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Sample records for age-matched control brains

  1. Semiquantitative proteomic analysis of human hippocampal tissues from Alzheimer’s disease and age-matched control brains

    PubMed Central

    2013-01-01

    Background Alzheimer’s disease (AD) is the most common type of dementia affecting people over 65 years of age. The hallmarks of AD are the extracellular deposits known as amyloid β plaques and the intracellular neurofibrillary tangles, both of which are the principal players involved in synaptic loss and neuronal cell death. Tau protein and Aβ fragment 1–42 have been investigated so far in cerebrospinal fluid as a potential AD biomarkers. However, an urgent need to identify novel biomarkers which will capture disease in the early stages and with better specificity remains. High-throughput proteomic and pathway analysis of hippocampal tissue provides a valuable source of disease-related proteins and biomarker candidates, since it represents one of the earliest affected brain regions in AD. Results In this study 2954 proteins were identified (with at least 2 peptides for 1203 proteins) from both control and AD brain tissues. Overall, 204 proteins were exclusively detected in AD and 600 proteins in control samples. Comparing AD and control exclusive proteins with cerebrospinal fluid (CSF) literature-based proteome, 40 out of 204 AD related proteins and 106 out of 600 control related proteins were also present in CSF. As most of these proteins were extracellular/secretory origin, we consider them as a potential source of candidate biomarkers that need to be further studied and verified in CSF samples. Conclusions Our semiquantitative proteomic analysis provides one of the largest human hippocampal proteome databases. The lists of AD and control related proteins represent a panel of proteins potentially involved in AD pathogenesis and could also serve as prospective AD diagnostic biomarkers. PMID:23635041

  2. 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

  3. 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.

  4. 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

  5. Age-Matched, Case-Controlled Comparison of Clinical Indicators for Development of Entropion and Ectropion

    PubMed Central

    Michels, Kevin S.; Czyz, Craig N.; Cahill, Kenneth V.; Foster, Jill A.; Burns, John A.; Everman, Kelly R.

    2014-01-01

    Purpose. To analyze the clinical findings associated with involutional entropion and ectropion and compare them to each other and to age-matched controls. Methods. Prospective, age-matched cohort study involving 30 lids with involutional entropion, 30 lids with involutional ectropion, and 52 age-matched control lids. Results. The statistically significant differences associated with both the entropion and ectropion groups compared to the control group were presence of a retractor dehiscence, presence of a “white line,” occurrence of orbital fat prolapse in the cul-de-sac, decreased lower lid excursion, increased lid laxity by the snapback test, and an increased lower lid distraction. Entropion also differed from the control group with an increased lid crease height and decreased lateral canthal excursion. Statistically significant differences associated with entropion compared to ectropion were presence of a retractor dehiscence, decreased lateral canthal excursion, and less laxity in the snapback test. Conclusion. Entropic and ectropic lids demonstrate clinically and statistically significant anatomical and functional differences from normal, age-matched lids. Many clinical findings associated with entropion are also present in ectropion. Entropion is more likely to develop with a pronounced retractor deficiency. Ectropion is more likely to develop with diminished elasticity as measured by the snapback test. PMID:24734167

  6. 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…

  7. 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

  8. 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

  9. Oral contraceptive use among female elite athletes and age-matched controls and its relation to low back pain.

    PubMed

    Brynhildsen, J; Lennartsson, H; Klemetz, M; Dahlquist, P; Hedin, B; Hammar, M

    1997-10-01

    Exogenous and endogenous female sex steroids may influence the risk of low back pain. The fact that back pain is a very common symptom during pregnancy supports this theory. Back pain is also more common among female than male athletes. Oral contraceptives have been suggested to increase the risk of low back pain. The aim of this study was to evaluate whether the prevalence of low back pain is higher among oral contraceptive users than non-users and if it differs between women taking part in different sports. A questionnaire was sent to female elite athletes in volleyball (n = 205), basketball (n = 150), and soccer (n = 361) as well as to age-matched controls (n = 113). The questionnaire comprised questions about age, constitution, occupation, parity, and use of contraceptive method as well as previous and current back pain and possible consequences of the back problems. The response rate was 85%. Between 42% and 52% of the women in the different groups used oral contraceptives. The groups were similar in most background variables, except that the volleyball and basketball players were taller. The prevalence of current low back pain was between 21% and 34% in the different athlete groups, with an average of 30%, whereas only 18% of the controls suffered from low back pain (p 0.01). The prevalence of low back pain within each group--athletes as well as controls--was similar in women who used and did not use oral contraceptives. This study does not support the theory that low back pain is affected by the use of oral contraceptives. Instead, constitutional factors and mechanical stress during intense physical activity are probably more important.

  10. 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

  11. Preserved Learning during the Symbol–Digit Substitution Test in Patients with Schizophrenia, Age-Matched Controls, and Elderly

    PubMed Central

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

    2015-01-01

    Objective: Speed of processing, one of the main cognitive deficits in schizophrenia is most frequently measured with a digit–symbol-coding test. Performance on this test is additionally affected by writing speed and the rate at which symbol–digit relationships are learned, two factors that may be impaired in schizophrenia. This study aims to investigate the effects of sensorimotor speed, short-term learning, and long-term learning on task performance in schizophrenia. In addition, the study aims to explore differences in learning effects between patients with schizophrenia and elderly individuals. Methods: Patients with schizophrenia (N = 30) were compared with age-matched healthy controls (N = 30) and healthy elderly volunteers (N = 30) during the Symbol–Digit Substitution Test (SDST). The task was administered on a digitizing tablet, allowing precise measurements of the time taken to write each digit (writing time) and the time to decode symbols into their corresponding digits (matching time). The SDST was administered on three separate days (day 1, day 2, day 7). Symbol–digit repetitions during the task represented short-term learning and repeating the task on different days represented long-term learning. Results: The repetition of the same symbol–digit combinations within one test and the repetition of the test over days resulted in significant decreases in matching time. Interestingly, these short-term and long-term learning effects were about equal among the three groups. Individual participants showed a large variation in the rate of short-term learning. In general, patients with schizophrenia had the longest matching time whereas the elderly had the longest writing time. Writing time remained the same over repeated testing. Conclusion: The rate of learning and sensorimotor speed was found to have a substantial influence on the SDST score. However, a large individual variation in learning rate should be taken into account in the

  12. Evaluation of Basal Renal Function in Treatment-naïve Patients with Malignancy and Comparison with Age Matched Healthy Control

    PubMed Central

    Barai, Sukanta; Gambhir, Sanjay; Jain, Suruchi; Rastogi, Neeraj

    2016-01-01

    There is a paucity of data regarding the prevalence of renal insufficiency in patients with malignancy at baseline before initiation of therapy. The published studies based on patient with prior exposure to cytotoxic therapy have reported a high prevalence of renal impairment. However, these studies have utilized creatinine-based glomerular filtration rate (GFR) prediction equations to assess the level of renal function. These equations are known to have some serious limitations in reliably predicting GFR. The aim of the study was to accurately document the state of renal function in treatment-naïve cancer patients and compare them against age-matched healthy controls using a reference “creatinine independent” GFR measurement technique. Age-matched comparison of GFR of 1,373 treatment-naïve cancer patients and 1,089 healthy controls were done retrospectively. There was no difference in GFR between cancer and healthy group when analyzed under various age groups, though the overall mean GFR in healthy controls was significantly higher compared to cancer group (80.14 ± 17.63 mL vs 74.43 ± 20.84, P 0≤ 0.01), whereas the mean age in control arm was significantly lower compared to cancer group (44.24 ± 17.63 years vs. 50.70 ± 20.84 years, P ≤ 0.01). Treatment-naïve cancer patients have identical renal function to their healthy age-matched peers. Malignancy per se does not directly lead to the decline in filtration capacity of the kidneys. PMID:27651734

  13. Evaluation of Basal Renal Function in Treatment-naïve Patients with Malignancy and Comparison with Age Matched Healthy Control

    PubMed Central

    Barai, Sukanta; Gambhir, Sanjay; Jain, Suruchi; Rastogi, Neeraj

    2016-01-01

    There is a paucity of data regarding the prevalence of renal insufficiency in patients with malignancy at baseline before initiation of therapy. The published studies based on patient with prior exposure to cytotoxic therapy have reported a high prevalence of renal impairment. However, these studies have utilized creatinine-based glomerular filtration rate (GFR) prediction equations to assess the level of renal function. These equations are known to have some serious limitations in reliably predicting GFR. The aim of the study was to accurately document the state of renal function in treatment-naïve cancer patients and compare them against age-matched healthy controls using a reference “creatinine independent” GFR measurement technique. Age-matched comparison of GFR of 1,373 treatment-naïve cancer patients and 1,089 healthy controls were done retrospectively. There was no difference in GFR between cancer and healthy group when analyzed under various age groups, though the overall mean GFR in healthy controls was significantly higher compared to cancer group (80.14 ± 17.63 mL vs 74.43 ± 20.84, P 0≤ 0.01), whereas the mean age in control arm was significantly lower compared to cancer group (44.24 ± 17.63 years vs. 50.70 ± 20.84 years, P ≤ 0.01). Treatment-naïve cancer patients have identical renal function to their healthy age-matched peers. Malignancy per se does not directly lead to the decline in filtration capacity of the kidneys.

  14. Evaluation of Basal Renal Function in Treatment-naïve Patients with Malignancy and Comparison with Age Matched Healthy Control.

    PubMed

    Barai, Sukanta; Gambhir, Sanjay; Jain, Suruchi; Rastogi, Neeraj

    2016-09-01

    There is a paucity of data regarding the prevalence of renal insufficiency in patients with malignancy at baseline before initiation of therapy. The published studies based on patient with prior exposure to cytotoxic therapy have reported a high prevalence of renal impairment. However, these studies have utilized creatinine-based glomerular filtration rate (GFR) prediction equations to assess the level of renal function. These equations are known to have some serious limitations in reliably predicting GFR. The aim of the study was to accurately document the state of renal function in treatment-naïve cancer patients and compare them against age-matched healthy controls using a reference "creatinine independent" GFR measurement technique. Age-matched comparison of GFR of 1,373 treatment-naïve cancer patients and 1,089 healthy controls were done retrospectively. There was no difference in GFR between cancer and healthy group when analyzed under various age groups, though the overall mean GFR in healthy controls was significantly higher compared to cancer group (80.14 ± 17.63 mL vs 74.43 ± 20.84, P 0≤ 0.01), whereas the mean age in control arm was significantly lower compared to cancer group (44.24 ± 17.63 years vs. 50.70 ± 20.84 years, P ≤ 0.01). Treatment-naïve cancer patients have identical renal function to their healthy age-matched peers. Malignancy per se does not directly lead to the decline in filtration capacity of the kidneys. PMID:27651734

  15. 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

  16. Functional Aspects of Gait in Essential Tremor: A Comparison with Age-Matched Parkinson’s Disease Cases, Dystonia Cases, and Controls

    PubMed Central

    Louis, Elan D.; Rao, Ashwini K.

    2015-01-01

    Background An understanding of the functional aspects of gait and balance has wide ramifications. Individuals with balance disorders often restrict physical activity, travel, and social commitments to avoid falling, and loss of balance confidence, itself, is a source of disability. We studied the functional aspects of gait in patients with essential tremor (ET), placing their findings within the context of two other neurological disorders (Parkinson’s disease [PD] and dystonia) and comparing them with age-matched controls. Methods We administered the six-item Activities of Balance Confidence (ABC-6) Scale and collected data on number of falls and near-falls, and use of walking aids in 422 participants (126 ET, 77 PD, 46 dystonia, 173 controls). Results Balance confidence was lowest in PD, intermediate in ET, and relatively preserved in dystonia compared with controls. This ordering reoccurred for each of the six ABC-6 items. The number of near-falls and falls followed a similar ordering. Use of canes, walkers, and wheelchairs was elevated in ET and even greater in PD. Several measures of balance confidence (ABC-6 items 1, 4, 5, and 6) were lower in torticollis cases than in those with blepharospasm, although the two groups did not differ with respect to falls or use of walking aids. Discussion Lower balance confidence, increased falls, and greater need for walking aids are variably features of a range of movement disorder patients compared to age-matched controls. While most marked among PD patients, these issues affected ET patients as well and, to a small degree, some patients with dystonia. PMID:26056611

  17. Sicca symptoms in Thai patients with rheumatoid arthritis, systemic lupus erythematosus and scleroderma: a comparison with age-matched controls and correlation with disease variables.

    PubMed

    Wangkaew, Suparaporn; Kasitanon, Nuntana; Sivasomboon, Chate; Wichainun, Ramjai; Sukitawut, Waraporn; Louthrenoo, Worawit

    2006-12-01

    This study was performed to determine the prevalence of ocular and oral sicca symptoms in Thai patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and scleroderma (Scl). The ocular symptoms and sign (the Schirmer's 1 test) and the oral sicca symptoms and sign (the Saxon's test) in each of 50 RA, SLE and Scl patients were compared with their age-matched controls. The correlation between the presence of sicca symptoms and signs with their clinical activity was also determined. Ocular sicca symptoms were found more common in patients with RA (38% vs 18%, p < 0.05), SLE (36% vs 14%, p < 0.05) and Scl (54% vs 16%, p < 0.01), and oral sicca symptoms were found more common in SLE (22% vs 0%, p < 0.01), and Scl (16% vs 4%, p < 0.05) than their controls. However, only RA patients had a significantly higher proportion of positive Schimer-1 test compared with their controls (p < 0.01). There was no strong correlation between sicca symptoms or signs and other clinical or laboratory variables (age, disease duration, disease activity, disease severity, and antibody to Ro and La antigens) in these three groups. In conclusion, sicca symptoms were seen significantly more common in Thai patients with connective tissue diseases, but the symptoms did not show a good correlation with the clinical and laboratory variables.

  18. 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

  19. Comparison of younger and older breast cancer survivors and age-matched controls on specific and overall QoL domains

    PubMed Central

    Champion, Victoria L.; Wagner, Lynne I.; Monahan, Patrick O.; Daggy, Joanne; Smith, Lisa; Cohee, Andrea; Ziner, Kim W.; Haase, Joan E.; Miller, Kathy; Pradhan, Kamnesh; Unverzagt, Frederick W.; Cella, David; Ansari, Bilal; Sledge, George W.

    2014-01-01

    Background Younger survivors (YS) of breast cancer often report more survivorship symptoms such as fatigue, depression, sexual difficulty, and cognitive problems than older survivors (OS). We sought to determine the effect of breast cancer and age at diagnosis on Quality of Life (QoL) by comparing 3 groups: 1) YS diagnosed at age 45 or before, 2) OS diagnosed between 55 and 70, and, 3) for the YS, age-matched controls (AC) of women not diagnosed with breast cancer. Methods Using a large Eastern Cooperative Oncology Group (ECOG) data base, we recruited 505 YS who were ages 45 or younger when diagnosed and 622 OS diagnosed at 55 to 70. YS, OS, and AC were compared on physical, psychological, social, spiritual, and overall QoL variables. Results Compared to both AC and to OS, YS reported more depressive symptoms (p=.005) and fatigue (p<.001), poorer self-reported attention function (p<.001), and poorer sexual function (p<.001) than either comparison group. However, YS also reported a greater sense of personal growth (p<.001) and perceived less social constraint (p<.001) from their partner than AC. Conclusions YS reported worse functioning than AC relative to depression, fatigue, attention, sexual function, and spirituality. Perhaps even more important, YS fared worse than both AC and OS on body image, anxiety, sleep, marital satisfaction, and fear of recurrence, indicating that YS are at greater risk for long term QoL problems than survivors diagnosed at a later age. PMID:24891116

  20. Differential gene expression in liver and small intestine from lactating rats compared to age-matched virgin controls detects increased mRNA of cholesterol biosynthetic genes

    PubMed Central

    2011-01-01

    Background Lactation increases energy demands four- to five-fold, leading to a two- to three-fold increase in food consumption, requiring a proportional adjustment in the ability of the lactating dam to absorb nutrients and to synthesize critical biomolecules, such as cholesterol, to meet the dietary needs of both the offspring and the dam. The size and hydrophobicity of the bile acid pool increases during lactation, implying an increased absorption and disposition of lipids, sterols, nutrients, and xenobiotics. In order to investigate changes at the transcriptomics level, we utilized an exon array and calculated expression levels to investigate changes in gene expression in the liver, duodenum, jejunum, and ileum of lactating dams when compared against age-matched virgin controls. Results A two-way mixed models ANOVA was applied to detect differentially expressed genes. Significance calls were defined as a p < 0.05 for the overall physiologic state effect (lactation vs. control), and a within tissue pairwise comparison of p < 0.01. The proportion of false positives, an estimate of the ratio of false positives in the list of differentially expressed genes, was calculated for each tissue. The number of differentially expressed genes was 420 in the liver, 337 in the duodenum, 402 in the jejunum, and 523 in the ileum. The list of differentially expressed genes was in turn analyzed by Ingenuity Pathways Analysis (IPA) to detect biological pathways that were overrepresented. In all tissues, sterol regulatory element binding protein (Srebp)-regulated genes involved in cholesterol synthesis showed increased mRNA expression, with the fewest changes detected in the jejunum. We detected increased Scap mRNA in the liver only, suggesting an explanation for the difference in response to lactation between the liver and small intestine. Expression of Cyp7a1, which catalyzes the rate limiting step in the bile acid biosynthetic pathway, was also significantly increased in liver. In

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

    PubMed

    Hsu, Hsinjen Julie; Bishop, Dorothy V M

    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 improvement, even

  2. Intensively-Managed Young Children with Type 1 Diabetes Consume High-Fat, Low-Fiber Diets Similar to Age-Matched Controls

    PubMed Central

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

    2014-01-01

    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), ages 2–12 years, attending a pediatric diabetes clinic were compared to 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 (HEI-2005). More children with T1D were overweight or obese compared to children participating in NHANES (42% vs. 30%, p=0.04). Greater proportions of children with T1D met daily recommendations for vegetables (22% vs. 13%, p=0.03), whole grains (12% vs. 5%, p=0.005), and dairy (55% vs. 36%, p=0.001) compared to NHANES children while similar proportions met daily fruit recommendations (40% vs. 33%, p=0.2). Less than one-third of all children limited total fat to recommended levels; children with T1D consumed more saturated fat than NHANES children (14% vs. 12% total energy intake, p=0.0009). Fiber intakes were very low in both groups. Compared to NHANES children, children with T1D had higher HEI-2005 scores (59.6 vs. 49.7, p=0.0006) primarily due to 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 to youth in the general population. PMID:24916556

  3. 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

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

    PubMed

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

    2012-04-01

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

  5. 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.

  6. Brain controlled robots

    PubMed Central

    Kawato, Mitsuo

    2008-01-01

    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

  7. 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

  8. 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

  9. 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

  10. 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.

  11. Brain activation during neurocognitive testing using functional near-infrared spectroscopy in patients following concussion compared to healthy controls.

    PubMed

    Kontos, A P; Huppert, T J; Beluk, N H; Elbin, R J; Henry, L C; French, J; Dakan, S M; Collins, M W

    2014-12-01

    There is no accepted clinical imaging modality for concussion, and current imaging modalities including fMRI, DTI, and PET are expensive and inaccessible to most clinics/patients. Functional near-infrared spectroscopy (fNIRS) is a non-invasive, portable, and low-cost imaging modality that can measure brain activity. The purpose of this study was to compare brain activity as measured by fNIRS in concussed and age-matched controls during the performance of cognitive tasks from a computerized neurocognitive test battery. Participants included nine currently symptomatic patients aged 18-45 years with a recent (15-45 days) sport-related concussion and five age-matched healthy controls. The participants completed a computerized neurocognitive test battery while wearing the fNIRS unit. Our results demonstrated reduced brain activation in the concussed subject group during word memory, (spatial) design memory, digit-symbol substitution (symbol match), and working memory (X's and O's) tasks. Behavioral performance (percent-correct and reaction time respectively) was lower for concussed participants on the word memory, design memory, and symbol match tasks than controls. The results of this preliminary study suggest that fNIRS could be a useful, portable assessment tool to assess reduced brain activation and augment current approaches to assessment and management of patients following concussion.

  12. Brain activation during neurocognitive testing using functional near-infrared spectroscopy in patients following concussion compared to healthy controls

    PubMed Central

    Huppert, T. J.; Beluk, N. H.; Elbin, R. J.; Henry, L. C.; French, J.; Dakan, S. M.; Collins, M. W.

    2016-01-01

    There is no accepted clinical imaging modality for concussion, and current imaging modalities including fMRI, DTI, and PET are expensive and inaccessible to most clinics/ patients. Functional near-infrared spectroscopy (fNIRS) is a non-invasive, portable, and low-cost imaging modality that can measure brain activity. The purpose of this study was to compare brain activity as measured by fNIRS in concussed and age-matched controls during the performance of cognitive tasks from a computerized neurocognitive test battery. Participants included nine currently symptomatic patients aged 18–45 years with a recent (15–45 days) sport-related concussion and five age-matched healthy controls. The participants completed a computerized neurocognitive test battery while wearing the fNIRS unit. Our results demonstrated reduced brain activation in the concussed subject group during word memory, (spatial) design memory, digit-symbol substitution (symbol match), and working memory (X’s and O’s) tasks. Behavioral performance (percent-correct and reaction time respectively) was lower for concussed participants on the word memory, design memory, and symbol match tasks than controls. The results of this preliminary study suggest that fNIRS could be a useful, portable assessment tool to assess reduced brain activation and augment current approaches to assessment and management of patients following concussion. PMID:24477579

  13. 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

  14. 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.

  15. 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,…

  16. Study on Control of Brain Temperature for Brain Hypothermia Treatment

    NASA Astrophysics Data System (ADS)

    Gaohua, Lu; Wakamatsu, Hidetoshi

    The brain hypothermia treatment is an attractive therapy for the neurologist because of its neuroprotection in hypoxic-ischemic encephalopathy patients. The present paper deals with the possibility of controlling the brain and other viscera in different temperatures from the viewpoint of system control. It is theoretically attempted to realize the special brain hypothermia treatment to cool only the head but to warm the body by using the simple apparatus such as the cooling cap, muffler and warming blanket. For this purpose, a biothermal system concerning the temperature difference between the brain and the other thoracico-abdominal viscus is synthesized from the biothermal model of hypothermic patient. The output controllability and the asymptotic stability of the system are examined on the basis of its structure. Then, the maximum temperature difference to be realized is shown dependent on the temperature range of the apparatus and also on the maximum gain determined from the coefficient matrices A, B and C of the biothermal system. Its theoretical analysis shows the realization of difference of about 2.5°C, if there is absolutely no constraint of the temperatures of the cooling cap, muffler and blanket. It is, however, physically unavailable. Those are shown by simulation example of the optimal brain temperature regulation using a standard adult database. It is thus concluded that the surface cooling and warming apparatus do no make it possible to realize the special brain hypothermia treatment, because the brain temperature cannot be cooled lower than those of other viscera in an appropriate temperature environment. This study shows that the ever-proposed good method of clinical treatment is in principle impossible in the actual brain hypothermia treatment.

  17. 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

  18. Fissioning in planarians: control by the brain.

    PubMed

    Best, J B; Goodman, A B; Pigon, A

    1969-05-01

    Reduced population densities lead to increased rates of fissioning in planarians whereas higher population densities suppress fissioning. This effect is not primarily due to mucus deposition or substances secreted into the water. Experiments are presented which show a system of population feedback control. In the presence of other planarians, the brain exerts an influence (probably neurohormonal) to suppress fissioning. This influence becomes attenuated with axial distance from the brain.

  19. 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…

  20. Language control in the bilingual brain.

    PubMed

    Crinion, J; Turner, R; Grogan, A; Hanakawa, T; Noppeney, U; Devlin, J T; Aso, T; Urayama, S; Fukuyama, H; Stockton, K; Usui, K; Green, D W; Price, C J

    2006-06-01

    How does the bilingual brain distinguish and control which language is in use? Previous functional imaging experiments have not been able to answer this question because proficient bilinguals activate the same brain regions irrespective of the language being tested. Here, we reveal that neuronal responses within the left caudate are sensitive to changes in the language or the meaning of words. By demonstrating this effect in populations of German-English and Japanese-English bilinguals, we suggest that the left caudate plays a universal role in monitoring and controlling the language in use.

  1. Multivariate morphological brain signatures predict chronic abdominal pain patients from healthy control subjects

    PubMed Central

    Labus, Jennifer S.; Van Horn, John D.; Gupta, Arpana; Alaverdyan, Mher; Torgerson, Carinna; Ashe-McNalley, Cody; Irimia, Andrei; Hong, Jui-Yang; Naliboff, Bruce; Tillisch, Kirsten; Mayer, Emeran A.

    2015-01-01

    Irritable bowel syndrome (IBS) is the most common chronic visceral pain disorder. The pathophysiology of IBS is incompletely understood, however evidence strongly suggests dysregulation of the brain-gut axis. The aim of this study was to apply multivariate pattern analysis to identify an IBS-related morphometric brain signature which could serve as a central biological marker and provide new mechanistic insights into the pathophysiology of IBS. Parcellation of 165 cortical and subcortical regions was performed using Freesurfer and the Destrieux and Harvard-Oxford atlases. Volume, mean curvature, surface area and cortical thickness were calculated for each region. Sparse partial least squares-discriminant analysis was applied to develop a diagnostic model using a training set of 160 females (80 healthy controls, 80 IBS). Predictive accuracy was assessed in an age matched holdout test set of 52 females (26 health controls, 26 IBS). A two-component classification algorithm comprised of the morphometry of 1) primary somato-sensory and motor regions, and 2) multimodal network regions, explained 36% of the variance. Overall predictive accuracy of the classification algorithm was 70%. Small effect size associations were observed between the somatosensory and motor signature and non-gastrointestinal somatic symptoms. The findings demonstrate the predictive accuracy of a classification algorithm based solely on regional brain morphometry is not sufficient but they do provide support for the utility of multivariate pattern analysis for identifying meaningful neurobiological markers in IBS. Perspective This article presents the development, optimization, and testing of a classification algorithm for discriminating female IBS patients from healthy controls using only brain morphometry data. The results provide support for utility of multivariate pattern analysis for identifying meaningful neurobiological markers in IBS. PMID:25906347

  2. 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

  3. 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.

  4. 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

  5. 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

  6. Efficient foot motor control by Neymar's brain.

    PubMed

    Naito, Eiichi; Hirose, Satoshi

    2014-01-01

    How very long-term (over many years) motor skill training shapes internal motor representation remains poorly understood. We provide valuable evidence that the football brain of Neymar da Silva Santos Júnior (the Brasilian footballer) recruits very limited neural resources in the motor-cortical foot regions during foot movements. We scanned his brain activity with a 3-tesla functional magnetic resonance imaging (fMRI) while he rotated his right ankle at 1 Hz. We also scanned brain activity when three other age-controlled professional footballers, two top-athlete swimmers and one amateur footballer performed the identical task. A comparison was made between Neymar's brain activity with that obtained from the others. We found activations in the left medial-wall foot motor regions during the foot movements consistently across all participants. However, the size and intensity of medial-wall activity was smaller in the four professional footballers than in the three other participants, despite no difference in amount of foot movement. Surprisingly, the reduced recruitment of medial-wall foot motor regions became apparent in Neymar. His medial-wall activity was smallest among all participants with absolutely no difference in amount of foot movement. Neymar may efficiently control given foot movements probably by largely conserving motor-cortical neural resources. We discuss this possibility in terms of over-years motor skill training effect, use-dependent plasticity, and efficient motor control.

  7. When "altering brain function" becomes "mind control".

    PubMed

    Koivuniemi, Andrew; Otto, Kevin

    2014-01-01

    Functional neurosurgery has seen a resurgence of interest in surgical treatments for psychiatric illness. Deep brain stimulation (DBS) technology is the preferred tool in the current wave of clinical experiments because it allows clinicians to directly alter the functions of targeted brain regions, in a reversible manner, with the intent of correcting diseases of the mind, such as depression, addiction, anorexia nervosa, dementia, and obsessive compulsive disorder. These promising treatments raise a critical philosophical and humanitarian question. "Under what conditions does 'altering brain function' qualify as 'mind control'?" In order to answer this question one needs a definition of mind control. To this end, we reviewed the relevant philosophical, ethical, and neurosurgical literature in order to create a set of criteria for what constitutes mind control in the context of DBS. We also outline clinical implications of these criteria. Finally, we demonstrate the relevance of the proposed criteria by focusing especially on serendipitous treatments involving DBS, i.e., cases in which an unintended therapeutic benefit occurred. These cases highlight the importance of gaining the consent of the subject for the new therapy in order to avoid committing an act of mind control.

  8. Atypical Brain Responses to Sounds in Children with Specific Language and Reading Impairments

    ERIC Educational Resources Information Center

    McArthur, Genevieve; Atkinson, Carmen; Ellis, Danielle

    2009-01-01

    This study tested if children with specific language impairment (SLI) or children with specific reading disability (SRD) have abnormal brain responses to sounds. We tested 6- to 12-year-old children with SLI (N = 19), children with SRD (N = 55), and age-matched controls (N = 36) for their passive auditory event-related potentials (ERPs) to tones,…

  9. 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

  10. Flexible brain network reconfiguration supporting inhibitory control

    PubMed Central

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

    2015-01-01

    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

  11. Brain regions and genes affecting postural control.

    PubMed

    Lalonde, R; Strazielle, C

    2007-01-01

    Postural control is integrated in all facets of motor commands. The role of cortico-subcortical pathways underlying postural control, including cerebellum and its afferents (climbing, mossy, and noradrenergic fibers), basal ganglia, motor thalamus, and parieto-frontal neocortex has been identified in animal models, notably through the brain lesion technique in rats and in mice with spontaneous and induced mutations. These studies are complemented by analyses of the factors underlying postural deficiencies in patients with cerebellar atrophy. With the gene deletion technique in mice, specific genes expressed in cerebellum encoding glutamate receptors (Grid2 and Grm1) and other molecules (Prkcc, Cntn6, Klf9, Syt4, and En2) have also been shown to affect postural control. In addition, transgenic mouse models of the synucleinopathies and of Huntington's disease cause deficiencies of motor coordination resembling those of patients with basal ganglia damage.

  12. 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.

  13. 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

  14. 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

  15. The bilingual brain: flexibility and control in the human cortex.

    PubMed

    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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging

    PubMed Central

    Bell, Robert D.; Winkler, Ethan A.; Sagare, Abhay P.; Singh, Itender; LaRue, Barb; Deane, Rashid; Zlokovic, Berislav V.

    2010-01-01

    SUMMARY Pericytes play a key role in the development of cerebral microcirculation. The exact role of pericytes in the neurovascular unit in the adult brain and during brain aging remains, however, elusive. Using adult viable pericyte-deficient mice, we show that pericyte loss leads to brain vascular damage by two parallel pathways: (1) reduction in brain microcirculation causing diminished brain capillary perfusion, cerebral blood flow and cerebral blood flow responses to brain activation which ultimately mediates chronic perfusion stress and hypoxia, and (2) blood-brain barrier breakdown associated with brain accumulation of serum proteins and several vasculotoxic and/or neurotoxic macromolecules ultimately leading to secondary neuronal degenerative changes. We show that age-dependent vascular damage in pericyte-deficient mice precedes neuronal degenerative changes, learning and memory impairment and the neuroinflammatory response. Thus, pericytes control key neurovascular functions that are necessary for proper neuronal structure and function, and pericytes loss results in a progressive age-dependent vascular-mediated neurodegeneration. PMID:21040844

  3. 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.

  4. 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.

  5. Stimulation-Based Control of Dynamic Brain Networks

    PubMed Central

    Pasqualetti, Fabio; Gu, Shi; Cieslak, Matthew

    2016-01-01

    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

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. Computed tomography-guided in vivo cardiac orientation and correlation with ECG in individuals without structural heart disease and in age-matched obese and older individuals.

    PubMed

    Sathananthan, Gnalini; Aggarwal, Gunjan; Zahid, Simmi; Byth, Karen; Chik, William; Friedman, Daniel; Thiagalingam, Aravinda

    2015-05-01

    The cardiac axis in a structurally normal heart is influenced by a number of factors. We investigated the anatomical and electrical cardiac axes in middle-aged individuals without structural heart disease and compared this with age-matched obese and older individuals without structural heart disease. A retrospective study of controls included those between 30 and 60 years old with a normal body mass index (BMI), who were then compared with obese individuals between 30 and 60 years old and with individuals more than 60 years old with a normal BMI. The anatomical cardiac axis was determined along the long axis by cardiac computed tomography (CT) and correlated with the electrical cardiac axis on a surface electrocardiogram (ECG) in the frontal plane. A total of 124 patients were included. In the controls (n = 59), the mean CT axis was 38.1° ± 7.8° whilst the mean ECG axis was 51.8° ± 26.6°, Pearson r value 0.12 (P = 0.365). In the obese (n = 36), the mean CT axis was 25.1° ± 6.2° whilst the mean ECG axis was 20.1° ± 23.9°, Pearson r value 0.05 (P = 0.808). In the older group (n = 29), the mean CT axis was 34.4° ± 9.1° whilst the mean ECG axis was 34.4° ± 30.3°, Pearson r value 0.26 (P = 0.209). Obese individuals have a more leftward rotation of both axes than age-matched normals (P <0.0001), which could be secondary to elevation of the diaphragm. Older individuals have a more leftward rotation only of their electrical cardiac axis (P = 0.01), which could be a normal variant or reflect underlying conduction disturbances in this age group.

  12. 3D of Brain Shape and Volume After Cranial Vault Remodeling Surgery for Craniosynostosis Correction in Infants

    PubMed Central

    Paniagua, Beatriz; Emodi, Omri; Hill, Jonathan; Fishbaugh, James; Pimenta, Luiz A; Aylward, Stephen R.; Andinet, Enquobahrie; Gerig, Guido; Gilmore, John; van Aalst, John A; Styner, Martin

    2013-01-01

    The skull of young children is made up of bony plates that enable growth. Craniosynostosis is a birth defect that causes one or more sutures on an infant’s skull to close prematurely. Corrective surgery focuses on cranial and orbital rim shaping to return the skull to a more normal shape. Functional problems caused by craniosynostosis such as speech and motor delay can improve after surgical correction, but a post-surgical analysis of brain development in comparison with age-matched healthy controls is necessary to assess surgical outcome. Full brain segmentations obtained from pre- and post-operative computed tomography (CT) scans of 8 patients with single suture sagittal (n=5) and metopic (n=3), non-syndromic craniosynostosis from 41 to 452 days-of-age were included in this study. Age-matched controls obtained via 4D acceleration-based regression of a cohort of 402 full brain segmentations from healthy controls magnetic resonance images (MRI) were also used for comparison (ages 38 to 825 days). 3D point-based models of patient and control cohorts were obtained using SPHARM-PDM shape analysis tool. From a full dataset of regressed shapes, 240 healthy regressed shapes between 30 and 588 days-of-age (time step = 2.34 days) were selected. Volumes and shape metrics were obtained for craniosynostosis and healthy age-matched subjects. Volumes and shape metrics in single suture craniosynostosis patients were larger than age-matched controls for pre- and post-surgery. The use of 3D shape and volumetric measurements show that brain growth is not normal in patients with single suture craniosynostosis. PMID:24465118

  13. Biothermal Model of Patient and Automatic Control System of Brain Temperature for Brain Hypothermia Treatment

    NASA Astrophysics Data System (ADS)

    Wakamatsu, Hidetoshi; Gaohua, Lu

    Various surface-cooling apparatus such as the cooling cap, muffler and blankets have been commonly used for the cooling of the brain to provide hypothermic neuro-protection for patients of hypoxic-ischemic encephalopathy. The present paper is aimed at the brain temperature regulation from the viewpoint of automatic system control, in order to help clinicians decide an optimal temperature of the cooling fluid provided for these three types of apparatus. At first, a biothermal model characterized by dynamic ambient temperatures is constructed for adult patient, especially on account of the clinical practice of hypothermia and anesthesia in the brain hypothermia treatment. Secondly, the model is represented by the state equation as a lumped parameter linear dynamic system. The biothermal model is justified from their various responses corresponding to clinical phenomena and treatment. Finally, the optimal regulator is tentatively designed to give clinicians some suggestions on the optimal temperature regulation of the patient’s brain. It suggests the patient’s brain temperature could be optimally controlled to follow-up the temperature process prescribed by the clinicians. This study benefits us a great clinical possibility for the automatic hypothermia treatment.

  14. 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

  15. Evidence of altered DNA integrity in the brain regions of suicidal victims of Bipolar Depression

    PubMed Central

    Mustak, Mohammed S.; Hegde, Muralidhar L.; Dinesh, Athira; Britton, Gabrielle B.; Berrocal, Ruben; Subba Rao, K.; Shamasundar, N. M.; Rao, K. S. J; Sathyanarayana Rao, T. S.

    2010-01-01

    Deoxyribonucleic acid (DNA) integrity plays a significant role in cell function. There are limited studies with regard to the role of DNA damage in bipolar affective disorder (BP). In the present study, we have assessed DNA integrity, conformation, and stability in the brain region of bipolar depression (BD) patients (n=10) compared to age-matched controls (n=8). Genomic DNA was isolated from 10 postmortem BD patients’ brain regions (frontal cortex, Pons, medulla, thalamus, cerebellum, hypothalamus, Parietal, temporal, occipital lobe, and hippocampus) and from the age-matched control subjects. DNA from the frontal cortex, pons, medulla, and thalamus showed significantly higher number of strand breaks in BD (P<0.01) compared to the age-matched controls. However, DNA from the hippocampus region was intact and did not show any strand breaks. The stability studies also indicated that the melting temperature and ethidium bromide binding pattern were altered in the DNA of BD patients’ brain regions, except in the hippocampus. The conformation studies showed B-A or secondary B-DNA conformation (instead of the normal B-DNA) in BD patients’ brain regions, with the exception of the hippocampus. The levels of redox metals such as Copper (Cu) and Iron (Fe) were significantly elevated in the brain regions of the sufferers of BD, while the Zinc (Zn) level was decreased. In the hippocampus, there was no change in the Fe or Cu levels, whereas, the Zn level was elevated. There was a clear correlation between Cu and Fe levels versus strand breaks in the brain regions of the BD. To date, as far as we are aware, this is a new comprehensive database on stability and conformations of DNA in different brain regions of patients affected with BD. The biological significance of these findings is discussed here. PMID:21180406

  16. Free Will Top-Down Control in the Brain

    NASA Astrophysics Data System (ADS)

    Frith, Chris D.

    I suggest that the physiological basis of free will, the spontaneous and intrinsic selection of one action rather than another, might be identified with mechanisms of top-down control. Top-down control is needed when, rather than responding to the most salient stimulus, we concentrate on the stimuli and actions relevant to the task we have chosen to perform. Top-down control is particularly relevant when we make our own decisions rather then following the instructions of an experimenter. Cognitive neuroscientists have studied top-down control extensively and have demonstrated an important role for dorsolateral prefrontal cortex and anterior cingulate cortex. If we consider the individual in isolation, then these regions are the likely location of will in the brain. However, individuals do not typically operate in isolation. The demonstration of will in even the simplest laboratory task depends upon an implicit agreement between the subject of the experiment and the experimenter. The top of top-down control is not to be found in the individual brain, but in the culture that is the human brain's unique environmental niche.

  17. 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.

  18. Control of Hepatic Glucose Metabolism by Islet and Brain

    PubMed Central

    Rojas, Jennifer M.; Schwartz, Michael W.

    2014-01-01

    Dysregulation of hepatic glucose uptake (HGU) and inability of insulin to suppress hepatic glucose production (HGP), both contribute to hyperglycemia in patients with type 2 diabetes (T2D). Growing evidence suggests that insulin can inhibit HGP not only through a direct effect on the liver, but also via a mechanism involving the brain. Yet the notion that insulin action in the brain plays a physiological role in the control of HGP continues to be controversial. Although studies in dogs suggest that the direct hepatic effect of insulin is sufficient to explain day-to-day control of HGP, a surprising outcome has been revealed by recent studies in mice investigating whether the direct hepatic action of insulin is necessary for normal HGP: when hepatic insulin signaling pathway was genetically disrupted, HGP was maintained normally even in the absence of direct input from insulin. Here we present evidence that points to a potentially important role of the brain in the physiological control of both HGU and HGP in response to input from insulin as well as other hormones and nutrients. PMID:25200294

  19. 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

  20. 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.

  1. 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 ...

  2. 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.

  3. Controlled cortical impact model for traumatic brain injury.

    PubMed

    Romine, Jennifer; Gao, Xiang; Chen, Jinhui

    2014-08-05

    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.

  4. Functional brain network changes associated with maintenance of cognitive function in multiple sclerosis.

    PubMed

    Helekar, Santosh A; Shin, Jae C; Mattson, Brandi J; Bartley, Krystle; Stosic, Milena; Saldana-King, Toni; Montague, P Read; Hutton, George J

    2010-01-01

    In multiple sclerosis (MS) functional changes in connectivity due to cortical reorganization could lead to cognitive impairment (CI), or reflect a re-adjustment to reduce the clinical effects of widespread tissue damage. Such alterations in connectivity could result in changes in neural activation as assayed by executive function tasks. We examined cognitive function in MS patients with mild to moderate CI and age-matched controls. We evaluated brain activity using functional magnetic resonance imaging (fMRI) during the successful performance of the Wisconsin card sorting (WCS) task by MS patients, showing compensatory maintenance of normal function, as measured by response latency and error rate. To assess changes in functional connectivity throughout the brain, we performed a global functional brain network analysis by computing voxel-by-voxel correlations on the fMRI time series data and carrying out a hierarchical cluster analysis. We found that during the WCS task there is a significant reduction in the number of smaller size brain functional networks, and a change in the brain areas representing the nodes of these networks in MS patients compared to age-matched controls. There is also a concomitant increase in the strength of functional connections between brain loci separated at intermediate-scale distances in these patients. These functional alterations might reflect compensatory neuroplastic reorganization underlying maintenance of relatively normal cognitive function in the face of white matter lesions and cortical atrophy produced by MS.

  5. Endocannabinoid functions controlling neuronal specification during brain development.

    PubMed

    Harkany, Tibor; Keimpema, Erik; Barabás, Klaudia; Mulder, Jan

    2008-04-16

    Endocannabinoids (eCBs) regulate a broad range of physiological functions in the postnatal brain and are implicated in the neuropathogenesis of psychiatric and metabolic diseases. Accumulating evidence indicates that eCB signaling also serves key functions during neurodevelopment; and is inherently involved in the control of neurogenesis, neural progenitor proliferation, lineage segregation, and the migration and phenotypic specification of immature neurons. Recent advances in developmental biology define fundamental eCB-driven cellular mechanisms that also contribute to our understanding of the molecular substrates of prenatal drug, in particular cannabis, actions. Here, we summarize known organizing principles of eCB-signaling systems in the developing telencephalon, and outline the sequence of decision points and underlying signaling pathways upon CB1 cannabinoid receptor activation that contribute to neuronal diversification in the developing brain. Finally, we discuss how these novel principles affect the formation of complex neuronal networks.

  6. Long-term meditation is associated with increased gray matter density in the brain stem.

    PubMed

    Vestergaard-Poulsen, Peter; van Beek, Martijn; Skewes, Joshua; Bjarkam, Carsten R; Stubberup, Michael; Bertelsen, Jes; Roepstorff, Andreas

    2009-01-28

    Extensive practice involving sustained attention can lead to changes in brain structure. Here, we report evidence of structural differences in the lower brainstem of participants engaged in the long-term practice of meditation. Using magnetic resonance imaging, we observed higher gray matter density in lower brain stem regions of experienced meditators compared with age-matched nonmeditators. Our findings show that long-term practitioners of meditation have structural differences in brainstem regions concerned with cardiorespiratory control. This could account for some of the cardiorespiratory parasympathetic effects and traits, as well as the cognitive, emotional, and immunoreactive impact reported in several studies of different meditation practices.

  7. 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

  8. Lactate: brain fuel in human traumatic brain injury: a comparison with normal healthy control subjects.

    PubMed

    Glenn, Thomas C; Martin, Neil A; Horning, Michael A; McArthur, David L; Hovda, David A; Vespa, Paul; Brooks, George A

    2015-06-01

    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-(2)H2]glucose, that is, D2-glucose, and [3-(13)C]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 (13)CO2 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-(13)C]lactate tracer and (13)C-glucose produced during hepatic and renal gluconeogenesis (GNG) showed that 75-80% of (13)CO2 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

  9. 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

  10. Pathological changes in Alzheimer"s brain evaluated with fluorescence emission analysis (FEA)

    NASA Astrophysics Data System (ADS)

    Christov, Alexander; Ottman, Todd; Grammas, Paula

    2004-07-01

    Development of AD is associated with cerebrovascular deposition of amyloid beta (Aβ) as well as a progressive increase in vasular collagen content. Both AΒ and collagen are naturally fluorescent compounds when exposed to UV light. We analyzed autofluorescence emitted from brain tissue samples and isolated brain resistance vessels harvested postmortem from patients with Alzheimer's disease (AD) and age-matched controls. Fluorescence emission, excited at 355 nm with an Nd:YAG laser, was measured using a fiber-optic based fluorescence spectroscopic system for tissue analysis. Significantly higher values of fluorescence emission intensity (P<0.001) in the spectral region from 465 to 490 nm were detected in brain resistance vessel samples from AD patients compared to the normal individuals. Results from western blot analysis showed elevated levels of type I and type III collagen, and reduced levels of type IV collagen in resistance vessels from AD patients, compared to control samples. In addition, using direct scanning of the cortical suface for fluoresxcence emission by the laser-induced fluorescence spectroscopy system we detected a significantly (P<0.05) higher level of apoptosis in AD brain tissue compared to age-matched controls. Fluorescence emission analysis (FEA) appears to be a sensitive technique for detecting structural changes in AD brain tissue.

  11. Sustained and transient language control in the bilingual brain.

    PubMed

    Wang, Yapeng; Kuhl, Patricia K; Chen, Chunhui; Dong, Qi

    2009-08-01

    Bilingual speakers must have effective neural mechanisms to control and manage their two languages, but it is unknown whether bilingual language control includes different control components. Using mixed blocked and event-related designs, the present study explored the sustained and transient neural control of two languages during language processing. 15 Chinese-English bilingual speakers were scanned when they performed language switching tasks. The results showed that, compared to the single language condition, sustained bilingual control (mixed language condition) induced activation in the bilateral inferior frontal, middle prefrontal and frontal gyri (BA 45/46). In contrast, relative to the no switch condition, transient bilingual control (language switching condition) activated the left inferior parietal lobule (BA 2/40), superior parietal lobule (BA 7), and middle frontal gyrus (BA 11/46). Importantly, the right superior parietal activity correlated with the magnitude of the mixing cost, and the left inferior and superior parietal activity covaried with the magnitude of the asymmetric switching costs. These results suggest that sustained and transient language control induced differential lateral activation patterns, and that sustained and transient activities in the human brain modulate the behavioral costs during switching-related language control.

  12. 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

  13. 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

  14. 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.

  15. Abnormal Brain Connectivity Patterns in Adults with ADHD: A Coherence Study

    PubMed Central

    Sato, João Ricardo; Hoexter, Marcelo Queiroz; Castellanos, Xavier Francisco; Rohde, Luis A.

    2012-01-01

    Studies based on functional magnetic resonance imaging (fMRI) during the resting state have shown decreased functional connectivity between the dorsal anterior cingulate cortex (dACC) and regions of the Default Mode Network (DMN) in adult patients with Attention-Deficit/Hyperactivity Disorder (ADHD) relative to subjects with typical development (TD). Most studies used Pearson correlation coefficients among the BOLD signals from different brain regions to quantify functional connectivity. Since the Pearson correlation analysis only provides a limited description of functional connectivity, we investigated functional connectivity between the dACC and the posterior cingulate cortex (PCC) in three groups (adult patients with ADHD, n = 21; TD age-matched subjects, n = 21; young TD subjects, n = 21) using a more comprehensive analytical approach – unsupervised machine learning using a one-class support vector machine (OC-SVM) that quantifies an abnormality index for each individual. The median abnormality index for patients with ADHD was greater than for TD age-matched subjects (p = 0.014); the ADHD and young TD indices did not differ significantly (p = 0.480); the median abnormality index of young TD was greater than that of TD age-matched subjects (p = 0.016). Low frequencies below 0.05 Hz and around 0.20 Hz were the most relevant for discriminating between ADHD patients and TD age-matched controls and between the older and younger TD subjects. In addition, we validated our approach using the fMRI data of children publicly released by the ADHD-200 Competition, obtaining similar results. Our findings suggest that the abnormal coherence patterns observed in patients with ADHD in this study resemble the patterns observed in young typically developing subjects, which reinforces the hypothesis that ADHD is associated with brain maturation deficits. PMID:23049834

  16. VIP+ interneurons control neocortical activity across brain states.

    PubMed

    Jackson, Jesse; Ayzenshtat, Inbal; Karnani, Mahesh M; Yuste, Rafael

    2016-06-01

    GABAergic interneurons are positioned to powerfully influence the dynamics of neural activity, yet the interneuron-mediated circuit mechanisms that control spontaneous and evoked neocortical activity remains elusive. Vasoactive intestinal peptide (VIP+) interneurons are a specialized cell class which synapse specifically on other interneurons, potentially serving to facilitate increases in cortical activity. In this study, using in vivo Ca(2+) imaging, we describe the interaction between local network activity and VIP+ cells and determine their role in modulating neocortical activity in mouse visual cortex. VIP+ cells were active across brain states including locomotion, nonlocomotion, visual stimulation, and under anesthesia. VIP+ activity correlated most clearly with the mean level of population activity of nearby excitatory neurons during all brain states, suggesting VIP+ cells enable high-excitability states in the cortex. The pharmacogenetic blockade of VIP+ cell output reduced network activity during locomotion, nonlocomotion, anesthesia, and visual stimulation, suggesting VIP+ cells exert a state-independent facilitation of neural activity in the cortex. Collectively, our findings demonstrate that VIP+ neurons have a causal role in the generation of high-activity regimes during spontaneous and stimulus evoked neocortical activity. PMID:26961109

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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)

  2. 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.

  3. Alternative splicing of the beta A4 amyloid gene of Alzheimer's disease in cortex of control and Alzheimer's disease patients.

    PubMed

    König, G; Salbaum, J M; Wiestler, O; Lang, W; Schmitt, H P; Masters, C L; Beyreuther, K

    1991-02-01

    An S1 nuclease protection assay was designed to study the splicing pattern of the alternatively spliced beta A4 amyloid gene (APP gene) of Alzheimer's disease (AD). We determined the splicing pattern of the APP gene in fetal, adult, aged adult and AD human cortex. The results suggest that alternative splicing of the APP gene in AD is not significantly different from age-matched controls, but distinct from the developing fetal brain.

  4. 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.

  5. 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

  6. Genes and experience shape brain networks of conscious control.

    PubMed

    Posner, Michael I

    2005-01-01

    One aspect of consciousness involves voluntary control over thoughts and feelings, often called will. Progress in neuroimaging and in sequencing the human genome makes it possible to think about voluntary control in terms of a specific neural network that includes midline and lateral frontal areas. A number of cognitive tasks involving conflict as well as the control of emotions have been shown to activate these brain areas. Studies have traced the development of this network in the ability to regulate cognition and emotion from about 2.5 to 7 years of age. Individual differences in this network have been related to parental reports of the ability of children to regulate their behavior, to delay reward and to develop a conscience. In adolescents these individual differences predict the propensity for antisocial behavior. Differences in specific genes are related to individual efficiency in performance of the network, and by neuroimaging, to the strength of its activation of this network. Future animal studies may make it possible to learn in detail how genes influence the common pattern of development of self-regulation made possible by this network. Moreover, a number of neurological and psychiatric pathologies involving difficulties in awareness and volition show deficits in parts of this network. We are now studying whether specific training experiences can influence the development of this network in 4-year-old children and if so, for whom it is most effective. Voluntary control is also important for the regulation of conscious input from the sensory environment. It seems likely that the same network involved in self-regulation is also crucial for focal attention to the sensory world.

  7. 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

  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. 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

  10. 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…

  11. Raft disorganization leads to reduced plasmin activity in Alzheimer's disease brains.

    PubMed

    Ledesma, Maria Dolores; Abad-Rodriguez, José; Galvan, Cristian; Biondi, Elisa; Navarro, Pilar; Delacourte, Andre; Dingwall, Colin; Dotti, Carlos G

    2003-12-01

    The serine protease plasmin can efficiently degrade amyloid peptide in vitro, and is found at low levels in the hippocampus of patients with Alzheimer's disease (AD). The cause of such paucity remains unknown. We show here that the levels of total brain plasminogen and plasminogen-binding molecules are normal in these brain samples, yet plasminogen membrane binding is greatly reduced. Biochemical analysis reveals that the membranes of these brains have a mild, still significant, cholesterol reduction compared to age-matched controls, and anomalous raft microdomains. This was reflected by the loss of raft-enriched proteins, including plasminogen-binding and -activating molecules. Using hippocampal neurons in culture, we demonstrate that removal of a similar amount of membrane cholesterol is sufficient to induce raft disorganization, leading to reduced plasminogen membrane binding and low plasmin activity. These results suggest that brain raft alterations may contribute to AD by rendering the plasminogen system inefficient.

  12. PAN-811 inhibits oxidative stress-induced cell death of human Alzheimer's disease-derived and age-matched olfactory neuroepithelial cells via suppression of intracellular reactive oxygen species.

    PubMed

    Nelson, Valery M; Dancik, Chantée M; Pan, Weiying; Jiang, Zhi-Gang; Lebowitz, Michael S; Ghanbari, Hossein A

    2009-01-01

    Oxidative stress plays a significant role in neurotoxicity associated with a variety of neurodegenerative diseases including Alzheimer's disease (AD). Increased oxidative stress has been shown to be a prominent and early feature of vulnerable neurons in AD. Olfactory neuroepithelial cells are affected at an early stage. Exposure to oxidative stress induces the accumulation of intracellular reactive oxygen species (ROS), which in turn causes cell damage in the form of protein, lipid, and DNA oxidations. Elevated ROS levels are also associated with increased deposition of amyloid-beta and formation of senile plaques, a hallmark of the AD brain. If enhanced ROS exceeds the basal level of cellular protective mechanisms, oxidative damage and cell death will result. Therefore, substances that can reduce oxidative stress are sought as potential drug candidates for treatment or preventative therapy of neurodegenerative diseases such as AD. PAN-811, also known as 3-aminopyridine-2-carboxaldehyde thiosemicarbazone or Triapine, is a small lipophilic compound that is currently being investigated in several Phase II clinical trials for cancer therapy due to its inhibition of ribonucleotide reductase activity. Here we show PAN-811 to be effective in preventing or reducing ROS accumulation and the resulting oxidative damages in both AD-derived and age-matched olfactory neuroepithelial cells.

  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. Epigenetic control of gene expression in the alcoholic brain.

    PubMed

    Ponomarev, Igor

    2013-01-01

    Chronic alcohol exposure causes widespread changes in brain gene expression in humans and animal models. Many of these contribute to cellular adaptations that ultimately lead to behavioral tolerance and alcohol dependence. There is an emerging appreciation for the role of epigenetic processes in alcohol-induced changes in brain gene expression and behavior. For example, chronic alcohol exposure produces changes in DNA and histone methylation, histone acetylation, and microRNA expression that affect expression of multiple genes in various types of brain cells (i.e., neurons and glia) and contribute to brain pathology and brain plasticity associated with alcohol abuse and dependence. Drugs targeting the epigenetic "master regulators" are emerging as potential therapeutics for neurodegenerative disorders and drug addiction.

  16. Epigenetic Control of Gene Expression in the Alcoholic Brain

    PubMed Central

    Ponomarev, Igor

    2013-01-01

    Chronic alcohol exposure causes widespread changes in brain gene expression in humans and animal models. Many of these contribute to cellular adaptations that ultimately lead to behavioral tolerance and alcohol dependence. There is an emerging appreciation for the role of epigenetic processes in alcohol-induced changes in brain gene expression and behavior. For example, chronic alcohol exposure produces changes in DNA and histone methylation, histone acetylation, and microRNA expression that affect expression of multiple genes in various types of brain cells (i.e., neurons and glia) and contribute to brain pathology and brain plasticity associated with alcohol abuse and dependence. Drugs targeting the epigenetic “master regulators” are emerging as potential therapeutics for neurodegenerative disorders and drug addiction. PMID:24313166

  17. Bilingual language control: an event-related brain potential study.

    PubMed

    Christoffels, Ingrid K; Firk, Christine; Schiller, Niels O

    2007-05-25

    This study addressed how bilingual speakers switch between their first and second language when speaking. Event-related brain potentials (ERPs) and naming latencies were measured while unbalanced German (L1)-Dutch (L2) speakers performed a picture-naming task. Participants named pictures either in their L1 or in their L2 (blocked language conditions), or participants switched between their first and second language unpredictably (mixed language condition). Furthermore, form similarity between translation equivalents (cognate status) was manipulated. A cognate facilitation effect was found for L1 and L2 indicating phonological activation of the non-response language in blocked and mixed language conditions. The ERP data also revealed small but reliable effects of cognate status. Language switching resulted in equal switching costs for both languages and was associated with a modulation in the ERP waveforms (time windows 275-375 ms and 375-475 ms). Mixed language context affected especially the L1, both in ERPs and in latencies, which became slower in L1 than L2. It is suggested that sustained and transient components of language control should be distinguished. Results are discussed in relation to current theories of bilingual language processing.

  18. Mildly Reduced Brain Swelling and Improved Neurological Outcome in Aquaporin-4 Knockout Mice following Controlled Cortical Impact Brain Injury

    PubMed Central

    Uchida, Kazuyoshi; Papadopoulos, Marios C.; Zador, Zsolt; Manley, Geoffrey T.; Verkman, Alan S.

    2015-01-01

    Abstract Brain edema following traumatic brain injury (TBI) is associated with considerable morbidity and mortality. Prior indirect evidence has suggested the involvement of astrocyte water channel aquaporin-4 (AQP4) in the pathogenesis of TBI. Here, focal TBI was produced in wild type (AQP4+/+) and knockout (AQP4−/−) mice by controlled cortical impact injury (CCI) following craniotomy with dura intact (parameters: velocity 4.5 m/sec, depth 1.7 mm, dwell time 150 msec). AQP4-deficient mice showed a small but significant reduction in injury volume in the first week after CCI, with a small improvement in neurological outcome. Mechanistic studies showed reduced intracranial pressure at 6 h after CCI in AQP4−/− mice, compared with AQP4+/+ control mice (11 vs. 19 mm Hg), with reduced local brain water accumulation as assessed gravimetrically. Transmission electron microscopy showed reduced astrocyte foot-process area in AQP4−/− mice at 24 h after CCI, with greater capillary lumen area. Blood–brain barrier disruption assessed by Evans blue dye extravasation was similar in AQP4+/+ and AQP4−/− mice. We conclude that the mildly improved outcome in AQP4−/− mice following CCI results from reduced cytotoxic brain water accumulation, though concurrent cytotoxic and vasogenic mechanisms in TBI make the differences small compared to those seen in disorders where cytotoxic edema predominates. PMID:25790314

  19. Increased Brain Fatty Acid Uptake in Metabolic Syndrome

    PubMed Central

    Karmi, Anna; Iozzo, Patricia; Viljanen, Antti; Hirvonen, Jussi; Fielding, Barbara A.; Virtanen, Kirsi; Oikonen, Vesa; Kemppainen, Jukka; Viljanen, Tapio; Guiducci, Letizia; Haaparanta-Solin, Merja; Någren, Kjell; Solin, Olof; Nuutila, Pirjo

    2010-01-01

    OBJECTIVE To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it. RESEARCH DESIGN AND METHODS We measured brain fatty acid uptake in a group of 23 patients with MS and 7 age-matched healthy control subjects during fasting conditions using positron emission tomography (PET) with [11C]-palmitate and [18F]fluoro-6-thia-heptadecanoic acid ([18F]-FTHA). Sixteen MS subjects were restudied after 6 weeks of very low calorie diet intervention. RESULTS At baseline, brain global fatty acid uptake derived from [18F]-FTHA was 50% higher in patients with MS compared with control subjects. The mean percentage increment was 130% in the white matter, 47% in the gray matter, and uniform across brain regions. In the MS group, the nonoxidized fraction measured using [11C]-palmitate was 86% higher. Brain fatty acid uptake measured with [18F]-FTHA-PET was associated with age, fasting serum insulin, and homeostasis model assessment (HOMA) index. Both total and nonoxidized fractions of fatty acid uptake were associated with BMI. Rapid weight reduction decreased brain fatty acid uptake by 17%. CONCLUSIONS To our knowledge, this is the first study on humans to observe enhanced brain fatty acid uptake in patients with MS. Both fatty acid uptake and accumulation appear to be increased in MS patients and reversed by weight reduction. PMID:20566663

  20. 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

  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

    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. 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

  4. Brain connectivity and postural control in young traumatic brain injury patients: A diffusion MRI based network analysis☆☆☆

    PubMed Central

    Caeyenberghs, K.; Leemans, A.; De Decker, C.; Heitger, M.; Drijkoningen, D.; Linden, C. Vander; Sunaert, S.; Swinnen, S.P.

    2012-01-01

    Our previous research on traumatic brain injury (TBI) patients has shown a strong relationship between specific white matter (WM) diffusion properties and motor deficits. The potential impact of TBI-related changes in network organization of the associated WM structural network on motor performance, however, remains largely unknown. Here, we used diffusion tensor imaging (DTI) based fiber tractography to reconstruct the human brain WM networks of 12 TBI and 17 control participants, followed by a graph theoretical analysis. A force platform was used to measure changes in body posture under conditions of compromised proprioceptive and/or visual feedback. Findings revealed that compared with controls, TBI patients showed higher betweenness centrality and normalized path length, and lower values of local efficiency, implying altered network organization. These results were not merely a consequence of differences in number of connections. In particular, TBI patients displayed reduced structural connectivity in frontal, parieto-premotor, visual, subcortical, and temporal areas. In addition, the decreased connectivity degree was significantly associated with poorer balance performance. We conclude that analyzing the structural brain networks with a graph theoretical approach provides new insights into motor control deficits following brain injury. PMID:24179743

  5. 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…

  6. Spatial heterogeneity analysis of brain activation in fMRI

    PubMed Central

    Gupta, Lalit; Besseling, René M.H.; Overvliet, Geke M.; Hofman, Paul A.M.; de Louw, Anton; Vaessen, Maarten J.; Aldenkamp, Albert P.; Ulman, Shrutin; Jansen, Jacobus F.A.; Backes, Walter H.

    2014-01-01

    In many brain diseases it can be qualitatively observed that spatial patterns in blood oxygenation level dependent (BOLD) activation maps appear more (diffusively) distributed than in healthy controls. However, measures that can quantitatively characterize this spatial distributiveness in individual subjects are lacking. In this study, we propose a number of spatial heterogeneity measures to characterize brain activation maps. The proposed methods focus on different aspects of heterogeneity, including the shape (compactness), complexity in the distribution of activated regions (fractal dimension and co-occurrence matrix), and gappiness between activated regions (lacunarity). To this end, functional MRI derived activation maps of a language and a motor task were obtained in language impaired children with (Rolandic) epilepsy and compared to age-matched healthy controls. Group analysis of the activation maps revealed no significant differences between patients and controls for both tasks. However, for the language task the activation maps in patients appeared more heterogeneous than in controls. Lacunarity was the best measure to discriminate activation patterns of patients from controls (sensitivity 74%, specificity 70%) and illustrates the increased irregularity of gaps between activated regions in patients. The combination of heterogeneity measures and a support vector machine approach yielded further increase in sensitivity and specificity to 78% and 80%, respectively. This illustrates that activation distributions in impaired brains can be complex and more heterogeneous than in normal brains and cannot be captured fully by a single quantity. In conclusion, heterogeneity analysis has potential to robustly characterize the increased distributiveness of brain activation in individual patients. PMID:25161893

  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. Brain modularity controls the critical behavior of spontaneous activity

    NASA Astrophysics Data System (ADS)

    Russo, R.; Herrmann, H. J.; de Arcangelis, L.

    2014-03-01

    The human brain exhibits a complex structure made of scale-free highly connected modules loosely interconnected by weaker links to form a small-world network. These features appear in healthy patients whereas neurological diseases often modify this structure. An important open question concerns the role of brain modularity in sustaining the critical behaviour of spontaneous activity. Here we analyse the neuronal activity of a model, successful in reproducing on non-modular networks the scaling behaviour observed in experimental data, on a modular network implementing the main statistical features measured in human brain. We show that on a modular network, regardless the strength of the synaptic connections or the modular size and number, activity is never fully scale-free. Neuronal avalanches can invade different modules which results in an activity depression, hindering further avalanche propagation. Critical behaviour is solely recovered if inter-module connections are added, modifying the modular into a more random structure.

  9. 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

  10. 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.

  11. Cannabinoid control of brain bioenergetics: Exploring the subcellular localization of the CB1 receptor.

    PubMed

    Hebert-Chatelain, Etienne; Reguero, Leire; Puente, Nagore; Lutz, Beat; Chaouloff, Francis; Rossignol, Rodrigue; Piazza, Pier-Vincenzo; Benard, Giovanni; Grandes, Pedro; Marsicano, Giovanni

    2014-07-01

    Brain mitochondrial activity is centrally involved in the central control of energy balance. When studying mitochondrial functions in the brain, however, discrepant results might be obtained, depending on the experimental approaches. For instance, immunostaining experiments and biochemical isolation of organelles expose investigators to risks of false positive and/or false negative results. As an example, the functional presence of cannabinoid type 1 (CB1) receptors on brain mitochondrial membranes (mtCB1) was recently reported and rapidly challenged, claiming that the original observation was likely due to artifact results. Here, we addressed this issue by directly comparing the procedures used in the two studies. Our results show that the use of appropriate controls and quantifications allows detecting mtCB1 receptor with CB1 receptor antibodies, and that, if mitochondrial fractions are enriched and purified, CB1 receptor agonists reliably decrease respiration in brain mitochondria. These data further underline the importance of adapted experimental procedures to study brain mitochondrial functions.

  12. 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…

  13. 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

  14. [The blood-brain barrier transport mechanism controlling analgesic effects of opioid drugs in CNS].

    PubMed

    Okura, Takashi; Higuchi, Kei; Deguchi, Yoshiharu

    2015-01-01

    The transport of opioid analgesics across the blood-brain barrier (BBB) is an important determinant of their therapeutic effects. The human brain is protected by the BBB, which consists of brain capillary endothelial cells linked with tight junctions. It is well established that the polarized expression of numerous transporters and receptors at the brain capillary endothelial cells controls the blood-brain exchange of nutrients, waste products deriving from neurotransmitter substances, and drugs. Morphine is a substrate of P-glycoprotein and the P-glycoprotein-mediated efflux transport at the BBB maintains a lower unbound concentration of morphine in the brain compared with plasma. On the other hand, oxycodone has 3 times higher unbound concentration in the brain than plasma, suggesting an active transport mechanism of oxycodone across the BBB into the brain. In vitro transport study using BBB model cells showed that oxycodone is efficiently transported by a proton-coupled organic cation antiporter. Human BBB model cells also retain the proton-coupled organic cation antiporter. Although adjuvant analgesics include many cationic drugs that interact with oxycodone transport across the BBB at relatively high concentrations, these drugs would enhance the antinociceptive effects of oxycodone with little effect on oxycodone pharmacokinetics, including brain distribution at therapeutically or pharmacologically relevant concentrations. These findings support the idea that proton-coupled organic cation antiporter-mediated transport of oxycodone at the BBB plays a role in determining the therapeutic efficacy of this opioid analgesic drug.

  15. Brain oxygen tension controls the expansion of outer subventricular zone-like basal progenitors in the developing mouse brain.

    PubMed

    Wagenführ, Lisa; Meyer, Anne K; Braunschweig, Lena; Marrone, Lara; Storch, Alexander

    2015-09-01

    The mammalian neocortex shows a conserved six-layered structure that differs between species in the total number of cortical neurons produced owing to differences in the relative abundance of distinct progenitor populations. Recent studies have identified a new class of proliferative neurogenic cells in the outer subventricular zone (OSVZ) in gyrencephalic species such as primates and ferrets. Lissencephalic brains of mice possess fewer OSVZ-like progenitor cells and these do not constitute a distinct layer. Most in vitro and in vivo studies have shown that oxygen regulates the maintenance, proliferation and differentiation of neural progenitor cells. Here we dissect the effects of fetal brain oxygen tension on neural progenitor cell activity using a novel mouse model that allows oxygen tension to be controlled within the hypoxic microenvironment in the neurogenic niche of the fetal brain in vivo. Indeed, maternal oxygen treatment of 10%, 21% and 75% atmospheric oxygen tension for 48 h translates into robust changes in fetal brain oxygenation. Increased oxygen tension in fetal mouse forebrain in vivo leads to a marked expansion of a distinct proliferative cell population, basal to the SVZ. These cells constitute a novel neurogenic cell layer, similar to the OSVZ, and contribute to corticogenesis by heading for deeper cortical layers as a part of the cortical plate.

  16. 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

  17. Control of brain development, function, and behavior by the microbiome.

    PubMed

    Sampson, Timothy R; Mazmanian, Sarkis K

    2015-05-13

    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.

  18. 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

  19. 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

  20. 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

  1. 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

  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

    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

    2015-04-01

    Brain tumor initiating cells (BTICs) co-opt the neuronal high affinity glucose transporter, GLUT3, to withstand metabolic stress. We investigated another mechanism critical to brain metabolism, mitochondrial morphology, in BTICs. BTIC mitochondria were fragmented relative to non-BTIC tumor cell mitochondria, suggesting that BTICs increase mitochondrial fission. The essential mediator of mitochondrial fission, dynamin-related protein 1 (DRP1), showed activating phosphorylation in BTICs and inhibitory phosphorylation in non-BTIC tumor cells. 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 targeting AMPK rescued the effects of DRP1 disruption. Cyclin-dependent kinase 5 (CDK5) phosphorylated DRP1 to increase its activity in BTICs, whereas Ca(2+)-calmodulin-dependent protein kinase 2 (CAMK2) inhibited DRP1 in non-BTIC tumor cells, suggesting that tumor cell differentiation induces a regulatory switch in mitochondrial morphology. DRP1 activation correlated with poor prognosis in glioblastoma, suggesting that mitochondrial dynamics may represent a therapeutic target for BTICs. PMID:25730670

  4. 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

  5. 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.

  6. 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

  7. 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

  8. Genome-wide assessment of post-transcriptional control in the fly brain.

    PubMed

    Mezan, Shaul; Ashwal-Fluss, Reut; Shenhav, Rom; Garber, Manuel; Kadener, Sebastian

    2013-01-01

    Post-transcriptional control of gene expression has central importance during development and adulthood and in physiology in general. However, little is known about the extent of post-transcriptional control of gene expression in the brain. Most post-transcriptional regulatory effectors (e.g., miRNAs) destabilize target mRNAs by shortening their polyA tails. Hence, the fraction of a given mRNA that it is fully polyadenylated should correlate with its stability and serves as a good measure of post-transcriptional control. Here, we compared RNA-seq datasets from fly brains that were generated either from total (rRNA-depleted) or polyA-selected RNA. By doing this comparison we were able to compute a coefficient that measures the extent of post-transcriptional control for each brain-expressed mRNA. In agreement with current knowledge, we found that mRNAs encoding ribosomal proteins, metabolic enzymes, and housekeeping genes are among the transcripts with least post-transcriptional control, whereas mRNAs that are known to be highly unstable, like circadian mRNAs and mRNAs expressing synaptic proteins and proteins with neuronal functions, are under strong post-transcriptional control. Surprisingly, the latter group included many specific groups of genes relevant to brain function and behavior. In order to determine the importance of miRNAs in this regulation, we profiled miRNAs from fly brains using oligonucleotide microarrays. Surprisingly, we did not find a strong correlation between the expression levels of miRNAs in the brain and the stability of their target mRNAs; however, genes identified as highly regulated post-transcriptionally were strongly enriched for miRNA targets. This demonstrates a central role of miRNAs for modulating the levels and turnover of brain-specific mRNAs in the fly. PMID:24367289

  9. 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

  10. 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…

  11. 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.

  12. 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

  13. 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

  14. Granulovacuolar degeneration in the ageing brain and in dementia.

    PubMed

    Ball, M J; Lo, P

    1977-05-01

    Quantitative morphometry with a sampling stage light microscope was performed to determine the severity of granulovacuolar degeneration of hippocampal neurones in serially sectioned temporal lobe from mentally normal subjects of different ages and from demented patients. The degree of granulovacuolar change in control brains increased slightly with increasing age; the "granulovacuolar index" of cases with Alzheimer's disease exceeded by many times that of age-matched controls. This significant difference was demonstrable whether the granulovacuolar severity was expressed as number of affected cells per volume of cortex analysed, or as the percentage involvement of total neurones counted in the hippocampus. The posterior half of each dement's hippocampus was found to be more susceptible to this augmented granulovacuolar degeneration than the anterior half, a selectivity already observed for neurofibrillary tangel formation in the same material.

  15. 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

  16. 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

  17. Toward brain-actuated car applications: Self-paced control with a motor imagery-based brain-computer interface.

    PubMed

    Yu, Yang; Zhou, Zongtan; Yin, Erwei; Jiang, Jun; Tang, Jingsheng; Liu, Yadong; Hu, Dewen

    2016-10-01

    This study presented a paradigm for controlling a car using an asynchronous electroencephalogram (EEG)-based brain-computer interface (BCI) and presented the experimental results of a simulation performed in an experimental environment outside the laboratory. This paradigm uses two distinct MI tasks, imaginary left- and right-hand movements, to generate a multi-task car control strategy consisting of starting the engine, moving forward, turning left, turning right, moving backward, and stopping the engine. Five healthy subjects participated in the online car control experiment, and all successfully controlled the car by following a previously outlined route. Subject S1 exhibited the most satisfactory BCI-based performance, which was comparable to the manual control-based performance. We hypothesize that the proposed self-paced car control paradigm based on EEG signals could potentially be used in car control applications, and we provide a complementary or alternative way for individuals with locked-in disorders to achieve more mobility in the future, as well as providing a supplementary car-driving strategy to assist healthy people in driving a car.

  18. Toward brain-actuated car applications: Self-paced control with a motor imagery-based brain-computer interface.

    PubMed

    Yu, Yang; Zhou, Zongtan; Yin, Erwei; Jiang, Jun; Tang, Jingsheng; Liu, Yadong; Hu, Dewen

    2016-10-01

    This study presented a paradigm for controlling a car using an asynchronous electroencephalogram (EEG)-based brain-computer interface (BCI) and presented the experimental results of a simulation performed in an experimental environment outside the laboratory. This paradigm uses two distinct MI tasks, imaginary left- and right-hand movements, to generate a multi-task car control strategy consisting of starting the engine, moving forward, turning left, turning right, moving backward, and stopping the engine. Five healthy subjects participated in the online car control experiment, and all successfully controlled the car by following a previously outlined route. Subject S1 exhibited the most satisfactory BCI-based performance, which was comparable to the manual control-based performance. We hypothesize that the proposed self-paced car control paradigm based on EEG signals could potentially be used in car control applications, and we provide a complementary or alternative way for individuals with locked-in disorders to achieve more mobility in the future, as well as providing a supplementary car-driving strategy to assist healthy people in driving a car. PMID:27544071

  19. Automatic Incubator-type Temperature Control System for Brain Hypothermia Treatment

    NASA Astrophysics Data System (ADS)

    Gaohua, Lu; Wakamatsu, Hidetoshi

    An automatic air-cooling incubator is proposed to replace the manual water-cooling blanket to control the brain tissue temperature for brain hypothermia treatment. Its feasibility is theoretically discussed as follows: First, an adult patient with the cooling incubator is modeled as a linear dynamical patient-incubator biothermal system. The patient is represented by an 18-compartment structure and described by its state equations. The air-cooling incubator provides almost same cooling effect as the water-cooling blanket, if a light breeze of speed around 3 m/s is circulated in the incubator. Then, in order to control the brain temperature automatically, an adaptive-optimal control algorithm is adopted, while the patient-blanket therapeutic system is considered as a reference model. Finally, the brain temperature of the patient-incubator biothermal system is controlled to follow up the given reference temperature course, in which an adaptive algorithm is confirmed useful for unknown environmental change and/or metabolic rate change of the patient in the incubating system. Thus, the present work ensures the development of the automatic air-cooling incubator for a better temperature regulation of the brain hypothermia treatment in ICU.

  20. Clinical usefulness of brain-computer interface-controlled functional electrical stimulation for improving brain activity in children with spastic cerebral palsy: a pilot randomized controlled trial

    PubMed Central

    Kim, Tae-Woo; Lee, Byoung-Hee

    2016-01-01

    [Purpose] Evaluating the effect of brain-computer interface (BCI)-based functional electrical stimulation (FES) training on brain activity in children with spastic cerebral palsy (CP) was the aim of this study. [Subjects and Methods] Subjects were randomized into a BCI-FES group (n=9) and a functional electrical stimulation (FES) control group (n=9). Subjects in the BCI-FES group received wrist and hand extension training with FES for 30 minutes per day, 5 times per week for 6 weeks under the BCI-based program. The FES group received wrist and hand extension training with FES for the same amount of time. Sensorimotor rhythms (SMR) and middle beta waves (M-beta) were measured in frontopolar regions 1 and 2 (Fp1, Fp2) to determine the effects of BCI-FES training. [Results] Significant improvements in the SMR and M-beta of Fp1 and Fp2 were seen in the BCI-FES group. In contrast, significant improvement was only seen in the SMR and M-beta of Fp2 in the control group. [Conclusion] The results of the present study suggest that BCI-controlled FES training may be helpful in improving brain activity in patients with cerebral palsy and may be applied as effectively as traditional FES training. PMID:27799677

  1. The Brain Renin-Angiotensin System Controls Divergent Efferent Mechanisms to Regulate Fluid and Energy Balance

    PubMed Central

    Grobe, Justin L.; Grobe, Connie L.; Beltz, Terry G.; Westphal, Scott G.; Morgan, Donald A.; Xu, Di; de Lange, Willem J.; Li, Huiping; Sakai, Koji; Thedens, Daniel R.; Cassis, Lisa A.; Rahmouni, Kamal; Mark, Allyn L.; Johnson, Alan Kim; Sigmund, Curt D.

    2010-01-01

    Summary The renin-angiotensin system (RAS), in addition to its endocrine functions, plays a role within individual tissues such as the brain. The brain RAS is thought to control blood pressure through effects on fluid intake, vasopressin release and sympathetic nerve activity (SNA), and may regulate metabolism through mechanisms which remain undefined. We used a double-transgenic mouse model that exhibits brain-specific RAS activity to examine mechanisms contributing to fluid and energy homeostasis. The mice exhibit high fluid turnover through increased adrenal steroids, which is corrected by adrenalectomy and attenuated by mineralocorticoid receptor blockade. They are also hyperphagic but lean because of a marked increase in body temperature and metabolic rate, mediated by increased SNA and suppression of the circulating RAS. β-adrenergic blockade or restoration of circulating angiotensin-II, but not adrenalectomy, normalized metabolic rate. Our data point to contrasting mechanisms by which the brain RAS regulates fluid intake and energy expenditure. PMID:21035755

  2. Towards brain-activity-controlled information retrieval: Decoding image relevance from MEG signals.

    PubMed

    Kauppi, Jukka-Pekka; Kandemir, Melih; Saarinen, Veli-Matti; Hirvenkari, Lotta; Parkkonen, Lauri; Klami, Arto; Hari, Riitta; Kaski, Samuel

    2015-05-15

    We hypothesize that brain activity can be used to control future information retrieval systems. To this end, we conducted a feasibility study on predicting the relevance of visual objects from brain activity. We analyze both magnetoencephalographic (MEG) and gaze signals from nine subjects who were viewing image collages, a subset of which was relevant to a predetermined task. We report three findings: i) the relevance of an image a subject looks at can be decoded from MEG signals with performance significantly better than chance, ii) fusion of gaze-based and MEG-based classifiers significantly improves the prediction performance compared to using either signal alone, and iii) non-linear classification of the MEG signals using Gaussian process classifiers outperforms linear classification. These findings break new ground for building brain-activity-based interactive image retrieval systems, as well as for systems utilizing feedback both from brain activity and eye movements.

  3. Differential impact of thalamic versus subthalamic deep brain stimulation on lexical processing.

    PubMed

    Krugel, Lea K; Ehlen, Felicitas; Tiedt, Hannes O; Kühn, Andrea A; Klostermann, Fabian

    2014-10-01

    Roles of subcortical structures in language processing are vague, but, interestingly, basal ganglia and thalamic Deep Brain Stimulation can go along with reduced lexical capacities. To deepen the understanding of this impact, we assessed word processing as a function of thalamic versus subthalamic Deep Brain Stimulation. Ten essential tremor patients treated with thalamic and 14 Parkinson׳s disease patients with subthalamic Deep Brain Stimulation performed an acoustic Lexical Decision Task ON and OFF stimulation. Combined analysis of task performance and event-related potentials allowed the determination of processing speed, priming effects, and N400 as neurophysiological correlate of lexical stimulus processing. 12 age-matched healthy participants acted as control subjects. Thalamic Deep Brain Stimulation prolonged word decisions and reduced N400 potentials. No comparable ON-OFF effects were present in patients with subthalamic Deep Brain Stimulation. In the latter group of patients with Parkinson' disease, N400 amplitudes were, however, abnormally low, whether under active or inactive Deep Brain Stimulation. In conclusion, performance speed and N400 appear to be influenced by state functions, modulated by thalamic, but not subthalamic Deep Brain Stimulation, compatible with concepts of thalamo-cortical engagement in word processing. Clinically, these findings specify cognitive sequels of Deep Brain Stimulation in a target-specific way. PMID:25194209

  4. 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

  5. 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

  6. The Gut's Little Brain in Control of Intestinal Immunity

    PubMed Central

    de Jonge, Wouter J.

    2013-01-01

    The gut immune system shares many mediators and receptors with the autonomic nervous system. Good examples thereof are the parasympathetic (vagal) and sympathetic neurotransmitters, for which many immune cell types in a gut context express receptors or enzymes required for their synthesis. For some of these the relevance for immune regulation has been recently defined. Earlier and more recent studies in neuroscience and immunology have indicated the anatomical and cellular basis for bidirectional interactions between the nervous and immune systems. Sympathetic immune modulation is well described earlier, and in the last decade the parasympathetic vagal nerve has been put forward as an integral part of an immune regulation network via its release of Ach, a system coined “the cholinergic anti-inflammatory reflex.” A prototypical example is the inflammatory reflex, comprised of an afferent arm that senses inflammation and an efferent arm: the cholinergic anti-inflammatory pathway, that inhibits innate immune responses. In this paper, the current understanding of how innate mucosal immunity can be influenced by the neuronal system is summarized, and cell types and receptors involved in this interaction will be highlighted. Focus will be given on the direct neuronal regulatory mechanisms, as well as current advances regarding the role of microbes in modulating communication in the gut-brain axis. PMID:23691339

  7. 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.

  8. 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

  9. Electroencephalography(EEG)-based instinctive brain-control of a quadruped locomotion robot.

    PubMed

    Jia, Wenchuan; Huang, Dandan; Luo, Xin; Pu, Huayan; Chen, Xuedong; Bai, Ou

    2012-01-01

    Artificial intelligence and bionic control have been applied in electroencephalography (EEG)-based robot system, to execute complex brain-control task. Nevertheless, due to technical limitations of the EEG decoding, the brain-computer interface (BCI) protocol is often complex, and the mapping between the EEG signal and the practical instructions lack of logic associated, which restrict the user's actual use. This paper presents a strategy that can be used to control a quadruped locomotion robot by user's instinctive action, based on five kinds of movement related neurophysiological signal. In actual use, the user drives or imagines the limbs/wrists action to generate EEG signal to adjust the real movement of the robot according to his/her own motor reflex of the robot locomotion. This method is easy for real use, as the user generates the brain-control signal through the instinctive reaction. By adopting the behavioral control of learning and evolution based on the proposed strategy, complex movement task may be realized by instinctive brain-control.

  10. Brain activity in predictive sensorimotor control for landings: an EEG pilot study.

    PubMed

    Baumeister, J; von Detten, S; van Niekerk, S-M; Schubert, M; Ageberg, E; Louw, Q A

    2013-12-01

    Landing from a jump is related to predictive sensorimotor control. Frontal, central and parietal brain areas are known to play a role in this process based on online sensory feedback. This can be measured by EEG. However, there is only limited knowledge about brain activity during predictive preparation for drop landings (DL). The purpose is to demonstrate changes in brain activity in preparation for DL in different conditions. After resting, 10 athletes performed a series of DLs and were asked to concentrate on the landing preparation for 10 s before an auditory signal required them to drop land from a 30 cm platform. This task was executed before and after a standardized fatigue protocol. EEG spectral power was calculated during DL preparation. Frontal Theta power was increased during preparation compared to rest. Parietal Alpha-2 power demonstrated higher values in preparation after fatigue condition while lower limb kinematics remained unchanged. Cortical activity in frontal and parietal brain areas is sensitive for predictive sensorimotor control of drop landings. Frontal Theta power demonstrates an increase and is related to higher attentional control. In a fatigued condition the parietal Alpha-2 power increase might be related to a deactivation in the somatosensory brain areas. PMID:23740338

  11. 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.

  12. 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

  13. Brain activity in predictive sensorimotor control for landings: an EEG pilot study.

    PubMed

    Baumeister, J; von Detten, S; van Niekerk, S-M; Schubert, M; Ageberg, E; Louw, Q A

    2013-12-01

    Landing from a jump is related to predictive sensorimotor control. Frontal, central and parietal brain areas are known to play a role in this process based on online sensory feedback. This can be measured by EEG. However, there is only limited knowledge about brain activity during predictive preparation for drop landings (DL). The purpose is to demonstrate changes in brain activity in preparation for DL in different conditions. After resting, 10 athletes performed a series of DLs and were asked to concentrate on the landing preparation for 10 s before an auditory signal required them to drop land from a 30 cm platform. This task was executed before and after a standardized fatigue protocol. EEG spectral power was calculated during DL preparation. Frontal Theta power was increased during preparation compared to rest. Parietal Alpha-2 power demonstrated higher values in preparation after fatigue condition while lower limb kinematics remained unchanged. Cortical activity in frontal and parietal brain areas is sensitive for predictive sensorimotor control of drop landings. Frontal Theta power demonstrates an increase and is related to higher attentional control. In a fatigued condition the parietal Alpha-2 power increase might be related to a deactivation in the somatosensory brain areas.

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. Brain stimulation reveals crucial role of overcoming self-centeredness in self-control

    PubMed Central

    Soutschek, Alexander; Ruff, Christian C.; Strombach, Tina; Kalenscher, Tobias; Tobler, Philippe N.

    2016-01-01

    Neurobiological models of self-control predominantly focus on the role of prefrontal brain mechanisms involved in emotion regulation and impulse control. We provide evidence for an entirely different neural mechanism that promotes self-control by overcoming bias for the present self, a mechanism previously thought to be mainly important for interpersonal decision-making. In two separate studies, we show that disruptive transcranial magnetic stimulation (TMS) of the temporo-parietal junction—a brain region involved in overcoming one’s self-centered perspective—increases the discounting of delayed and prosocial rewards. This effect of TMS on temporal and social discounting is accompanied by deficits in perspective-taking and does not reflect altered spatial reorienting and number recognition. Our findings substantiate a fundamental commonality between the domains of self-control and social decision-making and highlight a novel aspect of the neurocognitive processes involved in self-control. PMID:27774513

  1. Expression of Phenotypic Astrocyte Marker Is Increased in a Transgenic Mouse Model of Alzheimer's Disease versus Age-Matched Controls: A Presymptomatic Stage Study

    PubMed Central

    Doméné, Aurélie; Cavanagh, Chelsea; Page, Guylène; Bodard, Sylvie; Klein, Christophe; Delarasse, Cécile; Chalon, Sylvie

    2016-01-01

    Recent mouse studies of the presymptomatic stage of Alzheimer's disease (AD) have suggested that proinflammatory changes, such as glial activation and cytokine induction, may occur already at this early stage through unknown mechanisms. Because TNFα contributes to increased Aβ production from the Aβ precursor protein (APP), we assessed a putative correlation between APP/Aβ and TNFα during the presymptomatic stage as well as early astrocyte activation in the hippocampus of 3-month-old APPswe/PS1dE9 mice. While Western blots revealed significant APP expression, Aβ was not detectable by Western blot or ELISA attesting that 3-month-old, APPswe/PS1dE9 mice are at a presymptomatic stage of AD-like pathology. Western blots were also used to show increased GFAP expression in transgenic mice that positively correlated with both TNFα and APP, which were also mutually correlated. Subregional immunohistochemical quantification of phenotypic (GFAP) and functional (TSPO) markers of astrocyte activation indicated a selective and significant increase in GFAP-immunoreactive (IR) cells in the dentate gyrus of APPswe/PS1dE9 mice. Our data suggest that subtle morphological and phenotypic alterations, compatible with the engagement of astrocyte along the activation pathway, occur in the hippocampus already at the presymptomatic stage of AD. PMID:27672476

  2. Comparing the PPAT Drawings of Boys with AD/HD and Age-Matched Controls Using the Formal Elements Art Therapy Scale.

    ERIC Educational Resources Information Center

    Munley, Maripat

    2002-01-01

    Explores whether children with AD/HD respond differently to a specific art directive. Using the Formal Elements Art Therapy Scale to evaluate the drawings, results indicate three elements that would most accurately predict the artists into the AD/HD group: color prominence, details of objects and environments, and line quality. (Contains 29…

  3. 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…

  4. Expression of Phenotypic Astrocyte Marker Is Increased in a Transgenic Mouse Model of Alzheimer's Disease versus Age-Matched Controls: A Presymptomatic Stage Study

    PubMed Central

    Doméné, Aurélie; Cavanagh, Chelsea; Page, Guylène; Bodard, Sylvie; Klein, Christophe; Delarasse, Cécile; Chalon, Sylvie

    2016-01-01

    Recent mouse studies of the presymptomatic stage of Alzheimer's disease (AD) have suggested that proinflammatory changes, such as glial activation and cytokine induction, may occur already at this early stage through unknown mechanisms. Because TNFα contributes to increased Aβ production from the Aβ precursor protein (APP), we assessed a putative correlation between APP/Aβ and TNFα during the presymptomatic stage as well as early astrocyte activation in the hippocampus of 3-month-old APPswe/PS1dE9 mice. While Western blots revealed significant APP expression, Aβ was not detectable by Western blot or ELISA attesting that 3-month-old, APPswe/PS1dE9 mice are at a presymptomatic stage of AD-like pathology. Western blots were also used to show increased GFAP expression in transgenic mice that positively correlated with both TNFα and APP, which were also mutually correlated. Subregional immunohistochemical quantification of phenotypic (GFAP) and functional (TSPO) markers of astrocyte activation indicated a selective and significant increase in GFAP-immunoreactive (IR) cells in the dentate gyrus of APPswe/PS1dE9 mice. Our data suggest that subtle morphological and phenotypic alterations, compatible with the engagement of astrocyte along the activation pathway, occur in the hippocampus already at the presymptomatic stage of AD.

  5. Expression of Phenotypic Astrocyte Marker Is Increased in a Transgenic Mouse Model of Alzheimer's Disease versus Age-Matched Controls: A Presymptomatic Stage Study.

    PubMed

    Doméné, Aurélie; Cavanagh, Chelsea; Page, Guylène; Bodard, Sylvie; Klein, Christophe; Delarasse, Cécile; Chalon, Sylvie; Krantic, Slavica

    2016-01-01

    Recent mouse studies of the presymptomatic stage of Alzheimer's disease (AD) have suggested that proinflammatory changes, such as glial activation and cytokine induction, may occur already at this early stage through unknown mechanisms. Because TNFα contributes to increased Aβ production from the Aβ precursor protein (APP), we assessed a putative correlation between APP/Aβ and TNFα during the presymptomatic stage as well as early astrocyte activation in the hippocampus of 3-month-old APPswe/PS1dE9 mice. While Western blots revealed significant APP expression, Aβ was not detectable by Western blot or ELISA attesting that 3-month-old, APPswe/PS1dE9 mice are at a presymptomatic stage of AD-like pathology. Western blots were also used to show increased GFAP expression in transgenic mice that positively correlated with both TNFα and APP, which were also mutually correlated. Subregional immunohistochemical quantification of phenotypic (GFAP) and functional (TSPO) markers of astrocyte activation indicated a selective and significant increase in GFAP-immunoreactive (IR) cells in the dentate gyrus of APPswe/PS1dE9 mice. Our data suggest that subtle morphological and phenotypic alterations, compatible with the engagement of astrocyte along the activation pathway, occur in the hippocampus already at the presymptomatic stage of AD. PMID:27672476

  6. Brain-behavior relationships in young traumatic brain injury patients: DTI metrics are highly correlated with postural control.

    PubMed

    Caeyenberghs, Karen; Leemans, Alexander; Geurts, Monique; Taymans, Tom; Linden, Catharine Vander; Smits-Engelsman, Bouwien C M; Sunaert, Stefan; Swinnen, Stephan P

    2010-07-01

    Traumatic brain injury (TBI) is a major cause of impairment and functional disability in children and adolescents, including deterioration in fine as well as gross motor skills. The aim of this study was to assess deficits in sensory organization and postural ability in a young group of TBI patients versus controls by using quantitative force-platform recordings, and to test whether balance deficits are related to variation in structural properties of the motor and sensory white matter pathways. Twelve patients with TBI and 14 controls (aged 8-20 years) performed the Sensory Organisation Test (SOT) protocol of the EquiTest (Neurocom). All participants were scanned using Diffusion Tensor Imaging (DTI) along with standard anatomical scans. Quantitative comparisons of DTI parameters (fractional anisotropy, axial and radial diffusivity) between TBI patients and controls were performed. Correlations between DTI parameters and SOT balance scores were determined. Findings revealed that the TBI group scored generally lower than the control group on the SOT, indicative of deficits in postural control. In the TBI group, reductions in fractional anisotropy were noted in the cerebellum, posterior thalamic radiation, and corticospinal tract. Degree of white matter deterioration was highly correlated with balance deficits. This study supports the view that DTI is a valuable tool for assessing the integrity of white matter structures and for selectively predicting functional motor deficits in TBI patients. PMID:19998364

  7. Rapid control of male typical behaviors by brain-derived estrogens

    PubMed Central

    Cornil, Charlotte A.; Ball, Gregory F.; Balthazart, Jacques

    2012-01-01

    Beside their genomic mode of action, estrogens also activate a variety of cellular signaling pathways through non-genomic mechanisms. Until recently, little was known regarding the functional significance of such actions in males and the mechanism that control local estrogen concentration with a spatial and time resolution compatible with these non-genomic actions had rarely been examined. Here, we review evidence that estrogens rapidly modulate a variety of behaviors in male vertebrates. Then, we present in vitro work supporting the existence of a control mechanism of local brain estrogen synthesis by aromatase along with in vivo evidence that rapid changes in aromatase activity also occur in a region-specific manner in response to changes in the social or environmental context. Finally, we suggest that the brain estrogen provision may also play a significant role in females. Together these data bolster the hypothesis that brain-derived estrogens should be considered as neuromodulators. PMID:22983088

  8. 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.

  9. Brain-Computer Interface for Control of Wheelchair Using Fuzzy Neural Networks

    PubMed Central

    Akkaya, Nurullah; Aytac, Ersin; Günsel, Irfan; Çağman, Ahmet

    2016-01-01

    The design of brain-computer interface for the wheelchair for physically disabled people is presented. The design of the proposed system is based on receiving, processing, and classification of the electroencephalographic (EEG) signals and then performing the control of the wheelchair. The number of experimental measurements of brain activity has been done using human control commands of the wheelchair. Based on the mental activity of the user and the control commands of the wheelchair, the design of classification system based on fuzzy neural networks (FNN) is considered. The design of FNN based algorithm is used for brain-actuated control. The training data is used to design the system and then test data is applied to measure the performance of the control system. The control of the wheelchair is performed under real conditions using direction and speed control commands of the wheelchair. The approach used in the paper allows reducing the probability of misclassification and improving the control accuracy of the wheelchair. PMID:27777953

  10. 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.

  11. 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.

  12. 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

  13. 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

    2016-04-21

    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.

  14. 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

  15. 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

  16. 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…

  17. Allured or alarmed: counteractive control responses to food temptations in the brain.

    PubMed

    Smeets, Paul A M; Kroese, Floor M; Evers, Catharine; de Ridder, Denise T D

    2013-07-01

    Typically, it is believed that palatable, high caloric foods signal reward and trigger indulgent responses. However, Counteractive Control Theory suggests that, to the extent that people are concerned about their weight, a confrontation with palatable foods should also trigger 'alarm bell responses' which promote successful self-control. Our study is the first to investigate such counteractive control processes in the brain employing functional magnetic resonance imaging (fMRI) in a sample of successful self-regulators. Indeed, besides the traditional finding that foods elicit heightened attention as witnessed by greater activation of primary visual cortex, we found that viewing palatable foods elicited brain activation in areas associated with self-regulation. Crucially, brain activation in self-regulation areas was related to diet importance. Thus, our results are the first to show that food cues not only evoke hedonic brain responses; in successful self-regulators they also trigger alarm bell responses, which may reflect the neural processes underlying successful self-control.

  18. An 8-Month Randomized Controlled Exercise Trial Alters Brain Activation During Cognitive Tasks in Overweight Children

    PubMed Central

    Krafft, Cynthia E.; Schwarz, Nicolette F.; Chi, Lingxi; Weinberger, Abby L.; Schaeffer, David J.; Pierce, Jordan E.; Rodrigue, Amanda L.; Yanasak, Nathan E.; Miller, Patricia H.; Tomporowski, Phillip D.; Davis, Catherine L.; McDowell, Jennifer E.

    2014-01-01

    Objective Children who are less fit reportedly have lower performance on tests of cognitive control and differences in brain function. This study examined the effect of an exercise intervention on brain function during two cognitive control tasks in overweight children. Design and Methods Participants included 43 unfit, overweight (BMI ≥ 85th percentile) children 8- to 11-years old (91% Black), who were randomly divided into either an aerobic exercise (n = 24) or attention control group (n = 19). Each group was offered a separate instructor-led after-school program every school day for 8 months. Before and after the program, all children performed two cognitive control tasks during functional magnetic resonance imaging (fMRI): antisaccade and flanker. Results Compared to the control group, the exercise group decreased activation in several regions supporting antisaccade performance, including precentral gyrus and posterior parietal cortex, and increased activation in several regions supporting flanker performance, including anterior cingulate and superior frontal gyrus. Conclusions Exercise may differentially impact these two task conditions, or the paradigms in which cognitive control tasks were presented may be sensitive to distinct types of brain activation that show different effects of exercise. In sum, exercise appears to alter efficiency or flexible modulation of neural circuitry supporting cognitive control in overweight children. PMID:23788510

  19. 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

  20. Impaired decision-making and brain shrinkage in alcoholism.

    PubMed

    Le Berre, A-P; Rauchs, G; La Joie, R; Mézenge, F; Boudehent, C; Vabret, F; Segobin, S; Viader, F; Allain, P; Eustache, F; Pitel, A-L; Beaunieux, H

    2014-03-01

    Alcohol-dependent individuals usually favor instant gratification of alcohol use and ignore its long-term negative consequences, reflecting impaired decision-making. According to the somatic marker hypothesis, decision-making abilities are subtended by an extended brain network. As chronic alcohol consumption is known to be associated with brain shrinkage in this network, the present study investigated relationships between brain shrinkage and decision-making impairments in alcohol-dependent individuals early in abstinence using voxel-based morphometry. Thirty patients performed the Iowa Gambling Task and underwent a magnetic resonance imaging investigation (1.5T). Decision-making performances and brain data were compared with those of age-matched healthy controls. In the alcoholic group, a multiple regression analysis was conducted with two predictors (gray matter [GM] volume and decision-making measure) and two covariates (number of withdrawals and duration of alcoholism). Compared with controls, alcoholics had impaired decision-making and widespread reduced gray matter volume, especially in regions involved in decision-making. The regression analysis revealed links between high GM volume in the ventromedial prefrontal cortex, dorsal anterior cingulate cortex and right hippocampal formation, and high decision-making scores (P<0.001, uncorrected). Decision-making deficits in alcoholism may result from impairment of both emotional and cognitive networks.

  1. Bridging language and attention: brain basis of the impact of bilingualism on cognitive control.

    PubMed

    Garbin, G; Sanjuan, A; Forn, C; Bustamante, J C; Rodriguez-Pujadas, A; Belloch, V; Hernandez, M; Costa, A; Avila, C

    2010-12-01

    Using two languages on an everyday basis appears to have a positive effect on general-purpose executive control in bilinguals. However, the neural correlates of this effect remain poorly understood. To investigate the brain bases of the bilingual advantage in executive control, we tested 21 Spanish monolinguals and 19 Spanish-Catalan early bilinguals in a non-verbal task-switching paradigm. As expected based on previous experiments on non-verbal task switching, we found activation in the right inferior frontal cortex and the anterior cingulate of monolingual participants. While bilingual participants showed a reduced switching cost, they activated the left inferior frontal cortex and the left striatum, a pattern of activation consistent with networks thought to underlie language control. Overall, these results support the hypothesis that bilinguals' early training in switching back and forth between their languages leads to the recruitment of brain regions involved in language control when performing non-linguistic cognitive tasks.

  2. 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.

  3. Association of amyloid burden, brain atrophy and memory deficits in aged apolipoprotein ε4 mice.

    PubMed

    Yin, Junxiang; Turner, Gregory H; Coons, Stephen W; Maalouf, Marwan; Reiman, Eric M; Shi, Jiong

    2014-03-01

    Apolipoprotein E ε4 allele (ApoE4) has been associated with increased risk of sporadic Alzheimer's disease (AD) and of conversion from mild cognitive impairment to AD. But the underlying mechanism of ApoE4 affecting brain atrophy and cognition is not fully understood. We investigated the effect of ApoE4 on amyloid beta (Aβ) protein burden and its correlation with the structure change of hippocampus and cortex, cognitive and behavioral changes in ApoE4 transgenic mice. Male ApoE4 transgenic mice and age-matched control mice at age 12 months and 24 months were tested in the Morris Water Maze (MWM). Brain volume changes (including whole brain, hippocampus, cortex, total ventricles and caudate putamen) were assessed by using small animal 7T-MRI. Aβ level was assessed by immunohistochemistry (IHC) and immunoprecipitation/western blot. In MWM, escape latency was longer and time spent in the target quadrant was shorter in aged ApoE4 mice (12- and 24-month-old), suggesting age- and ApoE4-dependent visuospatial deficits. Atrophy on MRI was prominent in the hippocampus (p=0.039) and cortex (p=0.013) of ApoE4 mice (24-month-old) as compared to age-matched control mice. IHC revealed elevated Aβ deposition in the hippocampus. Consistently, both soluble and insoluble Aβ aggregates were increased in aged ApoE4 mice. This increase was correlated inversely with hippocampal atrophy and cognitive deficits. These data give further evidence that ApoE4 plays an important role in brain atrophy and memory impairment by modulating amyloid production and deposition.

  4. Associations between regional brain physiology and trait impulsivity, motor inhibition, and impaired control over drinking

    PubMed Central

    Weafer, Jessica; Dzemidzic, Mario; Eiler, William; Oberlin, Brandon G.; Wang, Yang; Kareken, David A.

    2015-01-01

    Trait impulsivity and poor inhibitory control are well-established risk factors for alcohol misuse, yet little is known about the associated neurobiological endophenotypes. Here we examined correlations among brain physiology and self-reported trait impulsive behavior, impaired control over drinking, and a behavioral measure of response inhibition. A sample of healthy drinkers (n=117) completed a pulsed arterial spin labeling (PASL) scan to quantify resting regional cerebral blood flow (rCBF), and measures of self-reported impulsivity (Eysenck I7 Impulsivity scale) and impaired control over drinking. A subset of subjects (n=40) performed a stop signal task during blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging to assess brain regions involved in response inhibition. Eysenck I7 scores were inversely related to blood flow in the right precentral gyrus. Significant BOLD activation during response inhibition occurred in an overlapping right frontal motor/premotor region. Moreover, impaired control over drinking was associated with reduced BOLD response in the same region. These findings suggest that impulsive personality and impaired control over drinking are associated with brain physiology in areas implicated in response inhibition. This is consistent with the idea that difficulty controlling behavior is due in part to impairment in motor restraint systems. PMID:26065376

  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. Scoring Systems to Estimate Intracerebral Control and Survival Rates of Patients Irradiated for Brain Metastases;Brain metastases; Radiation therapy; Local control; Survival; Prognostic scores

    SciTech Connect

    Rades, Dirk; Dziggel, Liesa; Haatanen, Tiina; Veninga, Theo; Lohynska, Radka; Dunst, Juergen; Schild, Steven E.

    2011-07-15

    Purpose: To create and validate scoring systems for intracerebral control (IC) and overall survival (OS) of patients irradiated for brain metastases. Methods and Materials: In this study, 1,797 patients were randomly assigned to the test (n = 1,198) or the validation group (n = 599). Two scoring systems were developed, one for IC and another for OS. The scores included prognostic factors found significant on multivariate analyses. Age, performance status, extracerebral metastases, interval tumor diagnosis to RT, and number of brain metastases were associated with OS. Tumor type, performance status, interval, and number of brain metastases were associated with IC. The score for each factor was determined by dividing the 6-month IC or OS rate (given in percent) by 10. The total score represented the sum of the scores for each factor. The score groups of the test group were compared with the corresponding score groups of the validation group. Results: In the test group, 6-month IC rates were 17% for 14-18 points, 49% for 19-23 points, and 77% for 24-27 points (p < 0.0001). IC rates in the validation group were 19%, 52%, and 77%, respectively (p < 0.0001). In the test group, 6-month OS rates were 9% for 15-19 points, 41% for 20-25 points, and 78% for 26-30 points (p < 0.0001). OS rates in the validation group were 7%, 39%, and 79%, respectively (p < 0.0001). Conclusions: Patients irradiated for brain metastases can be given scores to estimate OS and IC. IC and OS rates of the validation group were similar to the test group demonstrating the validity and reproducibility of both scores.

  7. 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

  8. Occupation, socioeconomic status, and brain tumor mortality: a death certificate-based case-control study.

    PubMed

    Demers, P A; Vaughan, T L; Schommer, R R

    1991-09-01

    The relationships between brain tumor mortality and occupation and socioeconomic status (SES) were evaluated in a death certificate-based case-control study. The cases consisted of 904 white men aged 20 years and older who died of a brain tumor in Washington state between 1969 and 1978. For each case a white male control of the same age was chosen. A consistent pattern of increasing risk with increasing SES was seen for all brain tumors as well as for gliomas and astrocytomas. After adjustment for SES, stationary engineers were found to be at excess risk across all histologies based on six cases vs no controls with lower 95% confidence intervals of 2.3 for all brain tumors, 2.8 for gliomas (based on three cases), and 2.1 for astrocytic tumors (based on two cases). Excesses of astrocytic tumors also were observed for petroleum refinery workers (OR = 8.8, CI = 2.2-35.2), forestry workers (OR = 8.5, CI = 1.1-63.4), and cleaning service workers (OR = 2.7, CI = 1.1-6.7).

  9. Opposing brain differences in 16p11.2 deletion and duplication carriers.

    PubMed

    Qureshi, Abid Y; Mueller, Sophia; Snyder, Abraham Z; Mukherjee, Pratik; Berman, Jeffrey I; Roberts, Timothy P L; Nagarajan, Srikantan S; Spiro, John E; Chung, Wendy K; Sherr, Elliott H; Buckner, Randy L

    2014-08-20

    Deletions and duplications of the recurrent ~600 kb chromosomal BP4-BP5 region of 16p11.2 are associated with a broad variety of neurodevelopmental outcomes including autism spectrum disorder. A clue to the pathogenesis of the copy number variant (CNV)'s effect on the brain is that the deletion is associated with a head size increase, whereas the duplication is associated with a decrease. Here we analyzed brain structure in a clinically ascertained group of human deletion (N = 25) and duplication (N = 17) carriers from the Simons Variation in Individuals Project compared with age-matched controls (N = 29 and 33, respectively). Multiple brain measures showed increased size in deletion carriers and reduced size in duplication carriers. The effects spanned global measures of intracranial volume, brain size, compartmental measures of gray matter and white matter, subcortical structures, and the cerebellum. Quantitatively, the largest effect was on the thalamus, but the collective results suggest a pervasive rather than a selective effect on the brain. Detailed analysis of cortical gray matter revealed that cortical surface area displays a strong dose-dependent effect of CNV (deletion > control > duplication), whereas average cortical thickness is less affected. These results suggest that the CNV may exert its opposing influences through mechanisms that influence early stages of embryonic brain development. PMID:25143601

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

    PubMed

    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.

  11. 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.

  12. 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.

  13. 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, ...

  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. 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

  17. 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

  18. Flexible, AAV-equipped Genetic Modules for Inducible Control of Gene Expression in Mammalian Brain

    PubMed Central

    Dogbevia, Godwin K; Roβmanith, Martin; Sprengel, Rolf; Hasan, Mazahir T

    2016-01-01

    Controlling gene expression in mammalian brain is of utmost importance to causally link the role of gene function to cell circuit dynamics under normal conditions and disease states. We have developed recombinant adeno-associated viruses equipped with tetracycline-controlled genetic switches for inducible and reversible control of gene expression in a cell type specific and brain subregion selective manner. Here, we characterize a two-virus approach to efficiently and reliably switch gene expression on and off, repetitively, both in vitro and in vivo. Our recombinant adeno-associated virus (rAAV)-Tet approach is highly flexible and it has great potential for application in basic and biomedical neuroscience research and gene therapy. PMID:27070301

  19. 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

  20. 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.

  1. Default mode network functional and structural connectivity after traumatic brain injury.

    PubMed

    Sharp, David J; Beckmann, Christian F; Greenwood, Richard; Kinnunen, Kirsi M; Bonnelle, Valerie; De Boissezon, Xavier; Powell, Jane H; Counsell, Serena J; Patel, Maneesh C; Leech, Robert

    2011-08-01

    Traumatic brain injury often results in cognitive impairments that limit recovery. The underlying pathophysiology of these impairments is uncertain, which restricts clinical assessment and management. Here, we use magnetic resonance imaging to test the hypotheses that: (i) traumatic brain injury results in abnormalities of functional connectivity within key cognitive networks; (ii) these changes are correlated with cognitive performance; and (iii) functional connectivity within these networks is influenced by underlying changes in structural connectivity produced by diffuse axonal injury. We studied 20 patients in the chronic phase after traumatic brain injury compared with age-matched controls. Network function was investigated in detail using functional magnetic resonance imaging to analyse both regional brain activation, and the interaction of brain regions within a network (functional connectivity). We studied patients during performance of a simple choice-reaction task and at 'rest'. Since functional connectivity reflects underlying structural connectivity, diffusion tensor imaging was used to quantify axonal injury, and test whether structural damage correlated with functional change. The patient group showed typical impairments in information processing and attention, when compared with age-matched controls. Patients were able to perform the task accurately, but showed slow and variable responses. Brain regions activated by the task were similar between the groups, but patients showed greater deactivation within the default mode network, in keeping with an increased cognitive load. A multivariate analysis of 'resting' state functional magnetic resonance imaging was then used to investigate whether changes in network function were present in the absence of explicit task performance. Overall, default mode network functional connectivity was increased in the patient group. Patients with the highest functional connectivity had the least cognitive impairment. In

  2. 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

  3. 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

  4. 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).

  5. 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

  6. 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.

  7. Emulation of computer mouse control with a noninvasive brain computer interface

    NASA Astrophysics Data System (ADS)

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

    2008-06-01

    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 electroencephalographic (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 of 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.

  8. 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.

  9. 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

  10. Quality control parameters on a large dataset of regionally dissected human control brains for whole genome expression studies

    PubMed Central

    Trabzuni, Daniah; Ryten, Mina; Walker, Robert; Smith, Colin; Imran, Sabaena; Ramasamy, Adaikalavan; Weale, Michael E; Hardy, John

    2011-01-01

    We are building an open-access database of regional human brain expression designed to allow the genome-wide assessment of genetic variability on expression. Array and RNA sequencing technologies make assessment of genome-wide expression possible. Human brain tissue is a challenging source for this work because it can only be obtained several and variable hours post-mortem and after varying agonal states. These variables alter RNA integrity in a complex manner. In this report, we assess the effect of post-mortem delay, agonal state and age on gene expression, and the utility of pH and RNA integrity number as predictors of gene expression as measured on 1266 Affymetrix Exon Arrays. We assessed the accuracy of the array data using QuantiGene, as an independent non-PCR-based method. These quality control parameters will allow database users to assess data accuracy. We report that within the parameters of this study post-mortem delay, agonal state and age have little impact on array quality, array data are robust to variable RNA integrity, and brain pH has only a small effect on array performance. QuantiGene gave very similar expression profiles as array data. This study is the first step in our initiative to make human, regional brain expression freely available. PMID:21848658

  11. [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.

  12. Significance of neuro-cardiac control mechanisms governed by higher regions of the brain.

    PubMed

    Taggart, Peter; Critchley, Hugo; van Duijvendoden, Stefan; Lambiase, Pier D

    2016-08-01

    Advances in investigative techniques have led to an increasing awareness and understanding of the role of central neural control in the autonomic nervous system regulation of the heart. Substantial evidence exists for a role of the higher centres in neuro-cardiac control including the effect of focal brain stimulation and acute brain lesions on cardiac electrophysiology, blood pressure, contractile function and the development of arrhythmias. Mental stress and strong emotions have long been associated with sudden cardiac death. There is an emerging literature relating the gene-environment interactions in determining the neural patterning responsible for the stress response itself. The role of the higher brain centres in determining myocardial behaviour has become accessible through the utilisation of optogenetic techniques to modulate activity in specific brainstem nuclei, enabling the dissection of specific vagal and sympathetic inputs on cardiac electrophysiology and arrhythmogenesis. Central cardiac control mechanisms are modulated by afferent signals from the heart. Ascending interoceptive pathways from heart to several forebrain regions influence the behavioural response and autonomic output to the heart. These processes are expressed as control loops at multiple levels of the neuraxis and are assumed to converge in part at the level of the baroreflex to shape the efferent drive to the heart and vasculature. PMID:27595200

  13. 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

  14. 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.

  15. 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

  16. 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

  17. Meditation, mindfulness and executive control: the importance of emotional acceptance and brain-based performance monitoring.

    PubMed

    Teper, Rimma; Inzlicht, Michael

    2013-01-01

    Previous studies have documented the positive effects of mindfulness meditation on executive control. What has been lacking, however, is an understanding of the mechanism underlying this effect. Some theorists have described mindfulness as embodying two facets-present moment awareness and emotional acceptance. Here, we examine how the effect of meditation practice on executive control manifests in the brain, suggesting that emotional acceptance and performance monitoring play important roles. We investigated the effect of meditation practice on executive control and measured the neural correlates of performance monitoring, specifically, the error-related negativity (ERN), a neurophysiological response that occurs within 100 ms of error commission. Meditators and controls completed a Stroop task, during which we recorded ERN amplitudes with electroencephalography. Meditators showed greater executive control (i.e. fewer errors), a higher ERN and more emotional acceptance than controls. Finally, mediation pathway models further revealed that meditation practice relates to greater executive control and that this effect can be accounted for by heightened emotional acceptance, and to a lesser extent, increased brain-based performance monitoring.

  18. 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.

  19. 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.

  20. 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

    2015-08-25

    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.

  1. 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

  2. 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

  3. Vascular and Alzheimer's disease markers independently predict brain atrophy rate in Alzheimer's Disease Neuroimaging Initiative controls.

    PubMed

    Barnes, Josephine; Carmichael, Owen T; Leung, Kelvin K; Schwarz, Christopher; Ridgway, Gerard R; Bartlett, Jonathan W; Malone, Ian B; Schott, Jonathan M; Rossor, Martin N; Biessels, Geert Jan; DeCarli, Charlie; Fox, Nick C

    2013-08-01

    This study assessed relationships among white matter hyperintensities (WMH), cerebrospinal fluid (CSF), Alzheimer's disease (AD) pathology markers, and brain volume loss. Subjects included 197 controls, 331 individuals with mild cognitive impairment (MCI), and 146 individuals with AD with serial volumetric 1.5-T MRI. CSF Aβ1-42 (n = 351) and tau (n = 346) were measured. Brain volume change was quantified using the boundary shift integral (BSI). We assessed the association between baseline WMH volume and annualized BSI, adjusting for intracranial volume. We also performed multiple regression analyses in the CSF subset, assessing the relationships of WMH and Aβ1-42 and/or tau with BSI. WMH burden was positively associated with BSI in controls (p = 0.02) but not MCI or AD. In multivariable models, WMH (p = 0.003) and Aβ1-42 (p = 0.001) were independently associated with BSI in controls; in MCI Aβ1-42 (p < 0.001) and tau (p = 0.04) were associated with BSI. There was no evidence of independent effects of WMH or CSF measures on BSI in AD. These data support findings that vascular damage is associated with increased brain atrophy in the context of AD pathology in pre-dementia stages.

  4. 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.

  5. 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.

  6. 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

  7. On the need to better specify the concept of "control" in brain-computer-interfaces/neurofeedback research.

    PubMed

    Wood, Guilherme; Kober, Silvia Erika; Witte, Matthias; Neuper, Christa

    2014-01-01

    Aiming at a better specification of the concept of "control" in brain-computer-interfaces (BCIs) and neurofeedback (NF) research, we propose to distinguish "self-control of brain activity" from the broader concept of "BCI control", since the first describes a neurocognitive phenomenon and is only one of the many components of "BCI control". Based on this distinction, we developed a framework based on dual-processes theory that describes the cognitive determinants of self-control of brain activity as the interplay of automatic vs. controlled information processing. Further, we distinguish between cognitive processes that are necessary and sufficient to achieve a given level of self-control of brain activity and those which are not. We discuss that those cognitive processes which are not necessary for the learning process can hamper self-control because they cannot be completely turned-off at any time. This framework aims at a comprehensive description of the cognitive determinants of the acquisition of self-control of brain activity underlying those classes of BCI which require the user to achieve regulation of brain activity as well as NF learning.

  8. Simultaneous brain-computer interfacing and motor control: expanding the reach of non-invasive BCIs.

    PubMed

    Cheung, Willy; Sarma, Devapratim; Scherer, Reinhold; Rao, Rajesh P N

    2012-01-01

    Brain-computer interfaces (BCIs) have traditionally been developed for paralyzed and locked-in individuals with no motor control. However, there is a much larger population of patients with some residual motor function as well as the general population of able-bodied individuals, both of whom could benefit significantly from BCIs. An important question that has yet to be systematically studied is: can subjects use BCIs simultaneously with overt motor activity? We present results from a preliminary study aimed at exploring this question. Three subjects used hand motor imagery in an electroencephalographic (EEG) BCI while simultaneously using a joystick to control a cursor. Particular attention was paid to preventing potential muscle artifacts from influencing imagery-based control. All three subjects were able to use the hybrid "imagery+joystick" mode of control over two days, demonstrating the ability to learn and significantly improve performance. These results suggest that subjects can potentially augment their normal human sensorimotor capability by exercising direct brain control over devices concurrently with overt motor control. PMID:23367470

  9. Distinct brain networks for adaptive and stable task control in humans

    PubMed Central

    Dosenbach, Nico U. F.; Fair, Damien A.; Miezin, Francis M.; Cohen, Alexander L.; Wenger, Kristin K.; Dosenbach, Ronny A. T.; Fox, Michael D.; Snyder, Abraham Z.; Vincent, Justin L.; Raichle, Marcus E.; Schlaggar, Bradley L.; Petersen, Steven E.

    2007-01-01

    Control regions in the brain are thought to provide signals that configure the brain's moment-to-moment information processing. Previously, we identified regions that carried signals related to task-control initiation, maintenance, and adjustment. Here we characterize the interactions of these regions by applying graph theory to resting state functional connectivity MRI data. In contrast to previous, more unitary models of control, this approach suggests the presence of two distinct task-control networks. A frontoparietal network included the dorsolateral prefrontal cortex and intraparietal sulcus. This network emphasized start-cue and error-related activity and may initiate and adapt control on a trial-by-trial basis. The second network included dorsal anterior cingulate/medial superior frontal cortex, anterior insula/frontal operculum, and anterior prefrontal cortex. Among other signals, these regions showed activity sustained across the entire task epoch, suggesting that this network may control goal-directed behavior through the stable maintenance of task sets. These two independent networks appear to operate on different time scales and affect downstream processing via dissociable mechanisms. PMID:17576922

  10. 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.

  11. 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

  12. 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.

  13. [Mind control with optogenetic mice: exploring the causal relationships between brain activity and the mind].

    PubMed

    Matsui, Ko

    2013-06-01

    Every scientific endeavor starts with observation. However, observation alone can only lead to an analysis of correlations. Experimental perturbations are required to understand the causal relationships between the components that constitute the system under study. Our current understanding of the function of the brain, which is a complex multicellular organ, suggests that communication between cells underlies the formation of the mind. This has been mainly deduced from studies of correlations between cell activity and animal behavior. Recently developed tools have enabled the specific control of cell activity. For example, light-sensitive proteins, such as channelrhodopsin-2, that are found in microorganisms can now be genetically expressed in mammalian brain cells, allowing experimenters to optically control cell activity at will. In this review, I introduce the recently established method, Knockin-mediated ENhanced Gene Expression by the improved tetracycline-controlled gene induction (KENGE-tet) method, which has generated a repertoire of transgenic mice that express levels of the highly light-sensitive channelrhodopsin-2 mutant that are sufficient to stimulate multiple cell types. In addition to neurons, manipulations of the activities of nonexcitable glial cells in vivo have also proved possible. A recent report that used the KENGE-tet has shown that the selective optogenetic stimulation of glia can lead to the release of glutamate as a gliotransmitter, synaptic plasticity, and the acceleration of cerebellar-modulated motor learning. These findings have suggested that glia also participate in brain information processing, a function once thought to be solely mediated by neuronal activity. These reports have demonstrated the use of optogenetic tools in exploring the causal relationships between brain activity and the mind.

  14. Interstitial chemotherapy of the 9L gliosarcoma: controlled release polymers for drug delivery in the brain.

    PubMed

    Tamargo, R J; Myseros, J S; Epstein, J I; Yang, M B; Chasin, M; Brem, H

    1993-01-15

    The administration of drugs directly into the central nervous system using polymers as drug carriers may improve the treatment of malignant brain tumors. In this study, the effect of the interstitial, localized delivery of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) incorporated into controlled release polymers implanted adjacent to the 9L gliosarcoma was assessed in s.c. and intracranial (i.c.) models. In the s.c. experiment, the 9L gliosarcoma was implanted in the flank of rats and subsequently treated with BCNU either (a) delivered in controlled release polymers inserted adjacent to the tumor or (b) administered systemically by i.p. injections or by controlled release polymers inserted at a site distant from the tumor. The interstitial release of BCNU adjacent to the tumor in the flank resulted in a significant tumor growth delay of 16.3 days, as compared to a growth delay of 9.3 and 11.2 days obtained with the systemic administration of BCNU. In the i.c. experiment, the 9L gliosarcoma was implanted in the brain of Fischer 344 rats and treated either (a) with controlled release polymers containing BCNU inserted into the brain or (b) with the systemic i.p. administration of BCNU. The interstitial release of BCNU in the brain resulted in a significant 5.4- to 7.3-fold increased survival, compared with a 2.4-fold increased survival after the systemic administration of the same dose of BCNU. The two groups with i.c. tumors treated interstitially had 17 and 42% cures, but no long-term cures were obtained in the group treated with systemic therapy. The localized, controlled delivery of chemotherapeutic agents in the s.c. tissues and in the brain via polymeric carriers may be more effective than standard systemic chemotherapy. This approach could be used to deliver a wide variety of agents into the central nervous system to treat diverse neuropathological conditions which remain refractory to systemic therapy.

  15. Incentive Motivation, Cognitive Control, and the Adolescent Brain: Is It Time for a Paradigm Shift?

    PubMed Central

    Luciana, Monica; Collins, Paul F.

    2012-01-01

    It can be argued that adolescents’ decision making is biased more by motivational factors than by cognitively driven calculations of outcome probabilities. Brain-based models, derived from structural and functional neuroimaging perspectives to account for this bias, have focused on purported differences in rates of development of motivational and regulatory-control systems. This article proposes a neurochemically based framework for understanding adolescents’ behavioral biases_and suggests that there should be an increased focus on the dopaminergic substrates of incentive motivation, which increases into adolescence and decreases thereafter. The article also discusses the manner in which this increase interacts with executive control systems in affecting self-regulation. PMID:23543860

  16. 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

  17. Longitudinal Growth Curves of Brain Function Underlying Inhibitory Control through Adolescence

    PubMed Central

    Foran, William; Velanova, Katerina; Luna, Beatriz

    2013-01-01

    Neuroimaging studies suggest that developmental improvements in inhibitory control are primarily supported by changes in prefrontal executive function. However, studies are contradictory with respect to how activation in prefrontal regions changes with age, and they have yet to analyze longitudinal data using growth curve modeling, which allows characterization of dynamic processes of developmental change, individual differences in growth trajectories, and variables that predict any interindividual variability in trajectories. In this study, we present growth curves modeled from longitudinal fMRI data collected over 302 visits (across ages 9 to 26 years) from 123 human participants. Brain regions within circuits known to support motor response control, executive control, and error processing (i.e., aspects of inhibitory control) were investigated. Findings revealed distinct developmental trajectories for regions within each circuit and indicated that a hierarchical pattern of maturation of brain activation supports the gradual emergence of adult-like inhibitory control. Mean growth curves of activation in motor response control regions revealed no changes with age, although interindividual variability decreased with development, indicating equifinality with maturity. Activation in certain executive control regions decreased with age until adolescence, and variability was stable across development. Error-processing activation in the dorsal anterior cingulate cortex showed continued increases into adulthood and no significant interindividual variability across development, and was uniquely associated with task performance. These findings provide evidence that continued maturation of error-processing abilities supports the protracted development of inhibitory control over adolescence, while motor response control regions provide early-maturing foundational capacities and suggest that some executive control regions may buttress immature networks as error processing

  18. Nerve growth factor in Alzheimer's disease: increased levels throughout the brain coupled with declines in nucleus basalis.

    PubMed

    Scott, S A; Mufson, E J; Weingartner, J A; Skau, K A; Crutcher, K A

    1995-09-01

    The current study analyzed NGF protein levels in the brains of patients with Alzheimer's disease (AD) as compared with aged neurologically normal individuals. An established two-site ELISA was used to measure NGF-like immunoreactivity in the hippocampus, superior temporal gyrus, superior frontal gyrus, inferior parietal lobule, frontal and occipital cortical poles, cerebellum, amygdala, putamen, and nucleus basalis of Meynert (nbM). ChAT activity was assayed in adjacent tissue samples. NGF levels were also evaluated in Parkinson's disease for comparison with both AD and age-matched control cases. Regardless of the brain bank (University of Cincinnati, Rush Presbyterian St. Luke's Medical Center in Chicago, or University of Alabama at Birmingham), NGF-like activity was at least moderately increased with AD in virtually every brain region examined except for the nbM, in which significant declines were observed. NGF levels were also increased when compared with age-matched Parkinson's cases (frontal cortex). NGF-like activity was not related to age at onset or disease duration in AD cases, nor did NGF levels correlate with age at death in the control or AD groups. Correlations between ChAT and NGF-like activity across brains varied considerably and were generally not significant. The present findings indicate that AD is characterized by a widespread increase in cortical and subcortical NGF. Although a correlation with ChAT activity was not observed in cortex, the AD-related decline in NGF found in nbM is consistent with the possibility of impaired retrograde transport of NGF to this region.

  19. Event related potentials study of aberrations in voice control mechanisms in adults with Attention Deficit Hyperactivity Disorder

    PubMed Central

    Korzyukov, Oleg; Tapaskar, Natalie; Pflieger, Mark E.; Behroozmand, Roozbeh; Lodhavia, Anjli; Patel, Sona; Robin, Donald A.; Larson, Charles

    2014-01-01

    Objective The present study was designed to test for neural signs of impulsivity related to voice motor control in young adults with ADHD and healthy control young adults using EEG recordings in a voice pitch perturbation paradigm. Methods Two age-matched groups of young adults were presented with brief pitch shifts of auditory feedback during vocalization. Compensatory behavioral and corresponding bioelectrical brain responses were elicited by the pitch-shifted voice feedback. Results The analysis of bioelectrical responses showed that the ADHD group had shorter peak and onset latency of motor-related bioelectrical brain responses as compared to the controls. Conclusions These results were interpreted to suggest differences in executive functions between ADHD and control participants. Significance We hypothesize that more rapid motor-related bioelectrical responses found in the present study may be a manifestation of impulsiveness in adults with ADHD at the involuntary level of voice control. PMID:25308310

  20. 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

  1. Dimensionality of brain networks linked to life-long individual differences in self-control

    PubMed Central

    Berman, Marc G.; Yourganov, Grigori; Askren, Mary K.; Ayduk, Ozlem; Casey, B.J.; Gotlib, Ian H.; Kross, Ethan; McIntosh, Anthony R.; Strother, Stephen; Wilson, Nicole L.; Zayas, Vivian; Mischel, Walter; Shoda, Yuichi; Jonides, John

    2012-01-01

    The ability to delay gratification in childhood has been linked to positive outcomes in adolescence and adulthood. Here we examine a subsample of participants from a seminal longitudinal study of self-control throughout a subject’s lifespan. Self control, first studied in children at age 4, is now reexamined 40 years later, on a task that required control over the contents of working memory. We examine whether patterns of brain activation on this task can reliably distinguish participants with consistently low and high self-control abilities (low vs. high delayers). We find that low delayers recruit significantly higher-dimensional neural networks when performing the task compared to high delayers. High delayers are also more homogeneous as a group in their neural patterns compared to low delayers. From these brain patterns we can predict with 71% accuracy, whether a participant is a high or low delayer. The present results suggest that dimensionality of neural networks is a biological predictor of self-control abilities. PMID:23340413

  2. 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.

  3. 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.

  4. 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

  5. Focal dystonia: advances in brain imaging and understanding of fine motor control in musicians.

    PubMed

    Altenmüller, Eckart

    2003-08-01

    This article reviews the neuroanatomic and neurophysiologic foundations of music performance and learning. Music performance is regarded as complex voluntary sensorimotor behavior that becomes automated during extensive practice with auditory feedback. It involves all motor, somatosensory, and auditory areas of the brain. Because of the life-long plasticity of neuronal connections, practicing a musical instrument results first in a temporary and later in a stable increase in the amount of nerve tissue devoted to various component tasks. Motor and somatosensory brain regions corresponding to specific subtasks of music performance are larger in musicians starting younger than age 10 years than in the general population. In rare cases, overuse of movement patterns may induce a degradation of motor memory that results in a loss of voluntary control of movements, called musician's cramp. Specific therapeutic options for this condition are reviewed.

  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. 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.

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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.

  13. 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.

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

    PubMed

    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.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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

  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. 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.

  4. 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

  5. Addiction: Decreased reward sensitivity and increased expectation sensitivity conspire to overwhelm the brain's control circuit

    PubMed Central

    Volkow, Nora D.; Wang, Gene-Jack; Fowler, Joanna S.; Tomasi, Dardo; Telang, Frank; Baler, Ruben

    2010-01-01

    Based on brain imaging findings, we present a model according to which addiction emerges as an imbalance in the information processing and integration among various brain circuits and functions. The dysfunctions reflect (a) decreased sensitivity of reward circuits, (b) enhanced sensitivity of memory circuits to conditioned expectations to drugs and drug cues, stress reactivity, and (c) negative mood, and a weakened control circuit. Although initial experimentation with a drug of abuse is largely a voluntary behavior, continued drug use can eventually impair neuronal circuits in the brain that are involved in free will, turning drug use into an automatic compulsive behavior. The ability of addictive drugs to co-opt neuro-transmitter signals between neurons (including dopamine, glutamate, and GABA) modifies the function of different neuronal circuits, which begin to falter at different stages of an addiction trajectory. Upon exposure to the drug, drug cues or stress this results in unrestrained hyperactivation of the motivation/drive circuit that results in the compulsive drug intake that characterizes addiction. PMID:20730946

  6. 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

  7. 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.

  8. Adolescent drinking and brain morphometry: A co-twin control analysis.

    PubMed

    Wilson, Sylia; Malone, Stephen M; Thomas, Kathleen M; Iacono, William G

    2015-12-01

    Developmental changes in structure and functioning are thought to make the adolescent brain particularly sensitive to the negative effects of alcohol. Although alcohol use disorders are relatively rare in adolescence, the initiation of alcohol use, including problematic use, becomes increasingly prevalent during this period. The present study examined associations between normative drinking (alcohol initiation, binge drinking, intoxication) and brain morphometry in a sample of 96 adolescent monozygotic twins. A priori regions of interest included 11 subcortical and 20 cortical structures implicated in the existing empirical literature as associated with normative alcohol use in adolescence. In addition, co-twin control analyses were used to disentangle risk for alcohol use from consequences of alcohol exposure on the developing brain. Results indicated significant associations reflecting preexisting vulnerability toward problematic alcohol use, including reduced volume of the amygdala, increased volume of the cerebellum, and reduced cortical volume and thickness in several frontal and temporal regions, including the superior and middle frontal gyri, pars triangularis, and middle and inferior temporal gyri. Results also indicated some associations consistent with a neurotoxic effect of alcohol exposure, including reduced volume of the ventral diencephalon and the middle temporal gyrus.

  9. 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

  10. Using real-time fMRI to control a dynamical system by brain activity classification.

    PubMed

    Eklund, Anders; Ohlsson, Henrik; Andersson, Mats; Rydell, Joakim; Ynnerman, Anders; Knutsson, Hans

    2009-01-01

    We present a method for controlling a dynamical system using real-time fMRI. The objective for the subject in the MR scanner is to balance an inverted pendulum by activating the left or right hand or resting. The brain activity is classified each second by a neural network and the classification is sent to a pendulum simulator to change the force applied to the pendulum. The state of the inverted pendulum is shown to the subject in a pair of VR goggles. The subject was able to balance the inverted pendulum during several minutes, both with real activity and imagined activity. In each classification 9000 brain voxels were used and the response time for the system to detect a change of activity was on average 2-4 seconds. The developments here have a potential to aid people with communication disabilities, such as locked in people. Another future potential application can be to serve as a tool for stroke and Parkinson patients to be able to train the damaged brain area and get real-time feedback for more efficient training.

  11. 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.

  12. Speed of perceptual grouping in acquired brain injury.

    PubMed

    Kurylo, Daniel D; Larkin, Gabriella Brick; Waxman, Richard; Bukhari, Farhan

    2014-09-01

    Evidence exists that damage to white matter connections may contribute to reduced speed of information processing in traumatic brain injury and stroke. Damage to such axonal projections suggests a particular vulnerability to functions requiring integration across cortical sites. To test this prediction, measurements were made of perceptual grouping, which requires integration of stimulus components. A group of traumatic brain injury and cerebral vascular accident patients and a group of age-matched healthy control subjects viewed arrays of dots and indicated the pattern into which stimuli were perceptually grouped. Psychophysical measurements were made of perceptual grouping as well as processing speed. The patient group showed elevated grouping thresholds as well as extended processing time. In addition, most patients showed progressive slowing of processing speed across levels of difficulty, suggesting reduced resources to accommodate increased demands on grouping. These results support the prediction that brain injury results in a particular vulnerability to functions requiring integration of information across the cortex, which may result from dysfunction of long-range axonal connection.

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. Acquired self-control of insula cortex modulates emotion recognition and brain network connectivity in schizophrenia.

    PubMed

    Ruiz, Sergio; Lee, Sangkyun; Soekadar, Surjo R; Caria, Andrea; Veit, Ralf; Kircher, Tilo; Birbaumer, Niels; Sitaram, Ranganatha

    2013-01-01

    Real-time functional magnetic resonance imaging (rtfMRI) is a novel technique that has allowed subjects to achieve self-regulation of circumscribed brain regions. Despite its anticipated therapeutic benefits, there is no report on successful application of this technique in psychiatric populations. The objectives of the present study were to train schizophrenia patients to achieve volitional control of bilateral anterior insula cortex on multiple days, and to explore the effect of learned self-regulation on face emotion recognition (an extensively studied deficit in schizophrenia) and on brain network connectivity. Nine patients with schizophrenia were trained to regulate the hemodynamic response in bilateral anterior insula with contingent rtfMRI neurofeedback, through a 2-weeks training. At the end of the training stage, patients performed a face emotion recognition task to explore behavioral effects of learned self-regulation. A learning effect in self-regulation was found for bilateral anterior insula, which persisted through the training. Following successful self-regulation, patients recognized disgust faces more accurately and happy faces less accurately. Improvements in disgust recognition were correlated with levels of self-activation of right insula. RtfMRI training led to an increase in the number of the incoming and outgoing effective connections of the anterior insula. This study shows for the first time that patients with schizophrenia can learn volitional brain regulation by rtfMRI feedback training leading to changes in the perception of emotions and modulations of the brain network connectivity. These findings open the door for further studies of rtfMRI in severely ill psychiatric populations, and possible therapeutic applications.

  19. 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

  20. Control of a two-dimensional movement signal by a noninvasive brain-computer interface in humans

    NASA Astrophysics Data System (ADS)

    Wolpaw, Jonathan R.; McFarland, Dennis J.

    2004-12-01

    Brain-computer interfaces (BCIs) can provide communication and control to people who are totally paralyzed. BCIs can use noninvasive or invasive methods for recording the brain signals that convey the user's commands. Whereas noninvasive BCIs are already in use for simple applications, it has been widely assumed that only invasive BCIs, which use electrodes implanted in the brain, can provide multidimensional movement control of a robotic arm or a neuroprosthesis. We now show that a noninvasive BCI that uses scalp-recorded electroencephalographic activity and an adaptive algorithm can provide humans, including people with spinal cord injuries, with multidimensional point-to-point movement control that falls within the range of that reported with invasive methods in monkeys. In movement time, precision, and accuracy, the results are comparable to those with invasive BCIs. The adaptive algorithm used in this noninvasive BCI identifies and focuses on the electroencephalographic features that the person is best able to control and encourages further improvement in that control. The results suggest that people with severe motor disabilities could use brain signals to operate a robotic arm or a neuroprosthesis without needing to have electrodes implanted in their brains. brain-machine interface | electroencephalography

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

    PubMed

    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.

  2. [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

  3. [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.

  4. Vesicular acetylcholine transporter (VAChT) in the brain of spontaneously hypertensive rats (SHR): effect of treatment with an acetylcholinesterase inhibitor.

    PubMed

    Tayebati, S K; Di Tullio, M A; Amenta, F

    2008-11-01

    The cholinergic marker vesicular acetylcholine transporter (VAChT) was investigated in different cerebral areas of spontaneously hypertensive rats (SHR) by immunochemistry (Western blot analysis) and by immunohistochemistry. SHR were used as an animal model of hypertensive brain damage. The sensitivity of manipulation of cholinergic system on VAChT was assessed in rats treated for four weeks with the acetylcholinesterase (AChE) inhibitor galantamine (3 mg/Kg/day). VAChT concentrations were increased in the brain of control SHR compared to age-matched normotensive Wistar-Kyoto rats. This increase probably represents an up-regulation of VAChT to oppose cholinergic deficits reported in SHR and is countered by galantamine administration. The possibility that cholinergic neurotransmission enhancement may represent a therapeutic strategy in cerebrovascular disease is discussed.

  5. Pediatric traumatic brain injury: language outcomes and their relationship to the arcuate fasciculus.

    PubMed

    Liégeois, Frédérique J; Mahony, Kate; Connelly, Alan; Pigdon, Lauren; Tournier, Jacques-Donald; Morgan, Angela T

    2013-12-01

    Pediatric traumatic brain injury (TBI) may result in long-lasting language impairments alongside dysarthria, a motor-speech disorder. Whether this co-morbidity is due to the functional links between speech and language networks, or to widespread damage affecting both motor and language tracts, remains unknown. Here we investigated language function and diffusion metrics (using diffusion-weighted tractography) within the arcuate fasciculus, the uncinate fasciculus, and the corpus callosum in 32 young people after TBI (approximately half with dysarthria) and age-matched healthy controls (n=17). Only participants with dysarthria showed impairments in language, affecting sentence formulation and semantic association. In the whole TBI group, sentence formulation was best predicted by combined corpus callosum and left arcuate volumes, suggesting this "dual blow" seriously reduces the potential for functional reorganisation. Word comprehension was predicted by fractional anisotropy in the right arcuate. The co-morbidity between dysarthria and language deficits therefore seems to be the consequence of multiple tract damage.

  6. 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

  7. 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

  8. 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

  9. Trajectories of cortical thickness maturation in normal brain development--The importance of quality control procedures.

    PubMed

    Ducharme, Simon; Albaugh, Matthew D; Nguyen, Tuong-Vi; Hudziak, James J; Mateos-Pérez, J M; Labbe, Aurelie; Evans, Alan C; Karama, Sherif

    2016-01-15

    Several reports have described cortical thickness (CTh) developmental trajectories, with conflicting results. Some studies have reported inverted-U shape curves with peaks of CTh in late childhood to adolescence, while others suggested predominant monotonic decline after age 6. In this study, we reviewed CTh developmental trajectories in the NIH MRI Study of Normal Brain Development, and in a second step, evaluated the impact of post-processing quality control (QC) procedures on identified trajectories. The quality-controlled sample included 384 individual subjects with repeated scanning (1-3 per subject, total scans n=753) from 4.9 to 22.3years of age. The best-fit model (cubic, quadratic, or first-order linear) was identified at each vertex using mixed-effects models. The majority of brain regions showed linear monotonic decline of CTh. There were few areas of cubic trajectories, mostly in bilateral temporo-parietal areas and the right prefrontal cortex, in which CTh peaks were at, or prior to, age 8. When controlling for total brain volume, CTh trajectories were even more uniformly linear. The only sex difference was faster thinning of occipital areas in boys compared to girls. The best-fit model for whole brain mean thickness was a monotonic decline of 0.027mm per year. QC procedures had a significant impact on identified trajectories, with a clear shift toward more complex trajectories (i.e., quadratic or cubic) when including all scans without QC (n=954). Trajectories were almost exclusively linear when using only scans that passed the most stringent QC (n=598). The impact of QC probably relates to decreasing the inclusion of scans with CTh underestimation secondary to movement artifacts, which are more common in younger subjects. In summary, our results suggest that CTh follows a simple linear decline in most cortical areas by age 5, and all areas by age 8. This study further supports the crucial importance of implementing post-processing QC in CTh studies

  10. Trajectories of cortical thickness maturation in normal brain development--The importance of quality control procedures.

    PubMed

    Ducharme, Simon; Albaugh, Matthew D; Nguyen, Tuong-Vi; Hudziak, James J; Mateos-Pérez, J M; Labbe, Aurelie; Evans, Alan C; Karama, Sherif

    2016-01-15

    Several reports have described cortical thickness (CTh) developmental trajectories, with conflicting results. Some studies have reported inverted-U shape curves with peaks of CTh in late childhood to adolescence, while others suggested predominant monotonic decline after age 6. In this study, we reviewed CTh developmental trajectories in the NIH MRI Study of Normal Brain Development, and in a second step, evaluated the impact of post-processing quality control (QC) procedures on identified trajectories. The quality-controlled sample included 384 individual subjects with repeated scanning (1-3 per subject, total scans n=753) from 4.9 to 22.3years of age. The best-fit model (cubic, quadratic, or first-order linear) was identified at each vertex using mixed-effects models. The majority of brain regions showed linear monotonic decline of CTh. There were few areas of cubic trajectories, mostly in bilateral temporo-parietal areas and the right prefrontal cortex, in which CTh peaks were at, or prior to, age 8. When controlling for total brain volume, CTh trajectories were even more uniformly linear. The only sex difference was faster thinning of occipital areas in boys compared to girls. The best-fit model for whole brain mean thickness was a monotonic decline of 0.027mm per year. QC procedures had a significant impact on identified trajectories, with a clear shift toward more complex trajectories (i.e., quadratic or cubic) when including all scans without QC (n=954). Trajectories were almost exclusively linear when using only scans that passed the most stringent QC (n=598). The impact of QC probably relates to decreasing the inclusion of scans with CTh underestimation secondary to movement artifacts, which are more common in younger subjects. In summary, our results suggest that CTh follows a simple linear decline in most cortical areas by age 5, and all areas by age 8. This study further supports the crucial importance of implementing post-processing QC in CTh studies

  11. 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

  12. 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

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

    PubMed

    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.

  14. 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

  15. 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

  16. 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

  17. COMT Val158Met genotype influences neurodegeneration within dopamine-innervated brain structures

    PubMed Central

    Gennatas, E.D.; Cholfin, J.A.; Zhou, J.; Crawford, R.K.; Sasaki, D.A.; Karydas, A.; Boxer, A.L.; Bonasera, S.J.; Rankin, K.P.; Gorno-Tempini, M.L.; Rosen, H.J.; Kramer, J.H.; Weiner, M.; Miller, B.L.

    2012-01-01

    Objective: We sought to determine whether the Val158Met polymorphism in the catechol-O-methyltransferase (COMT) gene influences neurodegeneration within dopamine-innervated brain regions. Methods: A total of 252 subjects, including healthy controls and patients with Alzheimer disease, behavioral variant frontotemporal dementia, and semantic dementia, underwent COMT genotyping and structural MRI. Results: Whole-brain voxel-wise regression analyses revealed that COMT Val158Met Val allele dosage, known to produce a dose-dependent decrease in synaptic dopamine (DA) availability, correlated with decreased gray matter in the region of the ventral tegmental area (VTA), ventromedial prefrontal cortex, bilateral dorsal midinsula, left dorsolateral prefrontal cortex, and right ventral striatum. Unexpectedly, patients carrying a Met allele showed greater VTA volumes than age-matched controls. Gray matter intensities within COMT-related brain regions correlated with cognitive and behavioral deficits. Conclusions: The results are consistent with the hypothesis that increased synaptic DA catabolism promotes neurodegeneration within DA-innervated brain regions. PMID:22573634

  18. Non-fluent progressive aphasia: cerebral metabolic patterns and brain reserve.

    PubMed

    Perneczky, Robert; Diehl-Schmid, Janine; Pohl, Corina; Drzezga, Alexander; Kurz, Alexander

    2007-02-16

    Functional imaging studies suggest that brain reserve allows patients with Alzheimer's disease with more years of schooling to cope better with brain damage. No studies exist on patients with non-fluent progressive aphasia (NFPA). We aimed to explore metabolic patterns of patients with NFPA and to provide evidence for brain reserve in NFPA. 11 right-handed patients with NFPA and 16 age-matched controls underwent (18)F-FDG PET imaging. Scans of patients and controls were compared in SPM2. A linear regression analysis with glucose metabolism as dependent variable and years of schooling as the independent variable, adjusted for age, gender, and a total score of the CERAD neuropsychological battery was conducted. The NFPA group showed a hypometabolism of the left hemisphere including the middle frontal, and inferior temporal and angular gyri, and the bilateral caudate nuclei and thalami (p(corr)<0.05). The regression analysis revealed a significant inverse association between education and glucose metabolism in the left inferior temporal, parahippocampal, and supramarginal gyri (p(corr)<0.05). We conclude that brain reserve is also present in NFPA. PMID:17184752

  19. The effects of treatment for posterior fossa brain tumors on selective attention.

    PubMed

    Mabbott, Donald J; Snyder, Janice J; Penkman, Louise; Witol, Adrienne

    2009-03-01

    We sought to identify whether deficits in selective attention are present in pediatric brain tumor patients. Selective attention was assessed with covert-orienting, filtering, and visual-search tasks in 54 patients with either (1) posterior fossa (PF) tumors treated with cranial radiation and surgery (n = 22); (2) PF tumors treated with surgery alone (n = 17); or (3) non-CNS tumors (n = 15), who served as a patient control group. To account for normal development, patient performance was also compared with that of healthy age-matched controls (n = 10). We found that in PF tumor patients selective attention was impaired, regardless of whether they were treated with cranial radiation and surgery or surgery alone. However, patients treated with cranial radiation were most impaired. These patients may have greater damage to posterior brain regions know to mediate selective attention as the result of tumor location, effects of surgery, and higher doses of radiation to the posterior regions of the brain. These findings help to elucidate the potential impact of pediatric brain tumors and their treatment on discrete attentional skills.

  20. A study on small-world brain functional networks altered by postherpetic neuralgia.

    PubMed

    Zhang, Yue; Liu, Jing; Li, Longchuan; Du, Minyi; Fang, Wenxue; Wang, Dongxin; Jiang, Xuexiang; Hu, Xiaoping; Zhang, Jue; Wang, Xiaoying; Fang, Jing

    2014-05-01

    Understanding the effect of postherpetic neuralgia (PHN) pain on brain activity is important for clinical strategies. This is the first study, to our knowledge, to relate PHN pain to small-world properties of brain functional networks. Functional magnetic resonance imaging (fMRI) was used to construct functional brain networks of the subjects during the resting state. Sixteen patients with PHN pain and 16 (8 males, 8 females for both groups) age-matched controls were studied. The PHN patients exhibited decreased local efficiency along with non-significant changes of global efficiency in comparison with the healthy controls. Moreover, regional nodal efficiency was found to be significantly affected by PHN pain in the areas related to sense (postcentral gyrus, inferior parietal gyrus and thalamus), memory/affective processes (parahippocampal gyrus) and emotional activities (putamen). Significant correlation (p<0.05) was also found between the nodal efficiency of putamen and pain intensity in PHN patients. Our results suggest that PHN modulates the local efficiency, and the small-world properties of brain networks may have potentials to objectively evaluate pain information in clinic.

  1. Method for measurement of the blood-brain barrier permeability in the perfused mouse brain: application to amyloid-beta peptide in wild type and Alzheimer's Tg2576 mice.

    PubMed

    LaRue, Barbra; Hogg, Elizabeth; Sagare, Abhay; Jovanovic, Suzana; Maness, Lawrence; Maurer, Calvin; Deane, Rashid; Zlokovic, Berislav V

    2004-09-30

    The role of transport exchanges of neuroactive solutes across the blood-brain barrier (BBB) is increasingly recognized. To take full advantage of genetically altered mouse models of neurodegenerative disorders for BBB transport studies, we adapted a brain perfusion technique to the mouse. During a carotid brain perfusion with a medium containing sheep red blood cells and mock plasma, the physiological parameters in the arterial inflow, regional cerebral blood flow (14C-iodoantipyrine autoradiography), ultrastructural integrity of the tissue, barrier to lanthanum, brain water content, energy metabolites and lactate levels remain unchanged. Amyloid-beta peptides (Abeta) were iodinated by lactoperoxidase method. Non-oxidized mono-iodinated Abeta monomers were separated by HPLC (as confirmed by MALDI-TOF spectrometry) and used in transport measurements. Transport of intact 125I-Abeta40 across the BBB was time- and concentration-dependent in contrast to negligible 14C-inulin uptake. In 5-6 months old Alzheimer's Tg2576 mice, Abeta40 BBB transport was increased by >eight-fold compared to age-matched littermate controls, and was mediated via the receptor for advanced glycation endproducts. We conclude the present arterial brain perfusion method provides strictly controlled environment in cerebral microcirculation suitable for examining transport of rapidly and slowly penetrating molecules across the BBB in normal and transgenic mice.

  2. 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

  3. p21-Activated kinases 1 and 3 control brain size through coordinating neuronal complexity and synaptic properties.

    PubMed

    Huang, Wayne; Zhou, Zikai; Asrar, Suhail; Henkelman, Mark; Xie, Wei; Jia, Zhengping

    2011-02-01

    The molecular mechanisms that coordinate postnatal brain enlargement, synaptic properties, and cognition remain an enigma. Here, we demonstrate that neuronal complexity controlled by p21-activated kinases (PAKs) is a key determinant for postnatal brain enlargement and synaptic properties. We showed that double-knockout (DK) mice lacking both PAK1 and PAK3 were born healthy, with normal brain size and structure, but severely impaired in postnatal brain growth, resulting in a dramatic reduction in brain volume. Remarkably, the reduced brain size was accompanied by minimal changes in total cell count, due to a significant increase in cell density. However, the DK neurons have smaller soma, markedly simplified dendritic arbors/axons, and reduced synapse density. Surprisingly, the DK mice had elevated basal synaptic responses due to enhanced individual synaptic potency but were severely impaired in bidirectional synaptic plasticity. The actions of PAK1 and PAK3 are possibly mediated by cofilin-dependent actin regulation, because the activity of cofilin and the properties of actin filaments were altered in the DK mice. These results reveal an essential in vivo role of PAK1 and PAK3 in coordinating neuronal complexity and synaptic properties and highlight the critical importance of dendrite/axon growth in dictating postnatal brain growth and attainment of normal brain size and function.

  4. Brain monoamines and peptides: role in the control of eating behavior.

    PubMed

    Leibowitz, S F

    1986-04-01

    Studies of brain monoamines and neuropeptides have provided extensive evidence in support of their role in the control of normal eating behavior. In this process, the medial and lateral portions of the hypothalamus, working in conjunction with forebrain and hindbrain sites and with peripheral autonomic-endocrine systems, have a critical responsibility in balancing signals for hunger and satiety. Via its rich and biologically active neurotransmitter substances, the hypothalamus monitors and integrates the complex sensory and metabolic input concerning the nutritional status of the organism and transduces this information into appropriate quantitative and qualitative adjustments in food intake. The specific neurotransmitters for which there is the most extensive evidence for a physiological function include the eating-stimulatory substances norepinephrine (alpha 2), opioid peptides, pancreatic polypeptides, growth hormone-releasing factor, and gamma-aminobutyric acid; the eating-inhibitory substances dopamine, epinephrine, serotonin, cholecystokinin, neurotensin, calcitonin, glucagon, and corticotropin-releasing factor; and possibly other gut-brain peptides. From biochemical, pharmacological, and anatomical studies, hypotheses have been generated to explain the role of these various monoamines and neuropeptides in controlling total energy intake, in determining the amount and pattern of macronutrient selection, and in maintaining normal energy and nutrient stores under fluctuating conditions within the external environment.

  5. Use of bipolar parallel electrodes for well-controlled microstimulation in a mouse hippocampal brain slice.

    PubMed

    Neagu, Bogdan; Strominger, Norman L; Carpenter, David O

    2005-06-15

    In a hippocampal brain slice two types of stimulating electrodes [single (SE) or monopolar and parallel bipolar (PE)] were used to determine the optimal protocol for single pulse microstimulation. We show that even for a constant-current power source the amplitude of stimulating current (SC) is not constant, especially for short pulse widths (PW) (<200 micros). Recording the stimulating current and computing the amount of electric charge that is passed through the microelectrode gives the best estimate of the strength of electrical stimulation. For SE the evoked response is obstructed for a time interval larger than three times the PW. The stimulus artifact (SA) substantially decreases when a PE is used. The orientation of the stimulating current relative to the position of the targeted fibers (Schaffer collaterals) was controlled when using a PE. The use of PEs allowed the accurate recording of the physiological response that contains three clearly defined peaks. Stimulation can be elicited at PW as short as 30 micros when the main current is capacitive. The charge needed to elicit physiological responses was in the range of 1-40 nC (the lower values for the PE) suggesting that use of PEs is most advantageous for well-controlled microstimulation studies in brain slices.

  6. Neural control of cross-language asymmetry in the bilingual brain.

    PubMed

    Nakamura, Kimihiro; Kouider, Sid; Makuuchi, Michiru; Kuroki, Chihiro; Hanajima, Ritsuko; Ugawa, Yoshikazu; Ogawa, Seiji

    2010-09-01

    Most bilinguals understand their second language more slowly than their first. This behavioral asymmetry may arise from the perceptual, phonological, lexicosemantic, or strategic components of bilingual word processing. However, little is known about the neural source of such language dominance and how it is regulated in the bilingual brain. Using functional magnetic resonance imaging, we found that unconscious neural priming in bilingual word recognition is language nonselective in the left midfusiform gyrus but exhibits a preference for the dominant language in the left posterior middle temporal gyrus (MTG). These early-stage components of reading were located slightly upstream of the left midlateral MTG, which exhibited enhanced response during a conscious switch of language. Effective connectivity analysis revealed that this language switch is triggered by reentrant signals from inferior frontal cortex and not by bottom-up signals from occipitotemporal cortex. We further confirmed that magnetic stimulation of the same inferior frontal region interferes with conscious language control but does not disrupt unconscious priming by masked words. Collectively, our results demonstrate that the neural bottleneck in the bilingual brain is a cross-language asymmetry of form-meaning association in inferolateral temporal cortex, which is overcome by a top-down cognitive control for implementing a task schema in each language.

  7. Inflammation and white matter degeneration persist for years after a single traumatic brain injury.

    PubMed

    Johnson, Victoria E; Stewart, Janice E; Begbie, Finn D; Trojanowski, John Q; Smith, Douglas H; Stewart, William

    2013-01-01

    A single traumatic brain injury is associated with an increased risk of dementia and, in a proportion of patients surviving a year or more from injury, the development of hallmark Alzheimer's disease-like pathologies. However, the pathological processes linking traumatic brain injury and neurodegenerative disease remain poorly understood. Growing evidence supports a role for neuroinflammation in the development of Alzheimer's disease. In contrast, little is known about the neuroinflammatory response to brain injury and, in particular, its temporal dynamics and any potential role in neurodegeneration. Cases of traumatic brain injury with survivals ranging from 10 h to 47 years post injury (n = 52) and age-matched, uninjured control subjects (n = 44) were selected from the Glasgow Traumatic Brain Injury archive. From these, sections of the corpus callosum and adjacent parasaggital cortex were examined for microglial density and morphology, and for indices of white matter pathology and integrity. With survival of ≥3 months from injury, cases with traumatic brain injury frequently displayed extensive, densely packed, reactive microglia (CR3/43- and/or CD68-immunoreactive), a pathology not seen in control subjects or acutely injured cases. Of particular note, these reactive microglia were present in 28% of cases with survival of >1 year and up to 18 years post-trauma. In cases displaying this inflammatory pathology, evidence of ongoing white matter degradation could also be observed. Moreover, there was a 25% reduction in the corpus callosum thickness with survival >1 year post-injury. These data present striking evidence of persistent inflammation and ongoing white matter degeneration for many years after just a single traumatic brain injury in humans. Future studies to determine whether inflammation occurs in response to or, conversely, promotes white matter degeneration will be important. These findings may provide parallels for studying neurodegenerative disease

  8. 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.

  9. Increased levels of 4-hydroxynonenal and acrolein in the brain in preclinical Alzheimer’s disease (PCAD)

    PubMed Central

    Bradley, M. A.; Markesbery, W. R.

    2010-01-01

    Previous studies demonstrate increased levels of 4-hydroxynonenal (HNE) and acrolein in vulnerable brain regions of subjects with mild cognitive impairment (MCI) and late-stage Alzheimer’s disease (AD). Recently preclinical AD (PCAD) subjects, who demonstrate normal antemortem neuropsychological test scores but abundant AD pathology at autopsy, have become the focus of increased study. Levels of extractable HNE and acrolein were quantified by gas chromatography mass spectrometry with negative chemical ionization and protein-bound HNE and acrolein was quantified by dot-blot immunohistochemistry in the hippocampus/parahippocampal gyrus (HPG), superior and middle temporal gyri (SMTG), and cerebellum (CER) of 10 PCAD and 10 age-matched normal control (NC) subjects. Results of the analyses show a significant (p < 0.05) increase in levels of extractable acrolein in HPG of PCAD subjects compared to age-matched NC subjects and a significant decrease of extractable acrolein in PCAD CER. A significant increase in protein-bound HNE in HPG and a significant decrease in CER of PCAD subjects compared to NC subjects was observed. No significant alterations were observed in either extractable or protein-bound HNE or acrolein in the SMTG of PCAD subjects. Additionally, no significant differences in levels of protein carbonyls were observed in the HPG, SMTG, or CER of PCAD subjects compared to NC subjects. PMID:20171275

  10. 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

  11. 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

  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.

  13. Cocaine- and amphetamine-regulated transcript (CART) peptide immunoreactivity in feeding- and reward-related brain areas of young OLETF rats.

    PubMed

    Armbruszt, Simon; Abraham, Hajnalka; Figler, Maria; Kozicz, Tamas; Hajnal, Andras

    2013-05-01

    Cocaine- and amphetamine-regulated transcript (CART) peptide is expressed in brain areas involved in the control of appetite, drug reward and homeostatic regulation and it has an overall anorexigenic effect. Recently, we have shown that CART peptide immunoreactivity was significantly reduced in the rostral part of the nucleus accumbens and in the rostro-medial part of the nucleus of the solitary tract in adult CCK-1 receptor deficient obese diabetic Otsuka Long Evans Tokushima Fatty (OLETF) rats compared to Long Evans Tokushima Otsuka (LETO) lean controls. It is not clear, however, whether altered CART expression is caused primarily by the deficiency in CCK-1 signaling or whether is related to the obese and diabetic phenotype of the OLETF strain which develops at a later age. Therefore, in the present study, CART-immunoreaction in feeding-related areas of the brain was compared in young, age-matched (6-7 weeks old) non-obese, non-diabetic OLETF rats and in LETO controls. We found that, young, non-diabetic OLETF rats revealed unaltered distribution of CART-peptide expressing neurons and axons throughout the brain when compared to age-matched LETO rats. In contrast to previous results observed in the obese diabetic adult rats, intensity of CART immunoreaction did not differ in the areas related to control of food-intake and reward in the young OLETFs compared to young LETO rats. Our findings suggest that factors secondary to obesity and/or diabetes rather than impaired CCK-1 receptor signaling may contribute to altered CART expression in the OLETF strain. PMID:23545074

  14. Cocaine- and amphetamine-regulated transcript (CART) peptide immunoreactivity in feeding- and reward-related brain areas of young OLETF rats

    PubMed Central

    Armbruszt, Simon; Abraham, Hajnalka; Figler, Maria; Kozicz, Tamas; Hajnal, Andras

    2013-01-01

    Cocaine- and amphetamine regulated transcript (CART) peptide is expressed in brain areas involved in the control of appetite, drug reward and homeostatic regulation and it has an overall anorexigenic effect. Recently, we have shown that CART peptide immunoreactivity was significantly reduced in the rostral part of the nucleus accumbens and in the rostro-medial part of the nucleus of the solitary tract in adult CCK-1 receptor deficient obese diabetic Otsuka Long Evans Tokushima Fatty (OLETF) rats compared to Long Evans Tokushima Otsuka (LETO) lean controls. It is not clear, however, whether altered CART expression is caused primarily by the deficiency in CCK-1 signaling or whether is related to the obese and diabetic phenotype of the OLETF strain which develops at a later age. Therefore, in the present study, CART-immunoreaction in feeding-related areas of the brain was compared in young, age-matched (6-7 weeks old) non-obese, non-diabetic OLETF rats and in LETO controls. We found that, young, non-diabetic OLETF rats revealed unaltered distribution of CART-peptide expressing neurons and axons throughout the brain when compared to age-matched LETO rats. In contrast to previous results observed in the obese diabetic adult rats, intensity of CART immunoreaction did not differ in the areas related to control of food-intake and reward in the young OLETFs compared to young LETO rats. Our findings suggest that factors secondary to obesity and/or diabetes rather than impaired CCK-1 receptor signaling may contribute to altered CART expression in the OLETF strain. PMID:23545074

  15. 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

  16. Brain-controlled muscle stimulation for the restoration of motor function.

    PubMed

    Ethier, Christian; Miller, Lee E

    2015-11-01

    Loss of the ability to move, as a consequence of spinal cord injury or neuromuscular disorder, has devastating consequences for the paralyzed individual, and great economic consequences for society. Functional electrical stimulation (FES) offers one means to restore some mobility to these individuals, improving not only their autonomy, but potentially their general health and well-being as well. FES uses electrical stimulation to cause the paralyzed muscles to contract. Existing clinical systems require the stimulation to be preprogrammed, with the patient typically using residual voluntary movement of another body part to trigger and control the patterned stimulation. The rapid development of neural interfacing in the past decade offers the promise of dramatically improved control for these patients, potentially allowing continuous control of FES through signals recorded from motor cortex, as the patient attempts to control the paralyzed body part. While application of these 'brain-machine interfaces' (BMIs) has undergone dramatic development for control of computer cursors and even robotic limbs, their use as an interface for FES has been much more limited. In this review, we consider both FES and BMI technologies and discuss the prospect for combining the two to provide important new options for paralyzed individuals. PMID:25447224

  17. 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

  18. Brain-controlled muscle stimulation for the restoration of motor function

    PubMed Central

    Ethier, Christian; Miller, Lee E

    2014-01-01

    Loss of the ability to move, as a consequence of spinal cord injury or neuromuscular disorder, has devastating consequences for the paralyzed individual, and great economic consequences for society. Functional Electrical Stimulation (FES) offers one means to restore some mobility to these individuals, improving not only their autonomy, but potentially their general health and well-being as well. FES uses electrical stimulation to cause the paralyzed muscles to contract. Existing clinical systems require the stimulation to be preprogrammed, with the patient typically using residual voluntary movement of another body part to trigger and control the patterned stimulation. The rapid development of neural interfacing in the past decade offers the promise of dramatically improved control for these patients, potentially allowing continuous control of FES through signals recorded from motor cortex, as the patient attempts to control the paralyzed body part. While application of these ‘Brain Machine Interfaces’ (BMIs) has undergone dramatic development for control of computer cursors and even robotic limbs, their use as an interface for FES has been much more limited. In this review, we consider both FES and BMI technologies and discuss the prospect for combining the two to provide important new options for paralyzed individuals. PMID:25447224

  19. Brain-controlled muscle stimulation for the restoration of motor function.

    PubMed

    Ethier, Christian; Miller, Lee E

    2015-11-01

    Loss of the ability to move, as a consequence of spinal cord injury or neuromuscular disorder, has devastating consequences for the paralyzed individual, and great economic consequences for society. Functional electrical stimulation (FES) offers one means to restore some mobility to these individuals, improving not only their autonomy, but potentially their general health and well-being as well. FES uses electrical stimulation to cause the paralyzed muscles to contract. Existing clinical systems require the stimulation to be preprogrammed, with the patient typically using residual voluntary movement of another body part to trigger and control the patterned stimulation. The rapid development of neural interfacing in the past decade offers the promise of dramatically improved control for these patients, potentially allowing continuous control of FES through signals recorded from motor cortex, as the patient attempts to control the paralyzed body part. While application of these 'brain-machine interfaces' (BMIs) has undergone dramatic development for control of computer cursors and even robotic limbs, their use as an interface for FES has been much more limited. In this review, we consider both FES and BMI technologies and discuss the prospect for combining the two to provide important new options for paralyzed individuals.

  20. 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…

  1. Aerobic Fitness and Cognitive Development: Event-Related Brain Potential and Task Performance Indices of Executive Control in Preadolescent Children

    ERIC Educational Resources Information Center

    Hillman, Charles H.; Buck, Sarah M.; Themanson, Jason R.; Pontifex, Matthew B.; Castelli, Darla M.

    2009-01-01

    The relationship between aerobic fitness and executive control was assessed in 38 higher- and lower-fit children (M[subscript age] = 9.4 years), grouped according to their performance on a field test of aerobic capacity. Participants performed a flanker task requiring variable amounts of executive control while event-related brain potential…

  2. 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.

  3. Context, emotion, and the strategic pursuit of goals: interactions among multiple brain systems controlling motivated behavior.

    PubMed

    Gruber, Aaron J; McDonald, Robert J

    2012-01-01

    Motivated behavior exhibits properties that change with experience and partially dissociate among a number of brain structures. Here, we review evidence from rodent experiments demonstrating that multiple brain systems acquire information in parallel and either cooperate or compete for behavioral control. We propose a conceptual model of systems interaction wherein a ventral emotional memory network involving ventral striatum (VS), amygdala, ventral hippocampus, and ventromedial prefrontal cortex triages behavioral responding to stimuli according to their associated affective outcomes. This system engages autonomic and postural responding (avoiding, ignoring, approaching) in accordance with associated stimulus valence (negative, neutral, positive), but does not engage particular operant responses. Rather, this emotional system suppresses or invigorates actions that are selected through competition between goal-directed control involving dorsomedial striatum (DMS) and habitual control involving dorsolateral striatum (DLS). The hippocampus provides contextual specificity to the emotional system, and provides an information rich input to the goal-directed system for navigation and discriminations involving ambiguous contexts, complex sensory configurations, or temporal ordering. The rapid acquisition and high capacity for episodic associations in the emotional system may unburden the more complex goal-directed system and reduce interference in the habit system from processing contingencies of neutral stimuli. Interactions among these systems likely involve inhibitory mechanisms and neuromodulation in the striatum to form a dominant response strategy. Innate traits, training methods, and task demands contribute to the nature of these interactions, which can include incidental learning in non-dominant systems. Addition of these features to reinforcement learning models of decision-making may better align theoretical predictions with behavioral and neural correlates in

  4. Context, emotion, and the strategic pursuit of goals: interactions among multiple brain systems controlling motivated behavior

    PubMed Central

    Gruber, Aaron J.; McDonald, Robert J.

    2012-01-01

    Motivated behavior exhibits properties that change with experience and partially dissociate among a number of brain structures. Here, we review evidence from rodent experiments demonstrating that multiple brain systems acquire information in parallel and either cooperate or compete for behavioral control. We propose a conceptual model of systems interaction wherein a ventral emotional memory network involving ventral striatum (VS), amygdala, ventral hippocampus, and ventromedial prefrontal cortex triages behavioral responding to stimuli according to their associated affective outcomes. This system engages autonomic and postural responding (avoiding, ignoring, approaching) in accordance with associated stimulus valence (negative, neutral, positive), but does not engage particular operant responses. Rather, this emotional system suppresses or invigorates actions that are selected through competition between goal-directed control involving dorsomedial striatum (DMS) and habitual control involving dorsolateral striatum (DLS). The hippocampus provides contextual specificity to the emotional system, and provides an information rich input to the goal-directed system for navigation and discriminations involving ambiguous contexts, complex sensory configurations, or temporal ordering. The rapid acquisition and high capacity for episodic associations in the emotional system may unburden the more complex goal-directed system and reduce interference in the habit system from processing contingencies of neutral stimuli. Interactions among these systems likely involve inhibitory mechanisms and neuromodulation in the striatum to form a dominant response strategy. Innate traits, training methods, and task demands contribute to the nature of these interactions, which can include incidental learning in non-dominant systems. Addition of these features to reinforcement learning models of decision-making may better align theoretical predictions with behavioral and neural correlates in

  5. Context, emotion, and the strategic pursuit of goals: interactions among multiple brain systems controlling motivated behavior.

    PubMed

    Gruber, Aaron J; McDonald, Robert J

    2012-01-01

    Motivated behavior exhibits properties that change with experience and partially dissociate among a number of brain structures. Here, we review evidence from rodent experiments demonstrating that multiple brain systems acquire information in parallel and either cooperate or compete for behavioral control. We propose a conceptual model of systems interaction wherein a ventral emotional memory network involving ventral striatum (VS), amygdala, ventral hippocampus, and ventromedial prefrontal cortex triages behavioral responding to stimuli according to their associated affective outcomes. This system engages autonomic and postural responding (avoiding, ignoring, approaching) in accordance with associated stimulus valence (negative, neutral, positive), but does not engage particular operant responses. Rather, this emotional system suppresses or invigorates actions that are selected through competition between goal-directed control involving dorsomedial striatum (DMS) and habitual control involving dorsolateral striatum (DLS). The hippocampus provides contextual specificity to the emotional system, and provides an information rich input to the goal-directed system for navigation and discriminations involving ambiguous contexts, complex sensory configurations, or temporal ordering. The rapid acquisition and high capacity for episodic associations in the emotional system may unburden the more complex goal-directed system and reduce interference in the habit system from processing contingencies of neutral stimuli. Interactions among these systems likely involve inhibitory mechanisms and neuromodulation in the striatum to form a dominant response strategy. Innate traits, training methods, and task demands contribute to the nature of these interactions, which can include incidental learning in non-dominant systems. Addition of these features to reinforcement learning models of decision-making may better align theoretical predictions with behavioral and neural correlates in

  6. 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

  7. 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.

  8. 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.

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

    PubMed

    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 192Ir. 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 192Ir 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 192Ir 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 192Ir loads. The bedside shield reduces exposure from 192Ir implants by a factor of about 20, as expected, and the exposure from the lower energy radioisotope iodine-125 is barely detectable.

  10. 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.

  11. 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

  12. 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

  13. Adaptive deep brain stimulation (aDBS) controlled by local field potential oscillations.

    PubMed

    Priori, Alberto; Foffani, Guglielmo; Rossi, Lorenzo; Marceglia, Sara

    2013-07-01

    Despite their proven efficacy in treating neurological disorders, especially Parkinson's disease, deep brain stimulation (DBS) systems could be further optimized to maximize treatment benefits. In particular, because current open-loop DBS strategies based on fixed stimulation settings leave the typical parkinsonian motor fluctuations and rapid symptom variations partly uncontrolled, research has for several years focused on developing novel "closed-loop" or "adaptive" DBS (aDBS) systems. aDBS consists of a simple closed-loop model designed to measure and analyze a control variable reflecting the patient's clinical condition to elaborate new stimulation settings and send them to an "intelligent" implanted stimulator. The major problem in developing an aDBS system is choosing the ideal control variable for feedback. Here we review current evidence on the advantages of neurosignal-controlled aDBS that uses local field potentials (LFPs) as a control variable, and describe the technology already available to create new aDBS systems, and the potential benefits of aDBS for patients with Parkinson's disease. PMID:23022916

  14. 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

  15. 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.

  16. Dual-tasking postural control in patients with right brain damage.

    PubMed

    Bourlon, Clémence; Lehenaff, Laurent; Batifoulier, Cécile; Bordier, Aurélie; Chatenet, Aurélia; Desailly, Eric; Fouchard, Christian; Marsal, Muriel; Martinez, Marianne; Rastelli, Federica; Thierry, Anaïs; Bartolomeo, Paolo; Duret, Christophe

    2014-01-01

    The control of dual-tasking effects is a daily challenge in stroke neurorehabilitation. It maybe one of the reasons why there is poor functional prognosis after a stroke in the right hemisphere, which plays a dominant role in posture control. The purpose of this study was to explore cognitive motor interference in right brain-lesioned and healthy subjects maintaining a standing position while performing three different tasks: a control task, a simple attentional task and a complex attentional task. We measured the sway area of the subjects on a force platform, including the center of pressure and its displacements. Results showed that stroke patients presented a reduced postural sway compared to healthy subjects, who were able to maintain their posture while performing a concomitant attentional task in the same dual-tasking conditions. Moreover, in both groups, the postural sway decreased with the increase in attentional load from cognitive tasks. We also noticed that the stability of stroke patients in dual-tasking conditions increased together with the weight-bearing rightward deviation, especially when the attentional load of the cognitive tasks and lower limb motor impairments were high. These results suggest that stroke patients and healthy subjects adopt a similar postural regulation pattern aimed at maintaining stability in dual-tasking conditions involving a static standing position and different attention-related cognitive tasks. Our results indicate that attention processes might facilitate static postural control.

  17. 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

  18. 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.

  19. Bilingualism alters brain functional connectivity between "control" regions and "language" regions: Evidence from bimodal bilinguals.

    PubMed

    Li, Le; Abutalebi, Jubin; Zou, Lijuan; Yan, Xin; Liu, Lanfang; Feng, Xiaoxia; Wang, Ruiming; Guo, Taomei; Ding, Guosheng

    2015-05-01

    Previous neuroimaging studies have revealed that bilingualism induces both structural and functional neuroplasticity in the dorsal anterior cingulate cortex (dACC) and the left caudate nucleus (LCN), both of which are associated with cognitive control. Since these "control" regions should work together with other language regions during language processing, we hypothesized that bilingualism may also alter the functional interaction between the dACC/LCN and language regions. Here we tested this hypothesis by exploring the functional connectivity (FC) in bimodal bilinguals and monolinguals using functional MRI when they either performed a picture naming task with spoken language or were in resting state. We found that for bimodal bilinguals who use spoken and sign languages, the FC of the dACC with regions involved in spoken language (e.g. the left superior temporal gyrus) was stronger in performing the task, but weaker in the resting state as compared to monolinguals. For the LCN, its intrinsic FC with sign language regions including the left inferior temporo-occipital part and right inferior and superior parietal lobules was increased in the bilinguals. These results demonstrate that bilingual experience may alter the brain functional interaction between "control" regions and "language" regions. For different control regions, the FC alters in different ways. The findings also deepen our understanding of the functional roles of the dACC and LCN in language processing. PMID:25858600

  20. P300-based brain-computer interface for environmental control: an asynchronous approach

    NASA Astrophysics Data System (ADS)

    Aloise, F.; Schettini, F.; Aricò, P.; Leotta, F.; Salinari, S.; Mattia, D.; Babiloni, F.; Cincotti, F.

    2011-04-01

    Brain-computer interface (BCI) systems allow people with severe motor disabilities to communicate and interact with the external world. The P300 potential is one of the most used control signals for EEG-based BCIs. Classic P300-based BCIs work in a synchronous mode; the synchronous control assumes that the user is constantly attending to the stimulation, and the number of stimulation sequences is fixed a priori. This issue is an obstacle for the use of these systems in everyday life; users will be engaged in a continuous control state, their distractions will cause misclassification and the speed of selection will not take into account users' current psychophysical condition. An efficient BCI system should be able to understand the user's intentions from the ongoing EEG instead. Also, it has to refrain from making a selection when the user is engaged in a different activity and it should increase or decrease its speed of selection depending on the current user's state. We addressed these issues by introducing an asynchronous BCI and tested its capabilities for effective environmental monitoring, involving 11 volunteers in three recording sessions. Results show that this BCI system can increase the bit rate during control periods while the system is proved to be very efficient in avoiding false negatives when the users are engaged in other tasks.

  1. Bilingualism alters brain functional connectivity between "control" regions and "language" regions: Evidence from bimodal bilinguals.

    PubMed

    Li, Le; Abutalebi, Jubin; Zou, Lijuan; Yan, Xin; Liu, Lanfang; Feng, Xiaoxia; Wang, Ruiming; Guo, Taomei; Ding, Guosheng

    2015-05-01

    Previous neuroimaging studies have revealed that bilingualism induces both structural and functional neuroplasticity in the dorsal anterior cingulate cortex (dACC) and the left caudate nucleus (LCN), both of which are associated with cognitive control. Since these "control" regions should work together with other language regions during language processing, we hypothesized that bilingualism may also alter the functional interaction between the dACC/LCN and language regions. Here we tested this hypothesis by exploring the functional connectivity (FC) in bimodal bilinguals and monolinguals using functional MRI when they either performed a picture naming task with spoken language or were in resting state. We found that for bimodal bilinguals who use spoken and sign languages, the FC of the dACC with regions involved in spoken language (e.g. the left superior temporal gyrus) was stronger in performing the task, but weaker in the resting state as compared to monolinguals. For the LCN, its intrinsic FC with sign language regions including the left inferior temporo-occipital part and right inferior and superior parietal lobules was increased in the bilinguals. These results demonstrate that bilingual experience may alter the brain functional interaction between "control" regions and "language" regions. For different control regions, the FC alters in different ways. The findings also deepen our understanding of the functional roles of the dACC and LCN in language processing.

  2. Blood-Brain Barrier Disruption Is an Early Event That May Persist for Many Years After Traumatic Brain Injury in Humans.

    PubMed

    Hay, Jennifer R; Johnson, Victoria E; Young, Adam M H; Smith, Douglas H; Stewart, William

    2015-12-01

    Traumatic brain injury (TBI) is a risk factor for dementia. Mixed neurodegenerative pathologies have been described in late survivors of TBI, but the mechanisms driving post-TBI neurodegeneration remain elusive. Increasingly, blood-brain barrier (BBB) disruption has been recognized in a range of neurologic disorders including dementias, but little is known of the consequences of TBI on the BBB. Autopsy cases of single moderate or severe TBI from the Glasgow TBI Archive (n = 70) were selected to include a range from acute (10 hours-13 days) to long-term (1-47 years) survival, together with age-matched uninjured controls (n = 21). Multiple brain regions were examined using immunohistochemistry for the BBB integrity markers fibrinogen and immunoglobulin G. After TBI, 40% of patients dying in the acute phase and 47% of those surviving a year or more from injury showed multifocal, abnormal, perivascular, and parenchymal fibrinogen and immunoglobulin G immunostaining localized to the gray matter, with preferential distribution toward the crests of gyri and deep neocortical layers. In contrast, when present, controls showed only limited localized immunostaining. These preliminary data demonstrate evidence of widespread BBB disruption in a proportion of TBI patients emerging in the acute phase and, intriguingly, persisting in a high proportion of late survivors. PMID:26574669

  3. 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

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

    PubMed

    Coughlin, Jennifer M; Wang, Yuchuan; 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

    2015-02-01

    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 [(11)C]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 [(11)C]DPA-713 binding to TSPO, may be linked to history of NFL play. [(11)C]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

  5. Potential risk factors for brain tumors in children. An analysis of 200 cases.

    PubMed

    Giuffrè, R; Liccardo, G; Pastore, F S; Spallone, A; Vagnozzi, R

    1990-01-01

    Two hundred cases of verified brain tumors occurring in patients under 15 years of age were studied in relation to possible etiologic, genetic, and environmental risk factors. They were compared with 100 age-matched patients harboring solid neoplasms outside the nervous system, as well as with 100 normal children. In our study, first-degree relatives of a brain tumor child did not show a higher incidence of either tumors or of epilepsy and strokes as compared with controls. First-born children (46%) with higher birth weights showed a greater tendency to present brain tumors. Dystocia (18.5%), previous miscarriages (18%), and dietary restrictions during pregnancy (3%) were also noted in this study and compared with data in the literature. No evidence of a role of maternal chickenpox and toxoplasmosis could be found. The pharmacological risk also seemed to be minimal. The mother's hormonal profile is deduced from the age at menarche and delivery, as well as from a tendency to miscarriages and complicated pregnancies. With regard to the immunologic aspect, it is worth noting that 15% of the mothers complained of allergies. Live polio vaccine and zoonosis might suggest a possible role of virus-related factors in the oncogenesis of brain tumors in children. Radiation-related risk is possibly present in less than 5% of cases. Parental occupation is not relevant in this series.

  6. 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

  7. Acrolein is increased in Alzheimer's disease brain and is toxic to primary hippocampal cultures.

    PubMed

    Lovell, M A; Xie, C; Markesbery, W R

    2001-01-01

    Accumulating evidence implicates oxidative stress in the pathogenesis of several neurodegenerative diseases including Alzheimer's disease (AD). Increased lipid peroxidation, decreased levels of polyunsaturated fatty acids, and increased levels of 4-hydroxynonenal (HNE), F(2)-isoprostanes, and F(4)-neuroprostanes are present in the brain in AD. Acrolein, an alpha,beta-unsaturated aldehydic product of lipid peroxidation, is approximately 100 times more reactive than HNE and recently was demonstrated in neurofibrillary tangles in the brain in AD. In three brain regions of 10 AD patients compared with 8 age-matched control subjects, we found increased mean extractable acrolein, with the increases reaching statistical significance in the amygdala and hippocampus/parahippocampal gyrus. In hippocampal neuron cultures, acrolein was neurotoxic in a time- and concentration-dependent manner and more toxic than HNE at 5 microM concentrations of each. Acrolein exposure led to a significant concentration-dependent increase in intracellular calcium concentrations. Collectively, these data show that acrolein is increased in the brain in AD and demonstrate neurotoxicity mechanisms that might be important in the pathogenesis of neuron degeneration in AD.

  8. Cell cycle proteins in brain in mild cognitive impairment: insights into progression to Alzheimer disease.

    PubMed

    Keeney, Jeriel T R; Swomley, Aaron M; Harris, Jessica L; Fiorini, Ada; Mitov, Mihail I; Perluigi, Marzia; Sultana, Rukhsana; Butterfield, D Allan

    2012-10-01

    Recent studies have demonstrated the re-emergence of cell cycle proteins in brain as patients progress from the early stages of mild cognitive impairment (MCI) into Alzheimer's disease (AD). Oxidative stress markers present in AD have also been shown to be present in MCI brain suggesting that these events occur in early stages of the disease. The levels of key cell cycle proteins, such as CDK2, CDK5, cyclin G1, and BRAC1 have all been found to be elevated in MCI brain compared to age-matched control. Further, peptidyl prolyl cis-trans isomerase (Pin1), a protein that plays an important role in regulating the activity of key proteins, such as CDK5, GSK3-β, and PP2A that are involved in both the phosphorylation state of Tau and in the cell cycle, has been found to be oxidatively modified and downregulated in both AD and MCI brain. Hyperphosphorylation of Tau then results in synapse loss and the characteristic Tau aggregation as neurofibrillary tangles, an AD hallmark. In this review, we summarized the role of cell cycle dysregulation in the progression of disease from MCI to AD. Based on the current literature, it is tempting to speculate that a combination of oxidative stress and cell cycle dysfunction conceivably leads to neurodegeneration.

  9. Brain iron deposition in essential tremor: a quantitative 3-Tesla magnetic resonance imaging study.

    PubMed

    Novellino, Fabiana; Cherubini, Andrea; Chiriaco, Carmelina; Morelli, Maurizio; Salsone, Maria; Arabia, Gennarina; Quattrone, Aldo

    2013-02-01

    Studies have demonstrated brain iron deposition in neurodegenerative disease and in normal aging. Data on this topic are lacking in essential tremor (ET). The aim of our study was to investigate brain iron content in patients with ET, using quantitative magnetic resonance imaging (MRI) T2*-relaxometry. We enrolled 24 patients with ET and 25 age-matched healthy controls. Subjects were examined using a 3T MRI scanner. The protocol included conventional MRI sequences and quantitative T2*-relaxometry. Whole-brain voxel-based analyses showed significant differences in T2* values in bilateral globus pallidus, substantia nigra, and in right dentate nucleus (P < .001 uncorrected). In the bilateral pallidum, differences survived family-wise-error (FWE) correction for multiple comparisons (P < .05). The present study provides the first evidence of increased brain iron accumulation in ET patients. Our results are suggestive of a possible involvement of motor systems outside of the cerebellum/cerebellar pathway and, more specifically, of the globus pallidus.

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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

  19. 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

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

    NASA Astrophysics Data System (ADS)

    Rao, Mandavilli 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.

  1. Bilinguals use language-control brain areas more than monolinguals to perform non-linguistic switching tasks.

    PubMed

    Rodríguez-Pujadas, Aina; Sanjuán, Ana; Ventura-Campos, Noelia; Román, Patricia; Martin, Clara; Barceló, Francisco; Costa, Albert; Avila, 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.

  2. Modulation of Brain Activity during a Stroop Inhibitory Task by the Kind of Cognitive Control Required

    PubMed Central

    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

  3. 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

  4. Control of Drosophila Type I and Type II central brain neuroblast proliferation by bantam microRNA.

    PubMed

    Weng, Ruifen; Cohen, Stephen M

    2015-11-01

    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.

  5. Brain cancer and nonoccupational risk factors: a case-control study among workers at two nuclear facilities.

    PubMed Central

    Carpenter, A V; Flanders, W D; Frome, E L; Cole, P; Fry, S A

    1987-01-01

    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). PMID:3618849

  6. 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).

  7. 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

  8. Novel DTI Methodology to Detect and Quantify Injured Regions and Affected Brain Pathways in Traumatic Brain Injury

    PubMed Central

    Singh, Manbir; Jeong, Jeongwon; Hwang, Darryl; Sungkarat, Witaya; Gruen, Peter

    2009-01-01

    Purpose To develop and apply DTI based normalization methodology for the detection and quantification of traumatic brain injury (TBI) and the impact of injury along specific brain pathways in: a) individual TBI subjects, and b) a TBI group. Materials and Methods Normalized DTI tractography was conducted in the native space of 12 TBI and 10 age-matched control subjects using the same number of seeds in each subject, distributed at anatomically equivalent locations. Whole-brain tracts from the control group were mapped onto the head of each TBI subject. Differences in the Fractional Anisotropy (FA) maps between each TBI subject and the control group were computed in a common space using a t-test, transformed back to the individual TBI subject's head-space, and thresholded to form Regions of Interest (ROIs) that were used to sort tracts from the control group and the individual TBI subject. Tract-counts for a given ROI in each TBI subject were compared to group mean for the same ROI to quantify impact of injury along affected pathways. Same procedure was used to compare TBI group to control group in a common space. Results Sites of injury within individual TBI subjects and affected pathways included hippocampal/fornix, inferior fronto-occipital, inferior longitudinal fasciculus, corpus callosum (genu and splenium), cortico-spinal tracts and the uncinate fasciculus. Most of these regions were also detected in the group study. Conclusions The DTI normalization methodology presented here enables automatic delineation of ROIs within the heads of individual subjects (or in a group). These ROIs not only localize and quantify the extent of injury, but also quantify the impact of injury on affected pathways in an individual or a group of TBI subjects. PMID:19608369

  9. Brain-derived neurotrophic factor interacts with astrocytes and neurons to control respiration.

    PubMed

    Caravagna, Céline; Soliz, Jorge; Seaborn, Tommy

    2013-11-01

    Respiratory rhythm is generated and modulated in the brainstem. Neuronal involvement in respiratory control and rhythmogenesis is now clearly established. However, glial cells have also been shown to modulate the activity of brainstem respiratory groups. Although the potential involvement of other glial cell type(s) cannot be excluded, astrocytes are clearly involved in this modulation. In parallel, brain-derived neurotrophic factor (BDNF) also modulates respiratory rhythm. The currently available data on the respective roles of astrocytes and BDNF in respiratory control and rhythmogenesis lead us to hypothesize that there is BDNF-mediated control of the communication between neurons and astrocytes in the maintenance of a proper neuronal network capable of generating a stable respiratory rhythm. According to this hypothesis, progression of Rett syndrome, an autism spectrum disease with disordered breathing, can be stabilized in mouse models by re-expressing the normal gene pattern in astrocytes or microglia, as well as by stimulating the BDNF signaling pathway. These results illustrate how the signaling mechanisms by which glia exerts its effects in brainstem respiratory groups is of great interest for pathologies associated with neurological respiratory disorders.

  10. Cognitive control in mild traumatic brain injury: conflict monitoring and conflict adaptation.

    PubMed

    Larson, Michael J; Farrer, Thomas J; Clayson, Peter E

    2011-10-01

    Recent studies suggest that individuals who have experienced a concussion or mild traumatic brain injury (TBI) show deficits in cognitive control. We tested the hypothesis that behavioral (response time [RT] and error rate) and electrophysiological (N450 and conflict SP components of the event-related potential [ERP]) reflections of conflict monitoring and conflict adaptation would be attenuated in 29 individuals with mild TBI compared to 36 control participants. Groups did not differ in age, sex, years of education, or neuropsychological test performance. Conflict monitoring and conflict adaptation can be seen when behavioral and ERP indices are reduced following high-conflict trials relative to low-conflict trials. Participants completed a Stroop task with 50% congruent and 50% incongruent trials. Behaviorally, both groups showed statistically significant conflict adaptation effects for RTs and error rates; these effects did not differ as a function of group. For ERPs, both groups showed more negative N450 and more positive conflict SP amplitudes on incongruent trials relative to congruent trials. Groups significantly differed in level of conflict adaptation for the conflict SP; controls showed significant conflict adaptation, whereas individuals with mild TBI did not. ERP amplitudes did not correlate with indices of injury severity or time since injury. Findings replicate and extend previous work that suggests the conflict SP is sensitive to conflict adaptation in healthy individuals, but is decreased in individuals across the range of TBI severity. Findings also suggest that mild TBI is associated with intact conflict monitoring, but altered conflict adaptation and adjustment processes.

  11. 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

  12. 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.

  13. Childhood brain tumours and use of mobile phones: comparison of a case–control study with incidence data

    PubMed Central

    2012-01-01

    The first case–control study on mobile phone use and brain tumour risk among children and adolescents (CEFALO study) has recently been published. In a commentary published in Environmental Health, Söderqvist and colleagues argued that CEFALO suggests an increased brain tumour risk in relation to wireless phone use. In this article, we respond and show why consistency checks of case–control study results with observed time trends of incidence rates are essential, given the well described limitations of case–control studies and the steep increase of mobile phone use among children and adolescents during the last decade. There is no plausible explanation of how a notably increased risk from use of wireless phones would correspond to the relatively stable incidence time trends for brain tumours among children and adolescents observed in the Nordic countries. Nevertheless, an increased risk restricted to heavy mobile phone use, to very early life exposure, or to rare subtypes of brain tumours may be compatible with stable incidence trends at this time and thus further monitoring of childhood brain tumour incidence rate time trends is warranted. PMID:22607537

  14. Composition of gangliosides and neutral glycosphingolipids of brain in classical Tay-Sachs and Sandhoff disease: more lyso-GM2 in Sandhoff disease?

    PubMed

    Rosengren, B; Månsson, J E; Svennerholm, L

    1987-09-01

    The ganglioside composition of the brain from an individual with classical Tay-Sachs disease and from an individual with Sandhoff disease was examined using our new quantitative methods for ganglioside content determination and compared with that of age-matched control brains. The concentration of GM2 was found to be 12.2 and 13.0 mumol/g of fresh tissue in Tay-Sachs disease and in Sandhoff disease cerebral gray matter, respectively. GM2 was 86 and 87% respectively, of total gangliosides. The concentration of GM1 and, in particular, GM3 ganglioside was also found to be increased, whereas the concentration of the major di- and trisialogangliosides (GD1a, GD1b, and GT1b) had diminished markedly. There was no significant increase in level of any other ganglioside than lyso-GM2. Its concentration was 12 and 16 nmol/g in cerebral gray matter of two Tay-Sachs disease brains and 43 nmol/g in Sandhoff disease brain. The Sandhoff disease brain also differed from the classical Tay-Sachs disease brain by having a much higher concentration of gangliotriaosylceramide and globotetraosylceramide. The structures of relevant gangliosides and neutral glycolipids were established by fast atom bombardment-mass spectrometry and permethylation studies.

  15. The discrepancy between the absence of copper deposition and the presence of neuronal damage in the brain of Atp7b(-/-) mice.

    PubMed

    Dong, Yi; Shi, Sheng-Sheng; Chen, Sheng; Ni, Wang; Zhu, Min; Wu, Zhi-Ying

    2015-02-01

    Wilson's disease (WD) is caused by mutations within the copper-transporting ATPase (ATP7B), characterized by copper deposition in various organs, principally the liver and the brain. With the availability of Atp7b(-/-) mice, the valid animal model of WD, the mechanism underlying copper-induced hepatocyte necrosis has been well understood. Nonetheless, little is known about the adverse impact of copper accumulation on the brain in WD. Therefore, the aim of this study was to identify copper disturbances according to various brain compartments and further dissect the causal relationship between copper storage and neuronal damage using Atp7b(-/-) mice. Copper levels in the liver, whole brain, brain compartments and basal ganglia mitochondria of Atp7b(-/-) mice and age-matched controls were measured by atomic absorption spectroscopy. Delicate electron microscopic studies on hepatocytes and neurons in the basal ganglia were performed. Here we further confirmed the remarkably elevated copper content and abnormal ultrastructure findings in livers of Atp7b(-/-) mice. Interestingly, we found the ultrastructure abnormalities in neurons of the basal ganglia of Atp7b(-/-) mice, whereas copper deposition was not detected in the whole brain, even within the basal ganglia and its mitochondria. The disparity provided a new understanding of neuronal dysfunction in WD, and strongly indicated that copper might not be the sole causative player and other unidentified pathogenic factors could enhance the toxic effects of copper on neurons in WD.

  16. How the body controls brain temperature: the temperature shielding effect of cerebral blood flow.

    PubMed

    Zhu, Mingming; Ackerman, Joseph J H; Sukstanskii, Alexander L; Yablonskiy, Dmitriy A

    2006-11-01

    Normal brain functioning largely depends on maintaining brain temperature. However, the mechanisms protecting brain against a cooler environment are poorly understood. Reported herein is the first detailed measurement of the brain-temperature profile. It is found to be exponential, defined by a characteristic temperature shielding length, with cooler peripheral areas and a warmer brain core approaching body temperature. Direct cerebral blood flow (CBF) measurements with microspheres show that the characteristic temperature shielding length is inversely proportional to the square root of CBF in excellent agreement with a theoretical model. This "temperature shielding effect" quantifies the means by which CBF prevents "extracranial cold" from penetrating deep brain structures. The effect is crucial for research and clinical applications; the relationship between brain, body, and extracranial temperatures can now be quantitatively predicted.

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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

  2. Brain extracellular matrix retains connectivity in neuronal networks.

    PubMed

    Bikbaev, Arthur; Frischknecht, Renato; Heine, Martin

    2015-09-29

    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.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. Deficiency of Calcium-Independent Phospholipase A2 Beta Induces Brain Iron Accumulation through Upregulation of Divalent Metal Transporter 1

    PubMed Central

    Beck, Goichi; Shinzawa, Koei; Hayakawa, Hideki; Baba, Kousuke; Yasuda, Toru; Sumi-Akamaru, Hisae; Tsujimoto, Yoshihide; Mochizuki, Hideki

    2015-01-01

    Mutations in PLA2G6 have been proposed to be the cause of neurodegeneration with brain iron accumulation type 2. The present study aimed to clarify the mechanism underlying brain iron accumulation during the deficiency of calcium-independent phospholipase A2 beta (iPLA2β), which is encoded by the PLA2G6 gene. Perl’s staining with diaminobenzidine enhancement was used to visualize brain iron accumulation. Western blotting was used to investigate the expression of molecules involved in iron homeostasis, including divalent metal transporter 1 (DMT1) and iron regulatory proteins (IRP1 and 2), in the brains of iPLA2β-knockout (KO) mice as well as in PLA2G6-knockdown (KD) SH-SY5Y human neuroblastoma cells. Furthermore, mitochondrial functions such as ATP production were examined. We have discovered for the first time that marked iron deposition was observed in the brains of iPLA2β-KO mice since the early clinical stages. DMT1 and IRP2 were markedly upregulated in all examined brain regions of aged iPLA2β-KO mice compared to age-matched wild-type control mice. Moreover, peroxidized lipids were increased in the brains of iPLA2β-KO mice. DMT1 and IRPs were significantly upregulated in PLA2G6-KD cells compared with cells treated with negative control siRNA. Degeneration of the mitochondrial inner membrane and decrease of ATP production were observed in PLA2G6-KD cells. These results suggest that the genetic ablation of iPLA2β increased iron uptake in the brain through the activation of IRP2 and upregulation of DMT1, which may be associated with mitochondrial dysfunction. PMID:26506412

  10. Deficiency of Calcium-Independent Phospholipase A2 Beta Induces Brain Iron Accumulation through Upregulation of Divalent Metal Transporter 1.

    PubMed

    Beck, Goichi; Shinzawa, Koei; Hayakawa, Hideki; Baba, Kousuke; Yasuda, Toru; Sumi-Akamaru, Hisae; Tsujimoto, Yoshihide; Mochizuki, Hideki

    2015-01-01

    Mutations in PLA2G6 have been proposed to be the cause of neurodegeneration with brain iron accumulation type 2. The present study aimed to clarify the mechanism underlying brain iron accumulation during the deficiency of calcium-independent phospholipase A2 beta (iPLA2β), which is encoded by the PLA2G6 gene. Perl's staining with diaminobenzidine enhancement was used to visualize brain iron accumulation. Western blotting was used to investigate the expression of molecules involved in iron homeostasis, including divalent metal transporter 1 (DMT1) and iron regulatory proteins (IRP1 and 2), in the brains of iPLA2β-knockout (KO) mice as well as in PLA2G6-knockdown (KD) SH-SY5Y human neuroblastoma cells. Furthermore, mitochondrial functions such as ATP production were examined. We have discovered for the first time that marked iron deposition was observed in the brains of iPLA2β-KO mice since the early clinical stages. DMT1 and IRP2 were markedly upregulated in all examined brain regions of aged iPLA2β-KO mice compared to age-matched wild-type control mice. Moreover, peroxidized lipids were increased in the brains of iPLA2β-KO mice. DMT1 and IRPs were significantly upregulated in PLA2G6-KD cells compared with cells treated with negative control siRNA. Degeneration of the mitochondrial inner membrane and decrease of ATP production were observed in PLA2G6-KD cells. These results suggest that the genetic ablation of iPLA2β increased iron uptake in the brain through the activation of IRP2 and upregulation of DMT1, which may be associated with mitochondrial dysfunction. PMID:26506412

  11. 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

  12. 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’.

  13. 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

  14. 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

  15. 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

  16. Controlled Ultrasound-Induced Blood-Brain Barrier Disruption Using Passive Acoustic Emissions Monitoring

    PubMed Central

    Arvanitis, Costas D.; Livingstone, Margaret S.; Vykhodtseva, Natalia; McDannold, Nathan

    2012-01-01

    The ability of ultrasonically-induced oscillations of circulating microbubbles to permeabilize vascular barriers such as the blood-brain barrier (BBB) holds great promise for noninvasive targeted drug delivery. A major issue has been a lack of control over the procedure to ensure both safe and effective treatment. Here, we evaluated the use of passively-recorded acoustic emissions as a means to achieve this control. An acoustic emissions monitoring system was constructed and integrated into a clinical transcranial MRI-guided focused ultrasound system. Recordings were analyzed using a spectroscopic method that isolates the acoustic emissions caused by the microbubbles during sonication. This analysis characterized and quantified harmonic oscillations that occur when the BBB is disrupted, and broadband emissions that occur when tissue damage occurs. After validating the system's performance in pilot studies that explored a wide range of exposure levels, the measurements were used to control the ultrasound exposure level during transcranial sonications at 104 volumes over 22 weekly sessions in four macaques. We found that increasing the exposure level until a large harmonic emissions signal was observed was an effective means to ensure BBB disruption without broadband emissions. We had a success rate of 96% in inducing BBB disruption as measured by in contrast-enhanced MRI, and we detected broadband emissions in less than 0.2% of the applied bursts. The magnitude of the harmonic emissions signals was significantly (P<0.001) larger for sonications where BBB disruption was detected, and it correlated with BBB permeabilization as indicated by the magnitude of the MRI signal enhancement after MRI contrast administration (R2 = 0.78). Overall, the results indicate that harmonic emissions can be a used to control focused ultrasound-induced BBB disruption. These results are promising for clinical translation of this technology. PMID:23029240

  17. 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

  18. Instrumentation to record evoked potentials for closed-loop control of deep brain stimulation.

    PubMed

    Kent, Alexander R; Grill, Warren M

    2011-01-01

    Closed-loop deep brain stimulation (DBS) systems offer promise in relieving the clinical burden of stimulus parameter selection and improving treatment outcomes. In such a system, a feedback signal is used to adjust automatically stimulation parameters and optimize the efficacy of stimulation. We explored the feasibility of recording electrically evoked compound action potentials (ECAPs) during DBS for use as a feedback control signal. A novel instrumentation system was developed to suppress the stimulus artifact and amplify the small magnitude, short latency ECAP response during DBS with clinically relevant parameters. In vitro testing demonstrated the capabilities to increase the gain by a factor of 1,000× over a conventional amplifier without saturation, reduce distortion of mock ECAP signals, and make high fidelity recordings of mock ECAPs at latencies of only 0.5 ms following DBS pulses of 50 to 100 μs duration. Subsequently, the instrumentation was used to make in vivo recordings of ECAPs during thalamic DBS in cats, without contamination by the stimulus artifact. The signal characteristics were similar across three experiments, suggesting common neural activation patterns. The ECAP recordings enabled with this novel instrumentation may provide insight into the type and spatial extent of neural elements activated during DBS, and could serve as feedback control signals for closed-loop systems. PMID:22255894

  19. 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

  20. 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

  1. 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…

  2. 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

  3. Manganese uptake and distribution in the brain after methyl bromide-induced lesions in the olfactory epithelia.

    PubMed

    Thompson, Khristy J; Molina, Ramon M; Donaghey, Thomas; Savaliya, Sandeep; Schwob, James E; Brain, Joseph D

    2011-03-01

    Manganese (Mn) is an essential nutrient with potential neurotoxic effects. Mn deposited in the nose is apparently transported to the brain through anterograde axonal transport, bypassing the blood-brain barrier. However, the role of the olfactory epithelial cells in Mn transport from the nasal cavity to the blood and brain is not well understood. We utilized the methyl bromide (MeBr) lesion model wherein the olfactory epithelium fully regenerates in a time-dependent and cell type-specific manner over the course of 6-8 weeks postinjury. We instilled (54)MnCl(2) intranasally at different recovery periods to study the role of specific olfactory epithelial cell types in Mn transport. (54)MnCl(2) was instilled at 2, 4, 7, 21, and 56 days post-MeBr treatment. (54)Mn concentrations in the blood were measured over the first 4-h period and in the brain and other tissues at 7 days postinstillation. Age-matched control rats were similarly studied at 2 and 56 days. Blood and tissue (54)Mn levels were reduced initially but returned to control values by day 7 post-MeBr exposure, coinciding with the reestablishment of sustentacular cells. Brain (54)Mn levels also decreased but returned to control levels only by 21 days, the period near the completion of neuronal regeneration/bulbar reinnervation. Our data show that Mn transport to the blood and brain temporally correlated with olfactory epithelial regeneration post-MeBr injury. We conclude that (1) sustentacular cells are necessary for Mn transport to the blood and (2) intact axonal projections are required for Mn transport from the nasal cavity to the olfactory bulb and brain.

  4. 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.

  5. Surface-Based Parameters of Brain Imaging in Male Patients with Alcohol Use Disorder

    PubMed Central

    Im, Sungjin; Lee, Sang-Gu; Lee, Jeonghwan; Shin, Chul-Jin; Son, Jeong-Woo; Ju, Gawon; Lee, Sang-Ick

    2016-01-01

    Objective The structural alteration of brain shown in patients with alcohol use disorder (AUD) can originate from both alcohol effects and genetic or developmental processes. We compared surface-based parameters of patients with AUD with healthy controls to prove the applicability of surface-based morphometry with head size correction and to determine the areas that were sensitive to brain alteration related to AUD. Methods Twenty-six abstinent male patients with AUD (alcohol group, mean abstinence=13.2 months) and twenty-eight age-matched healthy participants (control group) were recruited from an inpatient mental hospital and community. All participants underwent a 3T MRI scan. Surface-based parameters were determined by using FreeSurfer. Results Every surface-based parameter of the alcohol group was lower than the corresponding control group parameter. There were large group differences in the whole brain, grey and white matter volume, and the differences were more prominent after head size correction. Significant group differences were shown in cortical thicknesses in entire brain regions, especially in parietal, temporal and frontal areas. There were no significant group differences in surface areas, but group difference trends in surface areas of the frontal and parietal cortices were shown after head size correction. Conclusion Most of the surface-based parameters in alcohol group were altered because of incomplete recovery from chronic alcohol exposure and possibly genetic or developmental factors underlying the risk of AUD. Surface-based morphometry with controlling for head size is useful in comparing the volumetric parameters and the surface area to a lesser extent in alcohol-related brain alteration. PMID:27757129

  6. Interaction between electrical modulation of the brain and pharmacotherapy to control pharmacoresistant epilepsy.

    PubMed

    Rocha, Luisa

    2013-05-01

    In spite of the high success rate of many surgical procedures for pharmacoresistant epilepsy, a substantial number of patients do not become seizure-free. Different strategies for electrical modulation of the brain such as Deep Brain Stimulation, Vagal Nerve Stimulation and Transcraneal Magnetic Stimulation have gained considerable interest in the last decade as alternative therapies for patients with medically refractory epilepsy. Research into the mechanism of action of the strategies for electrical modulation of the brain suggests a crucial role of different molecules and channels such as glutamate, γ-aminobutyric acid, adenosine, brain-derived neurotrophic factor, calcium channels, sodium channels as well as extracellular potassium. Electrical modulation of the brain may reduce the overexpression of P-glycoprotein, a drug efflux transporter that reduces the absorption of antiepileptic drugs. Electrical modulation of the brain induces long-term effects associated with beneficial consequences on clinical symptoms observed during the postictal state. In addition, electrical modulation of the brain might also promote the neurogenesis in subjects with pharmacoresistant epilepsy in whom this process is decreased. Targeting the regulatory pathways in charge of the effects of electrical modulation of the brain is discussed as a means to improve its efficacy. Electrical modulation of the brain combined with pharmacotherapy may represent an innovative approach to avoid epileptogenesis, reduce seizure activity, induce beneficial effects during the postictal state, diminish the amount of antiepileptic drugs, and improve alertness, memory and mood in pharmacoresistant epilepsy.

  7. 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

  8. 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

  9. 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

  10. 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

  11. Brain processing of consonance/dissonance in musicians and controls: a hemispheric asymmetry revisited.

    PubMed

    Proverbio, Alice Mado; Orlandi, Andrea; Pisanu, Francesca

    2016-09-01

    It was investigated to what extent musical expertise influences the auditory processing of harmonicity by recording event-related potentials. Thirty-four participants (18 musicians and 16 controls) were asked to listen to hundreds of chords, differing in their degree of consonance, their complexity (from two to six composing sounds) and their range (distance of two adjacent pitches, from quartertones to more than 18 semitone steps). The task consisted of detecting rare targets. An early auditory N1 was observed that was modulated by chord dissonance in both groups. The response was generated in the right medial temporal gyrus (MTG) for consonant chords but in the left MTG for dissonant chords according to swLORETA reconstruction performed. An anterior negativity (N2) was enhanced only in musicians in response to chords featuring quartertones, thus suggesting a greater pitch sensitivity for simultaneous pure tones in the skilled brain. The P300 was affected by the frequency range only in musicians, who also showed a greater sensitivity to sound complexity. A strong left hemispheric specialization for processing quartertones in the left temporal cortex of musicians was observed at N2 level (250-350 ms), which was observed on the right side in controls. Additionally, in controls, widespread activity of the right limbic area was associated with listening to close frequencies causing disturbing beats, possibly suggesting a negative aesthetic appreciation for these stimuli. Overall, the data show a finer and more tuned neural representation of pitch intervals in musicians, linked to a marked specialization of their left temporal cortex (BA21/38). PMID:27421883

  12. 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

  13. 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

  14. 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

  15. 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…

  16. 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…

  17. Dual role of cerebral blood flow in regional brain temperature control in the healthy newborn infant.

    PubMed

    Iwata, Sachiko; Tachtsidis, Ilias; Takashima, Sachio; Matsuishi, Toyojiro; Robertson, Nicola J; Iwata, Osuke

    2014-10-01

    Small shifts in brain temperature after hypoxia-ischaemia affect cell viability. The main determinants of brain temperature are cerebral metabolism, which contributes to local heat production, and brain perfusion, which removes heat. However, few studies have addressed the effect of cerebral metabolism and perfusion on regional brain temperature in human neonates because of the lack of non-invasive cot-side monitors. This study aimed (i) to determine non-invasive monitoring tools of cerebral metabolism and perfusion by combining near-infrared spectroscopy and echocardiography, and (ii) to investigate the dependence of brain temperature on cerebral metabolism and perfusion in unsedated newborn infants. Thirty-two healthy newborn infants were recruited. They were studied with cerebral near-infrared spectroscopy, echocardiography, and a zero-heat flux tissue thermometer. A surrogate of cerebral blood flow (CBF) was measured using superior vena cava flow adjusted for cerebral volume (rSVC flow). The tissue oxygenation index, fractional oxygen extraction (FOE), and the cerebral metabolic rate of oxygen relative to rSVC flow (CMRO₂ index) were also estimated. A greater rSVC flow was positively associated with higher brain temperatures, particularly for superficial structures. The CMRO₂ index and rSVC flow were positively coupled. However, brain temperature was independent of FOE and the CMRO₂ index. A cooler ambient temperature was associated with a greater temperature gradient between the scalp surface and the body core. Cerebral oxygen metabolism and perfusion were monitored in newborn infants without using tracers. In these healthy newborn infants, cerebral perfusion and ambient temperature were significant independent variables of brain temperature. CBF has primarily been associated with heat removal from the brain. However, our results suggest that CBF is likely to deliver heat specifically to the superficial brain. Further studies are required to assess the

  18. 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,…

  19. 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.…

  20. Effects of incentives, age, and behavior on brain activation during inhibitory control: a longitudinal fMRI study.

    PubMed

    Paulsen, David J; Hallquist, Michael N; Geier, Charles F; Luna, Beatriz

    2015-02-01

    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 X 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

  1. 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

  2. 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

  3. We have got you 'covered': how the meninges control brain development.

    PubMed

    Siegenthaler, Julie A; Pleasure, Samuel J

    2011-06-01

    The meninges have traditionally been viewed as specialized membranes surrounding and protecting the adult brain from injury. However, there is increasing evidence that the fetal meninges play important roles during brain development. Through the release of diffusible factors, the meninges influence the proliferative and migratory behaviors of neural progenitors and neurons in the forebrain and hindbrain. Meningeal cells also secrete and organize the pial basement membrane (BM), a critical anchor point for the radially oriented fibers of neuroepithelial stem cells. With its emerging role in brain development, the potential that defects in meningeal development may underlie certain congenital brain abnormalities in humans should be considered. In this review, we will discuss what is known about assembly of the fetal meninges and review the role of meningeal-derived proteins in mouse and human brain development.

  4. Impulse Control Disorders Following Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson's Disease: Clinical Aspects

    PubMed Central

    Demetriades, Polyvios; Rickards, Hugh; Cavanna, Andrea Eugenio

    2011-01-01

    Parkinson's disease (PD) has been associated with the development of impulse control disorders (ICDs), possibly due to overstimulation of the mesolimbic system by dopaminergic medication. Preliminary reports have suggested that deep brain stimulation (DBS), a neurosurgical procedure offered to patients with treatment-resistant PD, affects ICD in a twofold way. Firstly, DBS allows a decrease in dopaminergic medication and hence causes an improvement in ICDs. Secondly, some studies have proposed that specific ICDs may develop after DBS. This paper addresses the effects of DBS on ICDs in patients with PD. A literature search identified four original studies examining a total of 182 patients for ICDs and nine case reports of 39 patients that underwent DBS and developed ICDs at some point. Data analysis from the original studies did not identify a significant difference in ICDs between patients receiving dopaminergic medication and patients on DBS, whilst the case reports showed that 56% of patients undergoing DBS had poor outcome with regards to ICDs. We discuss these ambivalent findings in the light of proposed pathogenetic mechanisms. Longitudinal, prospective studies with larger number of patients are required in order to fully understand the role of DBS on ICDs in patients with PD. PMID:21403902

  5. 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.

  6. [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

  7. 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

  8. Covariate adjustment increased power in randomized controlled trials: an example in traumatic brain injury

    PubMed Central

    Turner, Elizabeth L.; Perel, Pablo; Clayton, Tim; Edwards, Phil; Hernández, Adrian V.; Roberts, Ian; Shakur, Haleema; Steyerberg, Ewout W.

    2013-01-01

    Objective We aimed to determine to what extent covariate adjustment could affect power in a randomized controlled trial (RCT) of a heterogeneous population with traumatic brain injury (TBI). Study Design and Setting We analyzed 14-day mortality in 9497 participants in the Corticosteroid Randomisation After Significant Head Injury (CRASH) RCT of corticosteroid vs. placebo. Adjustment was made using logistic regression for baseline covariates of two validated risk models derived from external data (IMPACT) and from the CRASH data. The relative sample size (RESS) measure, defined as the ratio of the sample size required by an adjusted analysis to attain the same power as the unadjusted reference analysis, was used to assess the impact of adjustment. Results Corticosteroid was associated with higher mortality compared to placebo (OR=1.25, 95% CI: 1.13, 1.39). RESS of 0.79 and 0.73 were obtained by adjustment using the IMPACT and CRASH models, respectively, which for example implies an increase from 80% to 88% and 91% power, respectively. Conclusion Moderate gains in power may be obtained using covariate adjustment from logistic regression in heterogeneous conditions such as TBI. Although analyses of RCTs might consider covariate adjustment to improve power, we caution against this approach in the planning of RCTs. PMID:22169080

  9. 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

  10. A Brain-Computer Interface (BCI) system to use arbitrary Windows applications by directly controlling mouse and keyboard.

    PubMed

    Spuler, Martin

    2015-08-01

    A Brain-Computer Interface (BCI) allows to control a computer by brain activity only, without the need for muscle control. In this paper, we present an EEG-based BCI system based on code-modulated visual evoked potentials (c-VEPs) that enables the user to work with arbitrary Windows applications. Other BCI systems, like the P300 speller or BCI-based browsers, allow control of one dedicated application designed for use with a BCI. In contrast, the system presented in this paper does not consist of one dedicated application, but enables the user to control mouse cursor and keyboard input on the level of the operating system, thereby making it possible to use arbitrary applications. As the c-VEP BCI method was shown to enable very fast communication speeds (writing more than 20 error-free characters per minute), the presented system is the next step in replacing the traditional mouse and keyboard and enabling complete brain-based control of a computer.

  11. Drug polyconsumption is associated with increased synchronization of brain electrical-activity at rest and in a counting task.

    PubMed

    Coullaut-Valera, R; Arbaiza, I; Bajo, R; Arrúe, R; López, M E; Coullaut-Valera, J; Correas, A; López-Sanz, D; Maestu, F; Papo, D

    2014-02-01

    Drug abusers typically consume not just one but several types of drugs, starting from alcohol and marijuana consumption, and then dramatically lapsing into addiction to harder drugs, such as cocaine, heroin, or amphetamine. The brain of drug abusers presents various structural and neurophysiological abnormalities, some of which may predate drug consumption onset. However, how these changes translate into modifications in functional brain connectivity is still poorly understood. To characterize functional connectivity patterns, we recorded Electroencephalogram (EEG) activity from 21 detoxified drug abusers and 20 age-matched control subjects performing a simple counting task and at rest activity. To evaluate the cortical brain connectivity network we applied the Synchronization Likelihood algorithm. The results showed that drug abusers had higher synchronization levels at low frequencies, mainly in the θ band (4-8 Hz) between frontal and posterior cortical regions. During the counting task, patients showed increased synchronization in the β (14-35 Hz), and γ (35-45 Hz) frequency bands, in fronto-posterior and interhemispheric temporal regions. Taken together 'slow-down' at rest and task-related 'over-exertion' could indicate that the brain of drug abusers is suffering from a premature form of ageing. Future studies will clarify whether this condition can be reversed following prolonged periods of abstinence.

  12. Regional brain gray and white matter changes in perinatally HIV-infected adolescents.

    PubMed

    Sarma, Manoj K; Nagarajan, Rajakumar; Keller, Margaret A; Kumar, Rajesh; Nielsen-Saines, Karin; Michalik, David E; Deville, Jaime; Church, Joseph A; Thomas, M Albert

    2014-01-01

    Despite the success of antiretroviral therapy (ART), perinatally infected HIV remains a major health problem worldwide. Although advance neuroimaging studies have investigated structural brain changes in HIV-infected adults, regional gray matter (GM) and white matter (WM) volume changes have not been reported in perinatally HIV-infected adolescents and young adults. In this cross-sectional study, we investigated regional GM and WM changes in 16 HIV-infected youths receiving ART (age 17.0 ± 2.9 years) compared with age-matched 14 healthy controls (age 16.3 ± 2.3 years) using magnetic resonance imaging (MRI)-based high-resolution T1-weighted images with voxel based morphometry (VBM) analyses. White matter atrophy appeared in perinatally HIV-infected youths in brain areas including the bilateral posterior corpus callosum (CC), bilateral external capsule, bilateral ventral temporal WM, mid cerebral peduncles, and basal pons over controls. Gray matter volume increase was observed in HIV-infected youths for several regions including the left superior frontal gyrus, inferior occipital gyrus, gyrus rectus, right mid cingulum, parahippocampal gyrus, bilateral inferior temporal gyrus, and middle temporal gyrus compared with controls. Global WM and GM volumes did not differ significantly between groups. These results indicate WM injury in perinatally HIV-infected youths, but the interpretation of the GM results, which appeared as increased regional volumes, is not clear. Further longitudinal studies are needed to clarify if our results represent active ongoing brain infection or toxicity from HIV treatment resulting in neuronal cell swelling and regional increased GM volume. Our findings suggest that assessment of regional GM and WM volume changes, based on VBM procedures, may be an additional measure to assess brain integrity in HIV-infected youths and to evaluate success of current ART therapy for efficacy in the brain.

  13. 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

  14. 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.

  15. Acute ischaemic brain lesions in intracerebral haemorrhage: multicentre cross-sectional magnetic resonance imaging study.

    PubMed

    Gregoire, Simone M; Charidimou, Andreas; Gadapa, Naveen; Dolan, Eamon; Antoun, Nagui; Peeters, Andre; Vandermeeren, Yves; Laloux, Patrice; Baron, Jean-Claude; Jäger, Hans R; Werring, David J

    2011-08-01

    Subclinical acute ischaemic lesions on brain magnetic resonance imaging have recently been described in spontaneous intracerebral haemorrhage, and may be important to understand pathophysiology and guide treatment. The underlying mechanisms are uncertain. We tested the hypothesis that ischaemic lesions are related to magnetic resonance imaging markers of the severity and type of small-vessel disease (hypertensive arteriopathy or cerebral amyloid angiopathy) in a multicentre, cross-sectional study. We studied consecutive patients with intracerebral haemorrhage from four specialist stroke centres, and age-matched stroke service referrals without intracerebral haemorrhage. Acute ischaemic lesions were assessed on magnetic resonance imaging (<3 months after intracerebral haemorrhage) using diffusion-weighted imaging. White matter changes and cerebral microbleeds were rated with validated scales. We investigated associations between diffusion-weighted imaging lesions, clinical and radiological characteristics. We included 114 patients with intracerebral haemorrhage (39 with clinically probable cerebral amyloid angiopathy) and 47 age-matched controls. The prevalence of diffusion-weighted imaging lesions was 9/39 (23%) in probable cerebral amyloid angiopathy-related intracerebral haemorrhage versus 6/75 (8%) in the remaining patients with intracerebral haemorrhage (P = 0.024); no diffusion-weighted imaging lesions were found in controls. Diffusion-weighted imaging lesions were mainly cortical and were associated with mean white matter change score (odds ratio 1.14 per unit increase, 95% confidence interval 1.02-1.28, P = 0.024) and the presence of strictly lobar cerebral microbleeds (odds ratio 3.85, 95% confidence interval 1.15-12.93, P = 0.029). Acute, subclinical ischaemic brain lesions are frequent but previously underestimated after intracerebral haemorrhage, and are three times more common in cerebral amyloid angiopathy-related intracerebral haemorrhage than in

  16. 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

  17. 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

  18. 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

  19. 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.

  20. Aberrant temporal and spatial brain activity during rest in patients with chronic pain

    PubMed Central

    Malinen, Sanna; Vartiainen, Nuutti; Hlushchuk, Yevhen; Koskinen, Miika; Ramkumar, Pavan; Forss, Nina; Kalso, Eija; Hari, Riitta

    2010-01-01

    In the absence of external stimuli, human hemodynamic brain activity displays slow intrinsic variations. To find out whether such fluctuations would be altered by persistent pain, we asked 10 patients with unrelenting chronic pain of different etiologies and 10 sex- and age-matched control subjects to rest with eyes open during 3-T functional MRI. Independent component analysis was used to identify functionally coupled brain networks. Time courses of an independent component comprising the insular cortices of both hemispheres showed stronger spectral power at 0.12 to 0.25 Hz in patients than in control subjects, with the largest difference at 0.16 Hz. A similar but weaker effect was seen in the anterior cingulate cortex, whereas activity of the precuneus and early visual cortex, used as a control site, did not differ between the groups. In the patient group, seed point-based correlation analysis revealed altered spatial connectivity between insulae and anterior cingulate cortex. The results im