention for infants with brain injury and who may have more significant factors contributing to their developmental outcome. PMID:17138264

  3. Unique Brain Areas Associated with Abstinence Control Are Damaged in Multiply Detoxified Alcoholics

    PubMed Central

    Duka, Theodora; Trick, Leanne; Nikolaou, Kyriaki; Gray, Marcus A.; Kempton, Matthew J.; Williams, Hugh; Williams, Steven C.R.; Critchley, Hugo D.; Stephens, David N.

    2011-01-01

    Background The ability to abstain from drinking, despite incentives to imbibe, is essential to recovery from alcoholism. Methods We used an incentive conflict task to investigate ability to abstain from responding during presentations of incentive cues. Both alcoholic (n = 23) and healthy subjects (n = 22) were required to withhold responding during the simultaneous presentation of two visual stimuli in which the individual presentation allowed responding for monetary reward. Brain structures activated during performance of the task were studied using functional magnetic resonance imaging in healthy volunteers (n = 8), and changes in gray matter volume were studied in a separate group of patients (n = 29) compared with control subjects (n = 31) in regions of interest identified on functional magnetic resonance imaging. Results Abstinent alcoholic patients were severely impaired on the incentive conflict task. The impairment was greater in patients with experience of several versus a single detoxification. Healthy volunteers, during the same incentive conflict task, showed distinct patterns of brain activation (including gyrus rectus, ventromedial prefrontal cortex, and superior frontal gyrus). Reduction of gray matter volume in ventromedial prefrontal cortex and superior frontal gyrus of patients was more extensive in those with multiple detoxifications. Conclusions Performance deficits in alcoholics are associated with withdrawal-induced impairments in prefrontal subfields, which are exacerbated following repeated episodes of detoxification. Detoxification thus compromises functional and structural integrity of prefrontal cortex and may thus impair the ability to control future drinking. Performance in the incentive conflict task is a sensitive biomarker for such deficits. PMID:21612768

  4. Using a cVEP-Based Brain-Computer Interface to Control a Virtual Agent.

    PubMed

    Riechmann, Hannes; Finke, Andrea; Ritter, Helge

    2016-06-01

    Brain-computer interfaces provide a means for controlling a device by brain activity alone. One major drawback of noninvasive BCIs is their low information transfer rate, obstructing a wider deployment outside the lab. BCIs based on codebook visually evoked potentials (cVEP) outperform all other state-of-the-art systems in that regard. Previous work investigated cVEPs for spelling applications. We present the first cVEP-based BCI for use in real-world settings to accomplish everyday tasks such as navigation or action selection. To this end, we developed and evaluated a cVEP-based on-line BCI that controls a virtual agent in a simulated, but realistic, 3-D kitchen scenario. We show that cVEPs can be reliably triggered with stimuli in less restricted presentation schemes, such as on dynamic, changing backgrounds. We introduce a novel, dynamic repetition algorithm that allows for optimizing the balance between accuracy and speed individually for each user. Using these novel mechanisms in a 12-command cVEP-BCI in the 3-D simulation results in ITRs of 50 bits/min on average and 68 bits/min maximum. Thus, this work supports the notion of cVEP-BCIs as a particular fast and robust approach suitable for real-world use. PMID:26469340

  5. Motor imaginary-based brain-machine interface design using programmable logic controllers for the disabled.

    PubMed

    Jeyabalan, Vickneswaran; Samraj, Andrews; Loo, Chu Kiong

    2010-10-01

    Aiming at the implementation of brain-machine interfaces (BMI) for the aid of disabled people, this paper presents a system design for real-time communication between the BMI and programmable logic controllers (PLCs) to control an electrical actuator that could be used in devices to help the disabled. Motor imaginary signals extracted from the brain’s motor cortex using an electroencephalogram (EEG) were used as a control signal. The EEG signals were pre-processed by means of adaptive recursive band-pass filtrations (ARBF) and classified using simplified fuzzy adaptive resonance theory mapping (ARTMAP) in which the classified signals are then translated into control signals used for machine control via the PLC. A real-time test system was designed using MATLAB for signal processing, KEP-Ware V4 OLE for process control (OPC), a wireless local area network router, an Omron Sysmac CPM1 PLC and a 5 V/0.3A motor. This paper explains the signal processing techniques, the PLC's hardware configuration, OPC configuration and real-time data exchange between MATLAB and PLC using the MATLAB OPC toolbox. The test results indicate that the function of exchanging real-time data can be attained between the BMI and PLC through OPC server and proves that it is an effective and feasible method to be applied to devices such as wheelchairs or electronic equipment. PMID:20336561

  6. [Brain edema treatment procedure using continuous controlled infusion of mannitol in neurosurgical patients].

    PubMed

    Taranova, I I; Kokhno, V N

    2010-01-01

    The paper evaluates the efficiency and safety of the developed osmotherapy protocol using controlled continuous infusion of 15% mannitol solution. Two hundred and nine patients with intracranial hypertension (ICH) syndrome of various etiologies had 15% mannitol infusion, the rate of which was determined by clinical criteria. The infusion rate was 50 ml/hr with midline brain structure dislocation of 8 mm or more and major depression of consciousness (a Glasgow coma scale (GCS) score of less than 8) and 25 ml/hr with brain dislocation of 7-mm or less and a GCS score of 8 or higher. The monitoring program was as follows: Block 1 comprised the clinical and instrumental data characterizing the adequacy of brain perfusion (GCS, the magnitude of focal neurological symptoms, ICH, mean blood pressure, computed tomographic dislocation); Block 2 involved the clinical and laboratory data identifying the extracerebral complications of osmotherapy (packed cell volume, plasma osmolarity, urine density, and renal ultrasonography); Block 3 consisted of cerebral oximetry (CO) and Neurotrend. The authors' early proposed integral indicators of OC, such as interhemispheric asymmetry coefficient and hemodynamic conformity index, were used to estimate the adequacy of brain perfusion. In cerebral vasospasm, a Neurotrend microsensor was implanted at 3-cm depth for the direct quantitative determination of pO2, pCO2, pH, and brain temperature. ICH was characterized by natural changes in the CO indicators. In vasospasm, the mean linear blood flow velocity was 245 +/- 14 cm/sec in the basilar arteries, which was attended by low pO2 and metabolic acidosis, as shown by readings. Optimization of artificial ventilation, stabilization of hemodynamics, and the use of postural exposures and osmo diuretics promoted ICH normalization and central perfusion pressure optimization, which was accompanied by the disappearance of tissue hypoxia and acidosis, as suggested by Neurotrend reading. The duration of

  7. IpsiHand Bravo: an improved EEG-based brain-computer interface for hand motor control rehabilitation.

    PubMed

    Holmes, Charles Damian; Wronkiewicz, Mark; Somers, Thane; Liu, Jenny; Russell, Elizabeth; Kim, DoHyun; Rhoades, Colleen; Dunkley, Jason; Bundy, David; Galboa, Elad; Leuthardt, Eric

    2012-01-01

    Stroke and other nervous system injuries can damage or destroy hand motor control and greatly upset daily activities. Brain computer interfaces (BCIs) represent an emerging technology that can bypass damaged nerves to restore basic motor function and provide more effective rehabilitation. A wireless BCI system was implemented to realize these goals using electroencephalographic brain signals, machine learning techniques, and a custom designed orthosis. The IpsiHand Bravo BCI system is designed to reach a large demographic by using non-traditional brain signals and improving on past BCI system pitfalls. PMID:23366248

  8. Robust Brain-Machine Interface Design Using Optimal Feedback Control Modeling and Adaptive Point Process Filtering.

    PubMed

    Shanechi, Maryam M; Orsborn, Amy L; Carmena, Jose M

    2016-04-01

    Much progress has been made in brain-machine interfaces (BMI) using decoders such as Kalman filters and finding their parameters with closed-loop decoder adaptation (CLDA). However, current decoders do not model the spikes directly, and hence may limit the processing time-scale of BMI control and adaptation. Moreover, while specialized CLDA techniques for intention estimation and assisted training exist, a unified and systematic CLDA framework that generalizes across different setups is lacking. Here we develop a novel closed-loop BMI training architecture that allows for processing, control, and adaptation using spike events, enables robust control and extends to various tasks. Moreover, we develop a unified control-theoretic CLDA framework within which intention estimation, assisted training, and adaptation are performed. The architecture incorporates an infinite-horizon optimal feedback-control (OFC) model of the brain's behavior in closed-loop BMI control, and a point process model of spikes. The OFC model infers the user's motor intention during CLDA-a process termed intention estimation. OFC is also used to design an autonomous and dynamic assisted training technique. The point process model allows for neural processing, control and decoder adaptation with every spike event and at a faster time-scale than current decoders; it also enables dynamic spike-event-based parameter adaptation unlike current CLDA methods that use batch-based adaptation on much slower adaptation time-scales. We conducted closed-loop experiments in a non-human primate over tens of days to dissociate the effects of these novel CLDA components. The OFC intention estimation improved BMI performance compared with current intention estimation techniques. OFC assisted training allowed the subject to consistently achieve proficient control. Spike-event-based adaptation resulted in faster and more consistent performance convergence compared with batch-based methods, and was robust to parameter

  9. Pilot Study on Long Term Effects of HZE Exposure on the Canine Brain

    NASA Astrophysics Data System (ADS)

    Budinger, T.; Brennan, K.; Pearlstein, R.

    (+ 3 additional age-matched controls) were in-situ perfused with 4% paraformaldehyde/01.M phosphate buffer. The brain was removed and fixed in the same fixative for 2 weeks. Brain sections were embedded in parafin and cut at 6 or 12 μm thickness. Histology included H&E, Luxol fast blue and Silver staining. Immunochemistry included Amyloidprecursor protein. There was no marked increase in amyloid plaque formation in the irradiated dogs. Imaging and histology results will be presented at the COSPAR conference.

  10. Brain glucose utilization in systemic lupus erythematosus with neuropsychiatric symptoms: a controlled positron emission tomography study.

    PubMed

    Otte, A; Weiner, S M; Peter, H H; Mueller-Brand, J; Goetze, M; Moser, E; Gutfleisch, J; Hoegerle, S; Juengling, F D; Nitzsche, E U

    1997-07-01

    In contrast to morphological imaging [such as magnetic resonance imaging (MRI) or computed tomography], functional imaging may be of advantage in the detection of brain abnormalities in cases of neuropsychiatric systemic lupus erythematosus (SLE). Therefore, we studied 13 patients (aged 40+/-14 years, 11 female, 2 male) with neuropsychiatric SLE who met four of the American Rheumatism Association criteria for the classification of SLE. Ten clinically and neurologically healthy volunteers served as controls (aged 40+/-12 years, 5 female, 5 male). Both groups were investigated using fluorine-18-labelled fluorodeoxyglucose brain positron emission tomography (PET) and cranial MRI. The normal controls and 11 of the 13 patients showed normal MRI scans. However, PET scan was abnormal in all 13 SLE patients. Significant group-to-group differences in the glucose metabolic index (GMI=region of interest uptake/global uptake at the level of the basal ganglia and thalamus) were found in the parieto-occipital region on both sides: the GMI of the parieto-occipital region on the right side was 0.922+/-0.045 in patients and 1.066+/-0.081 in controls (P<0.0001, Mann Whitney U test), while on the left side it was 0.892+/-0.060 in patients and 1. 034+/-0.051 in controls (P=0.0002). Parieto-occipital hypometabolism is a conspicuous finding in mainly MRI-negative neuropsychiatric SLE. As the parieto-occipital region is located at the boundary of blood supply of all three major arteries, it could be the most vulnerable zone of the cerebrum and may be affected at an early stage of the cerebrovascular disease. PMID:9211766

  11. Non-invasive brain stimulation enhances fine motor control of the hemiparetic ankle: implications for rehabilitation.

    PubMed

    Madhavan, Sangeetha; Weber, Kenneth A; Stinear, James W

    2011-03-01

    We set out to answer two questions with this study: 1. Can stroke patients improve voluntary control of their paretic ankle by practising a visuo-motor ankle-tracking task? 2. Are practice effects enhanced with non-invasive brain stimulation? A carefully selected sample of chronic stroke patients able to perform the experimental task attended three data collection sessions. Facilitatory transcranial direct current stimulation (tDCS) was applied in a random order over the lower limb primary motor cortex of the lesioned hemisphere or the non-lesioned hemisphere or sham stimulation was delivered over the lesioned hemisphere. In each session, tDCS was applied as patients practiced tracking a sinusoidal waveform for 15 min using dorsiflexion-plantarflexion movements of their paretic ankle. The difference in tracking error prior to, and after, the 15 min of practice was calculated. A practice effect was revealed following sham stimulation, and this effect was enhanced with tDCS applied over the lesioned hemisphere. The practice effect observed following sham stimulation was eliminated by tDCS applied over the non-lesioned hemisphere. The study provides the first evidence that non-invasive brain stimulation applied to the lesioned motor cortex of moderate- to well-recovered stroke patients enhances voluntary control of the paretic ankle. The results provide a basis for examining whether this enhanced ankle control can be induced in patients with greater impairments and whether enhanced control of a single or multiple lower limb joints improves hemiparetic gait patterns. PMID:21170708

  12. An exercise-based randomized controlled trial on brain, cognition, physical health and mental health in overweight/obese children (ActiveBrains project): Rationale, design and methods.

    PubMed

    Cadenas-Sánchez, Cristina; Mora-González, José; Migueles, Jairo H; Martín-Matillas, Miguel; Gómez-Vida, José; Escolano-Margarit, María Victoria; Maldonado, José; Enriquez, Gala María; Pastor-Villaescusa, Belén; de Teresa, Carlos; Navarrete, Socorro; Lozano, Rosa María; de Dios Beas-Jiménez, Juan; Estévez-López, Fernando; Mena-Molina, Alejandra; Heras, María José; Chillón, Palma; Campoy, Cristina; Muñoz-Hernández, Victoria; Martínez-Ávila, Wendy Daniela; Merchan, María Elisa; Perales, José C; Gil, Ángel; Verdejo-García, Antonio; Aguilera, Concepción M; Ruiz, Jonatan R; Labayen, Idoia; Catena, Andrés; Ortega, Francisco B

    2016-03-01

    The new and recent advances in neuroelectric and neuroimaging technologies provide a new era for further exploring and understanding how brain and cognition function can be stimulated by environmental factors, such as exercise, and particularly to study whether physical exercise influences brain development in early ages. The present study, namely the ActiveBrains project, aims to examine the effects of a physical exercise programme on brain and cognition, as well as on selected physical and mental health outcomes in overweight/obese children. A total of 100 participants aged 8 to 11 years are randomized into an exercise group (N=50) or a control group (N=50). The intervention lasts 20-weeks, with 3-5 sessions per week of 90 min each, and is mainly focused on high-intensity aerobic exercise yet also includes muscle-strengthening exercises. The extent to what the intervention effect remains 8-months after the exercise programme finishes is also studied in a subsample. Brain structure and function and cognitive performance are assessed using structural and functional magnetic resonance imaging and electroencephalographic recordings. Secondary outcomes include physical health outcomes (e.g. physical fitness, body fatness, bone mass and lipid-metabolic factors) and mental health outcomes (e.g. chronic stress indicators and overall behavioural and personality measurements such as anxiety or depression). This project will substantially contribute to the existing knowledge and will have an impact on societies, since early stimulation of brain development might have long lasting consequences on cognitive performance, academic achievement and in the prevention of behavioural problems and the promotion of psychological adjustment and mental health. Clinical trials. Gov identifier: NCT02295072. PMID:26924671

  13. Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium.

    PubMed

    van Erp, T G M; Hibar, D P; Rasmussen, J M; Glahn, D C; Pearlson, G D; Andreassen, O A; Agartz, I; Westlye, L T; Haukvik, U K; Dale, A M; Melle, I; Hartberg, C B; Gruber, O; Kraemer, B; Zilles, D; Donohoe, G; Kelly, S; McDonald, C; Morris, D W; Cannon, D M; Corvin, A; Machielsen, M W J; Koenders, L; de Haan, L; Veltman, D J; Satterthwaite, T D; Wolf, D H; Gur, R C; Gur, R E; Potkin, S G; Mathalon, D H; Mueller, B A; Preda, A; Macciardi, F; Ehrlich, S; Walton, E; Hass, J; Calhoun, V D; Bockholt, H J; Sponheim, S R; Shoemaker, J M; van Haren, N E M; Hulshoff Pol, H E; Pol, H E H; Ophoff, R A; Kahn, R S; Roiz-Santiañez, R; Crespo-Facorro, B; Wang, L; Alpert, K I; Jönsson, E G; Dimitrova, R; Bois, C; Whalley, H C; McIntosh, A M; Lawrie, S M; Hashimoto, R; Thompson, P M; Turner, J A

    2016-04-01

    The profile of brain structural abnormalities in schizophrenia is still not fully understood, despite decades of research using brain scans. To validate a prospective meta-analysis approach to analyzing multicenter neuroimaging data, we analyzed brain MRI scans from 2028 schizophrenia patients and 2540 healthy controls, assessed with standardized methods at 15 centers worldwide. We identified subcortical brain volumes that differentiated patients from controls, and ranked them according to their effect sizes. Compared with healthy controls, patients with schizophrenia had smaller hippocampus (Cohen's d=-0.46), amygdala (d=-0.31), thalamus (d=-0.31), accumbens (d=-0.25) and intracranial volumes (d=-0.12), as well as larger pallidum (d=0.21) and lateral ventricle volumes (d=0.37). Putamen and pallidum volume augmentations were positively associated with duration of illness and hippocampal deficits scaled with the proportion of unmedicated patients. Worldwide cooperative analyses of brain imaging data support a profile of subcortical abnormalities in schizophrenia, which is consistent with that based on traditional meta-analytic approaches. This first ENIGMA Schizophrenia Working Group study validates that collaborative data analyses can readily be used across brain phenotypes and disorders and encourages analysis and data sharing efforts to further our understanding of severe mental illness. PMID:26033243

  14. Building the Brain's "Air Traffic Control" System: How Early Experiences Shape the Development of Executive Function. Working Paper 11

    ERIC Educational Resources Information Center

    National Scientific Council on the Developing Child, 2011

    2011-01-01

    Being able to focus, hold, and work with information in mind, filter distractions, and switch gears is like having an air traffic control system at a busy airport to manage the arrivals and departures of dozens of planes on multiple runways. In the brain, this air traffic control mechanism is called executive functioning, a group of skills that…

  15. Brain-Machine Interface control of a robot arm using actor-critic rainforcement learning.

    PubMed

    Pohlmeyer, Eric A; Mahmoudi, Babak; Geng, Shijia; Prins, Noeline; Sanchez, Justin C

    2012-01-01

    Here we demonstrate how a marmoset monkey can use a reinforcement learning (RL) Brain-Machine Interface (BMI) to effectively control the movements of a robot arm for a reaching task. In this work, an actor-critic RL algorithm used neural ensemble activity in the monkey's motor cortext to control the robot movements during a two-target decision task. This novel approach to decoding offers unique advantages for BMI control applications. Compared to supervised learning decoding methods, the actor-critic RL algorithm does not require an explicit set of training data to create a static control model, but rather it incrementally adapts the model parameters according to its current performance, in this case requiring only a very basic feedback signal. We show how this algorithm achieved high performance when mapping the monkey's neural states (94%) to robot actions, and only needed to experience a few trials before obtaining accurate real-time control of the robot arm. Since RL methods responsively adapt and adjust their parameters, they can provide a method to create BMIs that are robust against perturbations caused by changes in either the neural input space or the output actions they generate under different task requirements or goals. PMID:23366831

  16. Two Agents in the Brain: Motor Control of Unimanual and Bimanual Reaching Movements

    PubMed Central

    Asai, Tomohisa; Sugimori, Eriko; Tanno, Yoshihiko

    2010-01-01

    Previous studies have suggested that the left and right hands have different specialties for motor control that can be represented as two agents in the brain. This study examined how coordinated movements are performed during bimanual reaching tasks to highlight differences in the characteristics of the hands. We examined motor movement accuracy, reaction time, and movement time in right-handed subjects performing a three-dimensional motor control task (visually guided reaching). In the no-visual-feedback condition, right-hand movement had lower accuracy and a shorter reaction time than did left-hand movement, whereas bimanual movement had the longest reaction time, but the best accuracy. This suggests that the two hands have different internal models and specialties: closed-loop control for the right hand and open-loop control for the left hand. Consequently, during bimanual movements, both models might be used, creating better control and planning (or prediction), but requiring more computation time compared to the use of one hand only. PMID:20386749

  17. Toward brain-computer interface based wheelchair control utilizing tactually-evoked event-related potentials

    PubMed Central

    2014-01-01

    Background People with severe disabilities, e.g. due to neurodegenerative disease, depend on technology that allows for accurate wheelchair control. For those who cannot operate a wheelchair with a joystick, brain-computer interfaces (BCI) may offer a valuable option. Technology depending on visual or auditory input may not be feasible as these modalities are dedicated to processing of environmental stimuli (e.g. recognition of obstacles, ambient noise). Herein we thus validated the feasibility of a BCI based on tactually-evoked event-related potentials (ERP) for wheelchair control. Furthermore, we investigated use of a dynamic stopping method to improve speed of the tactile BCI system. Methods Positions of four tactile stimulators represented navigation directions (left thigh: move left; right thigh: move right; abdomen: move forward; lower neck: move backward) and N = 15 participants delivered navigation commands by focusing their attention on the desired tactile stimulus in an oddball-paradigm. Results Participants navigated a virtual wheelchair through a building and eleven participants successfully completed the task of reaching 4 checkpoints in the building. The virtual wheelchair was equipped with simulated shared-control sensors (collision avoidance), yet these sensors were rarely needed. Conclusion We conclude that most participants achieved tactile ERP-BCI control sufficient to reliably operate a wheelchair and dynamic stopping was of high value for tactile ERP classification. Finally, this paper discusses feasibility of tactile ERPs for BCI based wheelchair control. PMID:24428900

  18. Memantine and brain atrophy in Alzheimer's disease: a 1-year randomized controlled trial.

    PubMed

    Wilkinson, David; Fox, Nick C; Barkhof, Frederik; Phul, Ravinder; Lemming, Ole; Scheltens, Philip

    2012-01-01

    The primary objective of this study was to evaluate the rate of total brain atrophy (TBA) with serial magnetic resonance imaging (MRI), using the Brain Boundary Shift Integral (BBSI), in patients with probable Alzheimer's disease (AD) over the course of 52 weeks of treatment with memantine or placebo. This was a multi-national, randomized, double-blind, placebo-controlled, fixed-dose 1-year study. Patients were randomized (1 : 1) to treatment with placebo or memantine. Patients randomized to memantine were up-titrated to the target dose of 20 mg/day over 4 weeks. MRI scans were collected at screening and at Weeks 4, 42, and 52. Secondary efficacy assessments included several cognitive and behavioral scales. 518 patients were screened, 278 patients were randomized, and 217 patients completed the study. In the primary efficacy analysis, the differences in TBA rates between memantine (15.2 mL/year) and placebo (15.3 mL/year) were not statistically significant (-0.04 mL/year [(95% CI: -2.60, 2.52), p = 0.98]). There was a statistically significant correlation between change in TBA and change in most cognitive and behavioral scale scores. Patients who were not treated with acetyl cholinesterase inhibitors (AChEIs) showed a significantly lower TBA rate than patients treated with AChEIs. Memantine had a placebo-level incidence of adverse events. There were no statistically significant differences between memantine and placebo in total brain or hippocampal atrophy rates in patients with probable AD treated for 1 year. The biological relevance of cerebral atrophy was supported by a significant correlation between rate of atrophy and decline in cognitive and behavioral outcomes. PMID:22269160

  19. Neuroinflammation and brain atrophy in former NFL players: An in vivo multimodal imaging pilot study

    PubMed Central

    Munro, Cynthia A.; Ma, Shuangchao; Yue, Chen; Chen, Shaojie; Airan, Raag; Kim, Pearl K.; Adams, Ashley V.; Garcia, Cinthya; Higgs, Cecilia; Sair, Haris I.; Sawa, Akira; Smith, Gwenn; Lyketsos, Constantine G.; Caffo, Brian; Kassiou, Michael; Guilarte, Tomas R.; Pomper, Martin G.

    2015-01-01

    There are growing concerns about potential delayed, neuropsychiatric consequences (e.g, cognitive decline, mood or anxiety disorders) of sports-related traumatic brain injury (TBI). Autopsy studies of brains from a limited number of former athletes have described characteristic, pathologic changes of chronic traumatic encephalopathy (CTE) leading to questions about the relationship between these pathologic and the neuropsychiatric disturbances seen in former athletes. Research in this area will depend on in vivo methods that characterize molecular changes in the brain, linking CTE and other sports-related pathologies with delayed emergence of neuropsychiatric symptoms. In this pilot project we studied former National Football League (NFL) players using new neuroimaging techniques and clinical measures of cognitive functioning. We hypothesized that former NFL players would show molecular and structural changes in medial temporal and parietal lobe structures as well as specific cognitive deficits, namely those of verbal learning and memory. We observed a significant increase in binding of [11C]DPA-713 to the translocator protein (TSPO), a marker of brain injury and repair, in several brain regions, such as the supramarginal gyrus and right amygdala, in 9 former NFL players compared to 9 age-matched, healthy controls. We also observed significant atrophy of the right hippocampus. Finally, we report that these same former players had varied performance on a test of verbal learning and memory, suggesting that these molecular and pathologic changes may play a role in cognitive decline. These results suggest that localized brain injury and repair, indicated by increased [11C]DPA-713 binding to TSPO, may be linked to history of NFL play. [11C]DPA-713 PET is a promising new tool that can be used in future study design to examine further the relationship between TSPO expression in brain injury and repair, selective regional brain atrophy, and the potential link to deficits

  20. Sustained hypoxia modulates mitochondrial DNA content in the neonatal rat brain.

    PubMed

    Lee, Heung M; Greeley, George H; Englander, Ella W

    2008-03-01

    The effects of placental insufficiency and preterm birth on neurodevelopment can be modeled in experimental settings of neonatal hypoxia in rodents. Here, rat pups were reared in reduced oxygen (9.5%) for 11 days, starting on postnatal day 3 (P3). This led to a significant reduction in brain and body weight gain in hypoxic pups compared to age-matched normoxia-reared controls, plausibly reflecting an inability to fulfill the energetic needs of normal growth and development. Adaptive processes designed to augment energetic capacity in eukaryotes include stimulation of mitochondrial biogenesis. We show that after 11 days of sustained hypoxia, the levels of nuclear respiratory factor-1 and mitochondrial transcription factor A are elevated and the content of mitochondrial DNA (mtDNA) is greater in the hypoxic P14 pup brain compared to normoxic conditions. Corresponding immunohistochemical analyses reveal increased density of mtDNA in large cortical neurons. In contrast, no changes in mtDNA content are observed in the brain of pups reared for 24 h (P3-P4) under hypoxic conditions. Together, these data suggest that prolonged inadequate oxygenation may trigger a compensatory increase in neuronal mitochondrial DNA content to partially mitigate compromised energy homeostasis and reduced energetic capacity in the developing hypoxic brain. PMID:18078825

  1. Aberrant topologies and reconfiguration pattern of functional brain network in children with second language reading impairment.

    PubMed

    Liu, Lanfang; Li, Hehui; Zhang, Manli; Wang, Zhengke; Wei, Na; Liu, Li; Meng, Xiangzhi; Ding, Guosheng

    2016-07-01

    Prior work has extensively studied neural deficits in children with reading impairment (RI) in their native language but has rarely examined those of RI children in their second language (L2). A recent study revealed that the function of the local brain regions was disrupted in children with RI in L2, but it is not clear whether the disruption also occurs at a large-scale brain network level. Using fMRI and graph theoretical analysis, we explored the topology of the whole-brain functional network during a phonological rhyming task and network reconfigurations across task and short resting phases in Chinese children with English reading impairment versus age-matched typically developing (TD) children. We found that, when completing the phonological task, the RI group exhibited higher local network efficiency and network modularity compared with the TD group. When switching between the phonological task and the short resting phase, the RI group showed difficulty with network reconfiguration, as reflected in fewer changes in the local efficiency and modularity properties and less rearrangement of the modular communities. These findings were reproducible after controlling for the effects of in-scanner accuracy, participant gender, and L1 reading performance. The results from the whole-brain network analyses were largely replicated in the task-activated network. These findings provide preliminary evidence supporting that RI in L2 is associated with not only abnormal functional network organization but also poor flexibility of the neural system in responding to changing cognitive demands. PMID:27321248

  2. Duodeno-Gastric-Esophageal Reflux—What is Pathologic? Comparison of Patients with Barrett’s Esophagus and Age-Matched Volunteers

    PubMed Central

    Wolfgarten, Eva; Pütz, Benito; Hölscher, Arnulf H.

    2007-01-01

    Introduction The aim of the study was to analyse pH- and bile-monitoring data in patients with Barrett’s esophagus and in age- and gender-matched controls. Subjects and Methods Twenty-four consecutive Barrett’s patients (8 females, 16 males, mean age 57 years), 21 patients with esophagitis (10 females, 11 males, mean age 58 years), and 19 healthy controls (8 females, 11 males, mean age 51 years), were included. Only patients underwent endoscopy with biopsy. All groups were investigated with manometry, gastric and esophageal 24-h pH, and simultaneous bile monitoring according to a standardized protocol. A bilirubin absorption >0.25 was determined as noxious bile reflux. The receiver operator characteristic (ROC) method was applied to determine the optimal cutoff value of pathologic bilirubin levels. Results Of Barrett’s patients, 79% had pathologic acidic gastric reflux (pH<4 >5% of total measuring time). However, 32% of healthy controls also had acid reflux (p < 0.05) without any symptoms. The median of esophageal bile reflux was 7.8% (lower quartile (LQ)–upper quartile (UQ) = 1.6–17.8%) in Barrett’s patients, in patients with esophagitis, 3.5% (LQ–UQ = 0.1–13.5), and in contrast to 0% (LQ–UQ = 0–1.0%) in controls, p = 0.001. ROC analysis showed the optimal dividing value for patients at more than 1% bile reflux over 24 h (75% sensitivity, 84% specificity). Conclusion An optimal threshold to differentiate between normal and pathological bile reflux into the esophagus is 1% (24-h bile monitoring with an absorbance >0.25). PMID:17436133

  3. The control of brain mitochondrial energization by cytosolic calcium: the mitochondrial gas pedal.

    PubMed

    Gellerich, Frank Norbert; Gizatullina, Zemfira; Gainutdinov, Timur; Muth, Katharina; Seppet, Enn; Orynbayeva, Zulfiya; Vielhaber, Stefan

    2013-03-01

    This review focuses on problems of the intracellular regulation of mitochondrial function in the brain via the (i) supply of mitochondria with ADP by means of ADP shuttles and channels and (ii) the Ca(2+) control of mitochondrial substrate supply. The permeability of the mitochondrial outer membrane for adenine nucleotides is low. Therefore rate dependent concentration gradients exist between the mitochondrial intermembrane space and the cytosol. The existence of dynamic ADP gradients is an important precondition for the functioning of ADP shuttles, for example CrP-shuttle. Cr at mM concentrations instead of ADP diffuses from the cytosol through the porin pores into the intermembrane space. The CrP-shuttle isoenzymes work in different directions which requires different metabolite concentrations mainly caused by dynamic ADP compartmentation. The ADP shuttle mechanisms alone cannot explain the load dependent changes in mitochondrial energization, and a complete model of mitochondrial regulation have to account the Ca(2+) -dependent substrate supply too. According to the old paradigmatic view, Ca(2+) (cyt) taken up by the mitochondrial Ca(2+) uniporter activates dehydrogenases within the matrix. However, recently it was found that Ca(2+) (cyt) at low nM concentrations exclusively activates the state 3 respiration via aralar, the mitochondrial glutamate/aspartate carrier. At higher Ca(2+) (cyt) (> 500 nM), brain mitochondria take up Ca(2+) for activation of substrate oxidation rates. Since brain mitochondrial pyruvate oxidation is only slightly influenced by Ca(2+) (cyt) , it was proposed that the cytosolic formation of pyruvate from its precursors is tightly controlled by the Ca(2+) dependent malate/aspartate shuttle. At low (50-100 nM) Ca(2+) (cyt) the pyruvate formation is suppressed, providing a substrate limitation control in neurons. This so called "gas pedal" mechanism explains why the energy metabolism of neurons in the nucleus suprachiasmaticus could be down

  4. A telepresence mobile robot controlled with a noninvasive brain-computer interface.

    PubMed

    Escolano, Carlos; Antelis, Javier Mauricio; Minguez, Javier

    2012-06-01

    This paper reports an electroencephalogram-based brain-actuated telepresence system to provide a user with presence in remote environments through a mobile robot, with access to the Internet. This system relies on a P300-based brain-computer interface (BCI) and a mobile robot with autonomous navigation and camera orientation capabilities. The shared-control strategy is built by the BCI decoding of task-related orders (selection of visible target destinations or exploration areas), which can be autonomously executed by the robot. The system was evaluated using five healthy participants in two consecutive steps: 1) screening and training of participants and 2) preestablished navigation and visual exploration telepresence tasks. On the basis of the results, the following evaluation studies are reported: 1) technical evaluation of the device and its main functionalities and 2) the users' behavior study. The overall result was that all participants were able to complete the designed tasks, reporting no failures, which shows the robustness of the system and its feasibility to solve tasks in real settings where joint navigation and visual exploration were needed. Furthermore, the participants showed great adaptation to the telepresence system. PMID:22180512

  5. Curing "moral disability": brain trauma and self-control in Victorian science and fiction.

    PubMed

    Schillace, Brandy L

    2013-12-01

    While, historically, the disabled body has appeared in literature as "monstrous," burgeoning psychological theories of the Victorian period predicated an unusual shift. In a culture of sexual anxiety and fears of devolution and moral decay, the physically disabled and "weak" are portrayed as strangely free from moral corruption. Unlike the cultural link between deviance and disability witnessed in the medical literature and eugenic approach to generation, authors of narrative fiction-particularly Charles Dickens, but Wilkie Collins, Charlotte Yonge, and others as well-portray disabled characters as "purified," and trauma itself as potentially sanitizing. This present paper argues that such constructions were made possible by developments in the treatment of insanity. "Curing 'Moral Disability': Brain Trauma and Self-Control in Victorian Fiction," examines the concept of trauma-as-cure. Throughout the Victorian period, case studies on brain trauma appeared in widely circulated journals like the Lancet, concurrently with burgeoning theories about psychological disturbance and "moral insanity." While not widely practiced until the early twentieth century, attempts at surgical "cures" aroused curiosity and speculation-the traumatic event that could free sufferers from deviance. This work provides a unique perspective on representations of disability as cure in the nineteenth century as a means of giving voice to the marginalized, disabled, and disempowered. PMID:24166450

  6. Radiation control in the intensive care unit for high intensity iridium-192 brain implants

    SciTech Connect

    Sewchand, W.; Drzymala, R.E.; Amin, P.P.; Salcman, M.; Salazar, O.M.

    1987-04-01

    A bedside lead cubicle was designed to minimize the radiation exposure of intensive care unit staff during routine interstitial brain irradiation by removable, high intensity iridium-192. The cubicle shields the patient without restricting intensive care routines. The design specifications were confirmed by exposure measurements around the shield with an implanted anthropomorphic phantom simulating the patient situation. The cubicle reduces the exposure rate around an implant patient by as much as 90%, with the exposure level not exceeding 0.1 mR/hour/mg of radium-equivalent /sup 192/Ir. Evaluation of data accumulated for the past 3 years has shown that the exposure levels of individual attending nurses are 0.12 to 0.36 mR/mg of radium-equivalent /sup 192/Ir per 12-hour shift. The corresponding range for entire nursing teams varies between 0.18 and 0.26. A radiation control index (exposure per mg of radium-equivalent /sup 192/Ir per nurse-hour) is thus defined for individual nurses and nursing teams; this index is a significant guide to the planning of nurse rotations for brain implant patients with various /sup 192/Ir loads. The bedside shield reduces exposure from /sup 192/Ir implants by a factor of about 20, as expected, and the exposure from the lower energy radioisotope iodine-125 is barely detectable.

  7. A study of brain white matter plasticity in early blinds using tract-based spatial statistics and tract statistical analysis.

    PubMed

    Lao, Yi; Kang, Yue; Collignon, Olivier; Brun, Caroline; Kheibai, Shadi B; Alary, Flamine; Gee, James; Nelson, Marvin D; Lepore, Franco; Lepore, Natasha

    2015-12-16

    Early blind individuals are known to exhibit structural brain reorganization. Particularly, early-onset blindness may trigger profound brain alterations that affect not only the visual system but also the remaining sensory systems. Diffusion tensor imaging (DTI) allows in-vivo visualization of brain white matter connectivity, and has been extensively used to study brain white matter structure. Among statistical approaches based on DTI, tract-based spatial statistics (TBSS) is widely used because of its ability to automatically perform whole brain white matter studies. Tract specific analysis (TSA) is a more recent method that localizes changes in specific white matter bundles. In the present study, we compare TBSS and TSA results of DTI scans from 12 early blind individuals and 13 age-matched sighted controls, with two aims: (a) to investigate white matter alterations associated with early visual deprivation; (b) to examine the relative sensitivity of TSA when compared with TBSS, for both deficit and hypertrophy of white matter microstructures. Both methods give consistent results for broad white matter regions of deficits. However, TBSS does not detect hypertrophy of white matter, whereas TSA shows a higher sensitivity in detecting subtle differences in white matter colocalized to the posterior parietal lobe. PMID:26559727

  8. Structural and Functional Brain Remodeling during Pregnancy with Diffusion Tensor MRI and Resting-State Functional MRI

    PubMed Central

    Chan, Russell W.; Ho, Leon C.; Zhou, Iris Y.; Gao, Patrick P.; Chan, Kevin C.; Wu, Ed X.

    2015-01-01

    Although pregnancy-induced hormonal changes have been shown to alter the brain at the neuronal level, the exact effects of pregnancy on brain at the tissue level remain unclear. In this study, diffusion tensor imaging (DTI) and resting-state functional MRI (rsfMRI) were employed to investigate and document the effects of pregnancy on the structure and function of the brain tissues. Fifteen Sprague-Dawley female rats were longitudinally studied at three days before mating (baseline) and seventeen days after mating (G17). G17 is equivalent to the early stage of the third trimester in humans. Seven age-matched nulliparous female rats served as non-pregnant controls and were scanned at the same time-points. For DTI, diffusivity was found to generally increase in the whole brain during pregnancy, indicating structural changes at microscopic levels that facilitated water molecular movement. Regionally, mean diffusivity increased more pronouncedly in the dorsal hippocampus while fractional anisotropy in the dorsal dentate gyrus increased significantly during pregnancy. For rsfMRI, bilateral functional connectivity in the hippocampus increased significantly during pregnancy. Moreover, fractional anisotropy increase in the dentate gyrus appeared to correlate with the bilateral functional connectivity increase in the hippocampus. These findings revealed tissue structural modifications in the whole brain during pregnancy, and that the hippocampus was structurally and functionally remodeled in a more marked manner. PMID:26658306

  9. Brain-Emulating Cognition and Control Architecture (BECCA) V1.0 beta

    2007-09-30

    BECCA is a learning and control method based on the function of the human brain. The goal behind its creation is to learn to control robots in unfamiliar environments in a way that is very robust, similar to the way that an infant learns to interact with her environment by trial and error. As of this release, this software contains two simulations of BECCA controlling robots: one is a one degree-of-freedom spinner robot and themore » other is a 7 degree-of-freedom serial link arm with a terminal gripper. In addition, the software contains code that identifies synonyms in a untagged corpus of ASCII words. This last is a demonstration of BECCA's ability to generate abstract concepts from concrete experience. The BECCA simulation is coded so as to make it extensible to new applications. It is modular, object-oriented code in which the portions of the code that are specific to one simulation are easily separable from those portions that are the constant between implementations. BECCA makes very few assumptions about the robot and environment it is learning, and so is applicable to a wide range of learning and control problems.« less

  10. Molecular control of brain size: Regulators of neural stem cell life, death and beyond

    SciTech Connect

    Joseph, Bertrand; Hermanson, Ola

    2010-05-01

    The proper development of the brain and other organs depends on multiple parameters, including strictly controlled expansion of specific progenitor pools. The regulation of such expansion events includes enzymatic activities that govern the correct number of specific cells to be generated via an orchestrated control of cell proliferation, cell cycle exit, differentiation, cell death etc. Certain proteins in turn exert direct control of these enzymatic activities and thus progenitor pool expansion and organ size. The members of the Cip/Kip family (p21Cip1/p27Kip1/p57Kip2) are well-known regulators of cell cycle exit that interact with and inhibit the activity of cyclin-CDK complexes, whereas members of the p53/p63/p73 family are traditionally associated with regulation of cell death. It has however become clear that the roles for these proteins are not as clear-cut as initially thought. In this review, we discuss the roles for proteins of the Cip/Kip and p53/p63/p73 families in the regulation of cell cycle control, differentiation, and death of neural stem cells. We suggest that these proteins act as molecular interfaces, or 'pilots', to assure the correct assembly of protein complexes with enzymatic activities at the right place at the right time, thereby regulating essential decisions in multiple cellular events.

  11. A Power-Efficient Wireless System With Adaptive Supply Control for Deep Brain Stimulation.

    PubMed

    Lee, Hyung-Min; Park, Hangue; Ghovanloo, Maysam

    2013-09-01

    A power-efficient wireless stimulating system for a head-mounted deep brain stimulator (DBS) is presented. A new adaptive rectifier generates a variable DC supply voltage from a constant AC power carrier utilizing phase control feedback, while achieving high AC-DC power conversion efficiency (PCE) through active synchronous switching. A current-controlled stimulator adopts closed-loop supply control to automatically adjust the stimulation compliance voltage by detecting stimulation site potentials through a voltage readout channel, and improve the stimulation efficiency. The stimulator also utilizes closed-loop active charge balancing to maintain the residual charge at each site within a safe limit, while receiving the stimulation parameters wirelessly from the amplitude-shift-keyed power carrier. A 4-ch wireless stimulating system prototype was fabricated in a 0.5-μm 3M2P standard CMOS process, occupying 2.25 mm². With 5 V peak AC input at 2 MHz, the adaptive rectifier provides an adjustable DC output between 2.5 V and 4.6 V at 2.8 mA loading, resulting in measured PCE of 72 ~ 87%. The adaptive supply control increases the stimulation efficiency up to 30% higher than a fixed supply voltage to 58 ~ 68%. The prototype wireless stimulating system was verified in vitro. PMID:24678126

  12. A Power-Efficient Wireless System With Adaptive Supply Control for Deep Brain Stimulation

    PubMed Central

    Lee, Hyung-Min; Park, Hangue; Ghovanloo, Maysam

    2014-01-01

    A power-efficient wireless stimulating system for a head-mounted deep brain stimulator (DBS) is presented. A new adaptive rectifier generates a variable DC supply voltage from a constant AC power carrier utilizing phase control feedback, while achieving high AC-DC power conversion efficiency (PCE) through active synchronous switching. A current-controlled stimulator adopts closed-loop supply control to automatically adjust the stimulation compliance voltage by detecting stimulation site potentials through a voltage readout channel, and improve the stimulation efficiency. The stimulator also utilizes closed-loop active charge balancing to maintain the residual charge at each site within a safe limit, while receiving the stimulation parameters wirelessly from the amplitude-shift-keyed power carrier. A 4-ch wireless stimulating system prototype was fabricated in a 0.5-μm 3M2P standard CMOS process, occupying 2.25 mm². With 5 V peak AC input at 2 MHz, the adaptive rectifier provides an adjustable DC output between 2.5 V and 4.6 V at 2.8 mA loading, resulting in measured PCE of 72 ~ 87%. The adaptive supply control increases the stimulation efficiency up to 30% higher than a fixed supply voltage to 58 ~ 68%. The prototype wireless stimulating system was verified in vitro. PMID:24678126

  13. Brain-Emulating Cognition and Control Architecture (BECCA) V1.0 beta

    SciTech Connect

    Rohrer, Brandon

    2007-09-30

    BECCA is a learning and control method based on the function of the human brain. The goal behind its creation is to learn to control robots in unfamiliar environments in a way that is very robust, similar to the way that an infant learns to interact with her environment by trial and error. As of this release, this software contains two simulations of BECCA controlling robots: one is a one degree-of-freedom spinner robot and the other is a 7 degree-of-freedom serial link arm with a terminal gripper. In addition, the software contains code that identifies synonyms in a untagged corpus of ASCII words. This last is a demonstration of BECCA's ability to generate abstract concepts from concrete experience. The BECCA simulation is coded so as to make it extensible to new applications. It is modular, object-oriented code in which the portions of the code that are specific to one simulation are easily separable from those portions that are the constant between implementations. BECCA makes very few assumptions about the robot and environment it is learning, and so is applicable to a wide range of learning and control problems.

  14. Plasticity of Hippocampal Excitatory-Inhibitory Balance: Missing the Synaptic Control in the Epileptic Brain.

    PubMed

    Bonansco, Christian; Fuenzalida, Marco

    2016-01-01

    Synaptic plasticity is the capacity generated by experience to modify the neural function and, thereby, adapt our behaviour. Long-term plasticity of glutamatergic and GABAergic transmission occurs in a concerted manner, finely adjusting the excitatory-inhibitory (E/I) balance. Imbalances of E/I function are related to several neurological diseases including epilepsy. Several evidences have demonstrated that astrocytes are able to control the synaptic plasticity, with astrocytes being active partners in synaptic physiology and E/I balance. Here, we revise molecular evidences showing the epileptic stage as an abnormal form of long-term brain plasticity and propose the possible participation of astrocytes to the abnormal increase of glutamatergic and decrease of GABAergic neurotransmission in epileptic networks. PMID:27006834

  15. Multimodal sensory integration in insects--towards insect brain control architectures.

    PubMed

    Wessnitzer, Jan; Webb, Barbara

    2006-09-01

    Although a variety of basic insect behaviours have inspired successful robot implementations, more complex capabilities in these 'simple' animals are often overlooked. By reviewing the general architecture of their nervous systems, we gain insight into how they are able to integrate behaviours, perform pattern recognition, context-dependent learning, and combine many sensory inputs in tasks such as navigation. We review in particular what is known about two specific 'higher' areas in the insect brain, the mushroom bodies and the central complex, and how they are involved in controlling an insect's behaviour. While much of the functional interpretation of this information is still speculative, it nevertheless suggests some promising new approaches to obtaining adaptive behaviour in robots. PMID:17671308

  16. Humanlike robot hands controlled by brain activity arouse illusion of ownership in operators

    NASA Astrophysics Data System (ADS)

    Alimardani, Maryam; Nishio, Shuichi; Ishiguro, Hiroshi

    2013-08-01

    Operators of a pair of robotic hands report ownership for those hands when they hold image of a grasp motion and watch the robot perform it. We present a novel body ownership illusion that is induced by merely watching and controlling robot's motions through a brain machine interface. In past studies, body ownership illusions were induced by correlation of such sensory inputs as vision, touch and proprioception. However, in the presented illusion none of the mentioned sensations are integrated except vision. Our results show that during BMI-operation of robotic hands, the interaction between motor commands and visual feedback of the intended motions is adequate to incorporate the non-body limbs into one's own body. Our discussion focuses on the role of proprioceptive information in the mechanism of agency-driven illusions. We believe that our findings will contribute to improvement of tele-presence systems in which operators incorporate BMI-operated robots into their body representations.

  17. Humanlike robot hands controlled by brain activity arouse illusion of ownership in operators.

    PubMed

    Alimardani, Maryam; Nishio, Shuichi; Ishiguro, Hiroshi

    2013-01-01

    Operators of a pair of robotic hands report ownership for those hands when they hold image of a grasp motion and watch the robot perform it. We present a novel body ownership illusion that is induced by merely watching and controlling robot's motions through a brain machine interface. In past studies, body ownership illusions were induced by correlation of such sensory inputs as vision, touch and proprioception. However, in the presented illusion none of the mentioned sensations are integrated except vision. Our results show that during BMI-operation of robotic hands, the interaction between motor commands and visual feedback of the intended motions is adequate to incorporate the non-body limbs into one's own body. Our discussion focuses on the role of proprioceptive information in the mechanism of agency-driven illusions. We believe that our findings will contribute to improvement of tele-presence systems in which operators incorporate BMI-operated robots into their body representations. PMID:23928891

  18. Comprehension through explanation as the interaction of the brain's coherence and cognitive control networks.

    PubMed

    Moss, Jarrod; Schunn, Christian D

    2015-01-01

    Discourse comprehension processes attempt to produce an elaborate and well-connected representation in the reader's mind. A common network of regions including the angular gyrus, posterior cingulate, and dorsal frontal cortex appears to be involved in constructing coherent representations in a variety of tasks including social cognition tasks, narrative comprehension, and expository text comprehension. Reading strategies that require the construction of explicit inferences are used in the present research to examine how this coherence network interacts with other brain regions. A psychophysiological interaction analysis was used to examine regions showing changed functional connectivity with this coherence network when participants were engaged in either a non-inferencing reading strategy, paraphrasing, or a strategy requiring coherence-building inferences, self-explanation. Results of the analysis show that the coherence network increases in functional connectivity with a cognitive control network that may be specialized for the manipulation of semantic representations and the construction of new relations among these representations. PMID:26557066

  19. The cognitive demands of second order manual control: Applications of the event related brain potential

    NASA Technical Reports Server (NTRS)

    Wickens, C.; Gill, R.; Kramer, A.; Ross, W.; Donchin, E.

    1981-01-01

    Three experiments are described in which tracking difficulty is varied in the presence of a covert tone discrimination task. Event related brain potentials (ERPs) elicited by the tones are employed as an index of the resource demands of tracking. The ERP measure reflected the control order variation, and this variable was thereby assumed to compete for perceptual/central processing resources. A fine-grained analysis of the results suggested that the primary demands of second order tracking involve the central processing operations of maintaining a more complex internal model of the dynamic system, rather than the perceptual demands of higher derivative perception. Experiment 3 varied tracking bandwidth in random input tracking, and the ERP was unaffected. Bandwidth was then inferred to compete for response-related processing resources that are independent of the ERP.

  20. Plasticity of Hippocampal Excitatory-Inhibitory Balance: Missing the Synaptic Control in the Epileptic Brain

    PubMed Central

    Bonansco, Christian; Fuenzalida, Marco

    2016-01-01

    Synaptic plasticity is the capacity generated by experience to modify the neural function and, thereby, adapt our behaviour. Long-term plasticity of glutamatergic and GABAergic transmission occurs in a concerted manner, finely adjusting the excitatory-inhibitory (E/I) balance. Imbalances of E/I function are related to several neurological diseases including epilepsy. Several evidences have demonstrated that astrocytes are able to control the synaptic plasticity, with astrocytes being active partners in synaptic physiology and E/I balance. Here, we revise molecular evidences showing the epileptic stage as an abnormal form of long-term brain plasticity and propose the possible participation of astrocytes to the abnormal increase of glutamatergic and decrease of GABAergic neurotransmission in epileptic networks. PMID:27006834

  1. Optical monitoring of cardiac and respiratory rhythms in the skin perfusion near the brain under controlled conditions

    NASA Astrophysics Data System (ADS)

    Mukunda Rao, M.; Blazek, Vladimir; Schmitt, Hans J.

    1998-04-01

    In this investigation an attempt is made to find the effects of controlled breathing on brain with the help of optical sensor mounted on the left and right temples of a subject. It has already been established that the brain activity can be monitored in terms of arterial blood volumetric changes to the left and right hemispheres of the brain recorded with the help of optical sensors. To investigate the influence of controlled breathing, an expert in controlled breathing is chosen as the subject. Pranayama is believed to be the controlled intake and outflow of breath in a firmly established posture. Some types of pranayama are believed to relieve mental stress. While the subject is practicing one such type of breath control, arterial blood volume changes in the brain are recorded using optical sensor mounted on the left and right temples of the subject. From these measurements at the beginning and end of the pranayama exercise, it could be noticed that the subject could induce changes in the cardiac and respiratory rhythms by controlled breathing. Rhythmic phenomena in the skin perfusion in the vicinity of the brian are also studied when the subject is holding his breath. The arterial blood volume changes to the left and right hemispheres of the brian, as monitored by the optical sensors during this period, exhibit asymmetric reaction when the subject is holding his breath. An attempt is made to understand whether these changes induced by stoppage of breathing are 'chaotic' or 'adaptive' in nature.

  2. Bilinguals Use Language-Control Brain Areas More Than Monolinguals to Perform Non-Linguistic Switching Tasks

    PubMed Central

    Rodríguez-Pujadas, Aina; Sanjuán, Ana; Ventura-Campos, Noelia; Román, Patricia; Martin, Clara; Barceló, Francisco; Costa, Albert; Ávila, César

    2013-01-01

    We tested the hypothesis that early bilinguals use language-control brain areas more than monolinguals when performing non-linguistic executive control tasks. We do so by exploring the brain activity of early bilinguals and monolinguals in a task-switching paradigm using an embedded critical trial design. Crucially, the task was designed such that the behavioural performance of the two groups was comparable, allowing then to have a safer comparison between the corresponding brain activity in the two groups. Despite the lack of behavioural differences between both groups, early bilinguals used language-control areas – such as left caudate, and left inferior and middle frontal gyri – more than monolinguals, when performing the switching task. Results offer direct support for the notion that, early bilingualism exerts an effect in the neural circuitry responsible for executive control. This effect partially involves the recruitment of brain areas involved in language control when performing domain-general executive control tasks, highlighting the cross-talk between these two domains. PMID:24058456

  3. Functional brain correlates of heterosexual paedophilia.

    PubMed

    Schiffer, Boris; Paul, Thomas; Gizewski, Elke; Forsting, Michael; Leygraf, Norbert; Schedlowski, Manfred; Kruger, Tillmann H C

    2008-05-15

    Although the neuronal mechanisms underlying normal sexual motivation and function have recently been examined, the alterations in brain function in deviant sexual behaviours such as paedophilia are largely unknown. The objective of this study was to identify paedophilia-specific functional networks implicated in sexual arousal. Therefore a consecutive sample of eight paedophile forensic inpatients, exclusively attracted to females, and 12 healthy age-matched heterosexual control participants from a comparable socioeconomic stratum participated in a visual sexual stimulation procedure during functional magnetic resonance imaging. The visual stimuli were sexually stimulating photographs and emotionally neutral photographs. Immediately after the imaging session subjective responses pertaining to sexual desire were recorded. Principally, the brain response of heterosexual paedophiles to heteropaedophilic stimuli was comparable to that of heterosexual males to heterosexual stimuli, including different limbic structures (amygdala, cingulate gyrus, and hippocampus), the substantia nigra, caudate nucleus, as well as the anterior cingulate cortex, different thalamic nuclei, and associative cortices. However, responses to visual sexual stimulation were found in the orbitofrontal cortex in healthy heterosexual males, but not in paedophiles, in whom abnormal activity in the dorsolateral prefrontal cortex was observed. Thus, in line with clinical observations and neuropsychological studies, it seems that central processing of sexual stimuli in heterosexual paedophiles may be altered by a disturbance in the prefrontal networks, which, as has already been hypothesized, may be associated with stimulus-controlled behaviours, such as sexual compulsive behaviours. Moreover, these findings may suggest a dysfunction (in the functional and effective connectivity) at the cognitive stage of sexual arousal processing. PMID:18358744

  4. Brain cancer and nonoccupational risk factors: a case-control study among workers at two nuclear facilities

    SciTech Connect

    Carpenter, A.V.; Flanders, W.D.; Frome, E.L.; Cole, P.; Fry, S.A.

    1987-09-01

    In a nested case-control study of nuclear workers, 82 brain cancer cases were compared with 328 matched controls to investigate the possible association with nonoccupational risk factors such as histories of epilepsy or head injury. We observed a moderately strong association between brain cancer occurrence and history of epilepsy (OR = 5.7, 95 per cent CI: 1.0, 32.1), but did not find a positive association with previous head injury (OR = 0.9, 95 per cent CI: 0.2, 4.2).

  5. Control of Drosophila Type I and Type II central brain neuroblast proliferation by bantam microRNA

    PubMed Central

    Weng, Ruifen; Cohen, Stephen M.

    2015-01-01

    Post-transcriptional regulation of stem cell self-renewal by microRNAs is emerging as an important mechanism controlling tissue homeostasis. Here, we provide evidence that bantam microRNA controls neuroblast number and proliferation in the Drosophila central brain. Bantam also supports proliferation of transit-amplifying intermediate neural progenitor cells in type II neuroblast lineages. The stem cell factors brat and prospero are identified as bantam targets acting on different aspects of these processes. Thus, bantam appears to act in multiple regulatory steps in the maintenance and proliferation of neuroblasts and their progeny to regulate growth of the central brain. PMID:26395494

  6. Traumatic Brain Injury in Latin America: Lifespan Analysis Randomized Control Trial Protocol

    PubMed Central

    Chesnut, Randall M.; Temkin, Nancy; Carney, Nancy; Dikmen, Sureyya; Pridgeon, Jim; Barber, Jason; Celix, Juanita M.; Chaddock, Kelley; Cherner, Marianna; Hendrix, Terence; Lujan, Silvia; Machamer, Joan; Petroni, Gustavo; Rondina, Carlos; Videtta, Walter

    2012-01-01

    Background Although in the developed world the intracranial pressure (ICP) monitor is considered “standard of care” for patients with severe traumatic brain injury (TBI), its usefulness to direct treatment decisions has never been tested rigorously. Objective The primary focus is to conduct a high quality randomized, controlled trial to determine if ICP monitoring used to direct TBI treatment improves patient outcomes. By providing education, equipment, and structure, the project will enhance the research capacity of the collaborating investigators and will foster the collaborations established during earlier studies (add refs to papers from earlier studies). Methods Study centers were selected that routinely treated ICP based on clinical examination and CT imaging using internal protocols. We randomize patients to either an ICP Monitor Group or an Imaging and Clinical Examination Group. Treatment decisions for the ICP Monitor Group are guided by ICP monitoring, based on established guidelines. Treatment decisions for the Imaging and Clinical Examination Group are made using a single protocol derived from those previously being used at those centers. Expected Outcomes There are two study hypotheses: 1) Patients with severe TBI whose acute care treatment is managed using ICP monitors will have improved outcomes and 2) incorporating ICP monitoring into the care of patients with severe TBI will minimize complications and decrease length of ICU stay. Discussion This clinical trial tests the effectiveness of a management protocol based on technology considered pivotal to brain trauma treatment in the developed world - the ICP monitor. A randomized controlled trial of ICP monitoring has never been performed - a critical gap in the evidence base that supports the role of ICP monitoring in TBI care. As such, the results of this RCT will have global implications regardless of the level of development of the trauma system. PMID:22986600

  7. Readability assessment of concussion and traumatic brain injury publications by Centers for Disease Control and Prevention.

    PubMed

    Gill, Preetinder S; Gill, Tejkaran S; Kamath, Ashwini; Whisnant, Billy

    2012-01-01

    Health literacy is associated with a person's capacity to find, access, contextualize, and understand information needed for health care-related decisions. The level of health literacy thus has an influence on an individual's health status. It can be argued that low health literacy is associated with poor health status. Health care literature (eg, pamphlets, brochures, postcards, posters, forms) are published by public and private organizations worldwide to provide information to the general public. The ability to read, use, and understand is critical to the successful application of knowledge disseminated by this literature. This study assessed the readability, suitability, and usability of health care literature associated with concussion and traumatic brain injury published by the United States Centers for Disease Control and Prevention. The Flesch-Kincaid Grade Level, Flesch Reading Ease, Gunning Fog, Simple Measure of Gobbledygook, and Suitability Assessment of Materials indices were used to assess 40 documents obtained from the Centers for Disease Control and Prevention website. The documents analyzed were targeted towards the general public. It was found that in order to be read properly, on average, these documents needed more than an eleventh grade/high school level education. This was consistent with the findings of other similar studies. However, the qualitative Suitability Assessment of Materials index showed that, on average, usability and suitability of these documents was superior. Hence, it was concluded that formatting, illustrations, layout, and graphics play a pivotal role in improving health care-related literature and, in turn, promoting health literacy. Based on the comprehensive literature review and assessment of the 40 documents associated with concussion and traumatic brain injury, recommendations have been made for improving the readability, suitability, and usability of health care-related documents. The recommendations are presented in

  8. Neuronal production, migration, and differentiation in a vocal control nucleus of the adult female canary brain.

    PubMed Central

    Goldman, S A; Nottebohm, F

    1983-01-01

    The vocal control nucleus designated HVc (hyperstriatum ventrale, pars caudalis) of adult female canaries expands in response to systemic testosterone administration, which also induces the females to sing in a male-like manner. We became interested in the possibility of neurogenesis as a potential basis for this phenomenon. Intact adult female canaries were injected with [3H]thymidine over a 2-day period. Some birds were given testosterone implants at various times before thymidine. The birds were sacrificed 5 wk after hormone implantation, and their brains were processed for autoradiography. In parallel control experiments, some birds were given implants of cholesterol instead of testosterone. All birds showed considerable numbers of labeled neurons, glia, endothelia, and ventricular zone cells in and around HVc. Ultrastructural analysis confirmed the identity of these labeled neurons. Cholesterol- and testosterone-treated birds had similar neuronal labeling indices, which ranged from 1.8% to 4.0% in HVc. Thus, neurogenesis occurred in these adults independently of exogenous hormone treatment. Conversely, both glial and endothelial proliferation rates were markedly stimulated by exogenous testosterone treatment. We determined the origin of the thymidine-incorporating neurons by sacrificing two thymidine-treated females soon after their thymidine injections, precluding any significant migration of newly labeled cells. Analysis of these brains revealed no cells of neuronal morphology present in HVc but a very heavily labeled ventricular zone overlying HVc. We conclude that neuronal precursors exist in the HVc ventricular zone that incorporate tritiated thymidine during the S phase preceding their mitosis; after division these cells migrate into, and to some extent beyond, HVc. This ventricular zone neurogenesis seems to be a normally occurring phenomenon in intact adult female canaries. Images PMID:6572982

  9. Readability assessment of concussion and traumatic brain injury publications by Centers for Disease Control and Prevention

    PubMed Central

    Gill, Preetinder S; Gill, Tejkaran S; Kamath, Ashwini; Whisnant, Billy

    2012-01-01

    Health literacy is associated with a person’s capacity to find, access, contextualize, and understand information needed for health care-related decisions. The level of health literacy thus has an influence on an individual’s health status. It can be argued that low health literacy is associated with poor health status. Health care literature (eg, pamphlets, brochures, postcards, posters, forms) are published by public and private organizations worldwide to provide information to the general public. The ability to read, use, and understand is critical to the successful application of knowledge disseminated by this literature. This study assessed the readability, suitability, and usability of health care literature associated with concussion and traumatic brain injury published by the United States Centers for Disease Control and Prevention. The Flesch–Kincaid Grade Level, Flesch Reading Ease, Gunning Fog, Simple Measure of Gobbledygook, and Suitability Assessment of Materials indices were used to assess 40 documents obtained from the Centers for Disease Control and Prevention website. The documents analyzed were targeted towards the general public. It was found that in order to be read properly, on average, these documents needed more than an eleventh grade/high school level education. This was consistent with the findings of other similar studies. However, the qualitative Suitability Assessment of Materials index showed that, on average, usability and suitability of these documents was superior. Hence, it was concluded that formatting, illustrations, layout, and graphics play a pivotal role in improving health care-related literature and, in turn, promoting health literacy. Based on the comprehensive literature review and assessment of the 40 documents associated with concussion and traumatic brain injury, recommendations have been made for improving the readability, suitability, and usability of health care-related documents. The recommendations are

  10. Modulation of brain activity during a Stroop inhibitory task by the kind of cognitive control required.

    PubMed

    Grandjean, Julien; D'Ostilio, Kevin; Phillips, Christophe; Balteau, Evelyne; Degueldre, Christian; Luxen, André; Maquet, Pierre; Salmon, Eric; Collette, Fabienne

    2012-01-01

    This study used a proportion congruency manipulation in the Stroop task in order to investigate, at the behavioral and brain substrate levels, the predictions derived from the Dual Mechanisms of Control (DMC) account of two distinct modes of cognitive control depending on the task context. Three experimental conditions were created that varied the proportion congruency: mostly incongruent (MI), mostly congruent (MC), and mostly neutral (MN) contexts. A reactive control strategy, which corresponds to transient interference resolution processes after conflict detection, was expected for the rare conflicting stimuli in the MC context, and a proactive strategy, characterized by a sustained task-relevant focus prior to the occurrence of conflict, was expected in the MI context. Results at the behavioral level supported the proactive/reactive distinction, with the replication of the classic proportion congruent effect (i.e., less interference and facilitation effects in the MI context). fMRI data only partially supported our predictions. Whereas reactive control for incongruent trials in the MC context engaged the expected fronto-parietal network including dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex, proactive control in the MI context was not associated with any sustained lateral prefrontal cortex activations, contrary to our hypothesis. Surprisingly, incongruent trials in the MI context elicited transient activation in common with incongruent trials in the MC context, especially in DLPFC, superior parietal lobe, and insula. This lack of sustained activity in MI is discussed in reference to the possible involvement of item-specific rather than list-wide mechanisms of control in the implementation of a high task-relevant focus. PMID:22911806

  11. Can Ketones Help Rescue Brain Fuel Supply in Later Life? Implications for Cognitive Health during Aging and the Treatment of Alzheimer's Disease.

    PubMed

    Cunnane, Stephen C; Courchesne-Loyer, Alexandre; Vandenberghe, Camille; St-Pierre, Valérie; Fortier, Mélanie; Hennebelle, Marie; Croteau, Etienne; Bocti, Christian; Fulop, Tamas; Castellano, Christian-Alexandre

    2016-01-01

    We propose that brain energy deficit is an important pre-symptomatic feature of Alzheimer's disease (AD) that requires closer attention in the development of AD therapeutics. Our rationale is fourfold: (i) Glucose uptake is lower in the frontal cortex of people >65 years-old despite cognitive scores that are normal for age. (ii) The regional deficit in brain glucose uptake is present in adults <40 years-old who have genetic or lifestyle risk factors for AD but in whom cognitive decline has not yet started. Examples include young adult carriers of presenilin-1 or apolipoprotein E4, and young adults with mild insulin resistance or with a maternal family history of AD. (iii) Regional brain glucose uptake is impaired in AD and mild cognitive impairment (MCI), but brain uptake of ketones (beta-hydroxybutyrate and acetoacetate), remains the same in AD and MCI as in cognitively healthy age-matched controls. These observations point to a brain fuel deficit which appears to be specific to glucose, precedes cognitive decline associated with AD, and becomes more severe as MCI progresses toward AD. Since glucose is the brain's main fuel, we suggest that gradual brain glucose exhaustion is contributing significantly to the onset or progression of AD. (iv) Interventions that raise ketone availability to the brain improve cognitive outcomes in both MCI and AD as well as in acute experimental hypoglycemia. Ketones are the brain's main alternative fuel to glucose and brain ketone uptake is still normal in MCI and in early AD, which would help explain why ketogenic interventions improve some cognitive outcomes in MCI and AD. We suggest that the brain energy deficit needs to be overcome in order to successfully develop more effective therapeutics for AD. At present, oral ketogenic supplements are the most promising means of achieving this goal. PMID:27458340

  12. Phenylethylamine N-methylation by human brain preparations

    SciTech Connect

    Mosnaim, A.D.; Callaghan, O.H.; Wolf, M.E.

    1986-03-05

    Alterations in the brain metabolism of biogenic amines has been postulated to play a role in the pathophysiology of several psychiatric disorders. There is some evidence suggesting schizogenic properties for some abnormal neuroamine methylated derivatives. The authors now report that postmortem human brain preparations, obtained from the putamen and thalamus, convert phenylethylamine (PEA) to its behaviorally active derivative N-methyl PEA, a reaction which is carried out by the 100,000 xg supernatant (in presence of 1 x 10 /sup -5/M pargyline) and enhanced by the addition of NADPH. PEA N-methylation occurred in schizophrenics as well as in sex and age matched controls. The formation of increased amounts of (/sup 3/H-) or (/sup 14/C-) N-methyl PEA when incubating either cold amine and /sup 3/H-SAM or 1-/sup 14/C PEA and cold SAM, respectively, indicates that SAM is a methyl group donor in this reaction. They will discuss the physiological and pharmacological implications of these results.

  13. Analysis of Mitochondrial haemoglobin in Parkinson's disease brain.

    PubMed

    Shephard, Freya; Greville-Heygate, Oliver; Liddell, Susan; Emes, Richard; Chakrabarti, Lisa

    2016-07-01

    Mitochondrial dysfunction is an early feature of neurodegeneration. We have shown there are mitochondrial haemoglobin changes with age and neurodegeneration. We hypothesised that altered physiological processes are associated with recruitment and localisation of haemoglobin to these organelles. To confirm a dynamic localisation of haemoglobin we exposed Drosophila melanogaster to cyclical hypoxia with recovery. With a single cycle of hypoxia and recovery we found a relative accumulation of haemoglobin in the mitochondria compared with the cytosol. An additional cycle of hypoxia and recovery led to a significant increase of mitochondrial haemoglobin (p<0.05). We quantified ratios of human mitochondrial haemoglobin in 30 Parkinson's and matched control human post-mortem brains. Relative mitochondrial/cytosolic quantities of haemoglobin were obtained for the cortical region, substantia nigra and cerebellum. In age matched post-mortem brain mitochondrial haemoglobin ratios change, decreasing with disease duration in female cerebellum samples (n=7). The change is less discernible in male cerebellum (n=18). In cerebellar mitochondria, haemoglobin localisation in males with long disease duration shifts from the intermembrane space to the outer membrane of the organelle. These new data illustrate dynamic localisation of mitochondrial haemoglobin within the cell. Mitochondrial haemoglobin should be considered in the context of gender differences characterised in Parkinson's disease. It has been postulated that cerebellar circuitry may be activated to play a protective role in individuals with Parkinson's. The changing localisation of intracellular haemoglobin in response to hypoxia presents a novel pathway to delineate the role of the cerebellum in Parkinson's disease. PMID:27181046

  14. Brain extracellular matrix retains connectivity in neuronal networks

    PubMed Central

    Bikbaev, Arthur; Frischknecht, Renato; Heine, Martin

    2015-01-01

    The formation and maintenance of connectivity are critically important for the processing and storage of information in neuronal networks. The brain extracellular matrix (ECM) appears during postnatal development and surrounds most neurons in the adult mammalian brain. Importantly, the removal of the ECM was shown to improve plasticity and post-traumatic recovery in the CNS, but little is known about the mechanisms. Here, we investigated the role of the ECM in the regulation of the network activity in dissociated hippocampal cultures grown on microelectrode arrays (MEAs). We found that enzymatic removal of the ECM in mature cultures led to transient enhancement of neuronal activity, but prevented disinhibition-induced hyperexcitability that was evident in age-matched control cultures with intact ECM. Furthermore, the ECM degradation followed by disinhibition strongly affected the network interaction so that it strongly resembled the juvenile pattern seen in naïve developing cultures. Taken together, our results demonstrate that the ECM plays an important role in retention of existing connectivity in mature neuronal networks that can be exerted through synaptic confinement of glutamate. On the other hand, removal of the ECM can play a permissive role in modification of connectivity and adaptive exploration of novel network architecture. PMID:26417723

  15. Figurative language processing after traumatic brain injury in adults: a preliminary study.

    PubMed

    Yang, Fanpei Gloria; Fuller, Jerome; Khodaparast, Navid; Krawczyk, Daniel C

    2010-06-01

    Figurative speech (e.g., proverb, irony, metaphor, and idiom) has been reported to be particularly sensitive to measurement of abstract thinking in patients who suffer from impaired abstraction and language abilities. Metaphor processing was investigated with fMRI in adults with moderate to severe post-acute traumatic brain injury (TBI) and healthy age-matched controls using a valence-judgment task. We hypothesized that TBI patients would display decreased activation of the left inferior frontal gyrus (LIFG), which is considered central to semantic memory retrieval and abstract thought, in comparison with healthy controls. We also predicted that decreased activation in TBI individuals would correlate with their behavioral response times. A whole-brain analysis across the two participant groups revealed that patients did not strongly engage frontal and temporal regions related to semantic processing for novel metaphor comprehension, whereas control participants exhibited more intensive and concentrated activation within frontal and temporal areas. A region of interest (ROI) analysis verified that the LIFG was underactivated in TBI patients compared to controls across all conditions. TBI patients' impaired abstraction of novel stimuli may stem from reduced prefrontal control of semantic memory as well as disrupted interconnectivity of prefrontal cortex with other regions. PMID:20230844

  16. Corticalization of motor control in humans is a consequence of brain scaling in primate evolution.

    PubMed

    Herculano-Houzel, Suzana; Kaas, Jon H; de Oliveira-Souza, Ricardo

    2016-02-15

    Control over spinal and brainstem somatomotor neurons is exerted by two sets of descending fibers, corticospinal/pyramidal and extrapyramidal. Although in nonhuman primates the effect of bilateral pyramidal lesions is mostly limited to an impairment of the independent use of digits in skilled manual actions, similar injuries in humans result in the locked-in syndrome, a state of mutism and quadriplegia in which communication can be established only by residual vertical eye movements. This behavioral contrast makes humans appear to be outliers compared with other primates because of our almost total dependence on the corticospinal/pyramidal system for the effectuation of movement. Here we propose, instead, that an increasing preponderance of the corticospinal/pyramidal system over motor control is an expected consequence of increasing brain size in primates because of the faster scaling of the number of neurons in the primary motor cortex over the brainstem and spinal cord motor neuron pools, explaining the apparent uniqueness of the corticalization of motor control in humans. PMID:25891512

  17. Design of a Mobile Brain Computer Interface-Based Smart Multimedia Controller

    PubMed Central

    Tseng, Kevin C.; Lin, Bor-Shing; Wong, Alice May-Kuen; Lin, Bor-Shyh

    2015-01-01

    Music is a way of expressing our feelings and emotions. Suitable music can positively affect people. However, current multimedia control methods, such as manual selection or automatic random mechanisms, which are now applied broadly in MP3 and CD players, cannot adaptively select suitable music according to the user’s physiological state. In this study, a brain computer interface-based smart multimedia controller was proposed to select music in different situations according to the user’s physiological state. Here, a commercial mobile tablet was used as the multimedia platform, and a wireless multi-channel electroencephalograph (EEG) acquisition module was designed for real-time EEG monitoring. A smart multimedia control program built in the multimedia platform was developed to analyze the user’s EEG feature and select music according his/her state. The relationship between the user’s state and music sorted by listener’s preference was also examined in this study. The experimental results show that real-time music biofeedback according a user’s EEG feature may positively improve the user’s attention state. PMID:25756862

  18. Design of a mobile brain computer interface-based smart multimedia controller.

    PubMed

    Tseng, Kevin C; Lin, Bor-Shing; Wong, Alice May-Kuen; Lin, Bor-Shyh

    2015-01-01

    Music is a way of expressing our feelings and emotions. Suitable music can positively affect people. However, current multimedia control methods, such as manual selection or automatic random mechanisms, which are now applied broadly in MP3 and CD players, cannot adaptively select suitable music according to the user's physiological state. In this study, a brain computer interface-based smart multimedia controller was proposed to select music in different situations according to the user's physiological state. Here, a commercial mobile tablet was used as the multimedia platform, and a wireless multi-channel electroencephalograph (EEG) acquisition module was designed for real-time EEG monitoring. A smart multimedia control program built in the multimedia platform was developed to analyze the user's EEG feature and select music according his/her state. The relationship between the user's state and music sorted by listener's preference was also examined in this study. The experimental results show that real-time music biofeedback according a user's EEG feature may positively improve the user's attention state. PMID:25756862

  19. Mass synchronization: Occurrence and its control with possible applications to brain dynamics

    NASA Astrophysics Data System (ADS)

    Chandrasekar, V. K.; Sheeba, Jane H.; Lakshmanan, M.

    2010-12-01

    Occurrence of strong or mass synchronization of a large number of neuronal populations in the brain characterizes its pathological states. In order to establish an understanding of the mechanism underlying such pathological synchronization, we present a model of coupled populations of phase oscillators representing the interacting neuronal populations. Through numerical analysis, we discuss the occurrence of mass synchronization in the model, where a source population which gets strongly synchronized drives the target populations onto mass synchronization. We hypothesize and identify a possible cause for the occurrence of such a synchronization, which is so far unknown: Pathological synchronization is caused not just because of the increase in the strength of coupling between the populations but also because of the strength of the strong synchronization of the drive population. We propose a demand controlled method to control this pathological synchronization by providing a delayed feedback where the strength and frequency of the synchronization determine the strength and the time delay of the feedback. We provide an analytical explanation for the occurrence of pathological synchronization and its control in the thermodynamic limit.

  20. Whole-brain voxel-based morphometry study of children and adolescents with Down syndrome

    PubMed Central

    Carducci, Filippo; Onorati, Paolo; Condoluci, Claudia; Di Gennaro, Giancarlo; Quarato, Pier Paolo; Pierallini, Alberto; Sarà, Marco; Miano, Silvia; Cornia, Riccardo; Albertini, Giorgio

    2013-01-01

    Summary In order to investigate alterations in brain morphology and a possible temporal pattern of neuroanatomical abnormalities in the gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF) of young patients with Down syndrome (DS), high-resolution magnetic resonance imaging (MRI) voxel-based morphometry (VBM) was performed on 21 children and adolescents with this chromosomal aberration and 27 age-matched participants as controls. In comparison with control subjects, children and adolescents with DS showed not only an overall smaller whole-brain volume, but also volume reductions of the GM in the cerebellum, frontal lobes, frontal region of the limbic lobe, parahippocampal gyri and hippocampi and of the WM in the cerebellum, frontal and parietal lobes, sub-lobar regions and brainstem. By contrast, volume preservation was observed in the GM of the parietal lobes, temporal lobe and sub-lobar regions and in the WM of the temporal lobe and temporal regions of the limbic lobe. A lower volume of CSF was also detected in the frontal lobes. This study is the first to use the high-resolution MRI VBM method to describe a whole-brain pattern of abnormalities in young DS patients falling within such a narrow age range and it provides new information on the neuroanatomically specific regional changes that occur during development in these patients. PMID:23731912

  1. Variations in Brain Volume and Growth in Young Children With Type 1 Diabetes.

    PubMed

    Mazaika, Paul K; Weinzimer, Stuart A; Mauras, Nelly; Buckingham, Bruce; White, Neil H; Tsalikian, Eva; Hershey, Tamara; Cato, Allison; Aye, Tandy; Fox, Larry; Wilson, Darrell M; Tansey, Michael J; Tamborlane, William; Peng, Daniel; Raman, Mira; Marzelli, Matthew; Reiss, Allan L

    2016-02-01

    Early-onset type 1 diabetes may affect the developing brain during a critical window of rapid brain maturation. Structural MRI was performed on 141 children with diabetes (4-10 years of age at study entry) and 69 age-matched control subjects at two time points spaced 18 months apart. For the children with diabetes, the mean (±SD) HbA1c level was 7.9 ± 0.9% (63 ± 9.8 mmol/mol) at both time points. Relative to control subjects, children with diabetes had significantly less growth of cortical gray matter volume and cortical surface area and significantly less growth of white matter volume throughout the cortex and cerebellum. For the population with diabetes, the change in the blood glucose level at the time of scan across longitudinal time points was negatively correlated with the change in gray and white matter volumes, suggesting that fluctuating glucose levels in children with diabetes may be associated with corresponding fluctuations in brain volume. In addition, measures of hyperglycemia and glycemic variation were significantly negatively correlated with the development of surface curvature. These results demonstrate that early-onset type 1 diabetes has widespread effects on the growth of gray and white matter in children whose blood glucose levels are well within the current treatment guidelines for the management of diabetes. PMID:26512024

  2. Evidence for Impaired Plasticity after Traumatic Brain Injury in the Developing Brain

    PubMed Central

    Li, Nan; Yang, Ya; Glover, David P.; Zhang, Jiangyang; Saraswati, Manda; Robertson, Courtney

    2014-01-01

    Abstract The robustness of plasticity mechanisms during brain development is essential for synaptic formation and has a beneficial outcome after sensory deprivation. However, the role of plasticity in recovery after acute brain injury in children has not been well defined. Traumatic brain injury (TBI) is the leading cause of death and disability among children, and long-term disability from pediatric TBI can be particularly devastating. We investigated the altered cortical plasticity 2–3 weeks after injury in a pediatric rat model of TBI. Significant decreases in neurophysiological responses across the depth of the noninjured, primary somatosensory cortex (S1) in TBI rats, compared to age-matched controls, were detected with electrophysiological measurements of multi-unit activity (86.4% decrease), local field potential (75.3% decrease), and functional magnetic resonance imaging (77.6% decrease). Because the corpus callosum is a clinically important white matter tract that was shown to be consistently involved in post-traumatic axonal injury, we investigated its anatomical and functional characteristics after TBI. Indeed, corpus callosum abnormalities in TBI rats were detected with diffusion tensor imaging (9.3% decrease in fractional anisotropy) and histopathological analysis (14% myelination volume decreases). Whole-cell patch clamp recordings further revealed that TBI results in significant decreases in spontaneous firing rate (57% decrease) and the potential to induce long-term potentiation in neurons located in layer V of the noninjured S1 by stimulation of the corpus callosum (82% decrease). The results suggest that post-TBI plasticity can translate into inappropriate neuronal connections and dramatic changes in the function of neuronal networks. PMID:24050267

  3. Cognitive function and brain structure after recurrent mild traumatic brain injuries in young-to-middle-aged adults

    PubMed Central

    List, Jonathan; Ott, Stefanie; Bukowski, Martin; Lindenberg, Robert; Flöel, Agnes

    2015-01-01

    Recurrent mild traumatic brain injuries (mTBIs) are regarded as an independent risk factor for developing dementia in later life. We here aimed to evaluate associations between recurrent mTBIs, cognition, and gray matter volume and microstructure as revealed by structural magnetic resonance imaging (MRI) in the chronic phase after mTBIs in young adulthood. We enrolled 20 young-to-middle-aged subjects, who reported two or more sports-related mTBIs, with the last mTBI > 6 months prior to study enrolment (mTBI group), and 21 age-, sex- and education matched controls with no history of mTBI (control group). All participants received comprehensive neuropsychological testing, and high resolution T1-weighted and diffusion tensor MRI in order to assess cortical thickness (CT) and microstructure, hippocampal volume, and ventricle size. Compared to the control group, subjects of the mTBI group presented with lower CT within the right temporal lobe and left insula using an a priori region of interest approach. Higher number of mTBIs was associated with lower CT in bilateral insula, right middle temporal gyrus and right entorhinal area. Our results suggest persistent detrimental effects of recurrent mTBIs on CT already in young-to-middle-aged adults. If additional structural deterioration occurs during aging, subtle neuropsychological decline may progress to clinically overt dementia earlier than in age-matched controls, a hypothesis to be assessed in future prospective trials. PMID:26052275

  4. A cerebellar model for predictive motor control tested in a brain-based device

    PubMed Central

    McKinstry, Jeffrey L.; Edelman, Gerald M.; Krichmar, Jeffrey L.

    2006-01-01

    The cerebellum is known to be critical for accurate adaptive control and motor learning. We propose here a mechanism by which the cerebellum may replace reflex control with predictive control. This mechanism is embedded in a learning rule (the delayed eligibility trace rule) in which synapses onto a Purkinje cell or onto a cell in the deep cerebellar nuclei become eligible for plasticity only after a fixed delay from the onset of suprathreshold presynaptic activity. To investigate the proposal that the cerebellum is a general-purpose predictive controller guided by a delayed eligibility trace rule, a computer model based on the anatomy and dynamics of the cerebellum was constructed. It contained components simulating cerebellar cortex and deep cerebellar nuclei, and it received input from a middle temporal visual area and the inferior olive. The model was incorporated in a real-world brain-based device (BBD) built on a Segway robotic platform that learned to traverse curved paths. The BBD learned which visual motion cues predicted impending collisions and used this experience to avoid path boundaries. During learning, the BBD adapted its velocity and turning rate to successfully traverse various curved paths. By examining neuronal activity and synaptic changes during this behavior, we found that the cerebellar circuit selectively responded to motion cues in specific receptive fields of simulated middle temporal visual areas. The system described here prompts several hypotheses about the relationship between perception and motor control and may be useful in the development of general-purpose motor learning systems for machines. PMID:16488974

  5. A cerebellar model for predictive motor control tested in a brain-based device.

    PubMed

    McKinstry, Jeffrey L; Edelman, Gerald M; Krichmar, Jeffrey L

    2006-02-28

    The cerebellum is known to be critical for accurate adaptive control and motor learning. We propose here a mechanism by which the cerebellum may replace reflex control with predictive control. This mechanism is embedded in a learning rule (the delayed eligibility trace rule) in which synapses onto a Purkinje cell or onto a cell in the deep cerebellar nuclei become eligible for plasticity only after a fixed delay from the onset of suprathreshold presynaptic activity. To investigate the proposal that the cerebellum is a general-purpose predictive controller guided by a delayed eligibility trace rule, a computer model based on the anatomy and dynamics of the cerebellum was constructed. It contained components simulating cerebellar cortex and deep cerebellar nuclei, and it received input from a middle temporal visual area and the inferior olive. The model was incorporated in a real-world brain-based device (BBD) built on a Segway robotic platform that learned to traverse curved paths. The BBD learned which visual motion cues predicted impending collisions and used this experience to avoid path boundaries. During learning, the BBD adapted its velocity and turning rate to successfully traverse various curved paths. By examining neuronal activity and synaptic changes during this behavior, we found that the cerebellar circuit selectively responded to motion cues in specific receptive fields of simulated middle temporal visual areas. The system described here prompts several hypotheses about the relationship between perception and motor control and may be useful in the development of general-purpose motor learning systems for machines. PMID:16488974

  6. Self-paced brain-computer interface control of ambulation in a virtual reality environment

    NASA Astrophysics Data System (ADS)

    Wang, Po T.; King, Christine E.; Chui, Luis A.; Do, An H.; Nenadic, Zoran

    2012-10-01

    Objective. Spinal cord injury (SCI) often leaves affected individuals unable to ambulate. Electroencephalogram (EEG) based brain-computer interface (BCI) controlled lower extremity prostheses may restore intuitive and able-body-like ambulation after SCI. To test its feasibility, the authors developed and tested a novel EEG-based, data-driven BCI system for intuitive and self-paced control of the ambulation of an avatar within a virtual reality environment (VRE). Approach. Eight able-bodied subjects and one with SCI underwent the following 10-min training session: subjects alternated between idling and walking kinaesthetic motor imageries (KMI) while their EEG were recorded and analysed to generate subject-specific decoding models. Subjects then performed a goal-oriented online task, repeated over five sessions, in which they utilized the KMI to control the linear ambulation of an avatar and make ten sequential stops at designated points within the VRE. Main results. The average offline training performance across subjects was 77.2±11.0%, ranging from 64.3% (p = 0.001 76) to 94.5% (p = 6.26×10-23), with chance performance being 50%. The average online performance was 8.5±1.1 (out of 10) successful stops and 303±53 s completion time (perfect = 211 s). All subjects achieved performances significantly different than those of random walk (p < 0.05) in 44 of the 45 online sessions. Significance. By using a data-driven machine learning approach to decode users’ KMI, this BCI-VRE system enabled intuitive and purposeful self-paced control of ambulation after only 10 minutes training. The ability to achieve such BCI control with minimal training indicates that the implementation of future BCI-lower extremity prosthesis systems may be feasible.

  7. Altered Recruitment of the Attention Network Is Associated with Disability and Cognitive Impairment in Pediatric Patients with Acquired Brain Injury

    PubMed Central

    Strazzer, Sandra; Rocca, Maria A.; Molteni, Erika; De Meo, Ermelinda; Recla, Monica; Valsasina, Paola; Arrigoni, Filippo; Galbiati, Susanna; Bardoni, Alessandra; Filippi, Massimo

    2015-01-01

    We assessed abnormalities of brain functional magnetic resonance imaging (fMRI) activity during a sustained attention task (Conners' Continuous Performance Test (CCPT)) in 20 right-handed pediatric acquired brain injury (ABI) patients versus 7 right-handed age-matched healthy controls, and we estimated the correlation of such abnormalities with clinical and cognitive deficits. Patients underwent the Wechsler Intelligence Scale for Children (WISC), Wisconsin Card Sorting Test, and Functional Independence Measure (FIM) evaluations. During fMRI, patients and controls activated regions of the attention network. Compared to controls, ABI patients experienced a decreased average fMRI recruitment of the left cerebellum and a decreased deactivation of the left anterior cingulate cortex. With increasing task demand, compared to controls, ABI patients had an impaired ability to increase the recruitment of several posterior regions of the attention network. They also experienced a greater activation of frontal regions, which was correlated with worse performance on FIM, WISC, and fMRI CCPT. Such abnormal brain recruitment was significantly influenced by the type of lesion (focal versus diffuse axonal injury) and time elapsed from the event. Pediatric ABI patients experienced an inability to optimize attention network recruitment, especially when task difficulty was increased, which likely contributes to their clinical and cognitive deficits. PMID:26448878

  8. Robust Brain-Machine Interface Design Using Optimal Feedback Control Modeling and Adaptive Point Process Filtering

    PubMed Central

    Carmena, Jose M.

    2016-01-01

    Much progress has been made in brain-machine interfaces (BMI) using decoders such as Kalman filters and finding their parameters with closed-loop decoder adaptation (CLDA). However, current decoders do not model the spikes directly, and hence may limit the processing time-scale of BMI control and adaptation. Moreover, while specialized CLDA techniques for intention estimation and assisted training exist, a unified and systematic CLDA framework that generalizes across different setups is lacking. Here we develop a novel closed-loop BMI training architecture that allows for processing, control, and adaptation using spike events, enables robust control and extends to various tasks. Moreover, we develop a unified control-theoretic CLDA framework within which intention estimation, assisted training, and adaptation are performed. The architecture incorporates an infinite-horizon optimal feedback-control (OFC) model of the brain’s behavior in closed-loop BMI control, and a point process model of spikes. The OFC model infers the user’s motor intention during CLDA—a process termed intention estimation. OFC is also used to design an autonomous and dynamic assisted training technique. The point process model allows for neural processing, control and decoder adaptation with every spike event and at a faster time-scale than current decoders; it also enables dynamic spike-event-based parameter adaptation unlike current CLDA methods that use batch-based adaptation on much slower adaptation time-scales. We conducted closed-loop experiments in a non-human primate over tens of days to dissociate the effects of these novel CLDA components. The OFC intention estimation improved BMI performance compared with current intention estimation techniques. OFC assisted training allowed the subject to consistently achieve proficient control. Spike-event-based adaptation resulted in faster and more consistent performance convergence compared with batch-based methods, and was robust to

  9. Physical Exercise Keeps the Brain Connected: Biking Increases White Matter Integrity in Patients With Schizophrenia and Healthy Controls.

    PubMed

    Svatkova, Alena; Mandl, René C W; Scheewe, Thomas W; Cahn, Wiepke; Kahn, René S; Hulshoff Pol, Hilleke E

    2015-07-01

    It has been shown that learning a new skill leads to structural changes in the brain. However, it is unclear whether it is the acquisition or continuous practicing of the skill that causes this effect and whether brain connectivity of patients with schizophrenia can benefit from such practice. We examined the effect of 6 months exercise on a stationary bicycle on the brain in patients with schizophrenia and healthy controls. Biking is an endemic skill in the Netherlands and thus offers an ideal situation to disentangle the effects of learning vs practice. The 33 participating patients with schizophrenia and 48 healthy individuals were assigned to either one of two conditions, ie, physical exercise or life-as-usual, balanced for diagnosis. Diffusion tensor imaging brain scans were made prior to and after intervention. We demonstrate that irrespective of diagnosis regular physical exercise of an overlearned skill, such as bicycling, significantly increases the integrity, especially of motor functioning related, white matter fiber tracts whereas life-as-usual leads to a decrease in fiber integrity. Our findings imply that exercise of an overlearned physical skill improves brain connectivity in patients and healthy individuals. This has important implications for understanding the effect of fitness programs on the brain in both healthy subjects and patients with schizophrenia. Moreover, the outcome may even apply to the nonphysical realm. PMID:25829377

  10. Physical Exercise Keeps the Brain Connected: Biking Increases White Matter Integrity in Patients With Schizophrenia and Healthy Controls

    PubMed Central

    Svatkova, Alena; Mandl, René C.W.; Scheewe, Thomas W.; Cahn, Wiepke; Kahn, René S.; Hulshoff Pol, Hilleke E.

    2015-01-01

    It has been shown that learning a new skill leads to structural changes in the brain. However, it is unclear whether it is the acquisition or continuous practicing of the skill that causes this effect and whether brain connectivity of patients with schizophrenia can benefit from such practice. We examined the effect of 6 months exercise on a stationary bicycle on the brain in patients with schizophrenia and healthy controls. Biking is an endemic skill in the Netherlands and thus offers an ideal situation to disentangle the effects of learning vs practice. The 33 participating patients with schizophrenia and 48 healthy individuals were assigned to either one of two conditions, ie, physical exercise or life-as-usual, balanced for diagnosis. Diffusion tensor imaging brain scans were made prior to and after intervention. We demonstrate that irrespective of diagnosis regular physical exercise of an overlearned skill, such as bicycling, significantly increases the integrity, especially of motor functioning related, white matter fiber tracts whereas life-as-usual leads to a decrease in fiber integrity. Our findings imply that exercise of an overlearned physical skill improves brain connectivity in patients and healthy individuals. This has important implications for understanding the effect of fitness programs on the brain in both healthy subjects and patients with schizophrenia. Moreover, the outcome may even apply to the nonphysical realm. PMID:25829377

  11. Is phosphorylated tau unique to chronic traumatic encephalopathy? Phosphorylated tau in epileptic brain and chronic traumatic encephalopathy.

    PubMed

    Puvenna, Vikram; Engeler, Madeline; Banjara, Manoj; Brennan, Chanda; Schreiber, Peter; Dadas, Aaron; Bahrami, Ashkon; Solanki, Jesal; Bandyopadhyay, Anasua; Morris, Jacqueline K; Bernick, Charles; Ghosh, Chaitali; Rapp, Edward; Bazarian, Jeffrey J; Janigro, Damir

    2016-01-01

    Repetitive traumatic brain injury (rTBI) is one of the major risk factors for the abnormal deposition of phosphorylated tau (PT) in the brain and chronic traumatic encephalopathy (CTE). CTE and temporal lobe epilepsy (TLE) affect the limbic system, but no comparative studies on PT distribution in TLE and CTE are available. It is also unclear whether PT pathology results from repeated head hits (rTBI). These gaps prevent a thorough understanding of the pathogenesis and clinical significance of PT, limiting our ability to develop preventative and therapeutic interventions. We quantified PT in TLE and CTE to unveil whether a history of rTBI is a prerequisite for PT accumulation in the brain. Six postmortem CTE (mean 73.3 years) and age matched control samples were compared to 19 surgically resected TLE brain specimens (4 months-58 years; mean 27.6 years). No history of TBI was present in TLE or control; all CTE patients had a history of rTBI. TLE and CTE brain displayed increased levels of PT as revealed by immunohistochemistry. No age-dependent changes were noted, as PT was present as early as 4 months after birth. In TLE and CTE, cortical neurons, perivascular regions around penetrating pial vessels and meninges were immunopositive for PT; white matter tracts also displayed robust expression of extracellular PT organized in bundles parallel to venules. Microscopically, there were extensive tau-immunoreactive neuronal, astrocytic and degenerating neurites throughout the brain. In CTE perivascular tangles were most prominent. Overall, significant differences in staining intensities were found between CTE and control (P<0.01) but not between CTE and TLE (P=0.08). pS199 tau analysis showed that CTE had the most high molecular weight tangle-associated tau, whereas epileptic brain contained low molecular weight tau. Tau deposition may not be specific to rTBI since TLE recapitulated most of the pathological features of CTE. PMID:26556772

  12. Phase II randomized, double-blind, placebo-controlled study of whole-brain irradiation with concomitant chloroquine for brain metastases

    PubMed Central

    2013-01-01

    Background and purpose Chloroquine (CLQ), an antimalarial drug, has a lysosomotropic effect associated with increased radiationsensibility, which is mediated by the leakage of hydrolytic enzymes, increased apoptosis, autophagy and increased oxidative stress in vitro. In this phase II study, we evaluated the efficacy and safety of radiosensibilization using CLQ concomitant with 30 Gray (Gy) of whole-brain irradiation (WBI) to treat patients with brain metastases (BM) from solid tumors. Methods Seventy-three eligible patients were randomized. Thirty-nine patients received WBI (30 Gy in 10 fractions over 2 weeks) concomitant with 150 mg of CLQ for 4 weeks (the CLQ arm). Thirty-four patients received the same schedule of WBI concomitant with a placebo for 4 weeks (the control arm). All the patients were evaluated for quality of life (QoL) using the EORTC Quality of Life (QoL) Questionnaire (EORTC QLQ-C30) (Mexican version) before beginning radiotherapy and one month later. Results The overall response rate (ORR) was 54% for the CLQ arm and 55% for the control arm (p=0.92). The progression-free survival of brain metastases (BMPFS) rates at one year were 83.9% (95% CI 69.4-98.4) for the CLQ arm and 55.1% (95% CI 33.6-77.6) for the control arm. Treatment with CLQ was independently associated with increased BMPFS (RR 0.31,95% CI [0.1-0.9], p=0.046).The only factor that was independently associated with increased overall survival (OS) was the presence of< 4 brain metastases (RR 1.9, 95% CI [1.12-3.3], p=0.017). WBI was associated with improvements in cognitive and emotional function but also with worsened nausea in both patients groups. No differences in QoL or toxicity were found between the study arms. Conclusion Treatment with CLQ plus WBI improved the control of BM (compared with the control arm) with no increase in toxicity; however, CLQ did not improve the RR or OS. A phase III clinical trial is warranted to confirm these findings. PMID:24010771

  13. Control of abdominal muscles by brain stem respiratory neurons in the cat.

    PubMed

    Miller, A D; Ezure, K; Suzuki, I

    1985-07-01

    Control of abdominal musculature by brain stem respiratory neurons was studied in decerebrate unanesthetized cats by determining 1) which brain stem respiratory neurons could be antidromically activated from the lumbar cord, from which the abdominal muscles receive part of their innervation, and 2) if lumbar-projecting respiratory neurons make monosynaptic connections with abdominal motoneurons. A total of 462 respiratory neurons, located between caudal C2 and the retrofacial nucleus (Bötzinger complex), were tested for antidromic activation from the upper lumbar cord. Fifty-eight percent of expiratory (E) neurons (70/121) in the caudal ventral respiratory group (VRG) between the obex and rostral C1 were antidromically activated from contralateral L1. Eight of these neurons were activated at low thresholds from lamina VIII and IX in the L1-2 gray matter. One-third (14/41) of the E neurons that projected to L1 could also be activated from L4-5. Almost all antidromic E neurons had an augmenting firing pattern. Ten scattered inspiratory (I) neurons projected to L1 but could not be activated from L4-5. No neurons that fired during both E and I phases (phase-spanning neurons) were antidromically activated from the lumbar cord. In order to test for possible monosynaptic connections between descending E neurons and abdominal motoneurons, cross-correlations were obtained between 27 VRG E neurons, which were antidromically activated from caudal L2 and contralateral L1 and L2 abdominal nerve activity (47 neuron-nerve combinations). Only two neurons showed a correlation with one of the two nerves tested. Although there is a large projection to the lumbar cord from expiratory neurons in the ventral respiratory group caudal to the obex, cross-correlation analyses suggest that strong monosynaptic connections between these neurons and abdominal motoneurons are scarce. PMID:3162005

  14. Neuronal LR11 expression does not differentiate between clinically-defined Alzheimer's disease and control brains.

    PubMed

    Sager, Kristen L; Wuu, Joanne; Herskowitz, Jeremy H; Mufson, Elliott J; Levey, Allan I; Lah, James J

    2012-01-01

    Alzheimer's disease (AD) is the leading cause of dementia in the elderly. Because the pathological changes underlying this disease can begin decades prior to the onset of cognitive impairment, identifying the earliest events in the AD pathological cascade has critical implications for both the diagnosis and treatment of this disease. We previously reported that compared to autopsy confirmed healthy control brain, expression of LR11 (or SorLA) is markedly reduced in AD brain as well as in a subset of people with mild cognitive impairment (MCI), a prodromal clinical stage of AD. Recent studies of the LR11 gene SORL1 have suggested that the association between SORL1 single nucleotide polymorphisms (SNPs) and AD risk may not be universal. Therefore, we sought to confirm our earlier findings in a population chosen solely based on clinical criteria, as in most genetic studies. Quantitative immunohistochemistry was used to measure LR11 expression in 43 cases from the Religious Orders Study that were chosen based on a final pre-mortem clinical diagnosis of MCI, mild/moderate AD or no cognitive impairment (NCI). LR11 expression was highly variable in all three diagnostic groups, with no significant group differences. Low LR11 cases were identified using the lowest tertile of LR11 expression observed across all cases as a threshold. Contrary to previous reports, low LR11 expression was found in only 29% of AD cases. A similar proportion of both the MCI and NCI cases also displayed low LR11 expression. AD-associated lesions were present in the majority of cases regardless of diagnostic group, although we found no association between LR11 levels and pathological variables. These findings suggest that the relationship between LR11 expression and the development of AD may be more complicated than originally believed. PMID:22927900

  15. Automatic motor task selection via a bandit algorithm for a brain-controlled button

    NASA Astrophysics Data System (ADS)

    Fruitet, Joan; Carpentier, Alexandra; Munos, Rémi; Clerc, Maureen

    2013-02-01

    Objective. Brain-computer interfaces (BCIs) based on sensorimotor rhythms use a variety of motor tasks, such as imagining moving the right or left hand, the feet or the tongue. Finding the tasks that yield best performance, specifically to each user, is a time-consuming preliminary phase to a BCI experiment. This study presents a new adaptive procedure to automatically select (online) the most promising motor task for an asynchronous brain-controlled button. Approach. We develop for this purpose an adaptive algorithm UCB-classif based on the stochastic bandit theory and design an EEG experiment to test our method. We compare (offline) the adaptive algorithm to a naïve selection strategy which uses uniformly distributed samples from each task. We also run the adaptive algorithm online to fully validate the approach. Main results. By not wasting time on inefficient tasks, and focusing on the most promising ones, this algorithm results in a faster task selection and a more efficient use of the BCI training session. More precisely, the offline analysis reveals that the use of this algorithm can reduce the time needed to select the most appropriate task by almost half without loss in precision, or alternatively, allow us to investigate twice the number of tasks within a similar time span. Online tests confirm that the method leads to an optimal task selection. Significance. This study is the first one to optimize the task selection phase by an adaptive procedure. By increasing the number of tasks that can be tested in a given time span, the proposed method could contribute to reducing ‘BCI illiteracy’.

  16. Mio acts in the Drosophila brain to control nutrient storage and feeding.

    PubMed

    Docherty, James E B; Manno, Joseph E; McDermott, Jacqueline E; DiAngelo, Justin R

    2015-09-01

    Animals recognize the availability of nutrients and regulate the intake and storage of these nutrients accordingly. However, the molecular mechanisms underlying nutrient sensing and subsequent changes in behavior and metabolism are not fully understood. Mlx interactor (Mio), the Drosophila homolog of carbohydrate response element binding protein (ChREBP), functions as a transcription factor in the fat body of the fly to control triglyceride storage as well as feeding, suggesting that Mio may act in a nutrient-sensing pathway to coordinate food consumption and metabolism. Here, we show that Mio functions in neurons in Drosophila to regulate feeding and nutrient storage. Pan-neuronal disruption of Mio function leads to increased triglyceride and glycogen storage, and this phenotype is not due to increased food consumption. Interestingly, targeted disruption of Mio specifically in the insulin-producing cells (IPCs) has little effect on nutrient storage, but increases food consumption suggesting that Mio acts in these neurons to control feeding behavior. Since Mio is a transcription factor, one possible way Mio may act in the IPCs to control feeding is through regulating the expression of Drosophila insulin-like peptides (dilps) or drosulfakinin (dsk), neuropeptides produced in the IPCs. Consistent with this hypothesis, IPC-specific knockdown of Mio leads to an increase in dilp3 expression, while not affecting dilp2, 5 or dsk levels. Together, this study indicates a new function for Mio in the Drosophila brain and specifically in the IPCs, controlling neuropeptide gene expression, feeding and metabolism in accordance with nutrient availability. PMID:26024590

  17. Effects of endurance training on brain structures in chronic schizophrenia patients and healthy controls.

    PubMed

    Malchow, Berend; Keeser, Daniel; Keller, Katriona; Hasan, Alkomiet; Rauchmann, Boris-Stephan; Kimura, Hiroshi; Schneider-Axmann, Thomas; Dechent, Peter; Gruber, Oliver; Ertl-Wagner, Birgit; Honer, William G; Hillmer-Vogel, Ursula; Schmitt, Andrea; Wobrock, Thomas; Niklas, Andree; Falkai, Peter

    2016-06-01

    The objective of this longitudinal magnetic resonance (MR) imaging study was to examine the effects of endurance training on hippocampal and grey matter volumes in schizophrenia patients and healthy controls. 20 chronic schizophrenia patients and 21 age- and gender-matched healthy controls underwent 3months of endurance training (30min, 3 times per week). 19 additionally recruited schizophrenia patients played table soccer ("foosball" in the USA) over the same period. MR imaging with 3D-volumetric T1-weighted sequences was performed on a 3T MR scanner at baseline, after 6weeks and after the 3-month intervention and 3 additional training-free months. In addition to voxel-based morphometry (VBM), we performed manual and automatic delineation of the hippocampus and its substructures. Endurance capacity and psychopathological symptoms were measured as secondary endpoints. No significant increases in the volumes of the hippocampus or hippocampal substructures were observed in schizophrenia patients or healthy controls. However, VBM analyses displayed an increased volume of the left superior, middle and inferior anterior temporal gyri compared to baseline in schizophrenia patients after the endurance training, whereas patients playing table soccer showed increased volumes in the motor and anterior cingulate cortices. After the additional training-free period, the differences were no longer present. While endurance capacity improved in exercising patients and healthy controls, psychopathological symptoms did not significantly change. The subtle changes in the left temporal cortex indicate an impact of exercise on brain volumes in schizophrenia. Subsequent studies in larger cohorts are warranted to address the question of response variability of endurance training. PMID:25623601

  18. Brain-Machine-Interface in Chronic Stroke Rehabilitation: A Controlled Study

    PubMed Central

    Ramos-Murguialday, Ander; Broetz, Doris; Rea, Massimiliano; Läer, Leonhard; Yilmaz, Özge; Brasil, Fabricio L; Liberati, Giulia; Curado, Marco R; Garcia-Cossio, Eliana; Vyziotis, Alexandros; Cho, Woosang; Agostini, Manuel; Soares, Ernesto; Soekadar, Surjo; Caria, Andrea; Cohen, Leonardo G; Birbaumer, Niels

    2013-01-01

    Objective Chronic stroke patients with severe hand weakness, respond poorly to rehabilitation efforts. Here, we evaluated efficacy of daily brain-machine-interface training to increase the hypothesized beneficial effects of physiotherapy alone in patients with severe paresis in a double blind sham-controlled design proof of concept study. Methods 32 chronic stroke patients with severe hand weakness, were randomly assigned to two matched groups and participated in 17.8 ± 1.4 days of training rewarding desynchronization of ipsilesional oscillatory sensorimotor rhythms (SMR) with contingent online movements of hand and arm orthoses (experimental group , n=16). In the control group (sham group, n=16) movements of the orthoses occurred randomly. Both groups received identical behavioral physiotherapy immediately following BMI training or the control intervention. Upper limb motor function scores, electromyography from arm and hand muscles, placebo-expectancy effects and functional magnetic resonance imaging (MRI) blood oxygenation level dependent activity were assessed before and after intervention. Results A significant group × time interaction in upper limb Fugl-Meyer motor (cFMA) scores was found. cFMA scores improved more in the experimental than in the control group, presenting a significant improvement of cFMA scores (3.41±0.563 points difference, p=0.018) reflecting a clinically meaningful change from no activity to some in paretic muscles. cFMA improvements in the experimental group correlated with changes in functional MRI laterality index and with paretic hand electromyography activity. Placebo-expectancy scores were comparable for both groups. Interpretation The addition of BMI training to behaviorally oriented physiotherapy can be used to induce functional improvements in motor function in chronic stroke patients without residual finger movements and may open a new door in stroke neurorehabilitation. PMID:23494615

  19. A Computationally Efficient, Exploratory Approach to Brain Connectivity Incorporating False Discovery Rate Control, A Priori Knowledge, and Group Inference

    PubMed Central

    Liu, Aiping; Li, Junning; Wang, Z. Jane; McKeown, Martin J.

    2012-01-01

    Graphical models appear well suited for inferring brain connectivity from fMRI data, as they can distinguish between direct and indirect brain connectivity. Nevertheless, biological interpretation requires not only that the multivariate time series are adequately modeled, but also that there is accurate error-control of the inferred edges. The PCfdr algorithm, which was developed by Li and Wang, was to provide a computationally efficient means to control the false discovery rate (FDR) of computed edges asymptotically. The original PCfdr algorithm was unable to accommodate a priori information about connectivity and was designed to infer connectivity from a single subject rather than a group of subjects. Here we extend the original PCfdr algorithm and propose a multisubject, error-rate-controlled brain connectivity modeling approach that allows incorporation of prior knowledge of connectivity. In simulations, we show that the two proposed extensions can still control the FDR around or below a specified threshold. When the proposed approach is applied to fMRI data in a Parkinson's disease study, we find robust group evidence of the disease-related changes, the compensatory changes, and the normalizing effect of L-dopa medication. The proposed method provides a robust, accurate, and practical method for the assessment of brain connectivity patterns from functional neuroimaging data. PMID:23251232

  20. Early Neuropsychological Tests as Correlates of Productivity 1 Year after Traumatic Brain Injury: A Preliminary Matched Case-Control Study

    ERIC Educational Resources Information Center

    Ryu, Won Hyung A.; Cullen, Nora K.; Bayley, Mark T.

    2010-01-01

    This study explored the relative strength of five neuropsychological tests in correlating with productivity 1 year after traumatic brain injury (TBI). Six moderate-to-severe TBI patients who returned to work at 1-year post-injury were matched with six controls who were unemployed after 1 year based on age, severity of injury, and Functional…

  1. Change Detection, Multiple Controllers, and Dynamic Environments: Insights from the brain

    PubMed Central

    Pearson, John M.; Platt, Michael L.

    2014-01-01

    Foundational studies in decision making focused on behavior as the most accessible and reliable data on which to build theories of choice. More recent work, however, has incorporated neural data to provide insights unavailable from behavior alone. Among other contributions, these studies have validated reinforcement learning models by demonstrating neural signals posited on the basis of behavioral work in classical and operant conditioning. In such models, the values of actions or options are updated incrementally based on the difference between expectations and outcomes, resulting in the gradual acquisition of stable behavior. By contrast, natural environments are often dynamic, including sudden, unsignaled shifts in reinforcement contingencies. Such rapid changes may necessitate frequent shifts in the behavioral mode, requiring dynamic sensitivity to environmental changes. Recently, we proposed a model in which cingulate cortex plays a key role in detecting behaviorally-relevant environmental changes and facilitating the update of multiple behavioral strategies. Here, we connect this framework to a model developed to handle the analogous problem in motor control. We offer a tentative dictionary of control signals in terms of brain structures and highlight key differences between motor and decision systems that may be important in evaluating the model. PMID:23344989

  2. Developmental changes in brain function underlying the influence of reward processing on inhibitory control

    PubMed Central

    Padmanabhan, Aarthi; Geier, Charles F; Ordaz, Sarah J; Teslovich, Theresa; Luna, Beatriz

    2011-01-01

    Adolescence is a period marked by changes in motivational and cognitive brain systems. However, the development of the interactions between reward and cognitive control processing are just beginning to be understood. Using event-related functional neuroimaging and an incentive modulated antisaccade task, we compared blood-oxygen level dependent activity underlying motivated response inhibition in children, adolescents, and adults. Behaviorally, children and adolescents performed significantly worse than adults during neutral trials. However, children and adolescents showed significant performance increases during reward trials. Adults showed no performance changes across conditions. fMRI results demonstrated that all groups recruited a similar circuitry to support task performance, including regions typically associated with rewards (striatum and orbital frontal cortex), and regions known to be involved in inhibitory control (putative frontal and supplementary eye fields, and posterior parietal cortex, and prefrontal loci). During rewarded trials adolescents showed increased activity in striatal regions, while adults demonstrated heightened activation in the OFC relative to children and adolescents. Children showed greater reliance on prefrontal executive regions that may be related to increased effort inhibiting responses. Overall, these results indicate that response inhibition is enhanced with reward contingencies over development. Adolescents’ heightened response in striatal regions may be one factor contributing to reward-biased decision making and perhaps risk taking behavior. PMID:21966352

  3. Progesterone for Acute Traumatic Brain Injury: A Systematic Review of Randomized Controlled Trials

    PubMed Central

    Ma, Junpeng; Xu, Jianguo

    2015-01-01

    Objective To evaluate the efficacy and safety of progesterone administrated in patients with acute traumatic brain injury (TBI). Methods PubMed/MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Clinicaltrials.gov, ISRCTN registry and WHO International Clinical Trials Registry Platform (ICTRP) were searched for randomized controlled trials (RCTs) comparing progesterone and placebo administrated in acute TBI patients. The primary outcome was mortality and the secondary outcomes were unfavorable outcomes and adverse events. A meta-analysis was conducted to evaluate the efficacy and safety of progesterone administrated in patients with acute TBI. Results A total of 6 studies met inclusion criteria, involving 2,476 patients. The risk of bias was considered to be low in 4 studies but high in the other 2 studies. The results of meta-analysis indicated progesterone did not reduce the mortality (RR = 0.83, 95% CI = 0.57–1.20) or unfavorable outcomes (RR = 0.89, 95% CI = 0.78–1.02) of acute TBI patients in comparison with placebo. Sensitivity analysis yielded consistent results. Progesterone was basically safe and well tolerated in TBI patients with the exception of increased risk of phlebitis or thrombophlebitis (RR = 3.03, 95% CI = 1.96–4.66). Conclusions Despite some modest bias, present evidence demonstrated that progesterone was well tolerated but did not reduce the mortality or unfavorable outcomes of adult patients with acute TBI. PMID:26473361

  4. Distribution and binding of 18F-labeled and 125I-labeled analogues of ACI-80, a prospective molecular imaging biomarker of disease: a whole hemisphere post mortem autoradiography study in human brains obtained from Alzheimer's disease patients.

    PubMed

    Gulyás, Balázs; Spenger, Christian; Beliczai, Zsuzsa; Gulya, Károly; Kása, Péter; Jahan, Mahabuba; Jia, Zhisheng; Weber, Urs; Pfeifer, Andrea; Muhs, Andreas; Willbold, Dieter; Halldin, Christer

    2012-01-01

    One of the major pathological landmarks of Alzheimer's disease and other neurodegenerative diseases is the presence of amyloid deposits in the brain. The early non-invasive visualization of amyloid is a major objective of recent diagnostic neuroimaging approaches, including positron emission tomography (PET), with an eye on follow-up of disease progression and/or therapy efficacy. The development of molecular imaging biomarkers with binding affinity to amyloid in the brain is therefore in the forefront of imaging biomarker and radiochemistry research. Recently, a dodecamer peptide (amino acid sequence=QSHYRHISPAQV; denominated D1 or ACI-80) was identified as a prospective ligand candidate, binding with high ex vivo affinity to L-Aβ-amyloid (K(d): 0.4 μM). In order to assess the ligand's capacity to visualize amyloid in Alzheimer's disease (AD), two (125)I labeled and three (18)F labeled analogues of the peptide were synthesized and tested in post mortem human autoradiography experiments using whole hemisphere brain slices obtained from deceased AD patients and age matched control subjects. The (18)F-labeled radioligands showed more promising visualization capacity of amyloid that the (125)I-labeled radioligands. In the case of each (18)F radioligands the grey matter uptake in the AD brains was significantly higher than that in control brains. Furthermore, the grey matter: white matter uptake ratio was over ~2, the difference being significant for each (18)F-radioligands. The regional distribution of the uptake of the various radioligands systematically shows a congruent pattern between the high uptake regions and spots in the autoradiographic images and the disease specific signals obtained in adjacent or identical brain slices labeled with histological, immunohistochemical or autoradiographic stains for amyloid deposits or activated astrocytes. The present data, using post mortem human brain autoradiography in whole hemisphere human brains obtained from deceased

  5. Rapid treatment-induced brain changes in pediatric CRPS.

    PubMed

    Erpelding, Nathalie; Simons, Laura; Lebel, Alyssa; Serrano, Paul; Pielech, Melissa; Prabhu, Sanjay; Becerra, Lino; Borsook, David

    2016-03-01

    To date, brain structure and function changes in children with complex regional pain syndrome (CRPS) as a result of disease and treatment remain unknown. Here, we investigated (a) gray matter (GM) differences between patients with CRPS and healthy controls and (b) GM and functional connectivity (FC) changes in patients following intensive interdisciplinary psychophysical pain treatment. Twenty-three patients (13 females, 9 males; average age ± SD = 13.3 ± 2.5 years) and 21 healthy sex- and age-matched controls underwent magnetic resonance imaging. Compared to controls, patients had reduced GM in the primary motor cortex, premotor cortex, supplementary motor area, midcingulate cortex, orbitofrontal cortex, dorsolateral prefrontal cortex (dlPFC), posterior cingulate cortex, precuneus, basal ganglia, thalamus, and hippocampus. Following treatment, patients had increased GM in the dlPFC, thalamus, basal ganglia, amygdala, and hippocampus, and enhanced FC between the dlPFC and the periaqueductal gray, two regions involved in descending pain modulation. Accordingly, our results provide novel evidence for GM abnormalities in sensory, motor, emotional, cognitive, and pain modulatory regions in children with CRPS. Furthermore, this is the first study to demonstrate rapid treatment-induced GM and FC changes in areas implicated in sensation, emotion, cognition, and pain modulation. PMID:25515312

  6. Self-awareness and traumatic brain injury outcome

    PubMed Central

    Robertson, Kayela; Schmitter-Edgecombe, Maureen

    2016-01-01

    Primary Objective Impaired self-awareness following a traumatic brain injury (TBI) can reduce the effectiveness of rehabilitation, resulting in poorer outcomes. However, little is understood about how the multi-dimensional aspects of self-awareness may differentially change with recovery and impact outcome. Thus, we examined four self-awareness variables represented in the Dynamic Comprehensive Model of Awareness: metacognitive awareness, anticipatory awareness, error-monitoring, and self-regulation. Research Design We evaluated change of the self-awareness measures with recovery from TBI and whether the self-awareness measures predicted community reintegration at follow-up. Methods and Procedures Participants were 90 individuals with moderate to severe TBI who were tested acutely following injury and 90 age-matched controls. Forty-nine of the TBI participants and 49 controls were re-tested after 6 months. Main Outcome and Results Results revealed that the TBI group’s error-monitoring performance was significantly poorer than controls at both baseline and follow-up. Regression analyses revealed that the self-awareness variables at follow-up were predictive of community reintegration, with error-monitoring being a unique predictor. Conclusions Our results highlight the importance of error-monitoring and suggest that interventions targeted at improving error-monitoring may be particularly beneficial. Understanding the multi-dimensional nature of self-awareness will further improve rehabilitation efforts and understanding of the theoretical basis of self-awareness. PMID:25915097

  7. The Relationship of Parental Warm Responsiveness and Negativity to Emerging Behavior Problems following Traumatic Brain Injury in Young Children

    ERIC Educational Resources Information Center

    Wade, Shari L.; Cassedy, Amy; Walz, Nicolay C.; Taylor, H. Gerry; Stancin, Terry; Yeates, Keith Owen

    2011-01-01

    Parenting behaviors play a critical role in the child's behavioral development, particularly for children with neurological deficits. This study examined the relationship of parental warm responsiveness and negativity to changes in behavior following traumatic brain injury (TBI) in young children relative to an age-matched cohort of children with…

  8. Productive Use of the English Past Tense in Children with Focal Brain Injury and Specific Language Impairment

    ERIC Educational Resources Information Center

    Marchman, Virginia A.; Saccuman, Cristina; Wulfeck, Beverly

    2004-01-01

    In this study, 22 children with early left hemisphere (LHD) or right hemisphere (RHD) focal brain lesions (FL, n=14 LHD, n=8 RHD) were administered an English past tense elicitation test (M=6.5 years). Proportion correct and frequency of overregularization and zero-marking errors were compared to age-matched samples of children with specific…

  9. Alcohol Use Disorder with and without Stimulant Use: Brain Morphometry and Its Associations with Cigarette Smoking, Cognition, and Inhibitory Control

    PubMed Central

    Pennington, David L.; Durazzo, Timothy C.; Schmidt, Thomas P.; Abé, Christoph; Mon, Anderson; Meyerhoff, Dieter J.

    2015-01-01

    Objective Little is known about the effects of polysubstance use and cigarette smoking on brain morphometry. This study examined neocortical brain morphometric differences between abstinent polysubstance dependent and alcohol-only dependent treatment seekers (ALC) as well as light drinking controls (CON), the associations of cigarette smoking in these polysubstance users (PSU), and morphometric relationships to cognition and inhibitory control. Methods All participants completed extensive neuropsychological assessments and 4 Tesla brain magnetic resonance imaging. PSU and ALC were abstinent for one month at the time of study. Parcellated morphological data (volume, surface area, thickness) were obtained with FreeSurfer methodology for the following bilateral components: dorso-prefrontal cortex (DPFC), anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and insula. Regional group differences were examined and structural data correlated with domains of cognition and inhibitory control. Results PSU had significantly smaller left OFC volume and surface area and trends to smaller right DPFC volume and surface area compared to CON; PSU did not differ significantly from ALC on these measures. PSU, however, had significantly thinner right ACC than ALC. Smoking PSU had significantly larger right OFC surface area than non-smoking PSU. No significant relationships between morphometry and quantity/frequency of substance use, alcohol use, or age of onset of heavy drinking were observed. PSU exhibited distinct relationships between brain structure and processing speed, cognitive efficiency, working memory and inhibitory control that were not observed in ALC or CON. Conclusion Polysubstance users have unique morphometric abnormalities and structure-function relationships when compared to individuals dependent only on alcohol and light drinking controls. Chronic cigarette smoking is associated with structural brain irregularities in polysubstance users. Further

  10. Effects of Normobaric Hyperoxia in Traumatic Brain Injury: A Randomized Controlled Clinical Trial

    PubMed Central

    Taher, Abbas; Pilehvari, Zahra; Poorolajal, Jalal; Aghajanloo, Mashhood

    2016-01-01

    Background Traumatic brain injury (TBI) is one of the important causes of morbidity and mortality throughout the world, especially in young people. In recent years normobaric hyperoxia has become an important and useful step for recovery and improvement of outcome in TBI. Objectives The purpose of this study was to evaluate the effects of normobaric hyperoxia on clinical neurological outcomes of patients with severe traumatic brain injuries. We used the Glasgow outcome scale (GOS), barthel index, and modified rankin scale (mRS) to measure the outcomes of patients with TBI. Patients and Methods Sixty-eight consecutive patients with severe TBI (mean Glasgow coma scale [GCS] score: 7.4) who met the inclusion criteria were entered in this randomized controlled clinical trial. The patients were randomized into two groups, as follows: 1) experimental: received 80% oxygen via mechanical ventilator in the first 6 hours of admission, 2) control: received 50% oxygen by mechanical ventilator in the first 6 hours of admission and then standard medical care. We measured the GOS, Barthel Index, and mRS at the time of discharge from hospital and reassessed these measurements at the 6-month follow-up after injury. Results According to our study, there were no significant sex or age differences between the two groups (P = 0.595 and 0.074). The number of days in the intensive care unit (ICU) in the control group and experimental group were 11.4 and 9.4 days, respectively (P = 0.28), while the numbers of days of general ward admission were 13.9 and 11.4 days (P = 0.137) respectively. The status of GOS at time of discharge were severe = 13 and 10, moderate = 16 and 19, and low = 5 and 5 in the control and experimental groups, respectively (P = 0.723); 6 months after injury, the scores were as follows: moderate = 16 and 9, low = 15 and 25, and severe = 3 and 0 (P = 0.024). The Barthel index scores in the control and experimental groups were 59.7 and 63.9 at time of discharge (P = 0

  11. ABCG2 is up-regulated in Alzheimer's brain with cerebral amyloid angiopathy and may act as a gatekeeper at the blood-brain barrier for Aβ1-40 peptides

    PubMed Central

    Xiong, Huaqi; Callaghan, Debbie; Jones, Aimee; Bai, Jianying; Rasquinha, Ingrid; Smith, Catherine; Pei, Ke; Walker, Douglas; Lue, Lih-Fen; Stanimirovic, Danica; Zhang, Wandong

    2009-01-01

    Alzheimer's disease (AD) is characterized by accumulation and deposition of Aβ peptides in the brain. Aβ deposition in cerebrovessels occurs in many AD patients and results in cerebral amyloid angiopathy (AD/CAA). Since Aβ can be transported across blood-brain barrier (BBB), aberrant Aβ trafficking across BBB may contribute to Aβ accumulation in the brain and CAA development. Expression analyses of 273 BBB-related genes performed in this study showed that the drug transporter, ABCG2, was significantly up-regulated in the brains of AD/CAA compared to age-matched controls. Increased ABCG2 expression was confirmed by Q-PCR, Western blot and immunohistochemistry. Abcg2 was also increased in mouse AD models, Tg-SwDI and 3XTg. Aβ alone or in combination with hypoxia/ischemia failed to stimulate ABCG2 expression in BBB endothelial cells; however, conditioned media from Aβ-activated microglia strongly induced ABCG2 expression. ABCG2 protein in AD/CAA brains interacted and co-immunoprecipitated with Aβ. Overexpression of hABCG2 reduced drug uptake in cells; however, interaction of Aβ1-40 with ABCG2 impaired ABCG2-mediated drug efflux. The role of Abcg2 in Aβ transport at the BBB was investigated in Abcg2-null and wild-type mice after intravenous injection of Cy5.5-labeled Aβ1-40 or scrambled Aβ40-1. Optical imaging analyses of live animals and their brains showed that Abcg2-null mice accumulated significantly more Aβ in their brains than wt mice. The finding was confirmed by immunohistochemistry. These results suggest that ABCG2 may act as a gatekeeper at the BBB to prevent blood Aβ from entering into brain. ABCG2 up-regulation may serve as a biomarker of CAA vascular pathology in AD patients. PMID:19403814

  12. Filling in the gaps: Anticipatory control of eye movements in chronic mild traumatic brain injury.

    PubMed

    Diwakar, Mithun; Harrington, Deborah L; Maruta, Jun; Ghajar, Jamshid; El-Gabalawy, Fady; Muzzatti, Laura; Corbetta, Maurizio; Huang, Ming-Xiong; Lee, Roland R

    2015-01-01

    A barrier in the diagnosis of mild traumatic brain injury (mTBI) stems from the lack of measures that are adequately sensitive in detecting mild head injuries. MRI and CT are typically negative in mTBI patients with persistent symptoms of post-concussive syndrome (PCS), and characteristic difficulties in sustaining attention often go undetected on neuropsychological testing, which can be insensitive to momentary lapses in concentration. Conversely, visual tracking strongly depends on sustained attention over time and is impaired in chronic mTBI patients, especially when tracking an occluded target. This finding suggests deficient internal anticipatory control in mTBI, the neural underpinnings of which are poorly understood. The present study investigated the neuronal bases for deficient anticipatory control during visual tracking in 25 chronic mTBI patients with persistent PCS symptoms and 25 healthy control subjects. The task was performed while undergoing magnetoencephalography (MEG), which allowed us to examine whether neural dysfunction associated with anticipatory control deficits was due to altered alpha, beta, and/or gamma activity. Neuropsychological examinations characterized cognition in both groups. During MEG recordings, subjects tracked a predictably moving target that was either continuously visible or randomly occluded (gap condition). MEG source-imaging analyses tested for group differences in alpha, beta, and gamma frequency bands. The results showed executive functioning, information processing speed, and verbal memory deficits in the mTBI group. Visual tracking was impaired in the mTBI group only in the gap condition. Patients showed greater error than controls before and during target occlusion, and were slower to resynchronize with the target when it reappeared. Impaired tracking concurred with abnormal beta activity, which was suppressed in the parietal cortex, especially the right hemisphere, and enhanced in left caudate and frontal

  13. Filling in the gaps: Anticipatory control of eye movements in chronic mild traumatic brain injury

    PubMed Central

    Diwakar, Mithun; Harrington, Deborah L.; Maruta, Jun; Ghajar, Jamshid; El-Gabalawy, Fady; Muzzatti, Laura; Corbetta, Maurizio; Huang, Ming-Xiong; Lee, Roland R.

    2015-01-01

    A barrier in the diagnosis of mild traumatic brain injury (mTBI) stems from the lack of measures that are adequately sensitive in detecting mild head injuries. MRI and CT are typically negative in mTBI patients with persistent symptoms of post-concussive syndrome (PCS), and characteristic difficulties in sustaining attention often go undetected on neuropsychological testing, which can be insensitive to momentary lapses in concentration. Conversely, visual tracking strongly depends on sustained attention over time and is impaired in chronic mTBI patients, especially when tracking an occluded target. This finding suggests deficient internal anticipatory control in mTBI, the neural underpinnings of which are poorly understood. The present study investigated the neuronal bases for deficient anticipatory control during visual tracking in 25 chronic mTBI patients with persistent PCS symptoms and 25 healthy control subjects. The task was performed while undergoing magnetoencephalography (MEG), which allowed us to examine whether neural dysfunction associated with anticipatory control deficits was due to altered alpha, beta, and/or gamma activity. Neuropsychological examinations characterized cognition in both groups. During MEG recordings, subjects tracked a predictably moving target that was either continuously visible or randomly occluded (gap condition). MEG source-imaging analyses tested for group differences in alpha, beta, and gamma frequency bands. The results showed executive functioning, information processing speed, and verbal memory deficits in the mTBI group. Visual tracking was impaired in the mTBI group only in the gap condition. Patients showed greater error than controls before and during target occlusion, and were slower to resynchronize with the target when it reappeared. Impaired tracking concurred with abnormal beta activity, which was suppressed in the parietal cortex, especially the right hemisphere, and enhanced in left caudate and frontal

  14. A neurochemical closed-loop controller for deep brain stimulation: toward individualized smart neuromodulation therapies.

    PubMed

    Grahn, Peter J; Mallory, Grant W; Khurram, Obaid U; Berry, B Michael; Hachmann, Jan T; Bieber, Allan J; Bennet, Kevin E; Min, Hoon-Ki; Chang, Su-Youne; Lee, Kendall H; Lujan, J L

    2014-01-01

    Current strategies for optimizing deep brain stimulation (DBS) therapy involve multiple postoperative visits. During each visit, stimulation parameters are adjusted until desired therapeutic effects are achieved and adverse effects are minimized. However, the efficacy of these therapeutic parameters may decline with time due at least in part to disease progression, interactions between the host environment and the electrode, and lead migration. As such, development of closed-loop control systems that can respond to changing neurochemical environments, tailoring DBS therapy to individual patients, is paramount for improving the therapeutic efficacy of DBS. Evidence obtained using electrophysiology and imaging techniques in both animals and humans suggests that DBS works by modulating neural network activity. Recently, animal studies have shown that stimulation-evoked changes in neurotransmitter release that mirror normal physiology are associated with the therapeutic benefits of DBS. Therefore, to fully understand the neurophysiology of DBS and optimize its efficacy, it may be necessary to look beyond conventional electrophysiological analyses and characterize the neurochemical effects of therapeutic and non-therapeutic stimulation. By combining electrochemical monitoring and mathematical modeling techniques, we can potentially replace the trial-and-error process used in clinical programming with deterministic approaches that help attain optimal and stable neurochemical profiles. In this manuscript, we summarize the current understanding of electrophysiological and electrochemical processing for control of neuromodulation therapies. Additionally, we describe a proof-of-principle closed-loop controller that characterizes DBS-evoked dopamine changes to adjust stimulation parameters in a rodent model of DBS. The work described herein represents the initial steps toward achieving a "smart" neuroprosthetic system for treatment of neurologic and psychiatric disorders

  15. Effect of DISC1 SNPs on brain structure in healthy controls and patients with a history of psychosis.

    PubMed

    Kähler, Anna K; Rimol, Lars M; Brown, Andrew Anand; Djurovic, Srdjan; Hartberg, Cecilie B; Melle, Ingrid; Dale, Anders M; Andreassen, Ole A; Agartz, Ingrid

    2012-09-01

    Disrupted-in-Schizophrenia-1 (DISC1) has been suggested as a susceptibility locus for a broad spectrum of psychiatric disorders. Risk variants have been associated with brain structural changes, which overlap alterations reported in schizophrenia and bipolar disorder patients. We used genome-wide genotyping data for a Norwegian sample of healthy controls (n = 171) and patients with a history of psychosis (n = 184), to investigate 61 SNPs in the DISC1 region for putative association with structural magnetic resonance imaging (sMRI) measures (hippocampal volume; mean cortical thickness; and total surface area, as well as cortical thickness and area divided into four lobar measures). SNP rs821589 was associated with mean temporal and total brain cortical thickness in controls (P(adjusted) = 0.009 and 0.02, respectively), but not in patients. SNPs rs11122319 and rs1417584 were associated with mean temporal cortical thickness in patients (P(adjusted) = 0.04 and 0.03, respectively), but not in controls, and both SNPs have previously been highly associated with DISC1 gene expression. There were significant genotype ×  case-control interactions. There was no significant association between SNPs and cortical area or hippocampal volume in controls, or with any of the structural measures in cases, after correction for multiple comparisons. In conclusion, DISC1 SNPs might impact brain structural variation, possibly differently in psychosis patients versus controls, but independent replication will be needed to confirm our findings. PMID:22815203

  16. Statins are Associated With a Reduced Risk of Brain Cancer: A Population-Based Case-Control Study.

    PubMed

    Chen, Brian K; Chiu, Hui-Fen; Yang, Chun-Yuh

    2016-04-01

    The aim of this study was to investigate whether statin utilization is associated with brain cancer risk.A population-based case-control study was conducted using nationally representative claims data from the National Health Insurance Bureau in Taiwan. Cases included all patients 50 years and older who received an index diagnosis of brain cancer between 2004 and 2011. Our controls were matched by age, sex, and index date. We estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) using multiple logistic regression.We examined 213 brain cancer cases and 852 controls. The unadjusted ORs for any statin prescription was 0.77 (95% CI = 0.50-1.18) and the adjusted OR was 0.59 (95% CI = 0.37-0.96). Compared with no use of statins, the adjusted ORs were 0.68 (95% CI = 0.38-1.24) for the group having been prescribed with statins with cumulative defined daily dose (DDD) below 144.67 DDDs and 0.50 (95% CI = 0.28-0.97) for the group with the cumulative statin use of 144.67 DDDs or more.The results of this study suggest that statins may reduce the risk of brain cancer. PMID:27124024

  17. Structural and Functional Brain Changes beyond Visual System in Patients with Advanced Glaucoma

    PubMed Central

    Motolese, Ilaria; De Leucio, Alessandro; Iester, Michele; Motolese, Eduardo; Federico, Antonio; De Stefano, Nicola

    2014-01-01

    In order to test the hypothesis that in primary open angle glaucoma (POAG), an important cause of irreversible blindness, a spreading of neurodegeneration occurs through the brain, we performed multimodal MRI and subsequent whole-brain explorative voxelwise analyses in 13 advanced POAG patients and 12 age-matched normal controls (NC). Altered integrity (decreased fractional anisotropy or increased diffusivities) of white matter (WM) tracts was found not only along the visual pathway of POAG but also in nonvisual WM tracts (superior longitudinal fascicle, anterior thalamic radiation, corticospinal tract, middle cerebellar peduncle). POAG patients also showed brain atrophy in both visual cortex and other distant grey matter (GM) regions (frontoparietal cortex, hippocampi and cerebellar cortex), decreased functional connectivity (FC) in visual, working memory and dorsal attention networks and increased FC in visual and executive networks. In POAG, abnormalities in structure and FC within and outside visual system correlated with visual field parameters in the poorer performing eyes, thus emphasizing their clinical relevance. Altogether, this represents evidence that a vision disorder such as POAG can be considered a widespread neurodegenerative condition. PMID:25162716

  18. Role of Intercellular Adhesion Molecule-1 in Radiation-Induced Brain Injury

    SciTech Connect

    Wu, K.-L.; Tu Ba; Li Yuqing; Wong, C. Shun

    2010-01-15

    Purpose: To determine the role of intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of brain injury after irradiation (IR). Methods and Materials: We assessed the expression of ICAM-1 in mouse brain after cranial IR and determined the histopathologic and behavioral changes in mice that were either wildtype (+/+) or knockout (-/-) of the ICAM-1 gene after IR. Results: There was an early dose-dependent increase in ICAM-1 mRNA and protein expression after IR. Increased ICAM-1 immunoreactivity was observed in endothelia and glia of ICAM-1+/+ mice up to 8 months after IR. ICAM-1-/- mice showed no expression. ICAM-1+/+ and ICAM-1-/- mice showed similar vascular abnormalities at 2 months after 10-17 Gy, and there was evidence for demyelination and inhibition of hippocampal neurogenesis at 8 months after 10 Gy. After 10 Gy, irradiated ICAM-1+/+ and ICAM-1-/- mice showed similar behavioral changes at 2-6 months in open field, light-dark chamber, and T-maze compared with age-matched genotype controls. Conclusion: There is early and late upregulation of ICAM-1 in the vasculature and glia of mouse brain after IR. ICAM-1, however, does not have a causative role in the histopathologic injury and behavioral dysfunction after moderate single doses of cranial IR.

  19. Deviant fMRI patterns of brain activity to speech in 2–3 year-old children with autism spectrum disorder

    PubMed Central

    Redcay, Elizabeth; Courchesne, Eric

    2010-01-01

    Background A failure to develop normal language is one of the most common first signs that a toddler might be at risk for autism. Currently the neural bases underlying this failure to develop language are unknown. Methods In this study, functional magnetic resonance imaging (fMRI) was utilized to identify the brain regions involved in speech perception in 12 2–3 year-old children with autism spectrum disorder (ASD) during natural sleep. We also recorded fMRI data from two typically developing control groups: a mental age-matched (MA) (n=11) and a chronological age-matched (CA) (n=12) group. During fMRI data acquisition, forward and backward speech stimuli were presented with intervening periods of no sound presentation. Results Direct statistical comparison between groups revealed significant differences in regions recruited to process speech. In comparison to their MA-matched controls, the ASD group showed reduced activity in an extended network of brain regions, which are recruited in typical early language acquisition. In comparison to their CA-matched controls, ASD participants showed greater activation primarily within right and medial frontal regions. Laterality analyses revealed a trend towards greater recruitment of right hemisphere regions in the ASD group and left hemisphere regions in the CA group during the forward speech condition. Furthermore, correlation analyses revealed a significant positive relationship between right hemisphere frontal and temporal activity to forward speech and receptive language skill. Conclusions These findings suggest that at 2–3 years, children with ASD may be on a deviant developmental trajectory characterized by a greater recruitment of right hemisphere regions during speech perception. PMID:18672231

  20. Ubiquitin-specific protease 4 controls metastatic potential through β-catenin stabilization in brain metastatic lung adenocarcinoma.

    PubMed

    Hwang, Su Jin; Lee, Hye Won; Kim, Hye Ree; Lee, Hong; Shin, Chang Hoon; Yun, Sun-Il; Lee, Dong Heon; Kim, Duk-Hwan; Kim, Kyeong Kyu; Joo, Kyeung Min; Kim, Hyeon Ho

    2016-01-01

    Brain metastasis is the most common type of intracranial cancer and is the main cause of cancer-associated mortality. Brain metastasis mainly originates from lung cancer. Using a previously established in vitro brain metastatic model, we found that brain metastatic PC14PE6/LvBr4 cells exhibited higher expression of β-catenin and increased migratory activity than parental PC14PE6 cells. Knockdown of β-catenin dramatically suppressed the motility and invasiveness of PC14PE6/LvBr4 cells, indicating β-catenin is involved in controlling metastatic potential. Since β-catenin protein was increased without a significant change in its mRNA levels, the mechanism underlying increased β-catenin stability was investigated. We found that ubiquitin-specific protease 4 (USP4), recently identified as a β-catenin-specific deubiquitinylating enzyme, was highly expressed in PC14PE6/LvBr4 cells and involved in the increased stability of β-catenin protein. Similar to β-catenin knockdown, USP4-silenced PC14PE6/LvBr4 cells showed decreased migratory and invasive abilities. Moreover, knockdown of both USP4 and β-catenin inhibited clonogenicity and induced mesenchymal-epithelial transition by downregulating ZEB1 in PC14PE6/LvBr4 cells. Using bioluminescence imaging, we found that knockdown of USP4 suppressed brain metastasis in vivo and significantly increased overall survival and brain metastasis-free survival. Taken together, our results indicate that USP4 is a promising therapeutic target for brain metastasis in patients with lung adenocarcinoma. PMID:26883469

  1. Ubiquitin-specific protease 4 controls metastatic potential through β-catenin stabilization in brain metastatic lung adenocarcinoma

    PubMed Central

    Hwang, Su Jin; Lee, Hye Won; Kim, Hye Ree; Lee, Hong; Shin, Chang Hoon; Yun, Sun-Il; Lee, Dong Heon; Kim, Duk-Hwan; Kim, Kyeong Kyu; Joo, Kyeung Min; Kim, Hyeon Ho

    2016-01-01

    Brain metastasis is the most common type of intracranial cancer and is the main cause of cancer-associated mortality. Brain metastasis mainly originates from lung cancer. Using a previously established in vitro brain metastatic model, we found that brain metastatic PC14PE6/LvBr4 cells exhibited higher expression of β-catenin and increased migratory activity than parental PC14PE6 cells. Knockdown of β-catenin dramatically suppressed the motility and invasiveness of PC14PE6/LvBr4 cells, indicating β-catenin is involved in controlling metastatic potential. Since β-catenin protein was increased without a significant change in its mRNA levels, the mechanism underlying increased β-catenin stability was investigated. We found that ubiquitin-specific protease 4 (USP4), recently identified as a β-catenin-specific deubiquitinylating enzyme, was highly expressed in PC14PE6/LvBr4 cells and involved in the increased stability of β-catenin protein. Similar to β-catenin knockdown, USP4-silenced PC14PE6/LvBr4 cells showed decreased migratory and invasive abilities. Moreover, knockdown of both USP4 and β-catenin inhibited clonogenicity and induced mesenchymal-epithelial transition by downregulating ZEB1 in PC14PE6/LvBr4 cells. Using bioluminescence imaging, we found that knockdown of USP4 suppressed brain metastasis in vivo and significantly increased overall survival and brain metastasis-free survival. Taken together, our results indicate that USP4 is a promising therapeutic target for brain metastasis in patients with lung adenocarcinoma. PMID:26883469

  2. Oxidative Stress and Protein Quality Control Systems in the Aged Canine Brain as a Model for Human Neurodegenerative Disorders

    PubMed Central

    2015-01-01

    Aged dogs are considered the most suitable spontaneous animal model for studying normal aging and neurodegenerative diseases. Elderly canines naturally develop cognitive dysfunction and neuropathological hallmarks similar to those seen in humans, especially Alzheimer's disease-like pathology. Pet dogs also share similar living conditions and diets to humans. Oxidative damage accumulates in the canine brain during aging, making dogs a valid model for translational antioxidant treatment/prevention studies. Evidence suggests the presence of detective protein quality control systems, involving ubiquitin-proteasome system (UPS) and Heat Shock Proteins (HSPs), in the aged canine brain. Further studies on the canine model are needed to clarify the role of age-related changes in UPS activity and HSP expression in neurodegeneration in order to design novel treatment strategies, such as HSP-based therapies, aimed at improving chaperone defences against proteotoxic stress affecting brain during aging. PMID:26078824

  3. Effects of incentives, age, and behavior on brain activation during inhibitory control: A longitudinal fMRI study

    PubMed Central

    Paulsen, David J.; Hallquist, Michael N.; Geier, Charles F.; Luna, Beatriz

    2014-01-01

    We investigated changes in brain function supporting inhibitory control under age-controlled incentivized conditions, separating age- and performance-related activation in an accelerated longitudinal design including 10- to 22-year-olds. Better inhibitory control correlated with striatal activation during neutral trials, while Age × Behavior interactions in the striatum indicated that in the absence of extrinsic incentives, younger subjects with greater reward circuitry activation successfully engage in greater inhibitory control. Age was negatively correlated with ventral amygdala activation during Loss trials, suggesting that amygdala function more strongly mediates bottom-up processing earlier in development when controlling the negative aspects of incentives to support inhibitory control. Together, these results indicate that with development, reward-modulated cognitive control may be supported by incentive processing transitions in the amygdala, and from facilitative to obstructive striatal function during inhibitory control. PMID:25284272

  4. Polygenic risk for schizophrenia associated with working memory-related prefrontal brain activation in patients with schizophrenia and healthy controls.

    PubMed

    Kauppi, Karolina; Westlye, Lars T; Tesli, Martin; Bettella, Francesco; Brandt, Christine L; Mattingsdal, Morten; Ueland, Torill; Espeseth, Thomas; Agartz, Ingrid; Melle, Ingrid; Djurovic, Srdjan; Andreassen, Ole A

    2015-05-01

    Schizophrenia is a highly heritable and polygenic disease, and identified common genetic variants have shown weak individual effects. Many studies have reported altered working memory (WM)-related brain activation in schizophrenia, preferentially in the frontal lobe. Such differences in brain activations could reflect inherited alterations possibly involved in the disease etiology, or rather secondary disease-related mechanisms. The use of polygenic risk scores (PGRS) based on a large number of risk polymorphisms with small effects is a valuable approach to examine the effect of cumulative genetic risk on brain functioning. This study examined the impact of cumulative genetic risk for schizophrenia on WM-related brain activations, assessed with functional magnetic resonance imaging. For each participant (63 schizophrenia patients and 118 healthy controls), we calculated a PGRS for schizophrenia based on 18 862 single-nucleotide polymorphism in a large multicenter genome-wide association study including 9146 schizophrenia patients and 12 111 controls, performed by the Psychiatric Genomics Consortium. As expected, the PGRS was significantly higher in patients compared with healthy controls. Further, the PGRS was related to differences in frontal lobe brain activation between high and low WM demand. Specifically, even in absence of main effects of diagnosis, increased PGRS was associated with decreased activation difference in the right middle-superior prefrontal cortex (BA 10/11) and the right inferior frontal gyrus (BA 45). This effect was seen in both cases and controls, and was not influenced by sex, age, or task performance. The findings support the notion of dysregulation of frontal lobe functioning as an inherited vulnerability factor in schizophrenia. PMID:25392519

  5. Interhemispheric and Intrahemispheric Control of Emotion: A Focus on Unilateral Brain Damage.

    ERIC Educational Resources Information Center

    Borod, Joan C.

    1992-01-01

    Discusses neocortical contributions to emotional processing. Examines parameters critical to neuropsychological study of emotion: interhemispheric and intrahemispheric factors, processing mode, and communication channel. Describes neuropsychological theories of emotion. Reviews studies of right-brain-damaged, left-brain-damaged, and normal adults,…

  6. Different Brain Wave Patterns and Cortical Control Abilities in Relation to Different Creative Potentials

    ERIC Educational Resources Information Center

    Li, Ying-Han; Tseng, Chao-Yuan; Tsai, Arthur Chih-Hsin; Huang, Andrew Chih-Wei; Lin, Wei-Lun

    2016-01-01

    Contemporary understanding of brain functions provides a way to probe into the mystery of creativity. However, the prior evidence regarding the relationship between creativity and brain wave patterns reveals inconsistent conclusions. One possible reason might be that the means of selecting creative individuals in the past has varied in each study.…

  7. Cerebral autoregulation and brain networks in occlusive processes of the internal carotid artery

    PubMed Central

    Avirame, Keren; Lesemann, Anne; List, Jonathan; Witte, Anja Veronica; Schreiber, Stephan Joachim; Flöel, Agnes

    2015-01-01

    Patients with unilateral occlusive processes of the internal carotid artery (ICA) show subtle cognitive deficits. Decline in cerebral autoregulation and in functional and structural integrity of brain networks have previously been reported in the affected hemisphere (AH). However, the association between cerebral autoregulation, brain networks, and cognition remains to be elucidated. Fourteen neurologically asymptomatic patients (65±11 years) with either ICA occlusion or high-grade ICA stenosis and 11 age-matched healthy controls (HC) (67±6 years) received neuropsychologic testing, transcranial Doppler sonography to assess cerebral autoregulation using vasomotor reactivity (VMR), and magnetic resonance imaging to probe white matter microstructure and resting-state functional connectivity (RSFC). Patients performed worse on memory and executive tasks when compared with controls. Vasomotor reactivity, white matter microstructure, and RSFC were lower in the AH of the patients when compared with the unaffected hemisphere and with controls. Lower VMR of the AH was associated with several ipsilateral clusters of lower white matter microstructure and lower bilateral RSFC in patients. No correlations were found between VMR and cognitive scores. In sum, impaired cerebral autoregulation was associated with reduced structural and functional connectivity in cerebral networks, indicating possible mechanisms by which severe unilateral occlusive processes of the ICA lead to cognitive decline. PMID:25388676

  8. [How does the brain control eye movements? Motor and premotor neurons of the brainstem].

    PubMed

    Coubard, O A

    2015-04-01

    Knowledge of cognitive and neural architecture and processes that control eye movements has advanced enough to allow precise and quantitative analysis of hitherto unsolved phenomena. In this review, we revisit from a neuropsychological viewpoint Hering vs. Helmholtz' hypotheses on binocular coordination. Specifically, we reexamine the behavior and the neural bases of saccade-vergence movement, to move the gaze in both direction and depth under natural conditions. From the psychophysical viewpoint, neo-Heringian and neo-Helmholtzian authors have accumulated arguments favoring distinct conjugate (for saccades) and disconjugate (for vergence) systems, as well as advocating for monocularly programmed eye movements. From the neurophysiological viewpoint, which reports brain cell recordings during the execution of a given task, neo-Heringian and neo-Helmholtzian physiologists have also provided arguments in favor of both hypotheses at the level of the brainstem premotor circuitry. Bridging the two, we propose that Hering and Helmholtz were both right. The emphasis placed by the latter on adaptive processes throughout life cycle is compatible with the importance of neurobiological constraints pointed out by the former. In the meanwhile, the study of saccade-vergence eye movements recalls how much the psychophysical definition of the task determines the interpretation that is made from neurophysiological data. PMID:25600699

  9. Measuring inhibitory control in children and adults: brain imaging and mental chronometry

    PubMed Central

    Houdé, Olivier; Borst, Grégoire

    2014-01-01

    Jean Piaget underestimated the cognitive capabilities of infants, preschoolers, and elementary schoolchildren, and overestimated the capabilities of adolescents and even adults which are often biased by illogical intuitions and overlearned strategies (i.e., “fast thinking” in Daniel Kahneman’s words). The crucial question is now to understand why, despite rich precocious knowledge about physical and mathematical principles observed over the last three decades in infants and young children, older children, adolescents and even adults are nevertheless so often bad reasoners. We propose that inhibition of less sophisticated solutions (or heuristics) by the prefrontal cortex is a domain-general executive ability that supports children’s conceptual insights associated with more advanced Piagetian stages, such as number-conservation and class inclusion. Moreover, this executive ability remains critical throughout the whole life and even adults may sometimes need “prefrontal pedagogy” in order to learn inhibiting intuitive heuristics (or biases) in deductive reasoning tasks. Here we highlight some of the discoveries from our lab in the field of cognitive development relying on two methodologies used for measuring inhibitory control: brain imaging and mental chronometry (i.e., the negative priming paradigm). We also show that this new approach opens an avenue for re-examining persistent errors in standard classroom-learning tasks. PMID:24994993

  10. Notch1-STAT3-ETBR signaling axis controls reactive astrocyte proliferation after brain injury.

    PubMed

    LeComte, Matthew D; Shimada, Issei S; Sherwin, Casey; Spees, Jeffrey L

    2015-07-14

    Defining the signaling network that controls reactive astrogliosis may provide novel treatment targets for patients with diverse CNS injuries and pathologies. We report that the radial glial cell antigen RC2 identifies the majority of proliferating glial fibrillary acidic protein-positive (GFAP(+)) reactive astrocytes after stroke. These cells highly expressed endothelin receptor type B (ETB(R)) and Jagged1, a Notch1 receptor ligand. To study signaling in adult reactive astrocytes, we developed a model based on reactive astrocyte-derived neural stem cells isolated from GFAP-CreER-Notch1 conditional knockout (cKO) mice. By loss- and gain-of-function studies and promoter activity assays, we found that Jagged1/Notch1 signaling increased ETB(R) expression indirectly by raising the level of phosphorylated signal transducer and activator of transcription 3 (STAT3), a previously unidentified EDNRB transcriptional activator. Similar to inducible transgenic GFAP-CreER-Notch1-cKO mice, GFAP-CreER-ETB(R)-cKO mice exhibited a defect in reactive astrocyte proliferation after cerebral ischemia. Our results indicate that the Notch1-STAT3-ETB(R) axis connects a signaling network that promotes reactive astrocyte proliferation after brain injury. PMID:26124113

  11. Measuring inhibitory control in children and adults: brain imaging and mental chronometry.

    PubMed

    Houdé, Olivier; Borst, Grégoire

    2014-01-01

    Jean Piaget underestimated the cognitive capabilities of infants, preschoolers, and elementary schoolchildren, and overestimated the capabilities of adolescents and even adults which are often biased by illogical intuitions and overlearned strategies (i.e., "fast thinking" in Daniel Kahneman's words). The crucial question is now to understand why, despite rich precocious knowledge about physical and mathematical principles observed over the last three decades in infants and young children, older children, adolescents and even adults are nevertheless so often bad reasoners. We propose that inhibition of less sophisticated solutions (or heuristics) by the prefrontal cortex is a domain-general executive ability that supports children's conceptual insights associated with more advanced Piagetian stages, such as number-conservation and class inclusion. Moreover, this executive ability remains critical throughout the whole life and even adults may sometimes need "prefrontal pedagogy" in order to learn inhibiting intuitive heuristics (or biases) in deductive reasoning tasks. Here we highlight some of the discoveries from our lab in the field of cognitive development relying on two methodologies used for measuring inhibitory control: brain imaging and mental chronometry (i.e., the negative priming paradigm). We also show that this new approach opens an avenue for re-examining persistent errors in standard classroom-learning tasks. PMID:24994993

  12. Brain-controlled functional electrical stimulation for lower-limb motor recovery in stroke survivors.

    PubMed

    McCrimmon, Colin M; King, Christine E; Wang, Po T; Cramer, Steven C; Nenadic, Zoran; Do, An H

    2014-01-01

    Despite the prevalence of stroke-induced gait impairment due to foot drop, current rehabilitative practices to improve gait function are limited, and orthoses can be uncomfortable and do not provide long-lasting benefits. Therefore, novel modalities that may facilitate lasting neurological and functional improvements, such as brain-computer interfaces (BCIs), have been explored. In this article, we assess the feasibility of BCI-controlled functional electrical stimulation (FES) as a novel physiotherapy for post-stroke foot drop. Three chronic stroke survivors with foot drop received three, 1-hour sessions of therapy during 1 week. All subjects were able to purposefully operate the BCI-FES system in real time. Furthermore, the salient electroencephalographic (EEG) features used for classification by the data-driven methodology were determined to be physiologically relevant. Over the course of this short therapy, the subjects' dorsiflexion active range of motion (AROM) improved by 3°, 4°, and 8°, respectively. These results indicate that chronic stroke survivors can operate the BCI-FES system, and that BCI-FES intervention may promote functional improvements. PMID:25570191

  13. Enhancement of Contralesional Motor Control Promotes Locomotor Recovery after Unilateral Brain Lesion

    PubMed Central

    Hua, Xu-Yun; Qiu, Yan-Qun; Wang, Meng; Zheng, Mou-Xiong; Li, Tie; Shen, Yun-Dong; Jiang, Su; Xu, Jian-Guang; Gu, Yu-Dong; Tsien, JoeZ.; Xu, Wen-Dong

    2016-01-01

    There have been controversies on the contribution of contralesional hemispheric compensation to functional recovery of the upper extremity after a unilateral brain lesion. Some studies have demonstrated that contralesional hemispheric compensation may be an important recovery mechanism. However, in many cases where the hemispheric lesion is large, this form of compensation is relatively limited, potentially due to insufficient connections from the contralesional hemisphere to the paralyzed side. Here, we used a new procedure to increase the effect of contralesional hemispheric compensation by surgically crossing a peripheral nerve at the neck in rats, which may provide a substantial increase in connections between the contralesional hemisphere and the paralyzed limb. This surgical procedure, named cross-neck C7-C7 nerve transfer, involves cutting the C7 nerve on the healthy side and transferring it to the C7 nerve on the paretic side. Intracortical microstimulation, Micro-PET and histological analysis were employed to explore the cortical changes in contralesional hemisphere and to reveal its correlation with behavioral recovery. These results showed that the contralesional hemispheric compensation was markedly strengthened and significantly related to behavioral improvements. The findings also revealed a feasible and effective way to maximize the potential of one hemisphere in controlling both limbs. PMID:26732072

  14. A wirelessly controlled implantable LED system for deep brain optogenetic stimulation

    PubMed Central

    Rossi, Mark A.; Go, Vinson; Murphy, Tracy; Fu, Quanhai; Morizio, James; Yin, Henry H.

    2015-01-01

    In recent years optogenetics has rapidly become an essential technique in neuroscience. Its temporal and spatial specificity, combined with efficacy in manipulating neuronal activity, are especially useful in studying the behavior of awake behaving animals. Conventional optogenetics, however, requires the use of lasers and optic fibers, which can place considerable restrictions on behavior. Here we combined a wirelessly controlled interface and small implantable light-emitting diode (LED) that allows flexible and precise placement of light source to illuminate any brain area. We tested this wireless LED system in vivo, in transgenic mice expressing channelrhodopsin-2 in striatonigral neurons expressing D1-like dopamine receptors. In all mice tested, we were able to elicit movements reliably. The frequency of twitches induced by high power stimulation is proportional to the frequency of stimulation. At lower power, contraversive turning was observed. Moreover, the implanted LED remains effective over 50 days after surgery, demonstrating the long-term stability of the light source. Our results show that the wireless LED system can be used to manipulate neural activity chronically in behaving mice without impeding natural movements. PMID:25713516

  15. USP11 regulates PML stability to control Notch-induced malignancy in brain tumours.

    PubMed

    Wu, Hsin-Chieh; Lin, Yu-Ching; Liu, Cheng-Hsin; Chung, Hsiang-Ching; Wang, Ya-Ting; Lin, Ya-Wen; Ma, Hsin-I; Tu, Pang-Hsien; Lawler, Sean E; Chen, Ruey-Hwa

    2014-01-01

    The promyelocytic leukaemia (PML) protein controls multiple tumour suppressive functions and is downregulated in diverse types of human cancers through incompletely characterized post-translational mechanisms. Here we identify USP11 as a PML regulator by RNAi screening. USP11 deubiquitinates and stabilizes PML, thereby counteracting the functions of PML ubiquitin ligases RNF4 and the KLHL20-Cul3 (Cullin 3)-Roc1 complex. We find that USP11 is transcriptionally repressed through a Notch/Hey1-dependent mechanism, leading to PML destabilization. In human glioma, Hey1 upregulation correlates with USP11 and PML downregulation and with high-grade malignancy. The Notch/Hey1-induced downregulation of USP11 and PML not only confers multiple malignant characteristics of aggressive glioma, including proliferation, invasiveness and tumour growth in an orthotopic mouse model, but also potentiates self-renewal, tumour-forming capacity and therapeutic resistance of patient-derived glioma-initiating cells. Our study uncovers a PML degradation mechanism through Notch/Hey1-induced repression of the PML deubiquitinase USP11 and suggests an important role for this pathway in brain tumour pathogenesis. PMID:24487962

  16. A Brain Motor Control Assessment (BMCA) Protocol for Upper Limb Function

    PubMed Central

    Zoghi, Maryam; Galea, Mary; Morgan, David

    2013-01-01

    The Brain Motor Control Assessment (BMCA) protocol is a surface electromyography (sEMG)-based measure of motor output from central nervous system during a variety of reflex and voluntary motor tasks performed under strictly controlled conditions. The aim of this study was to evaluate the BMCA protocol for upper limb with the addition of shoulder voluntary tasks. The voluntary response index (VRI) was calculated from quantitative analysis of sEMG data during defined voluntary movement in neurologically intact people for comparison with that of patients after neurological injuries. The BMCA protocol included one bilateral and 4 unilateral voluntary tasks at different joints of both arms. The VRI, measured from 19 neurologically intact participants, comprises the total muscle activity recorded for the voluntary motor task (magnitude). The calculated similarity index (SI) for each phase of each task show the similarity of “the distribution of activity across the recorded muscles” for that task in this group off participants. Results: The VRI magnitude values from right and left sides for different tasks showed no significant difference (ANOVA: FSide: 0.09, P = 0.77). Therefore these values were pooled before calculating SI. SI values were higher for tasks against gravity: elbow flexion (0.99±0.03), wrist flexion with palm up (0.98±0.03) and wrist extension with palm down (0.97±0.07). On the other hand, the SI values were the lowest for bilateral shoulder abduction (0.84±0.08) and shoulder adduction (0.84±0.08). Conclusion: To validate this index for clinical use, serial studies on patients with neurological impairments should be performed. Tasks involving movement against gravity may be more suitable in future BMCAs. PMID:24223953

  17. Diminished supraspinal pain modulation in patients with mild traumatic brain injury

    PubMed Central

    Shukla, Shivshil; Yang, Eric; Canlas, Bryan; Kadokana, Mawj; Heald, Jason; Davani, Ariea; Song, David; Lin, Lisa; Polston, Greg; Tsai, Alice; Lee, Roland

    2016-01-01

    Background Chronic pain conditions are highly prevalent in patients with mild traumatic brain injury. Supraspinal diffuse axonal injury is known to dissociate brain functional connectivity in these patients. The effect of this dissociated state on supraspinal pain network is largely unknown. A functional magnetic resonance imaging study was conducted to compare the supraspinal pain network in patients with mild traumatic brain injury to the gender and age-matched healthy controls with the hypothesis that the functional connectivities of the medial prefrontal cortices, a supraspinal pain modulatory region to other pain-related sensory discriminatory and affective regions in the mild traumatic brain injury subjects are significantly reduced in comparison to healthy controls. Results The mild traumatic brain injury group (N = 15) demonstrated significantly (P < 0.01, cluster threshold > 150 voxels) less activities in the thalamus, pons, anterior cingulate cortex, insula, dorsolateral prefrontal cortex, and medial prefrontal cortices than the healthy control group (N = 15). Granger Causality Analyses (GCA) indicated while the left medial prefrontal cortices of the healthy control group cast a noticeable degree of outward (to affect) causality inference to multiple pain processing related regions, this outward inference pattern was not observed in the mild traumatic brain injury group. On the other hand, only patients’ bilateral anterior cingulate cortex received multiple inward (to be affected) causality inferences from regions including the primary and secondary somatosensory cortices and the inferior parietal lobe. Resting state functional connectivity analyses indicated that the medial prefrontal cortices of the mild traumatic brain injury group demonstrated a significantly (P < 0.01, F = 3.6, cluster size > 150 voxels) higher degree of functional connectivity to the inferior parietal lobe, premotor and secondary somatosensory cortex

  18. Optimal control of directional deep brain stimulation in the parkinsonian neuronal network

    NASA Astrophysics Data System (ADS)

    Fan, Denggui; Wang, Zhihui; Wang, Qingyun

    2016-07-01

    The effect of conventional deep brain stimulation (DBS) on debilitating symptoms of Parkinson's disease can be limited because it can only yield the spherical field. And, some side effects are clearly induced with influencing their adjacent ganglia. Recent experimental evidence for patients with Parkinson's disease has shown that a novel DBS electrode with 32 independent stimulation source contacts can effectively optimize the clinical therapy by enlarging the therapeutic windows, when it is applied on the subthalamic nucleus (STN). This is due to the selective activation in clusters of various stimulation contacts which can be steered directionally and accurately on the targeted regions of interest. In addition, because of the serious damage to the neural tissues, the charge-unbalanced stimulation is not typically indicated and the real DBS utilizes charge-balanced bi-phasic (CBBP) pulses. Inspired by this, we computationally investigate the optimal control of directional CBBP-DBS from the proposed parkinsonian neuronal network of basal ganglia-thalamocortical circuit. By appropriately tuning stimulation for different neuronal populations, it can be found that directional steering CBBP-DBS paradigms are superior to the spherical case in improving parkinsonian dynamical properties including the synchronization of neuronal populations and the reliability of thalamus relaying the information from cortex, which is in a good agreement with the physiological experiments. Furthermore, it can be found that directional steering stimulations can increase the optimal stimulation intensity of desynchronization by more than 1 mA compared to the spherical case. This is consistent with the experimental result with showing that there exists at least one steering direction that can allow increasing the threshold of side effects by 1 mA. In addition, we also simulate the local field potential (LFP) and dominant frequency (DF) of the STN neuronal population induced by the activation

  19. Motor Network Plasticity and Low-Frequency Oscillations Abnormalities in Patients with Brain Gliomas: A Functional MRI Study

    PubMed Central

    Niu, Chen; Zhang, Ming; Min, Zhigang; Rana, Netra; Zhang, Qiuli; Liu, Xin; Li, Min; Lin, Pan

    2014-01-01

    Brain plasticity is often associated with the process of slow-growing tumor formation, which remodels neural organization and optimizes brain network function. In this study, we aimed to investigate whether motor function plasticity would display deficits in patients with slow-growing brain tumors located in or near motor areas, but who were without motor neurological deficits. We used resting-state functional magnetic resonance imaging to probe motor networks in 15 patients with histopathologically confirmed brain gliomas and 15 age-matched healthy controls. All subjects performed a motor task to help identify individual motor activity in the bilateral primary motor cortex (PMC) and supplementary motor area (SMA). Frequency-based analysis at three different frequencies was then used to investigate possible alterations in the power spectral density (PSD) of low-frequency oscillations. For each group, the average PSD was determined for each brain region and a nonparametric test was performed to determine the difference in power between the two groups. Significantly reduced inter-hemispheric functional connectivity between the left and right PMC was observed in patients compared with controls (P<0.05). We also found significantly decreased PSD in patients compared to that in controls, in all three frequency bands (low: 0.01–0.02 Hz; middle: 0.02–0.06 Hz; and high: 0.06–0.1 Hz), at three key motor regions. These findings suggest that in asymptomatic patients with brain tumors located in eloquent regions, inter-hemispheric connection may be more vulnerable. A comparison of the two approaches indicated that power spectral analysis is more sensitive than functional connectivity analysis for identifying the neurological abnormalities underlying motor function plasticity induced by slow-growing tumors. PMID:24806463

  20. Covert hepatic encephalopathy: elevated total glutathione and absence of brain water content changes.

    PubMed

    Oeltzschner, Georg; Butz, Markus; Wickrath, Frithjof; Wittsack, Hans-Jörg; Schnitzler, Alfons

    2016-06-01

    Recent pathophysiological models suggest that oxidative stress and hyperammonemia lead to a mild brain oedema in hepatic encephalopathy (HE). Glutathione (GSx) is a major cellular antioxidant and known to be involved in the interception of both. The aim of this work was to study total glutathione levels in covert HE (minimal HE and HE grade 1) and to investigate their relationship with local brain water content, levels of glutamine (Gln), myo-inositol (mI), neurotransmitter levels, critical flicker frequency (CFF), and blood ammonia. Proton magnetic resonance spectroscopy ((1)H MRS) data were analysed from visual and sensorimotor cortices of thirty patients with covert HE and 16 age-matched healthy controls. Total glutathione levels (GSx/Cr) were quantified with respect to creatine. Furthermore, quantitative MRI brain water content measures were evaluated. Data were tested for links with the CFF and blood ammonia. GSx/Cr was elevated in the visual (mHE) and sensorimotor (mHE, HE 1) MRS volumes and correlated with blood ammonia levels (both P < 0.001). It was further linked to Gln/Cr and mI/Cr (P < 0.01 in visual, P < 0.001 in sensorimotor) and to GABA/Cr (P < 0.01 in visual). Visual GSx/Cr correlated with brain water content in the thalamus, nucleus caudatus, and visual cortex (P < 0.01). Brain water measures did neither show group effects nor correlations with CFF or blood ammonia. Elevated total glutathione levels in covert HE (< HE 2) correlate with blood ammonia and may be a regional-specific reaction to hyperammonemia and oxidative stress. Brain water content is locally linked to visual glutathione levels, but appears not to be associated with changes of clinical parameters. This might suggest that cerebral oedema is only marginally responsible for the symptoms of covert HE. PMID:26563124

  1. 3D PATTERN OF BRAIN ABNORMALITIES IN WILLIAMS SYNDROME VISUALIZED USING TENSOR-BASED MORPHOMETRY

    PubMed Central

    Chiang, Ming-Chang; Reiss, Allan L.; Lee, Agatha D.; Bellugi, Ursula; Galaburda, Albert M.; Korenberg, Julie R.; Mills, Debra L.; Toga, Arthur W.; Thompson, Paul M.

    2009-01-01

    Williams syndrome (WS) is a neurodevelopmental disorder associated with deletion of ~20 contiguous genes in chromosome band 7q11.23. Individuals with WS exhibit mild to moderate mental retardation, but are relatively more proficient in specific language and musical abilities. We used tensor-based morphometry (TBM) to visualize the complex pattern of gray/white matter reductions in WS, based on fluid registration of structural brain images. Methods 3D T1-weighted brain MRIs of 41 WS subjects (age: 29.2±9.2SD years; 23F/18M) and 39 age-matched healthy controls (age: 27.5±7.4 years; 23F/16M) were fluidly registered to a minimum deformation target. Fine-scale volumetric differences were mapped between diagnostic groups. Local regions were identified where regional structure volumes were associated with diagnosis, and with intelligence quotient (IQ) scores. Brain asymmetry was also mapped and compared between diagnostic groups. Results WS subjects exhibited widely distributed brain volume reductions (~10–15% reduction; P < 0.0002, permutation test). After adjusting for total brain volume, the frontal lobes, anterior cingulate, superior temporal gyrus, amygdala, fusiform gyrus and cerebellum were found to be relatively preserved in WS, but parietal and occipital lobes, thalamus and basal ganglia, and midbrain were disproportionally decreased in volume (P < 0.0002). These regional volumes also correlated positively with performance IQ in adult WS subjects (age ≥ 30 years, P = 0.038). Conclusion TBM facilitates 3D visualization of brain volume reductions in WS. Reduced parietal/occipital volumes may be associated with visuospatial deficits in WS. By contrast, frontal lobes, amygdala, and cingulate gyrus are relatively preserved or even enlarged, consistent with unusual affect regulation and language production in WS. PMID:17512756

  2. Differential Pharmacological Effects on Brain Reactivity and Plasticity in Alzheimer’s Disease

    PubMed Central

    Brem, Anna-Katharine; Atkinson, Natasha J.; Seligson, Erica E.; Pascual-Leone, Alvaro

    2013-01-01

    Acetylcholinesterase inhibitors (AChEIs) are the most commonly prescribed monotherapeutic medications for Alzheimer’s disease (AD). However, their underlying neurophysiological effects remain largely unknown. We investigated the effects of monotherapy (AChEI) and combination therapy (AChEI and memantine) on brain reactivity and plasticity. Patients treated with monotherapy (AChEI) (N = 7) were compared to patients receiving combination therapy (COM) (N = 9) and a group of age-matched, healthy controls (HCs) (N = 13). Cortical reactivity and plasticity of the motor cortex were examined using transcranial magnetic stimulation. Cognitive functions were assessed with the cognitive subscale of the Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), activities of daily living (ADLs) with the ADCS-ADL. In addition we assessed the degree of brain atrophy by measuring brain-scalp distances in seven different brain areas. Patient groups differed in resting motor threshold and brain atrophy, with COM showing a lower motor threshold but less atrophy than AChEI. COM showed similar plasticity effects as the HC group, while plasticity was reduced in AChEI. Long-interval intracortical inhibition (LICI) was impaired in both patient groups when compared to HC. ADAS-Cog scores were positively correlated with LICI measures and with brain atrophy, specifically in the left inferior parietal cortex. AD patients treated with mono- or combination-therapy show distinct neurophysiological patterns. Further studies should investigate whether these measures might serve as biomarkers of treatment response and whether they could guide other therapeutic interventions. PMID:24109459

  3. Decreased functional connectivity density in pain-related brain regions of female migraine patients without aura.

    PubMed

    Gao, Qing; Xu, Fei; Jiang, Cui; Chen, Zhifeng; Chen, Huafu; Liao, Huaqiang; Zhao, Ling

    2016-02-01

    Migraine is one of the most prevalent neurological disorders which is suggested to be associated with dysfunctions of the central nervous system. The purpose of the present study was to detect the altered functional connectivity architecture in the large-scale network of the whole brain in migraine without aura (MWoA). Meanwhile, the brain functional hubs which are targeted by MWoA could be identified. A new voxel-based method named functional connectivity density (FCD) mapping was applied to resting-state functional magnetic resonance imaging data of 55 female MWoA patients and 44 age-matched female healthy controls (HC). Comparing to HC, MWoA patients showed abnormal short-range FCD values in bilateral hippocampus, bilateral insula, right amygdale, right anterior cingulate cortex, bilateral putamen, bilateral caudate nucleus and the prefrontal cortex. The results suggested decreased intraregional connectivity of these pain-related brain regions in female MWoA. In addition, short-range FCD values in left prefrontal cortex, putamen and caudate nucleus were significantly negatively correlated with duration of disease in MWoA group, implying the repeated migraine attacks over time may consistently affect the resting-state functional connectivity architecture of these brain hubs. Our findings revealed the dysfunction of brain hubs in female MWoA, and suggested the left prefrontal cortex, putamen and caudate nucleus served as sensitive neuroimaging markers for reflecting the disease duration of female MWoA. This may provide us new insights into the changes in the organization of the large-scale brain network in MWoA. PMID:26688226

  4. Hybrid Neuroprosthesis for the Upper Limb: Combining Brain-Controlled Neuromuscular Stimulation with a Multi-Joint Arm Exoskeleton.

    PubMed

    Grimm, Florian; Walter, Armin; Spüler, Martin; Naros, Georgios; Rosenstiel, Wolfgang; Gharabaghi, Alireza

    2016-01-01

    Brain-machine interface-controlled (BMI) neurofeedback training aims to modulate cortical physiology and is applied during neurorehabilitation to increase the responsiveness of the brain to subsequent physiotherapy. In a parallel line of research, robotic exoskeletons are used in goal-oriented rehabilitation exercises for patients with severe motor impairment to extend their range of motion (ROM) and the intensity of training. Furthermore, neuromuscular electrical stimulation (NMES) is applied in neurologically impaired patients to restore muscle strength by closing the sensorimotor loop. In this proof-of-principle study, we explored an integrated approach for providing assistance as needed to amplify the task-related ROM and the movement-related brain modulation during rehabilitation exercises of severely impaired patients. For this purpose, we combined these three approaches (BMI, NMES, and exoskeleton) in an integrated neuroprosthesis and studied the feasibility of this device in seven severely affected chronic stroke patients who performed wrist flexion and extension exercises while receiving feedback via a virtual environment. They were assisted by a gravity-compensating, seven degree-of-freedom exoskeleton which was attached to the paretic arm. NMES was applied to the wrist extensor and flexor muscles during the exercises and was controlled by a hybrid BMI based on both sensorimotor cortical desynchronization (ERD) and electromyography (EMG) activity. The stimulation intensity was individualized for each targeted muscle and remained subthreshold, i.e., induced no overt support. The hybrid BMI controlled the stimulation significantly better than the offline analyzed ERD (p = 0.028) or EMG (p = 0.021) modality alone. Neuromuscular stimulation could be well integrated into the exoskeleton-based training and amplified both the task-related ROM (p = 0.009) and the movement-related brain modulation (p = 0.019). Combining a hybrid BMI with neuromuscular stimulation

  5. Hybrid Neuroprosthesis for the Upper Limb: Combining Brain-Controlled Neuromuscular Stimulation with a Multi-Joint Arm Exoskeleton

    PubMed Central

    Grimm, Florian; Walter, Armin; Spüler, Martin; Naros, Georgios; Rosenstiel, Wolfgang; Gharabaghi, Alireza

    2016-01-01

    Brain-machine interface-controlled (BMI) neurofeedback training aims to modulate cortical physiology and is applied during neurorehabilitation to increase the responsiveness of the brain to subsequent physiotherapy. In a parallel line of research, robotic exoskeletons are used in goal-oriented rehabilitation exercises for patients with severe motor impairment to extend their range of motion (ROM) and the intensity of training. Furthermore, neuromuscular electrical stimulation (NMES) is applied in neurologically impaired patients to restore muscle strength by closing the sensorimotor loop. In this proof-of-principle study, we explored an integrated approach for providing assistance as needed to amplify the task-related ROM and the movement-related brain modulation during rehabilitation exercises of severely impaired patients. For this purpose, we combined these three approaches (BMI, NMES, and exoskeleton) in an integrated neuroprosthesis and studied the feasibility of this device in seven severely affected chronic stroke patients who performed wrist flexion and extension exercises while receiving feedback via a virtual environment. They were assisted by a gravity-compensating, seven degree-of-freedom exoskeleton which was attached to the paretic arm. NMES was applied to the wrist extensor and flexor muscles during the exercises and was controlled by a hybrid BMI based on both sensorimotor cortical desynchronization (ERD) and electromyography (EMG) activity. The stimulation intensity was individualized for each targeted muscle and remained subthreshold, i.e., induced no overt support. The hybrid BMI controlled the stimulation significantly better than the offline analyzed ERD (p = 0.028) or EMG (p = 0.021) modality alone. Neuromuscular stimulation could be well integrated into the exoskeleton-based training and amplified both the task-related ROM (p = 0.009) and the movement-related brain modulation (p = 0.019). Combining a hybrid BMI with neuromuscular stimulation

  6. A prospective comparative clinical study of peripheral blood counts and indices in patients with primary brain tumors

    PubMed Central

    Subeikshanan, V; Dutt, A; Basu, D; Tejus, MN; Maurya, VP; Madhugiri, VS

    2016-01-01

    Background: Elevation of the neutrophil to lymphocyte ratio (NLR) has been shown to be an indicator of poor prognosis in many malignancies including recurrent glioblastoma multiforme. Objectives: This study was aimed at assessing if the NLR and other leukocyte counts and indices were deranged in treatment-naïve patients with primary brain tumors when compared with an age-matched healthy control group. Materials and Methods: This was a prospective comparative clinical observational study by design. A healthy control population was compared with treatment-naïve patients diagnosed with intra- and extraaxial brain tumors. Leukocyte counts (neutrophil, lymphocyte, monocyte, eosinophil, and basophil counts) as well as leukocyte ratios such as the NLR and the monocyte to lymphocyte ratio (MLR) were calculated. We also evaluated if the counts and indices were related to the tumor volume. Results: In all patients with tumors, the platelet and neutrophil counts were elevated when compared to the controls. In contrast, monocyte counts and the MLR were found to be decreased in patients with tumors when compared to the controls. The subset of patients with glioblastoma showed a significant increase in NLR when compared to the controls. Conclusions: Significant changes in the neutrophil, monocyte, and platelet counts as well as NLR and MLR were observed. Prospective longitudinal studies are required to determine the prognostic and therapeutic implications of these findings. PMID:27089106

  7. Control of the blood-brain barrier function in cancer cell metastasis.

    PubMed

    Blecharz, Kinga G; Colla, Ruben; Rohde, Veit; Vajkoczy, Peter

    2015-10-01

    Cerebral metastases are the most common brain neoplasms seen clinically in the adults and comprise more than half of all brain tumours. Actual treatment options for brain metastases that include surgical resection, radiotherapy and chemotherapy are rarely curative, although palliative treatment improves survival and life quality of patients carrying brain-metastatic tumours. Chemotherapy in particular has also shown limited or no activity in brain metastasis of most tumour types. Many chemotherapeutic agents used systemically do not cross the blood-brain barrier (BBB), whereas others may transiently weaken the BBB and allow extravasation of tumour cells from the circulation into the brain parenchyma. Increasing evidence points out that the interaction between the BBB and tumour cells plays a key role for implantation and growth of brain metastases in the central nervous system. The BBB, as the tightest endothelial barrier, prevents both early detection and treatment by creating a privileged microenvironment. Therefore, as observed in several in vivo studies, precise targetting the BBB by a specific transient opening of the structure making it permeable for therapeutic compounds, might potentially help to overcome this difficult clinical problem. Moreover, a better understanding of the molecular features of the BBB, its interrelation with metastatic tumour cells and the elucidation of cellular mechanisms responsible for establishing cerebral metastasis must be clearly outlined in order to promote treatment modalities that particularly involve chemotherapy. This in turn would substantially expand the survival and quality of life of patients with brain metastasis, and potentially increase the remission rate. Therefore, the focus of this review is to summarise the current knowledge on the role and function of the BBB in cancer metastasis. PMID:26032862

  8. Can Ketones Help Rescue Brain Fuel Supply in Later Life? Implications for Cognitive Health during Aging and the Treatment of Alzheimer’s Disease

    PubMed Central

    Cunnane, Stephen C.; Courchesne-Loyer, Alexandre; Vandenberghe, Camille; St-Pierre, Valérie; Fortier, Mélanie; Hennebelle, Marie; Croteau, Etienne; Bocti, Christian; Fulop, Tamas; Castellano, Christian-Alexandre

    2016-01-01

    We propose that brain energy deficit is an important pre-symptomatic feature of Alzheimer’s disease (AD) that requires closer attention in the development of AD therapeutics. Our rationale is fourfold: (i) Glucose uptake is lower in the frontal cortex of people >65 years-old despite cognitive scores that are normal for age. (ii) The regional deficit in brain glucose uptake is present in adults <40 years-old who have genetic or lifestyle risk factors for AD but in whom cognitive decline has not yet started. Examples include young adult carriers of presenilin-1 or apolipoprotein E4, and young adults with mild insulin resistance or with a maternal family history of AD. (iii) Regional brain glucose uptake is impaired in AD and mild cognitive impairment (MCI), but brain uptake of ketones (beta-hydroxybutyrate and acetoacetate), remains the same in AD and MCI as in cognitively healthy age-matched controls. These observations point to a brain fuel deficit which appears to be specific to glucose, precedes cognitive decline associated with AD, and becomes more severe as MCI progresses toward AD. Since glucose is the brain’s main fuel, we suggest that gradual brain glucose exhaustion is contributing significantly to the onset or progression of AD. (iv) Interventions that raise ketone availability to the brain improve cognitive outcomes in both MCI and AD as well as in acute experimental hypoglycemia. Ketones are the brain’s main alternative fuel to glucose and brain ketone uptake is still normal in MCI and in early AD, which would help explain why ketogenic interventions improve some cognitive outcomes in MCI and AD. We suggest that the brain energy deficit needs to be overcome in order to successfully develop more effective therapeutics for AD. At present, oral ketogenic supplements are the most promising means of achieving this goal. PMID:27458340

  9. Brain morphology in children with 47,XYY syndrome: a voxel-and surface-based morphometric study

    PubMed Central

    Lepage, Jean-Francois; Hong, David S.; Raman, Mira; Marzelli, Matthew; Roeltgen, David P.; Lai, Song; Ross, Judith; Reiss, Allan L.

    2013-01-01

    The neurocognitive and behavioral profile of individuals with 47,XYY is increasingly documented; however, very little is known about the effect of a supernumerary Y-chromosome on brain development. Establishing the neural phenotype associated with 47,XYY may prove valuable in clarifying the role of Y-chromosome gene dosage effects, a potential factor in several neuropsychiatric disorders that show a prevalence bias towards males, including autism spectrum disorders. Here, we investigated brain structure in 10 young boys with 47,XYY and 10 age-matched healthy controls by combining voxel-based morphometry (VBM) and surface-based morphometry (SBM). VBM results show the existence of altered grey matter volume in the insular and parietal regions of 47,XYY relative to controls, changes that were paralleled by extensive modifications in white matter bilaterally in the frontal and superior parietal lobes. SBM analyses corroborated these findings and revealed the presence of abnormal surface area and cortical thinning in regions with abnormal grey matter and white matter volumes. Overall, these preliminary results demonstrate a significant impact of a supernumerary Y-chromosome on brain development, provide a neural basis for the motor, speech, and behavior regulation difficulties associated with 47,XYY, and may relate to sexual dimorphism in these areas. PMID:24308542

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

    PubMed

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

    2014-04-01

    Childhood adversity represents a major risk factor for drug addiction and other mental disorders. However, the specific mechanisms by which childhood adversity impacts human brain organization to confer greater vulnerability for negative outcomes in adulthood is largely unknown. As an impaired process in drug addiction, inhibitory control of behavior was investigated as a target of childhood maltreatment (abuse and neglect). Forty adults without Axis-I psychiatric disorders (21 females) completed a Childhood Trauma Questionnaire (CTQ) and underwent functional MRI (fMRI) while performing a stop-signal task. A group independent component analysis identified a putative brain inhibitory control network. Graph theoretical analyses and structural equation modeling investigated the impact of childhood maltreatment on the functional organization of this neural processing network. Graph theory outcomes revealed sex differences in the relationship between network functional connectivity and inhibitory control which were dependent on the severity of childhood maltreatment exposure. A network effective connectivity analysis indicated that a maltreatment dose-related negative modulation of dorsal anterior cingulate (dACC) activity by the left inferior frontal cortex (IFC) predicted better response inhibition and lesser attention deficit hyperactivity disorder (ADHD) symptoms in females, but poorer response inhibition and greater ADHD symptoms in males. Less inhibition of the right IFC by dACC in males with higher CTQ scores improved inhibitory control ability. The childhood maltreatment-related reorganization of a brain inhibitory control network provides sex-dependent mechanisms by which childhood adversity may confer greater risk for drug use and related disorders and by which adaptive brain responses protect individuals from this risk factor. PMID:23616424

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

    PubMed Central

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

    2013-01-01

    Childhood adversity represents a major risk factor for drug addiction and other mental disorders. However the specific mechanisms by which childhood adversity impacts human brain organization to confer greater vulnerability for negative outcomes in adulthood is largely unknown. As an impaired process in drug addiction, inhibitory control of behavior was investigated as a target of childhood maltreatment (abuse and neglect). Forty adults without Axis-I psychiatric disorders (21 female) completed a Childhood Trauma Questionnaire (CTQ) and underwent functional MRI (fMRI) while performing a stop-signal task. A group independent component analysis identified a putative brain inhibitory control network. Graph theoretical analyses and structural equation modeling investigated the impact of childhood maltreatment on the functional organization of this neural processing network. Graph theory outcomes revealed sex differences in the relationship between network functional connectivity and inhibitory control which were dependent on the severity of childhood maltreatment exposure. A network effective connectivity analysis indicated that a maltreatment dose-related negative modulation of dorsal anterior cingulate (dACC) activity by the left inferior frontal cortex (IFC) predicted better response inhibition and lesser attention deficit hyperactivity disorder (ADHD) symptoms in females, but poorer response inhibition and greater ADHD symptoms in males. Less inhibition of the right IFC by dACC in males with higher CTQ scores improved inhibitory control ability. The childhood maltreatment-related reorganization of a brain inhibitory control network provides sex-dependent mechanisms by which childhood adversity may confer greater risk for drug use and related disorders and by which adaptive brain responses protect individuals from this risk factor. PMID:23616424

  12. A neural network-based design of an on-off adaptive control for Deep Brain Stimulation in movement disorders.

    PubMed

    Shukla, Pitamber; Basu, Ishita; Graupe, Daniel; Tuninetti, Daniela; Slavin, Konstantin V

    2012-01-01

    The current Food and Drug Administration approved system for the treatment of tremor disorders through Deep Brain Stimulation (DBS) of the area of the brain that controls movement, operates open-loop. It does not automatically adapt to the instantaneous patient's needs or to the progression of the disease. This paper demonstrates an adaptive closed-loop controlled DBS that, after switching off stimulation, tracks few physiological signals to predict the reappearance of tremor before the patient experiences discomfort, at which point it instructs the DBS controller to switch on stimulation again. The core of the proposed approach is a Neural Network (NN) which effectively extracts tremor predictive information from non-invasively recorded surface-electromyogram(sEMG) and accelerometer signals measured at the symptomatic extremities. A simple feed-forward back-propagation NN architecture is shown to successfully predict tremor in 31 out of 33 trials in two Parkinson's Disease patients with an overall accuracy of 75.8% and sensitivity of 92.3%. This work therefore shows that closed-loop DBS control is feasible in the near future and that it can be achieved without modifications of the electrodes implanted in the brain, i.e., is backward compatible with approved DBS systems. PMID:23366839

  13. Metabolic Changes in the Rodent Brain after Acute Administration of Salvinorin A

    PubMed Central

    Hooker, Jacob M.; Patel, Vinal; Kothari, Shiva; Schiffer, Wynne K.

    2009-01-01

    Purpose Salvinorin A (SA) is a potent and highly selective kappa opioid receptor (KOR) agonist with rapid kinetics and commensurate behavioral effects; however, brain regions associated with these effects have not been determined. Procedures Freely moving adult male rats were given SA intraperitoneally during uptake and trapping of the brain metabolic radiotracer, 18FDG, followed by image acquisition in a dedicated animal PET system. Age-matched control animals received vehicle treatment. Animal behavior during 18FDG uptake was recorded digitally and later analyzed for locomotion. Group differences in regional 18FDG uptake normalized to whole brain were determined using Statistical Parametric Mapping (SPM) and verified by region of interest (ROI) analysis. Results SA treated animals demonstrated significant increases in 18FDG uptake compared to controls in several brain regions associated with the distribution of KOR such as the periaqueductal grey, bed nucleus of the stria terminalis and the cerbellar vermis, as well as in the hypothalamus. Significant bilateral activations were also observed in the auditory, sensory and frontal cortices. Regional decreases in metabolic demand were observed bilaterally in the dorsolateral striatum and hippocampus. Locomotor activity did not differ between SA and vehicle during 18FDG uptake. Conclusions We have provided the first extensive maps of cerebral metabolic activation due to the potent κ-opioid agonist, salvinorin A. A major finding from our small animal PET studies using 18FDG was that neural circuits affected by SA may not be limited to direct activation or inhibition of kappa receptor-expressing cells. Instead, salvinorin A may trigger brain circuits that mediate the effects of the drug on cognition, mood, fear and anxiety, and motor output. PMID:19132449

  14. Enhancement of Functional Connectivity, Working Memory and Inhibitory Control on Multi-modal Brain MR Imaging with Rifaximin in Cirrhosis: Implications for the Gut-Liver-Brain Axis

    PubMed Central

    Ahluwalia, Vishwadeep; Wade, James B; Heuman, Douglas M; Hammeke, Thomas A; Sanyal, Arun J; Sterling, Richard K; Stravitz, R. Todd; Luketic, Velimir; Siddiqui, Mohammad S; Puri, Puneet; Fuchs, Michael; Lennon, Micheal J; Kraft, Kenneth A; Gilles, HoChong; White, Melanie B; Noble, Nicole A; Bajaj, Jasmohan S

    2014-01-01

    Objective Minimal hepatic encephalopathy (MHE) impairs daily functioning in cirrhosis, but its functional brain impact is not completely understood. Aim To evaluate the effect of rifaximin, a gut-specific antibiotic, on the gut-liver-brain axis in MHE. Hypothesis Rifaximin will reduce endotoxemia, enhance cognition, increase activation during working memory(N-back) and reduce activation needed for inhibitory control tasks. Methods Cirrhotics with MHE underwent baseline endotoxin and cognitive testing, then underwent fMRI, diffusion tensor imaging and MR spectroscopy(MRS). On fMRI, two tasks; N-back (outcome: correct responses) and inhibitory control tests(outcomes: lure inhibition) were performed. All procedures were repeated after 8 weeks of rifaximin. Results were compared before/after rifaximin. Results 20 MHE patients (59.7 years) were included; sixteen completed pre/post-rifaximin scanning with 92% medication compliance. Pre-rifaximin patients had cognitive impairment. At trial-end, there was a significantly higher correct 2-back responses, ICT lure inhibitions and reduced endotoxemia(p=0.002). This was accompanied by significantly higher activation from baseline in subcortical structures (thalamus, caudate, insula and hippocampus) and left parietal operculum (LPO) during N-back, decrease in fronto-parietal activation required for inhibiting lures, including LPO during ICT compared to baseline values. Connectivity studies in N-back showed significant shifts in linkages after therapy in fronto-parietal regions with a reduction in fractional anisotropy (FA) but not mean diffusivity (MD), and no change in MRS metabolites at the end of the trial. Conclusion A significant improvement in cognition including working memory and inhibitory control, and fractional anisotropy without effect on MD or MRS, through modulation of fronto-parietal and subcortical activation and connectivity was seen after open-label rifaximin therapy in MHE. PMID:24590688

  15. Brain glucose metabolism in adults with ataxia-telangiectasia and their asymptomatic relatives.

    PubMed

    Volkow, Nora D; Tomasi, Dardo; Wang, Gene-Jack; Studentsova, Yana; Margus, Brad; Crawford, Thomas O

    2014-06-01

    Ataxia-telangiectasia is a recessive genetic disorder (ATM is the mutated gene) of childhood with severe motor impairments and whereas homozygotes manifest the disorder, heterozygotes are asymptomatic. Structural brain imaging and post-mortem studies in individuals with ataxia-telangiectasia have reported cerebellar atrophy; but abnormalities of motor control characteristic of extrapyramidal dysfunction suggest impairment of broader motor networks. Here, we investigated possible dysfunction in other brain areas in individuals with ataxia-telangiectasia and tested for brain changes in asymptomatic relatives to assess if heterozygocity affects brain function. We used positron emission tomography and (18)F-fluorodeoxyglucose to measure brain glucose metabolism (quantified as µmol/100 g/min), which serves as a marker of brain function, in 10 adults with ataxia-telangiectasia, 19 non-affected adult relatives (12 siblings, seven parents) and 29 age-matched healthy controls. Statistical parametric mapping and region of interest analyses were used to compare individuals with ataxia-telangiectasia, asymptomatic relatives, and unrelated controls. We found that participants with ataxia-telangiectasia had lower metabolism in cerebellar hemispheres (14%, P < 0.001), anterior vermis (40%, P < 0.001) and fusiform gyrus (20%, P < 0.001) compared with controls or siblings, and lower metabolism in hippocampus (12%, P = 0.05) compared with controls, and showed significant intersubject variability (decreases in vermis ranged from 18% to 60%). Participants with ataxia-telangiectasia also had higher metabolism in globus pallidus (16%, P = 0.05), which correlated negatively with motor performance. Asymptomatic relatives had lower metabolism in anterior vermis (12%; P = 0.01) and hippocampus (19%; P = 0.002) than controls. Our results indicate that, in addition to the expected decrease in cerebellar metabolism, participants with ataxia-telangiectasia had widespread changes in metabolic

  16. Assessing dynamic brain graphs of time-varying connectivity in fMRI data: application to healthy controls and patients with schizophrenia

    PubMed Central

    Yu, Qingbao; Erhardt, Erik B.; Sui, Jing; Du, Yuhui; He, Hao; Hjelm, Devon; Cetin, Mustafa S.; Rachakonda, Srinivas; Miller, Robyn L.; Pearlson, Godfrey; Calhoun, Vince D.

    2014-01-01

    Graph theory-based analysis has been widely employed in brain imaging studies, and altered topological properties of brain connectivity have emerged as important features of mental diseases such as schizophrenia. However, most previous studies have focused on graph metrics of stationary brain graphs, ignoring that brain connectivity exhibits fluctuations over time. Here we develop a new framework for accessing dynamic graph properties of time-varying functional brain connectivity in resting state fMRI data and apply it to healthy controls (HCs) and patients with schizophrenia (SZs). Specifically, nodes of brain graphs are defined by intrinsic connectivity networks (ICNs) identified by group independent component analysis (ICA). Dynamic graph metrics of the time-varying brain connectivity estimated by the correlation of sliding time-windowed ICA time courses of ICNs are calculated. First- and second-level connectivity states are detected based on the correlation of nodal connectivity strength between time-varying brain graphs. Our results indicate that SZs show decreased variance in the dynamic graph metrics. Consistent with prior stationary functional brain connectivity works, graph measures of identified first-level connectivity states show lower values in SZs. In addition, more first-level connectivity states are disassociated with the second-level connectivity state which resembles the stationary connectivity pattern computed by the entire scan. Collectively, the findings provide new evidence about altered dynamic brain graphs in schizophrenia which may underscore the abnormal brain performance in this mental illness. PMID:25514514

  17. Assessing dynamic brain graphs of time-varying connectivity in fMRI data: application to healthy controls and patients with schizophrenia.

    PubMed

    Yu, Qingbao; Erhardt, Erik B; Sui, Jing; Du, Yuhui; He, Hao; Hjelm, Devon; Cetin, Mustafa S; Rachakonda, Srinivas; Miller, Robyn L; Pearlson, Godfrey; Calhoun, Vince D

    2015-02-15

    Graph theory-based analysis has been widely employed in brain imaging studies, and altered topological properties of brain connectivity have emerged as important features of mental diseases such as schizophrenia. However, most previous studies have focused on graph metrics of stationary brain graphs, ignoring that brain connectivity exhibits fluctuations over time. Here we develop a new framework for accessing dynamic graph properties of time-varying functional brain connectivity in resting-state fMRI data and apply it to healthy controls (HCs) and patients with schizophrenia (SZs). Specifically, nodes of brain graphs are defined by intrinsic connectivity networks (ICNs) identified by group independent component analysis (ICA). Dynamic graph metrics of the time-varying brain connectivity estimated by the correlation of sliding time-windowed ICA time courses of ICNs are calculated. First- and second-level connectivity states are detected based on the correlation of nodal connectivity strength between time-varying brain graphs. Our results indicate that SZs show decreased variance in the dynamic graph metrics. Consistent with prior stationary functional brain connectivity works, graph measures of identified first-level connectivity states show lower values in SZs. In addition, more first-level connectivity states are disassociated with the second-level connectivity state which resembles the stationary connectivity pattern computed by the entire scan. Collectively, the findings provide new evidence about altered dynamic brain graphs in schizophrenia, which may underscore the abnormal brain performance in this mental illness. PMID:25514514

  18. ALFY-Controlled DVL3 Autophagy Regulates Wnt Signaling, Determining Human Brain Size

    PubMed Central

    Kadir, Rotem; Harel, Tamar; Markus, Barak; Perez, Yonatan; Bakhrat, Anna; Cohen, Idan; Volodarsky, Michael; Feintsein-Linial, Miora; Chervinski, Elana; Zlotogora, Joel; Sivan, Sara; Birnbaum, Ramon Y.; Abdu, Uri; Shalev, Stavit; Birk, Ohad S.

    2016-01-01

    Primary microcephaly is a congenital neurodevelopmental disorder of reduced head circumference and brain volume, with fewer neurons in the cortex of the developing brain due to premature transition between symmetrical and asymmetrical cellular division of the neuronal stem cell layer during neurogenesis. We now show through linkage analysis and whole exome sequencing, that a dominant mutation in ALFY, encoding an autophagy scaffold protein, causes human primary microcephaly. We demonstrate the dominant effect of the mutation in drosophila: transgenic flies harboring the human mutant allele display small brain volume, recapitulating the disease phenotype. Moreover, eye-specific expression of human mutant ALFY causes rough eye phenotype. In molecular terms, we demonstrate that normally ALFY attenuates the canonical Wnt signaling pathway via autophagy-dependent removal specifically of aggregates of DVL3 and not of Dvl1 or Dvl2. Thus, autophagic attenuation of Wnt signaling through removal of Dvl3 aggregates by ALFY acts in determining human brain size. PMID:27008544

  19. Pre-frontal control of closed-loop limbic neurostimulation by rodents using a brain-computer interface

    PubMed Central

    Widge, Alik S.; Moritz, Chet T.

    2015-01-01

    Objective There is great interest in closed-loop neurostimulators that sense and respond to a patient’s brain state. Such systems may have value for neurological and psychiatric illnesses where symptoms have high intraday variability. Animal models of closed-loop stimulators would aid preclinical testing. We sought to demonstrate that rodents can directly control a closed-loop limbic neurostimulator via a brain-computer interface (BCI). Approach We trained rats to use an auditory BCI controlled by single units in prefrontal cortex (PFC). The BCI controlled electrical stimulation in the medial forebrain bundle (MFB), a limbic structure involved in reward-seeking. Rigorous offline analyses were performed to confirm volitional control of the neurostimulator. Main Results All animals successfully learned to use the BCI and neurostimulator, with closed-loop control of this challenging task demonstrated at 80% of PFC recording locations. Analysis across sessions and animals confirmed statistically robust BCI control and specific, rapid modulation of PFC activity. Significance Our results provide a preliminary demonstration of a method for emotion-regulating closed-loop neurostimulation. They further suggest that activity in prefrontal cortex can be used to control a BCI without pre-training on a predicate task. This offers the potential for BCI-based treatments in refractory neurological and mental illness. PMID:24608127

  20. Pre-frontal control of closed-loop limbic neurostimulation by rodents using a brain-computer interface

    NASA Astrophysics Data System (ADS)

    Widge, Alik S.; Moritz, Chet T.

    2014-04-01

    Objective. There is great interest in closed-loop neurostimulators that sense and respond to a patient's brain state. Such systems may have value for neurological and psychiatric illnesses where symptoms have high intraday variability. Animal models of closed-loop stimulators would aid preclinical testing. We therefore sought to demonstrate that rodents can directly control a closed-loop limbic neurostimulator via a brain-computer interface (BCI). Approach. We trained rats to use an auditory BCI controlled by single units in prefrontal cortex (PFC). The BCI controlled electrical stimulation in the medial forebrain bundle, a limbic structure involved in reward-seeking. Rigorous offline analyses were performed to confirm volitional control of the neurostimulator. Main results. All animals successfully learned to use the BCI and neurostimulator, with closed-loop control of this challenging task demonstrated at 80% of PFC recording locations. Analysis across sessions and animals confirmed statistically robust BCI control and specific, rapid modulation of PFC activity. Significance. Our results provide a preliminary demonstration of a method for emotion-regulating closed-loop neurostimulation. They further suggest that activity in PFC can be used to control a BCI without pre-training on a predicate task. This offers the potential for BCI-based treatments in refractory neurological and mental illness.

  1. Electromagnetic Controlled Cortical Impact Device for Precise, Graded Experimental Traumatic Brain Injury

    PubMed Central

    BRODY, DAVID L.; DONALD, CHRISTINE Mac; KESSENS, CHAD C.; YUEDE, CARLA; PARSADANIAN, MAIA; SPINNER, MIKE; KIM, EDDIE; SCHWETYE, KATHERINE E.; HOLTZMAN, DAVID M.; BAYLY, PHILIP V.

    2008-01-01

    Genetically modified mice represent useful tools for traumatic brain injury (TBI) research and attractive preclinical models for the development of novel therapeutics. Experimental methods that minimize the number of mice needed may increase the pace of discovery. With this in mind, we developed and characterized a prototype electromagnetic (EM) controlled cortical impact device along with refined surgical and behavioral testing techniques. By varying the depth of impact between 1.0 and 3.0 mm, we found that the EM device was capable of producing a broad range of injury severities. Histologically, 2.0-mm impact depth injuries produced by the EM device were similar to 1.0-mm impact depth injuries produced by a commercially available pneumatic device. Behaviorally, 2.0-, 2.5-, and 3.0-mm impacts impaired hidden platform and probe trial water maze performance, whereas 1.5-mm impacts did not. Rotorod and visible platform water maze deficits were also found following 2.5- and 3.0-mm impacts. No impairment of conditioned fear performance was detected. No differences were found between sexes of mice. Inter-operator reliability was very good. Behaviorally, we found that we could statistically distinguish between injury depths differing by 0.5 mm using 12 mice per group and between injury depths differing by 1.0 mm with 7-8 mice per group. Thus, the EM impactor and refined surgical and behavioral testing techniques may offer a reliable and convenient framework for preclinical TBI research involving mice. PMID:17439349

  2. Metalloproteinases control brain inflammation induced by pertussis toxin in mice overexpressing the chemokine CCL2 in the central nervous system.

    PubMed

    Toft-Hansen, Henrik; Buist, Richard; Sun, Xue-Jun; Schellenberg, Angela; Peeling, James; Owens, Trevor

    2006-11-15

    Inflammatory leukocytes infiltrate the CNS parenchyma in neuroinflammation. This involves cellular migration across various structures associated with the blood-brain barrier: the vascular endothelium, the glia limitans, and the perivascular space between them. Leukocytes accumulate spontaneously in the perivascular space in brains of transgenic (Tg) mice that overexpress CCL2 under control of a CNS-specific promoter. The Tg mice show no clinical symptoms, even though leukocytes have crossed the endothelial basement membrane. Pertussis toxin (PTx) given i.p. induced encephalopathy and weight loss in Tg mice. We used flow cytometry, ultra-small superparamagnetic iron oxide-enhanced magnetic resonance imaging, and immunofluorescent staining to show that encephalopathy involved leukocyte migration across the glia limitans into the brain parenchyma, identifying this as the critical step in inducing clinical symptoms. Metalloproteinase (MPs) enzymes are implicated in leukocyte infiltration in neuroinflammation. Unmanipulated Tg mice had elevated expression of tissue inhibitor of metalloproteinase-1, matrix metalloproteinase (MMP)-10, and -12 mRNA in the brain. PTx further induced expression of tissue inhibitor of metalloproteinase-1, metalloproteinase disintegrins-12, MMP-8, and -10 in brains of Tg mice. Levels of the microglial-associated MP MMP-15 were not affected in control or PTx-treated Tg mice. PTx also up-regulated expression of proinflammatory cytokines IL-1beta and TNF-alpha mRNA in Tg CNS. Weight loss and parenchymal infiltration, but not perivascular accumulation, were significantly inhibited by the broad-spectrum MP inhibitor BB-94/Batimastat. Our finding that MPs mediate PTx-induced parenchymal infiltration to the chemokine-overexpressing CNS has relevance for the pathogenesis of human diseases involving CNS inflammation, such as multiple sclerosis. PMID:17082642

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

    SciTech Connect

    Choi, Clara Y.H.; Chang, Steven D.; Gibbs, Iris C.; Adler, John R.; Harsh, Griffith R.; Lieberson, Robert E.; Soltys, Scott G.

    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 competing 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.

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

    PubMed Central

    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

  5. Structural brain abnormalities in the frontostriatal system and cerebellum in pedophilia.

    PubMed

    Schiffer, Boris; Peschel, Thomas; Paul, Thomas; Gizewski, Elke; Forsting, Michael; Leygraf, Norbert; Schedlowski, Manfred; Krueger, Tillmann H C

    2007-11-01

    Even though previous neuropsychological studies and clinical case reports have suggested an association between pedophilia and frontocortical dysfunction, our knowledge about the neurobiological mechanisms underlying pedophilia is still fragmentary. Specifically, the brain morphology of such disorders has not yet been investigated using MR imaging techniques. Whole brain structural T1-weighted MR images from 18 pedophile patients (9 attracted to males, 9 attracted to females) and 24 healthy age-matched control subjects (12 hetero- and 12 homosexual) from a comparable socioeconomic stratum were processed by using optimized automated voxel-based morphometry within multiple linear regression analyses. Compared to the homosexual and heterosexual control subjects, pedophiles showed decreased gray matter volume in the ventral striatum (also extending into the nucl. accumbens), the orbitofrontal cortex and the cerebellum. These observations further indicate an association between frontostriatal morphometric abnormalities and pedophilia. In this respect these findings may support the hypothesis that there is a shared etiopathological mechanism in all obsessive-compulsive spectrum disorders. PMID:16876824

  6. Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease.

    PubMed Central

    Griffin, W S; Stanley, L C; Ling, C; White, L; MacLeod, V; Perrot, L J; White, C L; Araoz, C

    1989-01-01

    Interleukin 1, an immune response-generated cytokine that stimulates astrocyte proliferation and reactivity (astrogliosis), was present in up to 30 times as many glial cells in tissue sections of brain from patients with Down syndrome and Alzheimer disease compared with age-matched control subjects. Most interleukin 1-immunoreactive glia in Down syndrome and Alzheimer disease were classified as microglia. The number of interleukin 1 immunoreactive neurons did not appear to differ in Down syndrome and Alzheimer disease compared with control brain. Numerous temporal lobe astrocytes in Alzheimer disease and postnatal Down syndrome were intensely interleukin 1-, S-100-, and glial fibrillary acidic protein-immunoreactive and had reactive structure. Interleukin 1 levels in Alzheimer disease temporal lobe homogenates were elevated, as were the levels of S-100 and glial fibrillary acidic protein, two proteins reportedly elevated in reactive astrocytes. These data suggest that increased expression of S-100 in Down syndrome, resulting from duplication of the gene on chromosome 21 that encodes the beta subunit of S-100, may be augmented by elevation of interleukin 1. As a corollary, the astrogliosis in Alzheimer disease may be promoted by elevation of interleukin 1. Images PMID:2529544

  7. Roles of the Insular Cortex in the Modulation of Pain: Insights from Brain Lesions

    PubMed Central

    Starr, Christopher J.; Sawaki, Lumy; Wittenberg, George F.; Burdette, Jonathan H.; Oshiro, Yoshitetsu; Quevedo, Alexandre S.; Coghill, Robert C.

    2009-01-01

    Subjective sensory experiences are constructed by the integration of afferent sensory information with information about the uniquely personal internal cognitive state. The insular cortex is anatomically positioned to serve as one potential interface between afferent processing mechanisms and more cognitively-oriented modulatory systems. However, the role of the insular cortex in such modulatory processes remain poorly understood. Two individuals with extensive lesions to the insula were examined to better understand the contribution of this brain region to the generation of subjective sensory experiences. Despite substantial differences in the extent of the damage to the insular cortex, three findings were common to both individuals. First, both subjects had substantially higher pain intensity ratings of acute experimental noxious stimuli than age-matched control subjects. Second, when pain-related activation of the primary somatosensory cortex was examined during left and right-sided stimulation, both individuals exhibited dramatically elevated activity of the primary somatosensory cortex ipsilateral to the lesioned insula in relation to healthy control subjects. Finally, both individuals retained the ability to evaluate pain despite substantial insular damage and no evidence of detectible insular activity. Taken together, these results indicate that the insula may be importantly involved in tuning cortical regions to appropriately utilize prior cognitive information during afferent processing. Finally, these data suggest that a subjectively available experience of pain can be instantiated by brain mechanisms that do not require the insular cortex. PMID:19261863

  8. Core brain networks interactions and cognitive control in internet gaming disorder individuals in late adolescence/early adulthood.

    PubMed

    Yuan, Kai; Qin, Wei; Yu, Dahua; Bi, Yanzhi; Xing, Lihong; Jin, Chenwang; Tian, Jie

    2016-04-01

    Regardless of whether it is conceptualized as a behavioral addiction or an impulse-control disorder, internet gaming disorder (IGD) has been speculated to be associated with impaired cognitive control. Efficient cognitive behavior involves the coordinated activity of large-scale brain networks, however, whether the interactions among these networks during resting state modulated cognitive control behavior in IGD adolescents remain unclear. Twenty-eight IGD adolescents and twenty-five age-, gender-, and education-matched healthy controls participated in our study. Stroop color-word task was conducted to evaluate the cognitive control deficits in IGD adolescents. Functional connectivity and Granger Causal Analysis were employed to investigate the functional and effective connections within and between the salience, central executive, and default mode networks. Meanwhile, diffusion tensor imaging was used to assess the structural integrity of abnormal network connections. The abnormal functional connectivity within central executive networks and effective connectivity within salience network in IGD adolescents were detected. Moreover, the inefficient interactions between these two brain networks were observed. In addition, we identified reduced fractional anisotropy in salience network, right central executive network tracts, and between-network (the anterior cingulate cortex-right dorsolateral prefrontal cortex tracts) pathways in IGD individuals. Notably, we observed a significant correlation between the effective and structural connection from salience network to central executive network and the number of errors during incongruent condition in Stroop task in both IGD and control subjects. Our results suggested that impaired cognitive control in IGD adolescents is likely to be mediated through the abnormal interactions and structural connection between intrinsic large-scale brain networks. PMID:25573247

  9. Orientation Dependent MR Signal Decay Differentiates between People with MS, Their Asymptomatic Siblings and Unrelated Healthy Controls

    PubMed Central

    Hametner, Simon; Baumeister, Tobias R.; Sadovnick, A. Dessa; Zhao, Yinshan; Machan, Lindsay; Li, David K. B.; Traboulsee, Anthony; Rauscher, Alexander

    2015-01-01

    R2* relaxometry of the brain is a quantitative magnetic resonance technique which is influenced by iron and myelin content across different brain regions. Multiple sclerosis (MS) is a common inflammatory, demyelinating disease affecting both white and grey matter regions of the CNS. Using R2*, increased iron deposition has been described in deep gray matter of MS patients. Iron accumulation might promote oxidative stress in the brain, which can lead to cell death and neurodegeneration. However, recent histological work indicates that iron may be reduced within the normal appearing white matter (WM) in MS. In the present study we analyzed the R2* signal across the white matter in 39 patients with MS, 31 asymptomatic age matched siblings of patients and 30 age-matched controls. The measurement of R2* in white matter is affected by the signal's dependency on white matter fibre orientation with respect to the main magnetic field which can be accounted using diffusion tensor imaging. We observed a clear separation of the three study groups in R2*. The values in the MS group were significantly lower compared to the siblings and controls, while the siblings group presented with significantly higher R2* values than both unrelated healthy controls and patients. Furthermore, we found significantly decreased normal-appearing white matter R2* values in patients with more severe disease course. Angle resolved analysis of R2* improves the sensitivity for detecting subtle differences in WM R2* compared to standard histogram based analyses. Our findings suggest that the decreased R2* values in MS are due to diffuse tissue damage and decreased myelin in the normal appearing and diffusely abnormal WM. The increased R2* in unaffected siblings may identify a predisposition to increased iron and the potential for oxidative stress as a risk factor for developing MS. PMID:26489078

  10. Control of a Wheelchair in an Indoor Environment Based on a Brain-Computer Interface and Automated Navigation.

    PubMed

    Zhang, Rui; Li, Yuanqing; Yan, Yongyong; Zhang, Hao; Wu, Shaoyu; Yu, Tianyou; Gu, Zhenghui

    2016-01-01

    The concept of controlling a wheelchair using brain signals is promising. However, the continuous control of a wheelchair based on unstable and noisy electroencephalogram signals is unreliable and generates a significant mental burden for the user. A feasible solution is to integrate a brain-computer interface (BCI) with automated navigation techniques. This paper presents a brain-controlled intelligent wheelchair with the capability of automatic navigation. Using an autonomous navigation system, candidate destinations and waypoints are automatically generated based on the existing environment. The user selects a destination using a motor imagery (MI)-based or P300-based BCI. According to the determined destination, the navigation system plans a short and safe path and navigates the wheelchair to the destination. During the movement of the wheelchair, the user can issue a stop command with the BCI. Using our system, the mental burden of the user can be substantially alleviated. Furthermore, our system can adapt to changes in the environment. Two experiments based on MI and P300 were conducted to demonstrate the effectiveness of our system. PMID:26054072

  11. Brain-state classification and a dual-state decoder dramatically improve the control of cursor movement through a brain-machine interface

    NASA Astrophysics Data System (ADS)

    Sachs, Nicholas A.; Ruiz-Torres, Ricardo; Perreault, Eric J.; Miller, Lee E.

    2016-02-01

    Objective. It is quite remarkable that brain machine interfaces (BMIs) can be used to control complex movements with fewer than 100 neurons. Success may be due in part to the limited range of dynamical conditions under which most BMIs are tested. Achieving high-quality control that spans these conditions with a single linear mapping will be more challenging. Even for simple reaching movements, existing BMIs must reduce the stochastic noise of neurons by averaging the control signals over time, instead of over the many neurons that normally control movement. This forces a compromise between a decoder with dynamics allowing rapid movement and one that allows postures to be maintained with little jitter. Our current work presents a method for addressing this compromise, which may also generalize to more highly varied dynamical situations, including movements with more greatly varying speed. Approach. We have developed a system that uses two independent Wiener filters as individual components in a single decoder, one optimized for movement, and the other for postural control. We computed an LDA classifier using the same neural inputs. The decoder combined the outputs of the two filters in proportion to the likelihood assigned by the classifier to each state. Main results. We have performed online experiments with two monkeys using this neural-classifier, dual-state decoder, comparing it to a standard, single-state decoder as well as to a dual-state decoder that switched states automatically based on the cursor’s proximity to a target. The performance of both monkeys using the classifier decoder was markedly better than that of the single-state decoder and comparable to the proximity decoder. Significance. We have demonstrated a novel strategy for dealing with the need to make rapid movements while also maintaining precise cursor control when approaching and stabilizing within targets. Further gains can undoubtedly be realized by optimizing the performance of the

  12. Age-related deficits in voluntary control over saccadic eye movements: consideration of electrical brain stimulation as a therapeutic strategy.

    PubMed

    Chen, Po Ling; Machado, Liana

    2016-05-01

    Sudden changes in our visual environment trigger reflexive eye movements, so automatically they often go unnoticed. Consequently, voluntary control over reflexive eye movements entails considerable effort. In relation to frontal-lobe deterioration, adult aging adversely impacts voluntary saccadic eye movement control in particular, which compromises effective performance of daily activities. Here, we review the nature of age-related changes in saccadic control, focusing primarily on the antisaccade task because of its assessment of 2 key age-sensitive control functions: reflexive saccade inhibition and voluntary saccade generation. With an ultimate view toward facilitating development of therapeutic strategies, we systematically review the neuroanatomy underpinning voluntary control over saccadic eye movements and natural mechanisms that kick in to compensate for age-related declines. We then explore the potential of noninvasive electrical brain stimulation to counteract aging deficits. Based on evidence that anodal transcranial direct current stimulation can confer a range of benefits specifically relevant to aging brains, we put forward this neuromodulation technique as a therapeutic strategy for improving voluntary saccadic eye movement control in older adults. PMID:27103518

  13. Estimating the risk of brain tumors from cellphone use: Published case-control studies.

    PubMed

    Morgan, L Lloyd

    2009-08-01

    This paper reviews the results of early cellphone studies, where exposure duration was too short to expect tumorigenesis, as well as two sets of more recent studies with longer exposure duration: the Interphone studies and the Swedish studies led by Dr. Lennart Hardell. The recent studies reach very different conclusions. With four exceptions the industry-funded Interphone studies found no increased risk of brain tumors from cellphone use, while the Swedish studies, independent of industry funding, reported numerous findings of significant increased brain tumor risk from cellphone and cordless phone use. An analysis of the data from the Interphone studies suggests that either the use of a cellphone protects the user from a brain tumor, or the studies had serious design flaws. Eleven flaws are identified: (1) selection bias, (2) insufficient latency time, (3) definition of 'regular' cellphone user, (4) exclusion of young adults and children, (5) brain tumor risk from cellphones radiating higher power levels in rural areas were not investigated, (6) exposure to other transmitting sources are excluded, (7) exclusion of brain tumor types, (8) tumors outside the cellphone radiation plume are treated as exposed, (9) exclusion of brain tumor cases because of death or illness, (10) recall accuracy of cellphone use, and (11) funding bias. The Interphone studies have all 11 flaws, and the Swedish studies have 3 flaws (8, 9 and 10). The data from the Swedish studies are consistent with what would be expected if cellphone use were a risk for brain tumors, while the Interphone studies data are incredulous. If a risk does exist, the public health cost will be large. These are the circumstances where application of the Precautionary Principle is indicated, especially if low-cost options could reduce the absorbed cellphone radiation by several orders of magnitude. PMID:19356911

  14. Decreased Brain Levels of Vitamin B12 in Aging, Autism and Schizophrenia.

    PubMed

    Zhang, Yiting; Hodgson, Nathaniel W; Trivedi, Malav S; Abdolmaleky, Hamid M; Fournier, Margot; Cuenod, Michel; Do, Kim Quang; Deth, Richard C

    2016-01-01

    Many studies indicate a crucial role for the vitamin B12 and folate-dependent enzyme methionine synthase (MS) in brain development and function, but vitamin B12 status in the brain across the lifespan has not been previously investigated. Vitamin B12 (cobalamin, Cbl) exists in multiple forms, including methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), serving as cofactors for MS and methylmalonylCoA mutase, respectively. We measured levels of five Cbl species in postmortem human frontal cortex of 43 control subjects, from 19 weeks of fetal development through 80 years of age, and 12 autistic and 9 schizophrenic subjects. Total Cbl was significantly lower in older control subjects (> 60 yrs of age), primarily reflecting a >10-fold age-dependent decline in the level of MeCbl. Levels of inactive cyanocobalamin (CNCbl) were remarkably higher in fetal brain samples. In both autistic and schizophrenic subjects MeCbl and AdoCbl levels were more than 3-fold lower than age-matched controls. In autistic subjects lower MeCbl was associated with decreased MS activity and elevated levels of its substrate homocysteine (HCY). Low levels of the antioxidant glutathione (GSH) have been linked to both autism and schizophrenia, and both total Cbl and MeCbl levels were decreased in glutamate-cysteine ligase modulatory subunit knockout (GCLM-KO) mice, which exhibit low GSH levels. Thus our findings reveal a previously unrecognized decrease in brain vitamin B12 status across the lifespan that may reflect an adaptation to increasing antioxidant demand, while accelerated deficits due to GSH deficiency may contribute to neurodevelopmental and neuropsychiatric disorders. PMID:26799654

  15. Spatial and Temporal Brain Responses to Noxious Heat Thermal Stimuli in Burning Mouth Syndrome.

    PubMed

    Shinozaki, T; Imamura, Y; Kohashi, R; Dezawa, K; Nakaya, Y; Sato, Y; Watanabe, K; Morimoto, Y; Shizukuishi, T; Abe, O; Haji, T; Tabei, K; Taira, M

    2016-09-01

    Burning mouth syndrome (BMS) is an idiopathic orofacial pain condition. Although the pathophysiology of BMS is not clearly understood, central and peripheral neuropathic mechanisms are thought to be involved. The authors compared brain response to noxious heat stimuli in 16 right-handed women with primary BMS and 15 sex- and age-matched right-handed healthy female controls. A thermal stimulus sequence of 32 °C to 40 °C to 32 °C to 49 °C was repeated 4 times in a cycle. Warm and noxious heat stimuli were delivered with a Peltier thermode placed on the right palm or right lower lip for 32 s each in a session. Functional magnetic resonance imaging data were obtained by recording echoplanar images with a block design. Statistical Parametric Mapping 8 software was used to analyze the data. Patients and controls both reported feeling more pain during palm stimulation than during lip stimulation. Repetition of noxious heat stimulus on the lower lip but not on the palm induced habituation in brain activity in the cingulate cortex without reduction in pain perception. Multiple regression analysis revealed a correlation between perceived pain intensity and suppression of brain activity in the anterior cingulate cortex when the repeated thermal sequence was applied at the lower lip. Furthermore, the response of the parahippocampal area differed in BMS patients and controls when the same repeated thermal sequence was applied at the palm. The authors' findings indicate that BMS patients show specific brain responses due to impaired function of the central and peripheral nervous systems (clinical trial registration: UMIN000015002). PMID:27302878

  16. Decreased Brain Levels of Vitamin B12 in Aging, Autism and Schizophrenia

    PubMed Central

    Zhang, Yiting; Hodgson, Nathaniel W.; Trivedi, Malav S.; Abdolmaleky, Hamid M.; Fournier, Margot; Cuenod, Michel; Do, Kim Quang; Deth, Richard C.

    2016-01-01

    Many studies indicate a crucial role for the vitamin B12 and folate-dependent enzyme methionine synthase (MS) in brain development and function, but vitamin B12 status in the brain across the lifespan has not been previously investigated. Vitamin B12 (cobalamin, Cbl) exists in multiple forms, including methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), serving as cofactors for MS and methylmalonylCoA mutase, respectively. We measured levels of five Cbl species in postmortem human frontal cortex of 43 control subjects, from 19 weeks of fetal development through 80 years of age, and 12 autistic and 9 schizophrenic subjects. Total Cbl was significantly lower in older control subjects (> 60 yrs of age), primarily reflecting a >10-fold age-dependent decline in the level of MeCbl. Levels of inactive cyanocobalamin (CNCbl) were remarkably higher in fetal brain samples. In both autistic and schizophrenic subjects MeCbl and AdoCbl levels were more than 3-fold lower than age-matched controls. In autistic subjects lower MeCbl was associated with decreased MS activity and elevated levels of its substrate homocysteine (HCY). Low levels of the antioxidant glutathione (GSH) have been linked to both autism and schizophrenia, and both total Cbl and MeCbl levels were decreased in glutamate-cysteine ligase modulatory subunit knockout (GCLM-KO) mice, which exhibit low GSH levels. Thus our findings reveal a previously unrecognized decrease in brain vitamin B12 status across the lifespan that may reflect an adaptation to increasing antioxidant demand, while accelerated deficits due to GSH deficiency may contribute to neurodevelopmental and neuropsychiatric disorders. PMID:26799654

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

    PubMed

    Ellis, Jesse M S; Riters, Lauren V

    2012-01-01

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

  18. Quadcopter control in three-dimensional space using a noninvasive motor imagery based brain-computer interface

    PubMed Central

    LaFleur, Karl; Cassady, Kaitlin; Doud, Alexander; Shades, Kaleb; Rogin, Eitan; He, Bin

    2013-01-01

    Objective At the balanced intersection of human and machine adaptation is found the optimally functioning brain-computer interface (BCI). In this study, we report a novel experiment of BCI controlling a robotic quadcopter in three-dimensional physical space using noninvasive scalp EEG in human subjects. We then quantify the performance of this system using metrics suitable for asynchronous BCI. Lastly, we examine the impact that operation of a real world device has on subjects’ control with comparison to a two-dimensional virtual cursor task. Approach Five human subjects were trained to modulate their sensorimotor rhythms to control an AR Drone navigating a three-dimensional physical space. Visual feedback was provided via a forward facing camera on the hull of the drone. Individual subjects were able to accurately acquire up to 90.5% of all valid targets presented while travelling at an average straight-line speed of 0.69 m/s. Significance Freely exploring and interacting with the world around us is a crucial element of autonomy that is lost in the context of neurodegenerative disease. Brain-computer interfaces are systems that aim to restore or enhance a user’s ability to interact with the environment via a computer and through the use of only thought. We demonstrate for the first time the ability to control a flying robot in the three-dimensional physical space using noninvasive scalp recorded EEG in humans. Our work indicates the potential of noninvasive EEG based BCI systems to accomplish complex control in three-dimensional physical space. The present study may serve as a framework for the investigation of multidimensional non-invasive brain-computer interface control in a physical environment using telepresence robotics. PMID:23735712

  19. Vocal Parameters That Indicate Threat Level Correlate with FOS Immunolabeling in Social and Vocal Control Brain Regions

    PubMed Central

    Ellis, Jesse M.S.; Riters, Lauren V.

    2012-01-01

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

  20. Alcohol-induced impairment of inhibitory control is linked to attenuated brain responses in right fronto-temporal cortex

    PubMed Central

    Gan, Gabriela; Guevara, Alvaro; Marxen, Michael; Neumann, Maike; Jünger, Elisabeth; Kobiella, Andrea; Mennigen, Eva; Pilhatsch, Maximilian; Schwarz, Daniel; Zimmermann, Ulrich S.; Smolka, Michael N.

    2014-01-01

    Background A self-enhancing loop between impaired inhibitory control under alcohol and alcohol consumption has been proposed as a possible mechanism underlying dysfunctional drinking in susceptible people. However, the neural underpinnings of alcohol-induced impairment of inhibitory control are widely unknown. Methods We measured inhibitory control in fifty young adults with a stop-signal task (SST) during functional magnetic resonance imaging (fMRI). In a single-blind placebo-controlled cross-over design, all participants performed the SST once under alcohol with a breath alcohol concentration (BrAC) of 0.6 g/kg, and once under placebo. In addition, alcohol consumption was assessed using a free-access alcohol self-administration (ASA) paradigm in the same participants. Results Inhibitory control was robustly decreased under alcohol compared to placebo indicated by longer stop-signal reaction times (SSRTs). On the neural level, impaired inhibitory control under alcohol was associated with attenuated brain responses in the right fronto-temporal portion of the inhibition network that supports the attentional capture of infrequent stop-signals, and subsequent updating of action plans from response execution to inhibition. Furthermore, the extent of alcohol-induced impairment of inhibitory control predicted free-access alcohol consumption. Conclusion We suggest that during inhibitory control alcohol affects cognitive processes preceding actual motor inhibition. Under alcohol, decreased brain responses in right fronto-temporal areas might slow down the attentional capture of infrequent stop-signals and subsequent updating of action plans which leads to impaired inhibitory control. In turn, pronounced alcohol-induced impairment of inhibitory control may enhance alcohol consumption in young adults which might promote future alcohol problems. PMID:24560581

  1. Assessment of the Molecular Expression and Structure of Gangliosides in Brain Metastasis of Lung Adenocarcinoma by an Advanced Approach Based on Fully Automated Chip-Nanoelectrospray Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Zamfir, Alina D.; Serb, Alina; Vukeli, Željka; Flangea, Corina; Schiopu, Catalin; Fabris, Dragana; Kalanj-Bognar, Svjetlana; Capitan, Florina; Sisu, Eugen

    2011-12-01

    Gangliosides (GGs), sialic acid-containing glycosphingolipids, are known to be involved in the invasive/metastatic behavior of brain tumor cells. Development of modern methods for determination of the variations in GG expression and structure during neoplastic cell transformation is a priority in the field of biomedical analysis. In this context, we report here on the first optimization and application of chip-based nanoelectrospray (NanoMate robot) mass spectrometry (MS) for the investigation of gangliosides in a secondary brain tumor. In our work a native GG mixture extracted and purified from brain metastasis of lung adenocarcinoma was screened by NanoMate robot coupled to a quadrupole time-of-flight MS. A native GG mixture from an age-matched healthy brain tissue, sampled and analyzed under identical conditions, served as a control. Comparative MS analysis demonstrated an evident dissimilarity in GG expression in the two tissue types. Brain metastasis is characterized by many species having a reduced N-acetylneuraminic acid (Neu5Ac) content, however, modified by fucosylation or O-acetylation such as Fuc-GM4, Fuc-GM3, di- O-Ac-GM1, O-Ac-GM3. In contrast, healthy brain tissue is dominated by longer structures exhibiting from mono- to hexasialylated sugar chains. Also, significant differences in ceramide composition were discovered. By tandem MS using collision-induced dissociation at low energies, brain metastasis-associated GD3 (d18:1/18:0) species as well as an uncommon Fuc-GM1 (d18:1/18:0) detected in the normal brain tissue could be structurally characterized. The novel protocol was able to provide a reliable compositional and structural characterization with high analysis pace and at a sensitivity situated in the fmol range.

  2. The role of brain biogenic amines in the control of pituitary-adrenocortical activity

    NASA Technical Reports Server (NTRS)

    Maickel, R. P.

    1975-01-01

    It was found that pretreatment of animals with desmethyl imipramine antagonized the reserpine-induced sedation without preventing the decline in brain amines or the hypersecretion of adrenocorticotropic hormone (ACTH). The antagonism of reserpine-induced ACTH hypersecretion by the monoamine oxidose (MAO) inhibitor pargyline (MO 911, N-methyl-N-benzyl-2-propynylamine) was studied. Evidence is presented that this antagonism is related to the level of brain biogenic amines maintained during the course of action of the drug. Pretreatment with MAO inhibitors does not affect the ACTH hypersecretion evoked by exposure to cold or chlorpromazine, lending further support to the hypothesis that reserpine-induced ACTH hypersecretion is related to brain amine changes.

  3. Gamma Knife irradiation method based on dosimetric controls to target small areas in rat brains

    SciTech Connect

    Constanzo, Julie; Paquette, Benoit; Charest, Gabriel; Masson-Côté, Laurence; Guillot, Mathieu

    2015-05-15

    Purpose: Targeted and whole-brain irradiation in humans can result in significant side effects causing decreased patient quality of life. To adequately investigate structural and functional alterations after stereotactic radiosurgery, preclinical studies are needed. The purpose of this work is to establish a robust standardized method of targeted irradiation on small regions of the rat brain. Methods: Euthanized male Fischer rats were imaged in a stereotactic bed, by computed tomography (CT), to estimate positioning variations relative to the bregma skull reference point. Using a rat brain atlas and the stereotactic bregma coordinates obtained from CT images, different regions of the brain were delimited and a treatment plan was generated. A single isocenter treatment plan delivering ≥100 Gy in 100% of the target volume was produced by Leksell GammaPlan using the 4 mm diameter collimator of sectors 4, 5, 7, and 8 of the Gamma Knife unit. Impact of positioning deviations of the rat brain on dose deposition was simulated by GammaPlan and validated with dosimetric measurements. Results: The authors’ results showed that 90% of the target volume received 100 ± 8 Gy and the maximum of deposited dose was 125 ± 0.7 Gy, which corresponds to an excellent relative standard deviation of 0.6%. This dose deposition calculated with GammaPlan was validated with dosimetric films resulting in a dose-profile agreement within 5%, both in X- and Z-axes. Conclusions: The authors’ results demonstrate the feasibility of standardizing the irradiation procedure of a small volume in the rat brain using a Gamma Knife.

  4. Modulation of Posterior Alpha Activity by Spatial Attention Allows for Controlling A Continuous Brain-Computer Interface.

    PubMed

    Horschig, Jörn M; Oosterheert, Wouter; Oostenveld, Robert; Jensen, Ole

    2015-11-01

    Here we report that the modulation of alpha activity by covert attention can be used as a control signal in an online brain-computer interface, that it is reliable, and that it is robust. Subjects were instructed to orient covert visual attention to the left or right hemifield. We decoded the direction of attention from the magnetoencephalogram by a template matching classifier and provided the classification outcome to the subject in real-time using a novel graphical user interface. Training data for the templates were obtained from a Posner-cueing task conducted just before the BCI task. Eleven subjects participated in four sessions each. Eight of the subjects achieved classification rates significantly above chance level. Subjects were able to significantly increase their performance from the first to the second session. Individual patterns of posterior alpha power remained stable throughout the four sessions and did not change with increased performance. We conclude that posterior alpha power can successfully be used as a control signal in brain-computer interfaces. We also discuss several ideas for further improving the setup and propose future research based on solid hypotheses about behavioral consequences of modulating neuronal oscillations by brain computer interfacing. PMID:25388661

  5. [Two patients having recurrent breast cancer with brain metastases well controlled with a gamma knife radio-surgery].

    PubMed

    Hojo, Shigeyuki; Maeura, Yoshiichi; Yoshioka, Setsuko; Fujie, Yujiro; Fukunaga, Hiroki; Okada, Yoshihiro; Ota, Hirofumi; Endo, Wakio

    2006-11-01

    We report two patients having recurrent breast cancer with brain metastases that was controlled well with a gamma knife radio-surgery. The patient is a 50-year-old woman. She underwent radical mastectomy for right breast cancer in September 1993. She suffered from multiple liver metastases in June 2000, so CEF therapy contained hepatic arterial infusion chemotherapy, and extended right lobectomy of the liver were performed in December 2001. Afterward, pleurodesis was carried out to the carcinomatous pleurisy. Then she underwent simple total hysterectomy and bilateral oophorectomy for torsion of the metastatic ovarian tumor. MRI study revealed brain metastases with a diameter of 1 cm in her right midbrain in April 2005, so a gamma knife radio-surgery was performed. After the radio-surgery, a weekly paclitaxel therapy followed by peroral chemotherapy with capecitabine was started, and she took the regimen continuously. Another patient is a 56-year-old woman. She underwent skin sparing mastectomy with axillary lymph node dissection for right breast cancer in November 2002. Metastases to the base of her skull were found in October 2004, so a gamma knife radio-surgery was carried out. After the radio-surgery, a weekly paclitaxel therapy with anastrozole was started. In both of the two patients, the metastatic brain tumors have not shown growth so far and are under good control as of March 2006. PMID:17212144

  6. Controlling feeding behavior by chemical or gene-directed targeting in the brain: what's so spatial about our methods?

    PubMed Central

    Khan, Arshad M.

    2013-01-01

    Intracranial chemical injection (ICI) methods have been used to identify the locations in the brain where feeding behavior can be controlled acutely. Scientists conducting ICI studies often document their injection site locations, thereby leaving kernels of valuable location data for others to use to further characterize feeding control circuits. Unfortunately, this rich dataset has not yet been formally contextualized with other published neuroanatomical data. In particular, axonal tracing studies have delineated several neural circuits originating in the same areas where ICI injection feeding-control sites have been documented, but it remains unclear whether these circuits participate in feeding control. Comparing injection sites with other types of location data would require careful anatomical registration between the datasets. Here, a conceptual framework is presented for how such anatomical registration efforts can be performed. For example, by using a simple atlas alignment tool, a hypothalamic locus sensitive to the orexigenic effects of neuropeptide Y (NPY) can be aligned accurately with the locations of neurons labeled by anterograde tracers or those known to express NPY receptors or feeding-related peptides. This approach can also be applied to those intracranial “gene-directed” injection (IGI) methods (e.g., site-specific recombinase methods, RNA expression or interference, optogenetics, and pharmacosynthetics) that involve viral injections to targeted neuronal populations. Spatial alignment efforts can be accelerated if location data from ICI/IGI methods are mapped to stereotaxic brain atlases to allow powerful neuroinformatics tools to overlay different types of data in the same reference space. Atlas-based mapping will be critical for community-based sharing of location data for feeding control circuits, and will accelerate our understanding of structure-function relationships in the brain for mammalian models of obesity and metabolic disorders

  7. Automatic quality control in clinical (1) H MRSI of brain cancer.

    PubMed

    Pedrosa de Barros, Nuno; McKinley, Richard; Knecht, Urspeter; Wiest, Roland; Slotboom, Johannes

    2016-05-01

    MRSI grids frequently show spectra with poor quality, mainly because of the high sensitivity of MRS to field inhomogeneities. These poor quality spectra are prone to quantification and/or interpretation errors that can have a significant impact on the clinical use of spectroscopic data. Therefore, quality control of the spectra should always precede their clinical use. When performed manually, quality assessment of MRSI spectra is not only a tedious and time-consuming task, but is also affected by human subjectivity. Consequently, automatic, fast and reliable methods for spectral quality assessment are of utmost interest. In this article, we present a new random forest-based method for automatic quality assessment of (1) H MRSI brain spectra, which uses a new set of MRS signal features. The random forest classifier was trained on spectra from 40 MRSI grids that were classified as acceptable or non-acceptable by two expert spectroscopists. To account for the effects of intra-rater reliability, each spectrum was rated for quality three times by each rater. The automatic method classified these spectra with an area under the curve (AUC) of 0.976. Furthermore, in the subset of spectra containing only the cases that were classified every time in the same way by the spectroscopists, an AUC of 0.998 was obtained. Feature importance for the classification was also evaluated. Frequency domain skewness and kurtosis, as well as time domain signal-to-noise ratios (SNRs) in the ranges 50-75 ms and 75-100 ms, were the most important features. Given that the method is able to assess a whole MRSI grid faster than a spectroscopist (approximately 3 s versus approximately 3 min), and without loss of accuracy (agreement between classifier trained with just one session and any of the other labelling sessions, 89.88%; agreement between any two labelling sessions, 89.03%), the authors suggest its implementation in the clinical routine. The method presented in this article was implemented

  8. Out-of-Hospital