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Sample records for impairs later-life cortical

  1. Prenatal Exposure to Benzo(a)pyrene Impairs Later-Life Cortical Neuronal Function

    PubMed Central

    McCallister, Monique M.; Maguire, Mark; Ramesh, Aramandla; Aimin, Qiao; Liu, Sheng; Khoshbouei, Habibeh; Aschner, Michael; Ebner, Ford F.; Hood, Darryl B.

    2009-01-01

    Prenatal exposure to environmental contaminants, such as Benzo(a)pyrene [B(a)P] has been shown to impair brain development. The overarching hypothesis of our work is that glutamate receptor subunit expression is crucial for cortical evoked responses and that prenatal B(a)P exposure modulates the temporal developmental expression of glutamatergic receptor subunits in the somatosensory cortex. To characterize prenatal B(a)P exposure on the development of cortical function, pregnant Long Evans rats were exposed to low-level B(a)P (300μg/kg BW) by oral gavage on gestational days 14 to 17. At this exposure dose, there was no significant effect of B(a)P on 1) the number of pups born per litter, 2) the pre-weaning growth curves and 3) initial and final brain to body weight ratios. Control and B(a)P-exposed offspring were profiled for B(a)P metabolites in plasma and whole brain during the pre-weaning period. No detectable levels of metabolites were found in the control offspring. However, a time-dependent decrease in total metabolite concentration was observed in B(a)P-exposed offspring. On PND100-120, cerebrocortical mRNA expression was determined for the glutamatergic NMDA receptor subunit (NR2B) in control and B(a)P-exposed offspring. Neural activity was also recorded from neurons in primary somatic sensory (barrel) cortex. Semiquantitative PCR from B(a)P-exposed offspring revealed a significant 50% reduction in NR2B mRNA expression in B(a)P-exposed offspring relative to controls. Recordings from B(a)P-exposed offspring revealed that N-methyl-D-aspartate (NMDA) receptor -dependent neuronal activity in barrel cortex evoked by whisker stimulation was also significantly reduced (70%) as compared to controls. Analysis showed that the greatest deficit in cortical neuronal responses occurred in the shorter latency epochs from 5-20ms post-stimulus. The results suggest that in utero exposure to benzo(a)pyrene results in diminished mRNA expression of the NMDA NR2B receptor

  2. Age of first exposure to football and later-life cognitive impairment in former NFL players

    PubMed Central

    Stamm, Julie M.; Bourlas, Alexandra P.; Baugh, Christine M.; Fritts, Nathan G.; Daneshvar, Daniel H.; Martin, Brett M.; McClean, Michael D.; Tripodis, Yorghos

    2015-01-01

    Objective: To determine the relationship between exposure to repeated head impacts through tackle football prior to age 12, during a key period of brain development, and later-life executive function, memory, and estimated verbal IQ. Methods: Forty-two former National Football League (NFL) players ages 40–69 from the Diagnosing and Evaluating Traumatic Encephalopathy using Clinical Tests (DETECT) study were matched by age and divided into 2 groups based on their age of first exposure (AFE) to tackle football: AFE <12 and AFE ≥12. Participants completed the Wisconsin Card Sort Test (WCST), Neuropsychological Assessment Battery List Learning test (NAB-LL), and Wide Range Achievement Test, 4th edition (WRAT-4) Reading subtest as part of a larger neuropsychological testing battery. Results: Former NFL players in the AFE <12 group performed significantly worse than the AFE ≥12 group on all measures of the WCST, NAB-LL, and WRAT-4 Reading tests after controlling for total number of years of football played and age at the time of evaluation, indicating executive dysfunction, memory impairment, and lower estimated verbal IQ. Conclusions: There is an association between participation in tackle football prior to age 12 and greater later-life cognitive impairment measured using objective neuropsychological tests. These findings suggest that incurring repeated head impacts during a critical neurodevelopmental period may increase the risk of later-life cognitive impairment. If replicated with larger samples and longitudinal designs, these findings may have implications for safety recommendations for youth sports. PMID:25632088

  3. Humor in Later Life.

    ERIC Educational Resources Information Center

    Frazier, Billie H.

    This document contains a brief bibliography of peer-reviewed literature, with abstracts, on humor in later life. It is one of 12 bibliographies on aging prepared by the National Agricultural Library for its "Pathfinders" series of publications. Topics covered by the other 11 bibliographies include aging parents, adult children, dementia and…

  4. Reflexive Planning for Later Life

    ERIC Educational Resources Information Center

    Denton, Margaret A.; Kemp, Candace L.; French, Susan; Gafni, Amiram; Joshi, Anju; Rosenthal, Carolyn J.; Davies, Sharon

    2004-01-01

    Informed by Giddens' (1991) concept of "reflexive life" planning and the notion of later life as a time of increasing social and financial risk, this research explores the idea of "reflexive planning for later life". We utilize a conceptual model that incorporates three types of planning for later life: public protection, self-insurance, and…

  5. Discontinuity of cortical gradients reflects sensory impairment

    PubMed Central

    Saadon-Grosman, Noam; Tal, Zohar; Itshayek, Eyal; Amedi, Amir; Arzy, Shahar

    2015-01-01

    Topographic maps and their continuity constitute a fundamental principle of brain organization. In the somatosensory system, whole-body sensory impairment may be reflected either in cortical signal reduction or disorganization of the somatotopic map, such as disturbed continuity. Here we investigated the role of continuity in pathological states. We studied whole-body cortical representations in response to continuous sensory stimulation under functional MRI (fMRI) in two unique patient populations—patients with cervical sensory Brown-Séquard syndrome (injury to one side of the spinal cord) and patients before and after surgical repair of cervical disk protrusion—enabling us to compare whole-body representations in the same study subjects. We quantified the spatial gradient of cortical activation and evaluated the divergence from a continuous pattern. Gradient continuity was found to be disturbed at the primary somatosensory cortex (S1) and the supplementary motor area (SMA), in both patient populations: contralateral to the disturbed body side in the Brown-Séquard group and before repair in the surgical group, which was further improved after intervention. Results corresponding to the nondisturbed body side and after surgical repair were comparable with control subjects. No difference was found in the fMRI signal power between the different conditions in the two groups, as well as with respect to control subjects. These results suggest that decreased sensation in our patients is related to gradient discontinuity rather than signal reduction. Gradient continuity may be crucial for somatotopic and other topographical organization, and its disruption may characterize pathological processing. PMID:26655739

  6. Discontinuity of cortical gradients reflects sensory impairment.

    PubMed

    Saadon-Grosman, Noam; Tal, Zohar; Itshayek, Eyal; Amedi, Amir; Arzy, Shahar

    2015-12-29

    Topographic maps and their continuity constitute a fundamental principle of brain organization. In the somatosensory system, whole-body sensory impairment may be reflected either in cortical signal reduction or disorganization of the somatotopic map, such as disturbed continuity. Here we investigated the role of continuity in pathological states. We studied whole-body cortical representations in response to continuous sensory stimulation under functional MRI (fMRI) in two unique patient populations-patients with cervical sensory Brown-Séquard syndrome (injury to one side of the spinal cord) and patients before and after surgical repair of cervical disk protrusion-enabling us to compare whole-body representations in the same study subjects. We quantified the spatial gradient of cortical activation and evaluated the divergence from a continuous pattern. Gradient continuity was found to be disturbed at the primary somatosensory cortex (S1) and the supplementary motor area (SMA), in both patient populations: contralateral to the disturbed body side in the Brown-Séquard group and before repair in the surgical group, which was further improved after intervention. Results corresponding to the nondisturbed body side and after surgical repair were comparable with control subjects. No difference was found in the fMRI signal power between the different conditions in the two groups, as well as with respect to control subjects. These results suggest that decreased sensation in our patients is related to gradient discontinuity rather than signal reduction. Gradient continuity may be crucial for somatotopic and other topographical organization, and its disruption may characterize pathological processing. PMID:26655739

  7. Living Arrangements in Later Life.

    ERIC Educational Resources Information Center

    Frazier, Billie H.

    This document contains a brief bibliography of peer-reviewed literature, with abstracts, on living arrangements in later life. It is one of 12 bibliographies on aging prepared by the National Agricultural Library for its "Pathfinders" series of publications. Topics covered by the other 11 bibliographies include aging parents, adult children,…

  8. Preserving Dignity in Later Life.

    PubMed

    São José, José Manuel

    2016-09-01

    This article examines how elders who receive social care in the community experience loss of dignity and how they preserve their dignity. Qualitative research revealed that loss of dignity is a major concern for these elders and that they preserve their dignity differently, ranging from actively engaging with life to detaching themselves from life. We conclude that, in later life, preserving dignity while receiving social care differs from preserving dignity in the context of health care, especially health care provided in institutional settings. Furthermore, preserving dignity in later life, while receiving social care, is a complex process, depending not only on performing activities and individual action and responsibility, but also on other actions, some of them involving a certain inactivity/passivity, and interactions with others, especially caregivers. This article offers some insights to developing better policies and care practices for promoting dignity in the context of community-based social care.

  9. Preserving Dignity in Later Life.

    PubMed

    São José, José Manuel

    2016-09-01

    This article examines how elders who receive social care in the community experience loss of dignity and how they preserve their dignity. Qualitative research revealed that loss of dignity is a major concern for these elders and that they preserve their dignity differently, ranging from actively engaging with life to detaching themselves from life. We conclude that, in later life, preserving dignity while receiving social care differs from preserving dignity in the context of health care, especially health care provided in institutional settings. Furthermore, preserving dignity in later life, while receiving social care, is a complex process, depending not only on performing activities and individual action and responsibility, but also on other actions, some of them involving a certain inactivity/passivity, and interactions with others, especially caregivers. This article offers some insights to developing better policies and care practices for promoting dignity in the context of community-based social care. PMID:27456751

  10. Neural-Based Visual Stimulation with Infants with Cortical Impairment.

    ERIC Educational Resources Information Center

    Powell, S. A.

    1996-01-01

    In order to shed light on the needs of children with cortical visual impairments, normal visual development of infants is described. Infant preferences for motion, faces, and black-and-white patterns are explained. Colors useful in stimulating vision development and the time needed for exposure to visual stimuli are discussed. (CR)

  11. Observations on the Habilitation of Children with Cortical Visual Impairment.

    ERIC Educational Resources Information Center

    Groenveld, M.; And Others

    1990-01-01

    This article discusses the increasing incidence of cortical visual impairments, resulting from medical advancements making possible the survival of critically ill children with severe brain damage. Discussed are the prevalence of multiple handicaps, formation of visual concepts, foreground/background distinction, potential for mainstreaming, use…

  12. Gender and Marital Happiness in Later Life

    ERIC Educational Resources Information Center

    Kaufman, Gayle; Taniguchi, Hiromi

    2006-01-01

    In this study, the authors examine the effect of gender ideology on marital happiness in later life. Studies of marital satisfaction in later life have tended to neglect such attitudes, although they have received increasing attention in the literature on younger marriages. The authors use data from married individuals who range in age from 51 to…

  13. Later Life: A Time to Learn

    ERIC Educational Resources Information Center

    Russell, Helen

    2008-01-01

    In this article, an emerging framework for investigating and interpreting the experiences of learning in later life is presented. This framework is contextualized by a study in which the lived experiences of later-life computer learners were investigated. Significant ontological and existential interpretations from the study provided insights into…

  14. Subcortical visual dysfunction in schizophrenia drives secondary cortical impairments.

    PubMed

    Butler, Pamela D; Martinez, Antigona; Foxe, John J; Kim, Dongsoo; Zemon, Vance; Silipo, Gail; Mahoney, Jeannette; Shpaner, Marina; Jalbrzikowski, Maria; Javitt, Daniel C

    2007-02-01

    dysfunction at the subcortical level that leads to secondary impairment in activation of cortical visual structures within dorsal and ventral stream visual pathways. Our finding of early visual dysfunction is consistent with and explanatory of classic literature showing subjective complaints of visual distortions and is consistent with early visual processing deficits reported in schizophrenia. Although deficits in visual processing have frequently been construed as resulting from failures of top-down processing, the present findings argue strongly for bottom-up rather than top-down dysfunction at least within the early visual pathway. Deficits in magnocellular processing in this task may reflect more general impairments in neuronal systems functioning, such as deficits in non-linear amplification and may thus represent an organizing principle for predicting neurocognitive dysfunction in schizophrenia. PMID:16984902

  15. The Reliability of the CVI Range: A Functional Vision Assessment for Children with Cortical Visual Impairment

    ERIC Educational Resources Information Center

    Newcomb, Sandra

    2010-01-01

    Children who are identified as visually impaired frequently have a functional vision assessment as one way to determine how their visual impairment affects their educational performance. The CVI Range is a functional vision assessment for children with cortical visual impairment. The purpose of the study presented here was to examine the…

  16. Religious Attendance and Loneliness in Later Life

    ERIC Educational Resources Information Center

    Rote, Sunshine; Hill, Terrence D.; Ellison, Christopher G.

    2013-01-01

    Purpose of the Study: Studies show that loneliness is a major risk factor for health issues in later life. Although research suggests that religious involvement can protect against loneliness, explanations for this general pattern are underdeveloped and undertested. In this paper, we propose and test a theoretical model, which suggests that social…

  17. Depression in Later Life: Recognition and Treatment.

    ERIC Educational Resources Information Center

    Schmall, Vicki L.; And Others

    This guide is designed to help readers understand depression and factors related to its onset in later life; recognize signs of depression and potential suicide; and know actions they can take if they suspect an older family member or friend may be depressed or contemplating suicide. Following a brief introduction, a chapter on depression…

  18. Protein Kinase C Overactivity Impairs Prefrontal Cortical Regulation of Working Memory

    NASA Astrophysics Data System (ADS)

    Birnbaum, S. G.; Yuan, P. X.; Wang, M.; Vijayraghavan, S.; Bloom, A. K.; Davis, D. J.; Gobeske, K. T.; Sweatt, J. D.; Manji, H. K.; Arnsten, A. F. T.

    2004-10-01

    The prefrontal cortex is a higher brain region that regulates thought, behavior, and emotion using representational knowledge, operations often referred to as working memory. We tested the influence of protein kinase C (PKC) intracellular signaling on prefrontal cortical cognitive function and showed that high levels of PKC activity in prefrontal cortex, as seen for example during stress exposure, markedly impair behavioral and electrophysiological measures of working memory. These data suggest that excessive PKC activation can disrupt prefrontal cortical regulation of behavior and thought, possibly contributing to signs of prefrontal cortical dysfunction such as distractibility, impaired judgment, impulsivity, and thought disorder.

  19. Transnational connections of later-life migrants.

    PubMed

    Heikkinen, Sari Johanna; Lumme-Sandt, Kirsi

    2013-04-01

    In this paper a transnational perspective is used to explain whether and how older migrants construct and sustain their social networks. The paper uses a transnational viewpoint on older migrants' lives by analysing their engagement with their former homeland, and the intensity and habitualness of those engagements in old age. The aim of this article is to study the transnational connections of later-life migrants'. Attention is especially paid to the features of old age while maintaining these connections. These considerations are based on analyses of transnational networks in the everyday lives of later-life migrants from the former Soviet Union residing in Finland. The data were collected from 11 later-life migrants. It is found that transnational relationships are a vital part of the everyday lives of older migrants, and that they are sustained in varied ways. These connections mean a concrete source of help, family affiliations, the sharing of emotions, and a larger social network. Economic limitations affect the frequency and type of communication, and various physical limitations may also cause inability to maintain contacts across borders. In these circumstances, family members or other close relatives or friends are needed to deliver messages on the older person's behalf. Old age and immigration status affect the amount and direction of communication across borders, thereby shaping these networks. PMID:23561285

  20. Greater cortical thinning in normal older adults predicts later cognitive impairment

    PubMed Central

    Pacheco, Jennifer; Goh, Joshua O.; Kraut, Michael A.; Ferrucci, Luigi; Resnick, Susan M.

    2014-01-01

    Cross-sectional studies have shown regional differences in cortical thickness between healthy older adults and patients with Alzheimer’s disease (AD) or mild cognitive impairment (MCI). We now demonstrate that participants who subsequently develop cognitive impairment leading to a diagnosis of MCI or AD (n=25) experience greater cortical thinning in specific neuroanatomical regions compared to control participants who remained cognitively normal (n=96). Based on 8 years of annual MRI scans beginning an average of 11 years prior to onset of cognitive impairment, participants who developed cognitive impairment subsequent to the scanning period had greater longitudinal cortical thinning in the temporal poles and left medial temporal lobe compared to controls. No significant regional cortical thickness differences were found at baseline between the two study groups indicating that we are capturing a critical time when brain changes occur before behavioral manifestations of impairment are detectable. Our findings suggest that early events of the pathway that leads to cognitive impairment may involve the temporal lobe, and that this increased atrophy could be considered an early biomarker of neurodegeneration predictive of cognitive impairment years later. PMID:25311277

  1. Religious Attendance and Loneliness in Later Life

    PubMed Central

    Rote, Sunshine; Hill, Terrence D.; Ellison, Christopher G.

    2013-01-01

    Purpose of the Study:  Studies show that loneliness is a major risk factor for health issues in later life. Although research suggests that religious involvement can protect against loneliness, explanations for this general pattern are underdeveloped and undertested. In this paper, we propose and test a theoretical model, which suggests that social integration and social support are key mechanisms that link religious attendance and loneliness. Design and Methods:  To formally test our theoretical model, we use data from the National Social Life Health and Aging Project (2005/2006), a large national probability sample of older adults aged 57–85 years. Results:  We find that religious attendance is associated with higher levels of social integration and social support and that social integration and social support are associated with lower levels of loneliness. A series of mediation tests confirm our theoretical model. Implications:  Taken together, our results suggest that involvement in religious institutions may protect against loneliness in later life by integrating older adults into larger and more supportive social networks. Future research should test whether these processes are valid across theoretically relevant subgroups. PMID:22555887

  2. Confronting the Material Convoy in Later Life

    PubMed Central

    Smith, Gabriella V.; Ekerdt, David J.

    2011-01-01

    We adapt a metaphor from life course studies to designate the whole of one’s possessions, across time, as a convoy of material support. This dynamic collection of things supports daily life and the self, but it can also present difficulty in later life. To alleviate the purported burdens of the material convoy, a discourse has arisen that urges elders and their family members to reduce the volume of possessions. An analysis of 11 such possession management texts shows authors addressing two distinct audiences about elders’ need to downsize: family members and elders themselves. Authors who speak to family members do so with an urgent, unsentimental tone that echoes mainstream clutter-control advice about disorderly, overfull households. In texts for elders, the standard critique about consumption and unruly lives is gentler, more sensitive to the meaning of things, and underplays the emotions of divestment. There is stress on the responsibility to spare the next generation and control one’s legacy. These latter texts seem to respect that downsizing in later life symbolizes a narrowing of the life world. PMID:21822336

  3. Auditory cortical activation in severe-to-profound hearing-impaired patients monitored by SPET.

    PubMed

    Di Nardo, W; Di Giuda, D; Scarano, E; Picciotti, P M; Galla, S; De Rossi, G

    2006-08-01

    Single photon emission tomography was used to map blood flow increase in temporal and parietal cortex after auditory stimulation in 25 subjects: 10 normal-hearing, 10 severe-profound hearing-impaired and 5 totally deaf. After a 500 Hz pure tone stimulation, a marked perfusion increase was observed, particularly at the level of the contralateral auditory temporal cortex. Blood flow increase in temporal and parietal cortical areas of normal subjects was significantly higher than that observed in severe-to-profound hearing-impaired patients. In all cases, following 500 Hz pure tone acoustic stimulation, the most lateral sagittal slice tomograms (48.75 and 56.25 mm) showed the highest blood flow increase. Statistically significant differences were also observed between normal subjects and hearing-impaired patients in the 48.75 mm sagittal tomogram. In 2 hearing-impaired patients, the single photon emission tomography pattern showed activation of the intermediate sagittal tomogram, suggesting a possible new tonotopic cortical arrangement. No significant activation was present in totally deaf patients. In conclusion, Single Photon Emission Tomography appears to be a useful tool in the evaluation of auditory cortical activation and cortical plasticity, in severe-to-profound hearing-impaired patients. Moreover, it could be a useful test for the study of auditory central pathways.

  4. Predicting Later-Life Outcomes of Early-Life Exposures

    EPA Science Inventory

    Background: In utero exposure of the fetus to a stressor can lead to disease in later life. Epigenetic mechanisms are likely mediators of later-life expression of early-life events.Objectives: We examined the current state of understanding of later-life diseases resulting from ea...

  5. Cortical Contributions to Impaired Contour Integration in Schizophrenia

    PubMed Central

    Silverstein, Steven M.; Harms, Michael P.; Carter, Cameron S.; Gold, James M.; Keane, Brian P.; MacDonald, Angus; Ragland, J. Daniel; Barch, Deanna M.

    2015-01-01

    Objectives Visual perceptual organization impairments in schizophrenia (SCZ) are well established, but their neurobiological bases are not. The current study used the previously validated Jittered Orientation Visual Integration (JOVI) task, along with fMRI, to examine the neural basis of contour integration (CI), and its impairment in SCZ. CI is an aspect of perceptual organization in which multiple distinct oriented elements are grouped into a single continuous boundary or shape. Methods On the JOVI, five levels of orientational jitter were added to non-contiguous closed contour elements embedded in background noise to progressively increase the difficulty in perceiving contour elements as left- or right-pointing ovals. Multi-site fMRI data were analyzed for 56 healthy control subjects and 47 people with SCZ. Results SCZ patients demonstrated poorer CI, and this was associated with increased activation in regions involved in global shape processing and visual attention, namely the lateral occipital complex and superior parietal lobules. There were no brain regions where controls demonstrated more activation than patients. Conclusions CI impairment in this sample of outpatients with SCZ was related to excessive activation in regions associated with object processing and allocation of visual-spatial attention. There was no evidence for basic impairments in contour element linking in the fMRI data. The latter may be limited to poor outcome patients, where more extensive structural and functional changes in the occipital lobe have been observed. PMID:26160288

  6. Outcomes and Opportunities: A Study of Children with Cortical Visual Impairment

    ERIC Educational Resources Information Center

    Roman Lantzy, Christine A.; Lantzy, Alan

    2010-01-01

    Pediatric View is an evaluation project that began in 1999 and is located at Western Pennsylvania Hospital in Pittsburgh. The purpose of Pediatric View is to provide developmental and functional vision evaluations to children who have ocular or cortical visual impairments. The evaluations are generally two hours in length, and a detailed report…

  7. A Survey of Parents of Children with Cortical or Cerebral Visual Impairment

    ERIC Educational Resources Information Center

    Jackel, Bernadette; Wilson, Michelle; Hartmann, Elizabeth

    2010-01-01

    Cortical or cerebral visual impairment (CVI) can result when the visual pathways and visual processing areas of the brain have been damaged. Children with CVI may have difficulty finding an object among other objects, viewing in the distance, orienting themselves in space, going from grass to pavement or other changes in surface, and copying…

  8. Visual Attention to Movement and Color in Children with Cortical Visual Impairment

    ERIC Educational Resources Information Center

    Cohen-Maitre, Stacey Ann; Haerich, Paul

    2005-01-01

    This study investigated the ability of color and motion to elicit and maintain visual attention in a sample of children with cortical visual impairment (CVI). It found that colorful and moving objects may be used to engage children with CVI, increase their motivation to use their residual vision, and promote visual learning.

  9. Visual Behaviors and Adaptations Associated with Cortical and Ocular Impairment in Children.

    ERIC Educational Resources Information Center

    Jan, J. E.; Groenveld, M.

    1993-01-01

    This article shows the usefulness of understanding visual behaviors in the diagnosis of various types of visual impairments that are due to ocular and cortical disorders. Behaviors discussed include nystagmus, ocular motor dyspraxia, head position, close viewing, field loss adaptations, mannerisms, photophobia, and abnormal color perception. (JDD)

  10. Possession Divestment by Sales in Later Life

    PubMed Central

    Ekerdt, David J.; Addington, Aislinn

    2015-01-01

    Residential relocation in later life is almost always a downsizing, with many possessions to be divested in a short period of time. This article examines older movers’ capacities for selling things, and ways that selling attenuates people's ties to those things, thus accomplishing the human dis-possession of the material convoy. In qualitative interviews in 79 households in the Midwestern United States, older adults reported their experience with possession sales associated with residential relocation. Among this group, three-quarters of the households downsized by selling some belongings. Informal sales seemed the least fraught of all strategies, estate sales had mixed reviews, and garage sales were recalled as laborious. Sellers’ efforts were eased by social relations and social networks as helpers and buyers came forward. As selling proceeded, sentiment about possessions waned as their materiality and economic value came to the fore, easing their detachment from the household. Possession selling is challenging because older adults are limited in the knowledge, skills, and efforts that they can apply to the recommodification of their belongings. Selling can nonetheless be encouraged as a divestment strategy as long as the frustrations and drawbacks are transparent, and the goal of ridding is kept in view. PMID:26162722

  11. Possession divestment by sales in later life.

    PubMed

    Ekerdt, David J; Addington, Aislinn

    2015-08-01

    Residential relocation in later life is almost always a downsizing, with many possessions to be divested in a short period of time. This article examines older movers' capacities for selling things, and ways that selling attenuates people's ties to those things, thus accomplishing the human dis-possession of the material convoy. In qualitative interviews in 79 households in the Midwestern United States, older adults reported their experience with possession sales associated with residential relocation. Among this group, three-quarters of the households downsized by selling some belongings. Informal sales seemed the least fraught of all strategies, estate sales had mixed reviews, and garage sales were recalled as laborious. Sellers' efforts were eased by social relations and social networks as helpers and buyers came forward. As selling proceeded, sentiment about possessions waned as their materiality and economic value came to the fore, easing their detachment from the household. Possession selling is challenging because older adults are limited in the knowledge, skills, and efforts that they can apply to the recommodification of their belongings. Selling can nonetheless be encouraged as a divestment strategy as long as the frustrations and drawbacks are transparent, and the goal of ridding is kept in view.

  12. Postnatal Erythropoietin Mitigates Impaired Cerebral Cortical Development Following Subplate Loss from Prenatal Hypoxia-Ischemia.

    PubMed

    Jantzie, Lauren L; Corbett, Christopher J; Firl, Daniel J; Robinson, Shenandoah

    2015-09-01

    Preterm birth impacts brain development and leads to chronic deficits including cognitive delay, behavioral problems, and epilepsy. Premature loss of the subplate, a transient subcortical layer that guides development of the cerebral cortex and axonal refinement, has been implicated in these neurological disorders. Subplate neurons influence postnatal upregulation of the potassium chloride co-transporter KCC2 and maturation of γ-amino-butyric acid A receptor (GABAAR) subunits. We hypothesized that prenatal transient systemic hypoxia-ischemia (TSHI) in Sprague-Dawley rats that mimic brain injury from extreme prematurity in humans would cause premature subplate loss and affect cortical layer IV development. Further, we predicted that the neuroprotective agent erythropoietin (EPO) could attenuate the injury. Prenatal TSHI induced subplate neuronal loss via apoptosis. TSHI impaired cortical layer IV postnatal upregulation of KCC2 and GABAAR subunits, and postnatal EPO treatment mitigated the loss (n ≥ 8). To specifically address how subplate loss affects cortical development, we used in vitro mechanical subplate ablation in slice cultures (n ≥ 3) and found EPO treatment attenuates KCC2 loss. Together, these results show that subplate loss contributes to impaired cerebral development, and EPO treatment diminishes the damage. Limitation of premature subplate loss and the resultant impaired cortical development may minimize cerebral deficits suffered by extremely preterm infants.

  13. Mild cognitive impairment in patients with Parkinson's disease is associated with increased cortical degeneration.

    PubMed

    Hanganu, Alexandru; Bedetti, Christophe; Jubault, Thomas; Gagnon, Jean-Francois; Mejia-Constain, Béatriz; Degroot, Clotilde; Lafontaine, Anne-Louise; Chouinard, Sylvain; Monchi, Oury

    2013-09-01

    Mild cognitive impairment (MCI) can occur early in the course of Parkinson's disease (PD), and its presence increases the risk of developing dementia. Determining the cortical changes associated with MCI in PD, thus, may be useful in predicting the future development of dementia. To address this objective, 37 patients with PD, divided into 2 groups according to the presence or absence MCI (18 with and 19 without) and 16 matched controls, underwent anatomic magnetic resonance imaging. Corticometry analyses were performed to measure the changes in cortical thickness and surface area as well as their correlation with disease duration. Compared with healthy controls, the PD-MCI group exhibited increased atrophy and changes of local surface area in the bilateral occipital, left temporal, and frontal cortices; whereas the PD non-MCI group exhibited only unilateral thinning and decreased surface area in the occipital lobe and in the frontal cortex. In addition, a comparison between the PD-MCI and PD non-MCI groups revealed increased local surface area in the occipital lobe, temporal lobe, and postcentral gyrus for the cognitively impaired patients. It is noteworthy that, in the PD-MCI group, cortical thickness had a significant negative correlation with disease duration in the precentral, supramarginal, occipital, and superior temporal cortices; whereas, in the PD non-MCI group, such a correlation was absent. The findings from this study reveal that, at the same stage of PD evolution, the presence of MCI is associated with a higher level of cortical changes, suggesting that cortical degeneration is increased in patients with PD because of the presence of MCI. PMID:23801590

  14. Hippocampal and cortical atrophy in amyloid-negative mild cognitive impairments: comparison with amyloid-positive mild cognitive impairment.

    PubMed

    Ye, Byoung Seok; Seo, Sang Won; Kim, Chi Hun; Jeon, Seun; Kim, Geon Ha; Noh, Young; Cho, Hanna; Yoon, Cindy W; Kim, Hee Jin; Jang, Eun Young; Lee, Jeongmin; Kim, Jung-Hyun; Chin, Juhee; Lee, Jong Min; Kim, Jeong-Hun; Seong, Joon-kyung; Kim, Chang-Hun; Choe, Yearn Seong; Lee, Kyung Han; Na, Duk L

    2014-02-01

    Although patients with amnestic mild cognitive impairment (aMCI) are at higher risk of developing Alzheimer's disease (AD), their pathologies could be heterogeneous. We aimed to evaluate structural changes in amyloid-negative and amyloid-positive aMCI patients. Forty-eight aMCI patients who underwent Pittsburgh compound B (PiB) positron emission tomography were recruited. They were classified as PiB (-) aMCI (N = 16) and PiB (+) (N = 32). Hippocampal shape and regional cortical thickness were compared with 41 subjects with normal cognition (NC). Relative to NC, PiB(-) aMCI exhibited hippocampal deformity in the right cornu ammonis 1, whereas PiB(+) aMCI exhibited hippocampal deformity in bilateral subiculum and cornu ammonis 1 subregions. Relative to NC, PiB(-) aMCI showed cortical thinning in the left medial prefrontal and right anterior temporal regions, whereas PiB(+) aMCI exhibited cortical thinning in bilateral medial temporal regions, temporoparietal junctions and precuneus, and prefrontal cortices. Our findings suggest that structural changes in PiB(-) aMCI might be due to several possible pathologic changes, whereas structural changes in PiB(+) aMCI reflect AD-like structural changes.

  15. White matter integrity of cerebellar-cortical tracts in reading impaired children: A probabilistic tractography study

    PubMed Central

    Fernandez, Vindia G.; Juranek, Jenifer; Romanowska-Pawliczek, Anna; Stuebing, Karla; Williams, Victoria J.; Fletcher, Jack M.

    2016-01-01

    Little is known about the white matter integrity of cerebellar-cortical pathways in individuals with dyslexia. Building on previous findings of decreased volume in the anterior lobe of the cerebellum, we utilized novel cerebellar segmentation procedures and probabilistic tractography to examine tracts that connect the anterior lobe of the cerebellum and cortical regions typically associated with reading: the temporoparietal (TP), occipitotemporal (OT), and inferior frontal (IF) regions. The sample included 29 reading impaired children and 27 typical readers. We found greater fractional anisotropy (FA) for the poor readers in tracts connecting the cerebellum with TP and IF regions relative to typical readers. In the OT region, FA was greater for the older poor readers, but smaller for the younger ones. This study provides evidence for discrete, regionally-bound functions of the cerebellum and suggests that projections from the anterior cerebellum appear to have a regulatory effect on cortical pathways important for reading. PMID:26307492

  16. Cognitive impairment in pain through amygdala-driven prefrontal cortical deactivation

    PubMed Central

    Ji, Guangchen; Sun, Hao; Fu, Yu; Li, Zhen; Pais-Vieira, Miguel; Galhardo, Vasco; Neugebauer, Volker

    2010-01-01

    Cognitive deficits such as impaired decision-making can be a consequence of persistent pain. Normal functions of the intact amygdala and prefrontal cortex are required for emotion-based decision-making that relies on the ability to assess risk, attribute value and identify advantageous strategies. We tested the hypothesis that pain-related cognitive deficits result from amygdala-driven impairment of medial prefrontal cortical (mPFC) function. To do this, we used electrophysiological single-unit recordings in vivo, patch-clamp in brain slices, and various behavioral assays to show that increased neuronal activity in the amygdala in an animal model of arthritis pain was accompanied by decreased mPFC activation and impaired decision-making. Further, pharmacologic inhibition (with a CRF1 receptor antagonist) of pain-related hyperactivity in the basolateral amygdala (BLA), but not central amygdala (CeA), reversed deactivation of mPFC pyramidal cells and improved decision-making deficits. Pain-related cortical deactivation resulted from a shift of balance between inhibitory and excitatory synaptic transmission. Direct excitatory transmission to mPFC pyramidal cells did not change in the pain model whereas polysynaptic inhibitory transmission increased. GABAergic transmission was reduced by non-NMDA receptor antagonists, suggesting synaptic inhibition was glutamate-driven. The results are consistent with a model of BLA-driven feed-forward inhibition of mPFC neurons. In contrast to the differential effects of BLA versus CeA hyperactivity on cortical-cognitive functions, both amygdala nuclei modulate emotional-affective pain behavior. Thus this study shows that the amygdala contributes not only to emotional-affective but also cognitive effects of pain. The novel amygdalo-cortical pain mechanism has important implications for our understanding of amygdala functions and amygdalo-cortical interactions. PMID:20392966

  17. Cortical Amyloid β Deposition and Current Depressive Symptoms in Alzheimer Disease and Mild Cognitive Impairment.

    PubMed

    Chung, Jun Ku; Plitman, Eric; Nakajima, Shinichiro; Chakravarty, M Mallar; Caravaggio, Fernando; Gerretsen, Philip; Iwata, Yusuke; Graff-Guerrero, Ariel

    2016-05-01

    Depressive symptoms are frequently seen in patients with dementia and mild cognitive impairment (MCI). Evidence suggests that there may be a link between current depressive symptoms and Alzheimer disease (AD)-associated pathological changes, such as an increase in cortical amyloid-β (Aβ). However, limited in vivo studies have explored the relationship between current depressive symptoms and cortical Aβ in patients with MCI and AD. Our study, using a large sample of 455 patients with MCI and 153 patients with AD from the Alzheimer's disease Neuroimaging Initiatives, investigated whether current depressive symptoms are related to cortical Aβ deposition. Depressive symptoms were assessed using the Geriatric Depression Scale and Neuropsychiatric Inventory-depression/dysphoria. Cortical Aβ was quantified using positron emission tomography with the Aβ probe(18)F-florbetapir (AV-45).(18)F-florbetapir standardized uptake value ratio (AV-45 SUVR) from the frontal, cingulate, parietal, and temporal regions was estimated. A global AV-45 SUVR, defined as the average of frontal, cingulate, precuneus, and parietal cortex, was also used. We observed that current depressive symptoms were not related to cortical Aβ, after controlling for potential confounds, including history of major depression. We also observed that there was no difference in cortical Aβ between matched participants with high and low depressive symptoms, as well as no difference between matched participants with the presence and absence of depressive symptoms. The association between depression and cortical Aβ deposition does not exist, but the relationship is highly influenced by stressful events in the past, such as previous depressive episodes, and complex interactions of different pathways underlying both depression and dementia. PMID:26400248

  18. Cortical Amyloid β Deposition and Current Depressive Symptoms in Alzheimer Disease and Mild Cognitive Impairment.

    PubMed

    Chung, Jun Ku; Plitman, Eric; Nakajima, Shinichiro; Chakravarty, M Mallar; Caravaggio, Fernando; Gerretsen, Philip; Iwata, Yusuke; Graff-Guerrero, Ariel

    2016-05-01

    Depressive symptoms are frequently seen in patients with dementia and mild cognitive impairment (MCI). Evidence suggests that there may be a link between current depressive symptoms and Alzheimer disease (AD)-associated pathological changes, such as an increase in cortical amyloid-β (Aβ). However, limited in vivo studies have explored the relationship between current depressive symptoms and cortical Aβ in patients with MCI and AD. Our study, using a large sample of 455 patients with MCI and 153 patients with AD from the Alzheimer's disease Neuroimaging Initiatives, investigated whether current depressive symptoms are related to cortical Aβ deposition. Depressive symptoms were assessed using the Geriatric Depression Scale and Neuropsychiatric Inventory-depression/dysphoria. Cortical Aβ was quantified using positron emission tomography with the Aβ probe(18)F-florbetapir (AV-45).(18)F-florbetapir standardized uptake value ratio (AV-45 SUVR) from the frontal, cingulate, parietal, and temporal regions was estimated. A global AV-45 SUVR, defined as the average of frontal, cingulate, precuneus, and parietal cortex, was also used. We observed that current depressive symptoms were not related to cortical Aβ, after controlling for potential confounds, including history of major depression. We also observed that there was no difference in cortical Aβ between matched participants with high and low depressive symptoms, as well as no difference between matched participants with the presence and absence of depressive symptoms. The association between depression and cortical Aβ deposition does not exist, but the relationship is highly influenced by stressful events in the past, such as previous depressive episodes, and complex interactions of different pathways underlying both depression and dementia.

  19. Early neonatal 192 IgG saporin induces learning impairments and disrupts cortical morphogenesis in rats.

    PubMed

    Ricceri, Laura; Hohmann, Christine; Berger-Sweeney, Joanne

    2002-11-01

    We have shown previously that neonatal intraventricular injections of the selective cholinergic immunotoxin 192 IgG saporin on postnatal day 7 (pnd 7) induce marked cholinergic loss in hippocampus and neocortex and a learning impairment on pnd 15. In the present study, we analysed the behavioural, morphological and neurochemical effects of earlier intraventricular injection of the immunotoxin 192 IgG saporin (pnd 1 and 3). We hypothesised that these earlier lesions would interrupt a critical stage in neocortical maturation, and impair behavior more profoundly than the later lesions. Passive avoidance (PA) learning and locomotor activity during the PA test were assessed on pnd 15. Retention of the PA task was assessed on pnd 16. Reactivity to spatial and object novelty was assessed on pnd 180 in a spatial open field test with five objects. Choline acetyltransferase (ChAT) activity was measured in basal forebrain targets on pnd 20 and pnd 180. Neonatal administration of 192 IgG saporin resulted in a slower acquisition of the PA task in females; retention and locomotor activity were not affected. On pnd 180, reaction to spatial novelty was mildly impaired in lesioned rats of both sexes. There was a marked reduction of ChAT in the hippocampus and neocortex of lesioned rats of both sexes, at both ages. Morphological analysis of the somatosensory cortex of lesioned rats revealed alterations in cortical development with sex specific variations in total cortical thickness. These results suggest that interrupting cholinergic basal forebrain innervation of neocortex and hippocampus during the first postnatal days affects the development of cognitive behaviour, neurochemistry and cortical organisation in a sex specific manner. Furthermore, the alterations in cortical organization are more profound than those noted after a lesion later in postnatal development. These behavioural and morphological abnormalities could be considered a model for several neurodevelopmental

  20. Anhedonia in the psychosis risk syndrome: associations with social impairment and basal orbitofrontal cortical activity

    PubMed Central

    Cressman, Victoria L; Schobel, Scott A; Steinfeld, Sara; Ben-David, Shelly; Thompson, Judy L; Small, Scott A; Moore, Holly; Corcoran, Cheryl M

    2015-01-01

    Background/Objectives: Anhedonia is associated with poor social function in schizophrenia. Here, we examined this association in individuals at clinical high risk (CHR) for schizophrenia and related psychotic disorders, taking into account social anxiety. We then explored correlations between anhedonia and basal metabolic activity in selected forebrain regions implicated in reward processing. Methods: In 62 CHR individuals and 37 healthy controls, we measured social adjustment (Social Adjustment Self-Report Scale), social and physical anhedonia (Chapman Revised Anhedonia Scales), and social anxiety (Social Anxiety Scale for Adolescents) in cross-section. In a subgroup of 25 CHR individuals for whom high-spatial-resolution basal-state functional magnetic resonance imaging data were available, we also assessed correlations of these socio-affective constructs with basal cerebral blood volume in orbitofrontal cortex and related regions involved in reward processing. Results: Relative to controls, CHR individuals reported social impairment, greater social and physical anhedonia, and more social anxiety, exhibiting impairments comparable to schizophrenia. Regression analyses showed that anhedonia predicted social impairment and correlated negatively with basal cerebral blood volume within the orbitofrontal cortex (all P’s<0.05). Conclusions: Anhedonia and social anxiety are prominent in CHR individuals. Trait-like anhedonia may be a core phenotype related to orbitofrontal cortical function that, independent of symptoms, predicts social impairment. These data provide a rationale for interventions that target anhedonia and related activity in orbitofrontal cortical circuits in CHR individuals. PMID:27336033

  1. Prenatal Exposure to Arsenic Impairs Behavioral Flexibility and Cortical Structure in Mice

    PubMed Central

    Aung, Kyaw H.; Kyi-Tha-Thu, Chaw; Sano, Kazuhiro; Nakamura, Kazuaki; Tanoue, Akito; Nohara, Keiko; Kakeyama, Masaki; Tohyama, Chiharu; Tsukahara, Shinji; Maekawa, Fumihiko

    2016-01-01

    Exposure to arsenic from well water in developing countries is suspected to cause developmental neurotoxicity. Although, it has been demonstrated that exposure to sodium arsenite (NaAsO2) suppresses neurite outgrowth of cortical neurons in vitro, it is largely unknown how developmental exposure to NaAsO2 impairs higher brain function and affects cortical histology. Here, we investigated the effect of prenatal NaAsO2 exposure on the behavior of mice in adulthood, and evaluated histological changes in the prelimbic cortex (PrL), which is a part of the medial prefrontal cortex that is critically involved in cognition. Drinking water with or without NaAsO2 (85 ppm) was provided to pregnant C3H mice from gestational days 8 to 18, and offspring of both sexes were subjected to cognitive behavioral analyses at 60 weeks of age. The brains of female offspring were subsequently harvested and used for morphometrical analyses. We found that both male and female mice prenatally exposed to NaAsO2 displayed an impaired adaptation to repetitive reversal tasks. In morphometrical analyses of Nissl- or Golgi-stained tissue sections, we found that NaAsO2 exposure was associated with a significant increase in the number of pyramidal neurons in layers V and VI of the PrL, but not other layers of the PrL. More strikingly, prenatal NaAsO2 exposure was associated with a significant decrease in neurite length but not dendrite spine density in all layers of the PrL. Taken together, our results indicate that prenatal exposure to NaAsO2 leads to behavioral inflexibility in adulthood and cortical disarrangement in the PrL might contribute to this behavioral impairment. PMID:27064386

  2. Prenatal Exposure to Arsenic Impairs Behavioral Flexibility and Cortical Structure in Mice.

    PubMed

    Aung, Kyaw H; Kyi-Tha-Thu, Chaw; Sano, Kazuhiro; Nakamura, Kazuaki; Tanoue, Akito; Nohara, Keiko; Kakeyama, Masaki; Tohyama, Chiharu; Tsukahara, Shinji; Maekawa, Fumihiko

    2016-01-01

    Exposure to arsenic from well water in developing countries is suspected to cause developmental neurotoxicity. Although, it has been demonstrated that exposure to sodium arsenite (NaAsO2) suppresses neurite outgrowth of cortical neurons in vitro, it is largely unknown how developmental exposure to NaAsO2 impairs higher brain function and affects cortical histology. Here, we investigated the effect of prenatal NaAsO2 exposure on the behavior of mice in adulthood, and evaluated histological changes in the prelimbic cortex (PrL), which is a part of the medial prefrontal cortex that is critically involved in cognition. Drinking water with or without NaAsO2 (85 ppm) was provided to pregnant C3H mice from gestational days 8 to 18, and offspring of both sexes were subjected to cognitive behavioral analyses at 60 weeks of age. The brains of female offspring were subsequently harvested and used for morphometrical analyses. We found that both male and female mice prenatally exposed to NaAsO2 displayed an impaired adaptation to repetitive reversal tasks. In morphometrical analyses of Nissl- or Golgi-stained tissue sections, we found that NaAsO2 exposure was associated with a significant increase in the number of pyramidal neurons in layers V and VI of the PrL, but not other layers of the PrL. More strikingly, prenatal NaAsO2 exposure was associated with a significant decrease in neurite length but not dendrite spine density in all layers of the PrL. Taken together, our results indicate that prenatal exposure to NaAsO2 leads to behavioral inflexibility in adulthood and cortical disarrangement in the PrL might contribute to this behavioral impairment. PMID:27064386

  3. Cortical Structure Alterations and Social Behavior Impairment in p50-Deficient Mice

    PubMed Central

    Bonini, Sara Anna; Mastinu, Andrea; Maccarinelli, Giuseppina; Mitola, Stefania; Premoli, Marika; La Rosa, Luca Rosario; Ferrari-Toninelli, Giulia; Grilli, Mariagrazia; Memo, Maurizio

    2016-01-01

    Alterations in genes that regulate neurodevelopment can lead to cortical malformations, resulting in malfunction during postnatal life. The NF-κB pathway has a key role during neurodevelopment by regulating the maintenance of the neural progenitor cell pool and inhibiting neuronal differentiation. In this study, we evaluated whether mice lacking the NF-κB p50 subunit (KO) present alterations in cortical structure and associated behavioral impairment. We found that, compared with wild type (WT), KO mice at postnatal day 2 present an increase in radial glial cells, an increase in Reelin protein expression levels, in addition to an increase of specific layer thickness. Moreover, adult KO mice display abnormal columnar organization in the somatosensory cortex, a specific decrease in somatostatin- and parvalbumin-expressing interneurons, altered neurite orientation, and a decrease in Synapsin I protein levels. Concerning behavior, KO mice, in addition to an increase in locomotor and exploratory activity, display impairment in social behaviors, with a reduction in social interaction. Finally, we found that risperidone treatment decreased hyperactivity of KO mice, but had no effect on defective social interaction. Altogether, these data add complexity to a growing body of data, suggesting a link between dysregulation of the NF-κB pathway and neurodevelopmental disorders pathogenesis. PMID:26946128

  4. Topological Properties of Large-Scale Cortical Networks Based on Multiple Morphological Features in Amnestic Mild Cognitive Impairment

    PubMed Central

    Li, Qiongling; Li, Xinwei; Wang, Xuetong; Li, Yuxia; Li, Kuncheng; Yu, Yang; Yin, Changhao; Li, Shuyu; Han, Ying

    2016-01-01

    Previous studies have demonstrated that amnestic mild cognitive impairment (aMCI) has disrupted properties of large-scale cortical networks based on cortical thickness and gray matter volume. However, it is largely unknown whether the topological properties of cortical networks based on geometric measures (i.e., sulcal depth, curvature, and metric distortion) change in aMCI patients compared with normal controls because these geometric features of cerebral cortex may be related to its intrinsic connectivity. Here, we compare properties in cortical networks constructed by six different morphological features in 36 aMCI participants and 36 normal controls. Six cortical features (3 volumetric and 3 geometric features) were extracted for each participant, and brain abnormities in aMCI were identified by cortical network based on graph theory method. All the cortical networks showed small-world properties. Regions showing significant differences mainly located in the medial temporal lobe and supramarginal and right inferior parietal lobe. In addition, we also found that the cortical networks constructed by cortical thickness and sulcal depth showed significant differences between the two groups. Our results indicated that geometric measure (i.e., sulcal depth) can be used to construct network to discriminate individuals with aMCI from controls besides volumetric measures. PMID:27057360

  5. Paternal programming of offspring cardiometabolic diseases in later life

    PubMed Central

    Li, Jian; Tsuprykov, Oleg; Yang, Xiaoping; Hocher, Berthold

    2016-01-01

    Early – intrauterine – environmental factors are linked to the development of cardiovascular disease in later life. Traditionally, these factors are considered to be maternal factors such as maternal under and overnutrition, exposure to toxins, lack of micronutrients, and stress during pregnancy. However, in the recent years, it became obvious that also paternal environmental factors before conception and during sperm development determine the health of the offspring in later life. We will first describe clinical observational studies providing evidence for paternal programming of adulthood diseases in progeny. Next, we describe key animal studies proving this relationship, followed by a detailed analysis of our current understanding of the underlying molecular mechanisms of paternal programming. Alterations of noncoding sperm micro-RNAs, histone acetylation, and targeted as well as global DNA methylation seem to be in particular involved in paternal programming of offspring's diseases in later life. PMID:27457668

  6. Paternal programming of offspring cardiometabolic diseases in later life.

    PubMed

    Li, Jian; Tsuprykov, Oleg; Yang, Xiaoping; Hocher, Berthold

    2016-11-01

    Early - intrauterine - environmental factors are linked to the development of cardiovascular disease in later life. Traditionally, these factors are considered to be maternal factors such as maternal under and overnutrition, exposure to toxins, lack of micronutrients, and stress during pregnancy. However, in the recent years, it became obvious that also paternal environmental factors before conception and during sperm development determine the health of the offspring in later life. We will first describe clinical observational studies providing evidence for paternal programming of adulthood diseases in progeny. Next, we describe key animal studies proving this relationship, followed by a detailed analysis of our current understanding of the underlying molecular mechanisms of paternal programming. Alterations of noncoding sperm micro-RNAs, histone acetylation, and targeted as well as global DNA methylation seem to be in particular involved in paternal programming of offspring's diseases in later life.

  7. Mechanisms of cortical neural synchronization related to healthy and impaired consciousness: evidence by quantitative electroencephalographic studies.

    PubMed

    Babiloni, Claudio; Vecchio, Fabrizio; Buffo, Paola; Iacoboni, Marco; Pistoia, Francesca; Sacco, Simona; Sara, Marco; Rossini, Paolo Maria

    2014-01-01

    In this paper, we review the contribution of our research group to the study of human consciousness by quantitative electroencephalographic (EEG) techniques. We posit that EEG techniques can be extremely useful for a direct measurement of brain electrophysiological activity related to human consciousness for their unsurpassable high temporal resolution (milliseconds). This activity can be expressed in terms of event-related potentials as well as changes of EEG rhythms of interest, for example the dominant alpha rhythms (about 8-12 Hz). The results of our studies, and those of several independent groups, lead support to the hypothesis that these techniques provide important insights about the neurophysiologic mechanisms underlying cortical neural synchronization/desynchronization and the regulation of neuromodulatory systems (e.g. dopaminergic, noradrenergic, cholinergic, etc.) at the basis of brain arousal and consciousness in healthy subjects and in patients with impairment of the consciousness. A possible interaction of these mechanisms and the drugs administered to patients with consciousness disorders is discussed.

  8. Summative effects of vascular risk factors on cortical thickness in mild cognitive impairment.

    PubMed

    Tchistiakova, Ekaterina; MacIntosh, Bradley J

    2016-09-01

    Vascular risk factors (VRFs) increase the risk of Alzheimer's disease (AD) and contribute to neurodegenerative processes. The purpose of this study was to investigate whether increasing number of VRFs contributes to within-cohort differences in cortical thickness (CThk) among adults with mild cognitive impairment (MCI) and cognitively intact older controls from the AD Neuroimaging Initiative 1, GO, and 2 data sets. Multivariate partial least squares analysis was used to investigate the effect of VRF index on regional CThk measurements, which produced a significant latent variable and identified patterns of cortical thinning in the MCI group but not controls. Subsequent analyses tested the interaction effects between VRF index and cognitive grouping and examined 1-year follow-up data. There was evidence of a VRF index by cognitive group interaction. Partial least squares results were replicated at 1-year follow-up among MCI cohort in a subset of baseline CThk regions. This study provides evidence that a summative VRF index accounts for some of the variance in brain tissue loss in regions implicated in AD among MCI adults. PMID:27459930

  9. Decisional impairments in cocaine addiction, reward bias, and cortical oscillation “unbalance”

    PubMed Central

    Balconi, Michela; Finocchiaro, Roberta

    2015-01-01

    A vast amount of research has suggested that subjects with substance use disorder (SUD) might have difficulty making advantageous decisions that opt in favor of a longer-term, larger reward than an immediate, smaller reward. The current research explored the impact of reward bias and cortical frontal asymmetry (left lateralization effect) in SUD in response to a decisional task (Iowa Gambling Task). Fifty SUD participants and 40 controls (CG) were tested using the Iowa Gambling Task. Electrophysiology (electroencephalography) recording was performed during task execution. We measured left and right dorsolateral prefrontal cortex power activity. Behavioral responses (gain/loss options); frequency band modulation (asymmetry index) for delta, theta, alpha, and beta band; and cortical source localization (standardized low-resolution brain electromagnetic tomography) were considered. The SUD group opted in favor of the immediate reward option (loss) more frequently than the long-term option (gain) when compared to the CG. Secondly, SUD showed increased left-hemisphere activation in response to losing (with immediate reward) choices in comparison with the CG. The left hemispheric unbalance effect and the “reward bias” were adduced to explain the decisional impairment in SUD. PMID:25848274

  10. Transitions into and out of Cohabitation in Later Life

    ERIC Educational Resources Information Center

    Brown, Susan L.; Bulanda, Jennifer Roebuck; Lee, Gary R.

    2012-01-01

    Cohabitation among adults over age 50 is rising rapidly, more than doubling from 1.2 million in 2000 to 2.75 million in 2010. A small literature provides a descriptive portrait of older cohabitors, but no study has investigated transitions into and out of cohabitation during later life. Drawing on demographic and life course perspectives, the…

  11. Engaging Later-Life Learners through Portfolio Writing

    ERIC Educational Resources Information Center

    Clarke, Egerton; Hornyak, Christine

    2012-01-01

    The ever increasing enrollment of later-life students in institutions of higher learning warrants innovative teaching strategies to promote successful learning outcomes. This article discusses the academic challenges that instructors face and argues in support of an important assessment method, that is, portfolio writing. This novel strategy was…

  12. Radical Creativity in Later Life. Occasional Papers Series: No. 3.

    ERIC Educational Resources Information Center

    Macdonald, Murdo

    The lives and work of many distinguished artists support the claim that, far from being a period of decline, later life can be the high point of creativity. Evidence from both the visual and written arts would appear to challenge the research of Harvey Lehman, whose 1953 study "Age and Achievement" claimed that artists produce their best paintings…

  13. Neighborhood Deterioration and Social Isolation in Later Life.

    ERIC Educational Resources Information Center

    Krause, Neal

    1993-01-01

    Tested conceptual model relating neighborhood characteristics to social isolation in later life. Data from nationwide survey supported theoretical sequence of older adults with low levels of educational attainment being more likely to experience financial problems, of elderly people confronted by financial difficulties being more likely to reside…

  14. Family Size and Mother-Child Relations in Later Life.

    ERIC Educational Resources Information Center

    Uhlenberg, Peter; Cooney, Teresa M.

    1990-01-01

    Examined effects of family size on mother-child relationships in later life. Subjects were taken from national probability sample which included adults aged 35-55 (n=3,083) who had a living mother and women aged 60-79 (n=1,101) with at least one living child. Found generally positive relationship between number of siblings and favorable…

  15. Network Type and Mortality Risk in Later Life

    ERIC Educational Resources Information Center

    Litwin, Howard; Shiovitz-Ezra, Sharon

    2006-01-01

    Purpose: The purpose of this study was to examine the association of baseline network type and 7-year mortality risk in later life. Design and Methods: We executed secondary analysis of all-cause mortality in Israel using data from a 1997 national survey of adults aged 60 and older (N = 5,055) that was linked to records from the National Death…

  16. Assortive Mating in Later Life: Some Initial Considerations.

    ERIC Educational Resources Information Center

    Dressel, Paula L.

    1980-01-01

    A theoretical model of structural and attitudinal variables is developed for use in the comparative study of endogamy and homogamy. Data indicate that information about young adults' courtship contexts and mate selection cannot necessarily be generalized to courtship and marriage in later life. (Author)

  17. Cortical Auditory Evoked Potentials in (Un)aided Normal-Hearing and Hearing-Impaired Adults.

    PubMed

    Van Dun, Bram; Kania, Anna; Dillon, Harvey

    2016-02-01

    Cortical auditory evoked potentials (CAEPs) are influenced by the characteristics of the stimulus, including level and hearing aid gain. Previous studies have measured CAEPs aided and unaided in individuals with normal hearing. There is a significant difference between providing amplification to a person with normal hearing and a person with hearing loss. This study investigated this difference and the effects of stimulus signal-to-noise ratio (SNR) and audibility on the CAEP amplitude in a population with hearing loss. Twelve normal-hearing participants and 12 participants with a hearing loss participated in this study. Three speech sounds-/m/, /g/, and /t/-were presented in the free field. Unaided stimuli were presented at 55, 65, and 75 dB sound pressure level (SPL) and aided stimuli at 55 dB SPL with three different gains in steps of 10 dB. CAEPs were recorded and their amplitudes analyzed. Stimulus SNRs and audibility were determined. No significant effect of stimulus level or hearing aid gain was found in normal hearers. Conversely, a significant effect was found in hearing-impaired individuals. Audibility of the signal, which in some cases is determined by the signal level relative to threshold and in other cases by the SNR, is the dominant factor explaining changes in CAEP amplitude. CAEPs can potentially be used to assess the effects of hearing aid gain in hearing-impaired users. PMID:27587919

  18. Prefrontal Cortical GABAergic Dysfunction Contributes to Age-Related Working Memory Impairment

    PubMed Central

    Bañuelos, Cristina; Beas, B. Sofia; McQuail, Joseph A.; Gilbert, Ryan J.; Frazier, Charles J.; Setlow, Barry

    2014-01-01

    Working memory functions supported by the prefrontal cortex decline in normal aging. Disruption of corticolimbic GABAergic inhibitory circuits can impair working memory in young subjects; however, relatively little is known regarding how aging impacts prefrontal cortical GABAergic signaling and whether such changes contribute to cognitive deficits. The current study used a rat model to evaluate the effects of aging on expression of prefrontal GABAergic synaptic proteins in relation to working memory decline, and to test whether pharmacological manipulations of prefrontal GABAergic signaling can improve working memory abilities in aged subjects. Results indicate that in aged medial prefrontal cortex (mPFC), expression of the vesicular GABA transporter VGAT was unchanged; however, there was a significant increase in expression of the GABA synthesizing enzyme GAD67, and a significant decrease in the primary neuronal GABA transporter GAT-1 and in both subunits of the GABA(B) receptor (GABA(B)R). Expression of VGAT, GAD67, and GAT-1 was not associated with working memory ability. In contrast, among aged rats, GABA(B)R expression was significantly and negatively associated with working memory performance, such that lower GABA(B)R expression predicted better working memory. Subsequent experiments showed that systemic administration of a GABA(B)R antagonist, CGP55845, dose-dependently enhanced working memory in aged rats. This enhancing effect of systemic CGP55845 was reproduced by direct intra-mPFC administration. Together, these data suggest that age-related dysregulation of GABAergic signaling in prefrontal cortex may play a causal role in impaired working memory and that targeting GABA(B)Rs may provide therapeutic benefit for age-related impairments in executive functions. PMID:24599447

  19. Change in Perceived Age in Middle and Later Life

    ERIC Educational Resources Information Center

    Ward, Russell A.

    2013-01-01

    Analyses examine change in the age people "feel" ("felt age") and "would like to be" ("ideal age") (relative to current age) in middle and later life. Data are from 1,815 respondents in two waves (1995-96, 2004-06) of the Midlife in the United States Survey (MIDUS) who were age 40+ at Wave 1. In aggregate, people feel about the same amount younger…

  20. Transitions Into and Out of Cohabitation in Later Life.

    PubMed

    Brown, Susan L; Bulanda, Jennifer Roebuck; Lee, Gary R

    2012-08-01

    Cohabitation among adults over age 50 is rising rapidly, more than doubling from 1.2 million in 2000 to 2.75 million in 2010. A small literature provides a descriptive portrait of older cohabitors, but no study has investigated transitions into and out of cohabitation during later life. Drawing on demographic and life course perspectives, the authors developed a framework for conceptualizing later life union behaviors. Using data from the 1998 - 2006 Health and Retirement Study, they estimated discrete -time event-history models predicting union formation (i.e., cohabitation or marriage) among older unmarried individuals (N = 3,736) as well as transitions to either marriage or separation among older cohabitors (N = 377). Those who formed a union were as likely to be in a cohabiting relationship as a marriage. Older adult cohabiting unions were quite stable and unlikely to culminate in either marriage or separation. During later life, cohabitation appears to operate as a long-term alternative to marriage.

  1. Cortical Source Multivariate EEG Synchronization Analysis on Amnestic Mild Cognitive Impairment in Type 2 Diabetes

    PubMed Central

    Bian, Zhijie; Li, Qiuli; Wang, Lei; Li, Xiaoli

    2014-01-01

    Is synchronization altered in amnestic mild cognitive impairment (aMCI) and normal cognitive functions subjects in type 2 diabetes mellitus (T2DM)? Resting eye-closed EEG data were recorded in 8 aMCI subjects and 11 age-matched controls in T2DM. Three multivariate synchronization algorithms (S-estimator (S), synchronization index (SI), and global synchronization index (GSI)) were used to measure the synchronization in five ROIs of sLORETA sources for seven bands. Results showed that aMCI group had lower synchronization values than control groups in parietal delta and beta2 bands, temporal delta and beta2 bands, and occipital theta and beta2 bands significantly. Temporal (r = 0.629; P = 0.004) and occipital (r = 0.648; P = 0.003) theta S values were significantly positive correlated with Boston Name Testing. In sum, each of methods reflected that the cortical source synchronization was significantly different between aMCI and control group, and these difference correlated with cognitive functions. PMID:25254248

  2. Herpes Simplex Virus-Type1 (HSV-1) Impairs DNA Repair in Cortical Neurons

    PubMed Central

    De Chiara, Giovanna; Racaniello, Mauro; Mollinari, Cristiana; Marcocci, Maria Elena; Aversa, Giorgia; Cardinale, Alessio; Giovanetti, Anna; Garaci, Enrico; Palamara, Anna Teresa; Merlo, Daniela

    2016-01-01

    Several findings suggest that Herpes simplex virus-1 (HSV-1) infection plays a role in the neurodegenerative processes that characterize Alzheimer’s disease (AD), but the underlying mechanisms have yet to be fully elucidated. Here we show that HSV-1 productive infection in cortical neurons causes the accumulation of DNA lesions that include both single (SSBs) and double strand breaks (DSBs), which are reported to be implicated in the neuronal loss observed in neurodegenerative diseases. We demonstrate that HSV-1 downregulates the expression level of Ku80, one of the main components of non-homologous end joining (NHEJ), a major pathway for the repair of DSBs. We also provide data suggesting that HSV-1 drives Ku80 for proteasomal degradation and impairs NHEJ activity, leading to DSB accumulation. Since HSV-1 usually causes life-long recurrent infections, it is possible to speculate that cumulating damages, including those occurring on DNA, may contribute to virus induced neurotoxicity and neurodegeneration, further suggesting HSV-1 as a risk factor for neurodegenerative conditions. PMID:27803664

  3. Chronic cortical visual impairment in children: aetiology, prognosis, and associated neurological deficits

    PubMed Central

    Huo, R.; Burden, S.; Hoyt, C.; Good, W.

    1999-01-01

    BACKGROUND/AIMS—To evaluate prevalence, aetiology, prognosis, and associated neurological and ophthalmological problems in children with cortical visual impairment (CVI).
METHODS—The records of 7200 outpatients seen in the paediatric ophthalmology practice over the past 15 years were reviewed in order to compile data concerning CVI. In addition, the authors devised and applied a system for grading visual recovery in order to assess prognosis.
RESULTS—CVI occurred in 2.4% of all patients examined. The four most common causes of CVI were perinatal hypoxia (22%), cerebral vascular accident (14%), meningitis (12%), and acquired hypoxia (10%). Most children with CVI had associated neurological abnormalities. The most common were seizures (53%), cerebral palsy (26%) hemiparesis (12%), and hypotonia (5%). Associated ophthalmological problems were esotropia (19%), exotropia (18%), optic nerve atrophy (16%), ocular motor apraxia (15%), nystagmus (11%), and retinal disease (3%). On average, CVI patients improved by two levels as measured by the authors' scale.
CONCLUSION—The majority of children with CVI showed at least some recovery. In this group of children, CVI is often accompanied by additional ophthalmological problems and is nearly always associated with other, serious neurological abnormalities.

 PMID:10340973

  4. Sterilization by gamma radiation impairs the tensile fatigue life of cortical bone by two orders of magnitude.

    PubMed

    Akkus, Ozan; Belaney, Ryan M

    2005-09-01

    Cortical bone grafts are utilized frequently for skeletal reconstruction, spinal fusion and tumor surgery. Due to its efficacy and convenience terminal sterilization by gamma radiation is often essential to minimize disease transmission and infection. However, the impairment in the material properties of bone tissue secondary to gamma radiation sterilization is a concern since the mechanical functionality of a bone graft is of primary importance. While the extent of this impairment is well investigated for monotonic loading conditions, there does not seem to exist any information on the effects of gamma radiation sterilization on cortical bone's fatigue properties, the physiologically relevant mode of loading. In this study we investigated the degradation in the high-cycle and low-cycle tensile fatigue lives of cortical bone tissue secondary to gamma radiation sterilization at a dose of 36.4 kGy which approximately falls in the higher end of the standard dose range used in tissue banking. The high-cycle and the low-cycle fatigue tests were conducted under load control at initial strain levels of 0.2% and 0.4%, respectively. Monotonic tensile tests were also conducted to compare the impairment of fatigue properties with the impairment of monotonic properties. Results demonstrated that the impairment in both the high-cycle and the low-cycle fatigue lives were two orders of magnitude following sterilization, a change much more pronounced than that observed for monotonic loading. In conclusion, the results suggest that the impairment of the mechanical function of gamma radiation sterilized allografts is even worse in fatigue than monotonically. Therefore, grafts should be designed to minimize functional strains and avoid stress raisers to prevent premature fatigue failures.

  5. DNA methylation: the pivotal interaction between early-life nutrition and glucose metabolism in later life.

    PubMed

    Zheng, Jia; Xiao, Xinhua; Zhang, Qian; Yu, Miao

    2014-12-14

    Traditionally, it has been widely acknowledged that genes together with adult lifestyle factors determine the risk of developing some metabolic diseases such as insulin resistance, obesity and diabetes mellitus in later life. However, there is now substantial evidence that prenatal and early-postnatal nutrition play a critical role in determining susceptibility to these diseases in later life. Maternal nutrition has historically been a key determinant for offspring health, and gestation is the critical time window that can affect the growth and development of offspring. The Developmental Origins of Health and Disease (DOHaD) hypothesis proposes that exposures during early life play a critical role in determining the risk of developing metabolic diseases in adulthood. Currently, there are substantial epidemiological studies and experimental animal models that have demonstrated that nutritional disturbances during the critical periods of early-life development can significantly have an impact on the predisposition to developing some metabolic diseases in later life. The hypothesis that epigenetic mechanisms may link imbalanced early-life nutrition with altered disease risk has been widely accepted in recent years. Epigenetics can be defined as the study of heritable changes in gene expression that do not involve alterations in the DNA sequence. Epigenetic processes play a significant role in regulating tissue-specific gene expression, and hence alterations in these processes may induce long-term changes in gene function and metabolism that persist throughout the life course. The present review focuses on how nutrition in early life can alter the epigenome, produce different phenotypes and alter disease susceptibilities, especially for impaired glucose metabolism.

  6. Psychosis in Later Life: A Review and Update.

    PubMed

    Colijn, Mark A; Nitta, Bradley H; Grossberg, George T

    2015-01-01

    Psychosis is relatively common in later life and can present in a wide variety of contexts, including early-onset and late-onset schizophrenia, delusional disorder, mood disorders, and various dementias. It can also occur as the result of numerous medical and neurological diseases and from the use of certain medications. Although identifying the cause of psychosis in older patients can be challenging, the unique clinical features associated with the different disorders can help in making the diagnosis. Accurate diagnosis of psychosis in older populations is essential, as its treatment varies depending on the context in which it appears. Despite the safety concerns regarding the use of antipsychotics in older patients, certain pharmacological treatments appear to be both efficacious and reasonably safe in treating psychosis in older populations. Additionally, although research is limited, numerous psychosocial therapies appear promising. This review summarizes the literature on the epidemiology, clinical characteristics, neuroimaging, and treatment of psychosis in later life, and serves as an update to past reviews on this topic. PMID:26332218

  7. The retirement transition and the later life family unit.

    PubMed

    Smith, S D

    1997-08-01

    The purpose of this investigation was to determine to what extent family worldview and problem-solving communication style influence individual and family unit adaptation during retirement. A cross-sectional correlational survey design utilized Pearson correlations and stepwise multiple regressions. The sample consisted of 368 individuals representing 184 later life family units. Operationalized as family unit data, family worldview and family problem-solving communication style were examined in two series: (1) with outcome variable of family unit adaptation and (2) with outcome variable of individual adaptation. Scoring of family unit data was conceptually, procedurally, and analytically congruent. The investigation extended McCubbins' work into the later life family unit giving empirical support for two propositions of the Resiliency Model (M.A. McCubbin & H.I. McCubbin, 1993). This investigation also extended A. Antonovsky's (1987) work as the second study to apply the Antonovsky Sense of Coherence Scale to a family measurement. Conclusions are that although the way the family views the world is important during retirement, being affirmed by family members is more important. The investigation highlights the importance of a positive problem-solving communication style for a positive level of family adaptation. Individual adaptation during retirement was more influenced by family worldview.

  8. Impairment of Oligodendroglia Maturation Leads to Aberrantly Increased Cortical Glutamate and Anxiety-Like Behaviors in Juvenile Mice

    PubMed Central

    Chen, Xianjun; Zhang, Weiguo; Li, Tao; Guo, Yu; Tian, Yanping; Wang, Fei; Liu, Shubao; Shen, Hai-Ying; Feng, Yue; Xiao, Lan

    2015-01-01

    Adolescence is the critical time for developing proper oligodendrocyte (OL)-neuron interaction and the peak of onset for many cognitive diseases, among which anxiety disorders display the highest prevalence. However, whether impairment of de novo OL development causes neuronal abnormalities and contributes to the early onset of anxiety phenotype in childhood still remains unexplored. In this study, we tested the hypothesis that defects in OL maturation manifests cortical neuron function and leads to anxiety-like behaviors in juvenile mice. We report here that conditional knockout of the Olig2 gene (Olig2 cKO) specifically in differentiating OLs in the mouse brain preferentially impaired OL maturation in the gray matter of cerebral cortex. Interestingly, localized proton magnetic resonance spectroscopy revealed that Olig2 cKO mice displayed abnormally elevated cortical glutamate levels. In addition, transmission electron microscopy demonstrated increased vesicle density in excitatory glutamatergic synapses in the cortex of the Olig2 cKO mice. Moreover, juvenile Olig2 cKO mice exhibited anxiety-like behaviors and impairment in behavioral inhibition. Taken together, our results suggest that impaired OL development affects glutamatergic neuron function in the cortex and causes anxiety-related behaviors in juvenile mice. These discoveries raise an intriguing possibility that OL defects may be a contributing mechanism for the onset of anxiety in childhood. PMID:26696827

  9. Prefrontal cortical thinning in HIV infection is associated with impaired striatal functioning.

    PubMed

    du Plessis, Stéfan; Vink, Matthijs; Joska, John A; Koutsilieri, Eleni; Bagadia, Asif; Stein, Dan J; Emsley, Robin

    2016-06-01

    While cortical thinning has been associated with HIV infection, it is unclear whether this reflects a direct effect of the virus, whether it is related to disruption of subcortical function or whether it is better explained by epiphenomena, such as drug abuse or comorbid medical conditions. The present study investigated the relationship between cortical thickness and subcortical function in HIV+ patients. Specifically, we examined the relationship between prefrontal cortical thickness and striatal function. Twenty-three largely treatment naïve, non-substance abusing HIV+ participants and 19 healthy controls matched for age, gender, and educational status were included. Cortical morphometry was performed using FreeSurfer software analysis. Striatal function was measured during an fMRI stop-signal anticipation task known to engage the striatum. Any cortical regions showing significant thinning were entered as dependent variables into a single linear regression model which included subcortical function, age, CD4 count, and a measure of global cognitive performance as independent predictors. The only cortical region that was significantly reduced after correction for multiple comparisons was the right superior frontal gyrus. Striatal activity was found to independently predict superior frontal gyral cortical thickness. While cortical thinning in HIV infection is likely multifactorial, viral induced subcortical dysfunction appears to play a role.

  10. Prefrontal cortical thinning in HIV infection is associated with impaired striatal functioning.

    PubMed

    du Plessis, Stéfan; Vink, Matthijs; Joska, John A; Koutsilieri, Eleni; Bagadia, Asif; Stein, Dan J; Emsley, Robin

    2016-06-01

    While cortical thinning has been associated with HIV infection, it is unclear whether this reflects a direct effect of the virus, whether it is related to disruption of subcortical function or whether it is better explained by epiphenomena, such as drug abuse or comorbid medical conditions. The present study investigated the relationship between cortical thickness and subcortical function in HIV+ patients. Specifically, we examined the relationship between prefrontal cortical thickness and striatal function. Twenty-three largely treatment naïve, non-substance abusing HIV+ participants and 19 healthy controls matched for age, gender, and educational status were included. Cortical morphometry was performed using FreeSurfer software analysis. Striatal function was measured during an fMRI stop-signal anticipation task known to engage the striatum. Any cortical regions showing significant thinning were entered as dependent variables into a single linear regression model which included subcortical function, age, CD4 count, and a measure of global cognitive performance as independent predictors. The only cortical region that was significantly reduced after correction for multiple comparisons was the right superior frontal gyrus. Striatal activity was found to independently predict superior frontal gyral cortical thickness. While cortical thinning in HIV infection is likely multifactorial, viral induced subcortical dysfunction appears to play a role. PMID:27173383

  11. Municipality and Neighborhood Influences on Volunteering in Later Life.

    PubMed

    Dury, Sarah; Willems, Jurgen; De Witte, Nico; De Donder, Liesbeth; Buffel, Tine; Verté, Dominique

    2016-06-01

    This article explores the relationships between municipality features and volunteering by older adults. In the literature, strong evidence exists of the influence of place on older people's health. However, the question how neighborhoods and municipalities promote or hinder volunteer participation remains under-explored. Data for the research are derived from the Belgian Aging Studies. We estimate logistic multilevel models for older individuals' engagement in volunteering across 141 municipalities in Belgium (N = 67,144). Analysis shows that neighborhood connectedness, neighborhood satisfaction, home ownership, and presence of services predict voluntary engagement at older ages. The findings support that perceptions and quality of social resources that relate to neighborhoods may be important factors to explain volunteering among older adults. Moreover, the findings suggest that volunteering in later life must be considered within a broader framework.

  12. Self-realization and cultural narratives about later life.

    PubMed

    Laceulle, Hanne; Baars, Jan

    2014-12-01

    In late modern circumstances, aging individuals are confronted with the task of creating a meaningful individual life trajectory. However, these personal narratives are situated in the context of broader cultural narratives. It is argued that current cultural narratives about aging are often stereotyping and demeaning, being based on either a decline ideology or an age-defying ideology. This complicates the ascription of meaning to later life. We argue that narrative gerontology could profit from integrating a more cultural critical stance in its investigations. Dominant cultural narratives need to be challenged by viable counter narratives aimed at repairing and strengthening the moral agency of aging individuals. We discuss the criteria such counter narratives have to answer to and consider how the moral discourse on self-realization can provide an ideological foundation for meaning-generating cultural counter narratives on aging. PMID:25456620

  13. Later life care planning conversations for older adults and families.

    PubMed

    Stolee, Paul; Zaza, Christine; Sharratt, Michael T

    2014-09-01

    While most older adults have thought about their future care needs, few have discussed their preferences with family members. We interviewed older persons (24), adult children (24), health professionals (23), and representatives of stakeholder associations (3) to understand their views and experiences on later life care (LLC) planning conversations, in terms of (a) their respective roles, and (b) barriers and facilitators that should be taken into account when having these conversations. Roles described included that of information user (older persons), information seeker (family members), and information provider (health care providers). The study identified practical and emotional considerations relevant to LLC planning conversations. This study found strong support for planning for LLC before the need arises, as well as important potential benefits for older adults, family members, and health professionals. There is interest in, and need for, resources to guide families in LLC planning. PMID:24652903

  14. Self-realization and cultural narratives about later life.

    PubMed

    Laceulle, Hanne; Baars, Jan

    2014-12-01

    In late modern circumstances, aging individuals are confronted with the task of creating a meaningful individual life trajectory. However, these personal narratives are situated in the context of broader cultural narratives. It is argued that current cultural narratives about aging are often stereotyping and demeaning, being based on either a decline ideology or an age-defying ideology. This complicates the ascription of meaning to later life. We argue that narrative gerontology could profit from integrating a more cultural critical stance in its investigations. Dominant cultural narratives need to be challenged by viable counter narratives aimed at repairing and strengthening the moral agency of aging individuals. We discuss the criteria such counter narratives have to answer to and consider how the moral discourse on self-realization can provide an ideological foundation for meaning-generating cultural counter narratives on aging.

  15. Amyloid beta-peptide impairs glucose transport in hippocampal and cortical neurons: involvement of membrane lipid peroxidation.

    PubMed

    Mark, R J; Pang, Z; Geddes, J W; Uchida, K; Mattson, M P

    1997-02-01

    A deficit in glucose uptake and a deposition of amyloid beta-peptide (A beta) each occur in vulnerable brain regions in Alzheimer's disease (AD). It is not known whether mechanistic links exist between A beta deposition and impaired glucose transport. We now report that A beta impairs glucose transport in cultured rat hippocampal and cortical neurons by a mechanism involving membrane lipid peroxidation. A beta impaired 3H-deoxy-glucose transport in a concentration-dependent manner and with a time course preceding neurodegeneration. The decrease in glucose transport was followed by a decrease in cellular ATP levels. Impairment of glucose transport, ATP depletion, and cell death were each prevented in cultures pretreated with antioxidants. Exposure to FeSO4, an established inducer of lipid peroxidation, also impaired glucose transport. Immunoprecipitation and Western blot analyses showed that exposure of cultures to A beta induced conjugation of 4-hydroxynonenal (HNE), an aldehydic product of lipid peroxidation, to the neuronal glucose transport protein GLUT3. HNE induced a concentration-dependent impairment of glucose transport and subsequent ATP depletion. Impaired glucose transport was not caused by a decreased energy demand in the neurons, because ouabain, which inhibits Na+/K(+)-ATPase activity and thereby reduces neuronal ATP hydrolysis rate, had little or no effect on glucose transport. Collectively, the data demonstrate that lipid peroxidation mediates A beta-induced impairment of glucose transport in neurons and suggest that this action of A beta may contribute to decreased glucose uptake and neuronal degeneration in AD. PMID:8994059

  16. Prediction of Alzheimer's disease in subjects with mild cognitive impairment from the ADNI cohort using patterns of cortical thinning.

    PubMed

    Eskildsen, Simon F; Coupé, Pierrick; García-Lorenzo, Daniel; Fonov, Vladimir; Pruessner, Jens C; Collins, D Louis

    2013-01-15

    Predicting Alzheimer's disease (AD) in individuals with some symptoms of cognitive decline may have great influence on treatment choice and disease progression. Structural magnetic resonance imaging (MRI) has the potential of revealing early signs of neurodegeneration in the human brain and may thus aid in predicting and diagnosing AD. Surface-based cortical thickness measurements from T1-weighted MRI have demonstrated high sensitivity to cortical gray matter changes. In this study we investigated the possibility for using patterns of cortical thickness measurements for predicting AD in subjects with mild cognitive impairment (MCI). We used a novel technique for identifying cortical regions potentially discriminative for separating individuals with MCI who progress to probable AD, from individuals with MCI who do not progress to probable AD. Specific patterns of atrophy were identified at four time periods before diagnosis of probable AD and features were selected as regions of interest within these patterns. The selected regions were used for cortical thickness measurements and applied in a classifier for testing the ability to predict AD at the four stages. In the validation, the test subjects were excluded from the feature selection to obtain unbiased results. The accuracy of the prediction improved as the time to conversion from MCI to AD decreased, from 70% at 3 years before the clinical criteria for AD was met, to 76% at 6 months before AD. By inclusion of test subjects in the feature selection process, the prediction accuracies were artificially inflated to a range of 73% to 81%. Two important results emerge from this study. First, prediction accuracies of conversion from MCI to AD can be improved by learning the atrophy patterns that are specific to the different stages of disease progression. This has the potential to guide the further development of imaging biomarkers in AD. Second, the results show that one needs to be careful when designing training

  17. MEC-17 deficiency leads to reduced α-tubulin acetylation and impaired migration of cortical neurons.

    PubMed

    Li, Lei; Wei, Dan; Wang, Qiong; Pan, Jing; Liu, Rong; Zhang, Xu; Bao, Lan

    2012-09-12

    Neuronal migration is a fundamental process during the development of the cerebral cortex and is regulated by cytoskeletal components. Microtubule dynamics can be modulated by posttranslational modifications to tubulin subunits. Acetylation of α-tubulin at lysine 40 is important in regulating microtubule properties, and this process is controlled by acetyltransferase and deacetylase. MEC-17 is a newly discovered α-tubulin acetyltransferase that has been found to play a major role in the acetylation of α-tubulin in different species in vivo. However, the physiological function of MEC-17 during neural development is largely unknown. Here, we report that MEC-17 is critical for the migration of cortical neurons in the rat. MEC-17 was strongly expressed in the cerebral cortex during development. MEC-17 deficiency caused migratory defects in the cortical projection neurons and interneurons, and perturbed the transition of projection neurons from the multipolar stage to the unipolar/bipolar stage in the intermediate zone of the cortex. Furthermore, knockdown of α-tubulin deacetylase HDAC6 or overexpression of tubulin(K40Q) to mimic acetylated α-tubulin could reduce the migratory and morphological defects caused by MEC-17 deficiency in cortical projection neurons. Thus, MEC-17, which regulates the acetylation of α-tubulin, appears to control the migration and morphological transition of cortical neurons. This finding reveals the importance of MEC-17 and α-tubulin acetylation in cortical development.

  18. A longitudinal study of atrophy in amnestic mild cognitive impairment and normal aging revealed by cortical thickness.

    PubMed

    Yao, Zhijun; Hu, Bin; Liang, Chuanjiang; Zhao, Lina; Jackson, Mike

    2012-01-01

    In recent years, amnestic mild cognitive impairment (aMCI) has attracted significant attention as an indicator of high risk for Alzheimer's disease. An understanding of the pathology of aMCI may benefit the development of effective clinical treatments for dementia. In this work, we measured the cortical thickness of 109 aMCI subjects and 99 normal controls (NC) twice over two years. The longitudinal changes and the cross-sectional differences between the two types of participants were explored using the vertex thickness values. The thickness of the cortex in aMCI was found significantly reduced in both longitudinal and between-group comparisons, mainly in the temporal lobe, superolateral parietal lobe and some regions of the frontal cortices. Compared to NC, the aMCI showed a significantly high atrophy rate in the left lateral temporal lobe and left parahippocampal gyrus over two years. Additionally, a significant positive correlation between brain atrophy and the decline of Mini-Mental State Examination (MMSE) scores was also found in the left superior and left middle temporal gyrus in aMCI. These findings demonstrated specific longitudinal spatial patterns of cortical atrophy in aMCI and NC. The higher atrophy rate in aMCI might be responsible for the accelerated functional decline in the aMCI progression process.

  19. Poverty and transitions in health in later life.

    PubMed

    Adena, Maja; Myck, Michal

    2014-09-01

    Using a sample of Europeans aged 50+ from 12 countries in the Survey of Health, Ageing and Retirement in Europe (SHARE), we analyse the role of poor material conditions as a determinant of changes in health over a four- to five-year period. We find that poverty defined with respect to relative income has no effect on changes in health. However, broader measures of poor material conditions, such as subjective poverty or low wealth, significantly increase the probability of transition to poor health among the healthy and reduce the chance of recovery from poor health over the time interval analysed. In addition to this, the subjective measure of poverty has a significant effect on mortality, increasing it by 65% among men and by 68% among those aged 50-64. Material conditions affect health among older people. We suggest that if attempts to reduce poverty in later life and corresponding policy targets are to focus on the relevant measures, they should take into account broader definitions of poverty than those based only on relative incomes.

  20. Anosognosia in mild cognitive impairment: Relationship to activation of cortical midline structures involved in self-appraisal

    PubMed Central

    Ries, Michele L.; Jabbar, Britta M.; Schmitz, Taylor W.; Trivedi, Mehul A.; Gleason, Carey E.; Carlsson, Cynthia M.; Rowley, Howard A.; Asthana, Sanjay; Johnson, Sterling C.

    2009-01-01

    Awareness of cognitive dysfunction shown by individuals with Mild Cognitive Impairment (MCI), a condition conferring risk for Alzheimer’s disease (AD), is variable. Anosognosia, or unawareness of loss of function, is beginning to be recognized as an important clinical symptom of MCI. However, little is known about the brain substrates underlying this symptom. We hypothesized that MCI participants’ activation of cortical midline structures (CMS) during self-appraisal would covary with level of insight into cognitive difficulties (indexed by a discrepancy score between patient and informant ratings of cognitive decline in each MCI participant). To address this hypothesis, we first compared 16 MCI participants and 16 age-matched controls, examining brain regions showing conjoint or differential BOLD response during self-appraisal. Second, we used regression to investigate the relationship between awareness of deficit in MCI and BOLD activity during self-appraisal, controlling for extent of memory impairment. Between-group comparisons indicated that MCI participants show subtly attenuated CMS activity during self-appraisal. Regression analysis revealed a highly-significant relationship between BOLD response during self-appraisal and self-awareness of deficit in MCI. This finding highlights the level of anosognosia in MCI as an important predictor of response to self-appraisal in cortical midline structures, brain regions vulnerable to changes in early AD. PMID:17445294

  1. Impaired cortical neurogenesis in plexin-B1 and -B2 double deletion mutant.

    PubMed

    Daviaud, Nicolas; Chen, Karen; Huang, Yong; Friedel, Roland H; Zou, Hongyan

    2016-08-01

    Mammalian cortical expansion is tightly controlled by fine-tuning of proliferation and differentiation of neural progenitors in a region-specific manner. How extrinsic cues interface with cell-intrinsic programs to balance proliferative versus neurogenic decisions remains an unsolved question. We examined the function of Semaphorin receptors Plexin-B1 and -B2 in corticogenesis by generating double mutants, whereby Plexin-B2 was conditionally ablated in the developing brain in a Plexin-B1 null mutant background. Absence of both Plexin-Bs resulted in cortical thinning, particularly in the caudomedial cortex. Plexin-B1/B2 double, but not single, mutants exhibited a reduced neural progenitor pool, attributable to decreased proliferation and an altered division mode favoring cell cycle exit. This resulted in deficient production of neurons throughout the neurogenic period, proportionally affecting all cortical laminae. Consistent with the in vivo data, cultured neural progenitors lacking both Plexin-B1 and -B2 displayed decreased proliferative capacity and increased spontaneous differentiation. Our study therefore defines a novel function of Plexin-B1 and -B2 in transmitting extrinsic signals to maintain proliferative and undifferentiated states of neural progenitors. As single mutants displayed no apparent cortical defects, we conclude that Plexin-B1 and -B2 play redundant or compensatory roles during forebrain development to ensure proper neuronal production and neocortical expansion. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 882-899, 2016.

  2. Impaired Cognition in Rats with Cortical Dysplasia: Additional Impact of Early-Life Seizures

    ERIC Educational Resources Information Center

    Lucas, Marcella M.; Lenck-Santini, Pierre-Pascal; Holmes, Gregory L.; Scott, Rod C.

    2011-01-01

    One of the most common and serious co-morbidities in patients with epilepsy is cognitive impairment. While early-life seizures are considered a major cause for cognitive impairment, it is not known whether it is the seizures, the underlying neurological substrate or a combination that has the largest impact on eventual learning and memory. Teasing…

  3. Impaired learning-dependent cortical plasticity in Huntington's disease transgenic mice.

    PubMed

    Cybulska-Klosowicz, Anita; Mazarakis, Nektarios K; Van Dellen, Anton; Blakemore, Colin; Hannan, Anthony J; Kossut, Malgorzata

    2004-12-01

    Huntington's disease (HD) is a genetically transmitted neurodegenerative disorder. The neuropathology in HD is a selective neuronal cell death in several brain regions including cortex. Although changes in synaptic plasticity were shown within the hippocampus and striatum of HD transgenic mice, there are no studies considering neocortical synaptic plasticity abnormalities in HD. We examined the impact of the HD transgene upon learning-dependent plasticity of cortical representational maps. The effect of associative learning, in which stimulation of a row of vibrissae was paired with appetitive stimulus, upon functional representations of vibrissae in the barrel cortex, was investigated with 2-deoxyglucose brain mapping in presymptomatic R6/1 HD mice. In wild-type mice, cortical representation of the row of vibrissae involved in the training was expanded, while in HD mice the representation of this row was not expanded. The results suggest that presymptomatic R6/1 HD transgenic mice show deficits in plasticity of primary somatosensory cortex.

  4. Gendered emotion work around physical health problems in mid- and later-life marriages☆

    PubMed Central

    Thomeer, Mieke Beth; Reczek, Corinne; Umberson, Debra

    2015-01-01

    The provision and receipt of emotion work—defined as intentional activities done to promote another’s emotional well-being—are central dimensions of marriage. However, emotion work in response to physical health problems is a largely unexplored, yet likely important, aspect of the marital experience. We analyze dyadic in-depth interviews with husbands and wives in 21 mid-to later-life couples to examine the ways that health-impaired people and their spouses provide, interpret, and explain emotion work. Because physical health problems, emotion work, and marital dynamics are gendered, we consider how these processes differ for women and men. We find that wives provide emotion work regardless of their own health status. Husbands provide emotion work less consistently, typically only when the husbands see themselves as their wife’s primary source of stability or when the husbands view their marriage as balanced. Notions of traditional masculinity preclude some husbands from providing emotion work even when their wife is health-impaired. This study articulates emotion work around physical health problems as one factor that sustains and exacerbates gender inequalities in marriage with implications for emotional and physical well-being. PMID:25661852

  5. Cognitive, affective and eudemonic well-being in later life

    PubMed Central

    Vanhoutte, Bram; Nazroo, James

    2016-01-01

    The hedonic view on well-being, consisting of both cognitive and affective aspects, assumes that through maximizing pleasurable experiences, and minimizing suffering, the highest levels of well-being can be achieved. The eudemonic approach departs from the concept of a good life that is not just about pleasure and happiness, but involves developing one-self, being autonomous and realizing one’s potential. While these approaches are often positioned against each other on theoretical grounds, this paper investigates the empirical plausibility of this two dimensional view on subjective well-being. The interrelations between common measures such as the General Health Questionnaire, the CES-D inventory of depressive symptoms, the satisfaction with life scale and the eudemonic CASP scale are examined in a confirmatory factor analysis framework using the third wave of the English Longitudinal Study of Ageing (ELSA). A multidimensional structure of well-being, distinguishing cognitive, affective and eudemonic well-being, is shown to be the best fitting empirical solution. This three dimensional second order structure is neutral to gender in its measurement. A lower influence of feeling energetic on self-actualisation, and of somatic symptoms of depression on affective well-being was noted for respondents in the fourth age in comparison to respondents in the third age. These small measurement artefacts underline that somatic symptoms of later life depression should be distinguished from mood symptoms. Two main social facts are confirmed when we compare the different forms of well-being over gender and life stage: men tend to have a higher level of well-being than women, and well-being is lower in the fourth age than in the third age. Although the three measures are very closely related, with high correlations between .74 and .88, they each have their specific meaning. While affective and cognitive well-being emphasize the use of an internal yardstick to measure well

  6. Does vestibular stimulation activate thalamocortical mechanisms that reintegrate impaired cortical regions?

    PubMed

    Schiff, N D; Pulver, M

    1999-02-22

    Caloric stimulation induced a transient reversal of multimodal hemispatial cognitive deficits in an 81-year-old woman with an acute left cerebral hemisphere stroke. The patient had unawareness of her right hand (asomatognosia), right-sided visual unawareness (hemineglect), aphasia and right-sided weakness (hemiplegia) prior to the stimulation. Transient improvements in impaired sensory, motor, linguistic and cognitive function developed within 30 s following application of the caloric stimulus and onset of horizontal nystagmus. The effect persisted for 3 min and ceased completely after 5 min. While several recent reports have described the capacity of caloric stimulation to transiently improve or reverse a wide range of attentional, cognitive and motor impairments, most examples are in right-hemisphere-damaged patients with long-standing brain injury. Typically, patients have been tested several months or years after the onset of the deficit. A possible mechanism for the temporary reintegration of multiple cognitive functions in this patient is discussed. PMID:10097398

  7. Role of hippocampal and prefrontal cortical signaling pathways in dextromethorphan effect on morphine-induced memory impairment in rats.

    PubMed

    Ghasemzadeh, Zahra; Rezayof, Ameneh

    2016-02-01

    Evidence suggests that dextromethorphan (DM), an NMDA receptor antagonist, induces memory impairment. Considering that DM is widely used in cough-treating medications, and the co-abuse of DM with morphine has recently been reported, the aims of the present study was (1) to investigate whether there is a functional interaction between morphine and DM in passive avoidance learning and (2) to assess the possible role of the hippocampal and prefrontal cortical (PFC) signaling pathways in the effects of the drugs on memory formation. Our findings indicated that post-training or pre-test administration of morphine (2 and 6 mg/kg) or DM (10-30 mg/kg) impaired memory consolidation and retrieval which was associated with the attenuation of the levels of phosphorylated Ca(2+)/calmodulin-dependent protein kinase II (p-CAMKII) and cAMP responsive element-binding protein (p-CREB) in the targeted sites. Moreover, the memory impairment induced by post-training administration of morphine was reversed by pre-test administration of the same dose of morphine or DM (30 mg/kg), indicating state-dependent learning (SDL) and a cross-SDL between the drugs. It is important to note that the levels of p-CAMKII/CAMKII and p-CREB/CREB in the hippocampus and the PFC increased in drugs-induced SDL. In addition, DM administration potentiated morphine-induced SDL which was related to the enhanced levels of hippocampal and PFC CAMKII-CREB signaling pathways. It can be concluded that there is a relationship between the hippocampus and the PFC in the effect of DM and/or morphine on memory retrieval. Moreover, a cross SDL can be induced between the co-administration of DM and morphine. Interestingly, CAMKII-CREB signaling pathways also mediate the drugs-induced SDL.

  8. Sensitivity of cortical auditory evoked potential detection for hearing-impaired infants in response to short speech sounds

    PubMed Central

    Van Dun, Bram; Carter, Lyndal; Dillon, Harvey

    2012-01-01

    Cortical auditory evoked potentials (CAEPs) are an emerging tool for hearing aid fitting evaluation in young children who cannot provide reliable behavioral feedback. It is therefore useful to determine the relationship between the sensation level of speech sounds and the detection sensitivity of CAEPs, which is the ratio between the number of detections and the sum of detections and non-detections. Twenty-five sensorineurally hearing impaired infants with an age range of 8 to 30 months were tested once, 18 aided and 7 unaided. First, behavioral thresholds of speech stimuli /m/, /g/, and /t/ were determined using visual reinforcement orientation audiometry. Afterwards, the same speech stimuli were presented at 55, 65, and 75 dB sound pressure level, and CAEPs were recorded. An automatic statistical detection paradigm was used for CAEP detection. For sensation levels above 0, 10, and 20 dB respectively, detection sensitivities were equal to 72±10, 75±10, and 78±12%. In 79% of the cases, automatic detection P-values became smaller when the sensation level was increased by 10 dB. The results of this study suggest that the presence or absence of CAEPs can provide some indication of the audibility of a speech sound for infants with sensorineural hearing loss. The detection of a CAEP might provide confidence, to a degree commensurate with the detection probability, that the infant is detecting that sound at the level presented. When testing infants where the audibility of speech sounds has not been established behaviorally, the lack of a cortical response indicates the possibility, but by no means a certainty, that the sensation level is 10 dB or less. PMID:26557328

  9. Impaired long-term potentiation-like cortical plasticity in presymptomatic genetic frontotemporal dementia.

    PubMed

    Benussi, Alberto; Cosseddu, Maura; Filareto, Ilaria; Dell'Era, Valentina; Archetti, Silvana; Sofia Cotelli, Maria; Micheli, Anna; Padovani, Alessandro; Borroni, Barbara

    2016-09-01

    Neurophysiological biomarkers were assessed using a transcranial magnetic stimulation multiparadigm approach in 13 presymptomatic (n = 13 Granulin) and 14 symptomatic (n = 11 Granulin, n = 3 C9orf72) subjects with a pathogenic mutation for frontotemporal dementia (FTD). Intracortical facilitation and long-term potentiation-like plasticity were impaired in presymptomatic carriers, compared to healthy controls, more than 15 years before expected symptom onset. In symptomatic carriers, a decrease in short-interval intracortical inhibition, compared to presymptomatic carriers, was found. In conclusion, these biomarkers could provide the footprints of specific physiopathological processes in the development of this disease and possibly support the diagnosis of autosomal-dominant FTD. Ann Neurol 2016;80:472-476. PMID:27438089

  10. Mild cognitive impairment, poor episodic memory, and late-life depression are associated with cerebral cortical thinning and increased white matter hyperintensities

    PubMed Central

    Fujishima, Motonobu; Maikusa, Norihide; Nakamura, Kei; Nakatsuka, Masahiro; Matsuda, Hiroshi; Meguro, Kenichi

    2014-01-01

    In various independent studies to date, cerebral cortical thickness and white matter hyperintensity (WMH) volume have been associated with episodic memory, depression, and mild cognitive impairment (MCI). The aim of this study was to uncover variations in cortical thickness and WMH volume in association with episodic memory, depressive state, and the presence of MCI simultaneously in a single study population. The participants were 186 individuals with MCI (clinical dementia rating [CDR] of 0.5) and 136 healthy elderly controls (HCs; CDR of 0) drawn from two community-based cohort studies in northern Japan. We computed cerebral cortical thickness and WMH volume by using MR scans and statistically analyzed differences in these indices between HCs and MCI participants. We also assessed the associations of these indices with memory performance and depressive state in participants with MCI. Compared with HCs, MCI participants exhibited thinner cortices in the temporal and inferior parietal lobes and greater WMH volumes in the corona radiata and semioval center. In MCI participants, poor episodic memory was associated with thinner cortices in the left entorhinal region and increased WMH volume in the posterior periventricular regions. Compared with non-depressed MCI participants, depressed MCI participants showed reduced cortical thickness in the anterior medial temporal lobe and gyrus adjacent to the amygdala bilaterally, as well as greater WMH volume as a percentage of the total intracranial volume (WMHr). A higher WMHr was associated with cortical thinning in the frontal, temporal, and parietal regions in MCI participants. These results demonstrate that episodic memory and depression are associated with both cortical thickness and WMH volume in MCI participants. Additional longitudinal studies are needed to clarify the dynamic associations and interactions among these indices. PMID:25426066

  11. A Course on Humanistic Creativity in Later Life: Literature Review, Case Histories, and Recommendations.

    ERIC Educational Resources Information Center

    Nuessel, Frank; Van Stewart, Arthur; Cedeno, Aristofanes

    2001-01-01

    Presents case histories of late-life creativity in literature (May Sarton), painting (Marcel Duchamp), music (Leos Janacek), dance (Martha Graham), and theatre (Jessica Tandy). Offers suggestions for a course on humanistic creativity in later life. (Contains 74 references.) (SK)

  12. Cortical Amyloid Burden Differences Across Empirically-Derived Mild Cognitive Impairment Subtypes and Interaction with APOE ε4 Genotype

    PubMed Central

    Bangen, Katherine J.; Clark, Alexandra L.; Werhane, Madeline; Edmonds, Emily C.; Nation, Daniel A.; Evangelista, Nicole; Libon, David J.; Bondi, Mark W.; Delano-Wood, Lisa

    2016-01-01

    We examined cortical amyloid-β (Aβ) levels and interactions with apolipoprotein (APOE) ε4 genotype status across empirically-derived mild cognitive impairment (MCI) subgroups and cognitively normal older adults. Participants were 583 ADNI participants (444 MCI, 139 normal controls [NC]) with baseline florbetapir positron emission tomography (PET) amyloid imaging and neuropsychological testing. Of those with ADNI-defined MCI, a previous cluster analysis [1] classified 51% (n = 227) of the current sample as amnestic MCI, 8% (n = 37) as dysexecutive/mixed MCI, and 41% (n = 180) as cluster-derived normal (cognitively normal). Results demonstrated that the dysexecutive/mixed and amnestic MCI groups showed significantly greater levels of amyloid relative to the cluster-derived normal and NC groups who did not differ from each other. Additionally, 78% of the dysexecutive/mixed, 63% of the amnestic MCI, 42% of the cluster-derived normal, and 34% of the NC group exceeded the amyloid positivity threshold. Finally, a group by APOE genotype interaction demonstrated that APOE ε4 carriers within the amnestic MCI, cluster-derived normal, and NC groups showed significantly greater amyloid accumulation compared to non-carriers of their respective group. Such an interaction was not revealed within the dysexecutive/mixed MCI group which was characterized by both greater cognitive impairment and amyloid accumulation compared to the other participant groups. Our results from the ADNI cohort show considerable heterogeneity in Aβ across all groups studied, even within a group of robust NC participants. Findings suggest that conventional criteria for MCI may be susceptible to false positive diagnostic errors, and that onset of Aβ accumulation may occur earlier in APOE ε4 carriers compared to non-carriers. PMID:27031472

  13. Cortical Amyloid Burden Differences Across Empirically-Derived Mild Cognitive Impairment Subtypes and Interaction with APOE ɛ4 Genotype.

    PubMed

    Bangen, Katherine J; Clark, Alexandra L; Werhane, Madeline; Edmonds, Emily C; Nation, Daniel A; Evangelista, Nicole; Libon, David J; Bondi, Mark W; Delano-Wood, Lisa

    2016-03-29

    We examined cortical amyloid-β (Aβ) levels and interactions with apolipoprotein (APOE) ɛ4 genotype status across empirically-derived mild cognitive impairment (MCI) subgroups and cognitively normal older adults. Participants were 583 ADNI participants (444 MCI, 139 normal controls [NC]) with baseline florbetapir positron emission tomography (PET) amyloid imaging and neuropsychological testing. Of those with ADNI-defined MCI, a previous cluster analysis [1] classified 51% (n = 227) of the current sample as amnestic MCI, 8% (n = 37) as dysexecutive/mixed MCI, and 41% (n = 180) as cluster-derived normal (cognitively normal). Results demonstrated that the dysexecutive/mixed and amnestic MCI groups showed significantly greater levels of amyloid relative to the cluster-derived normal and NC groups who did not differ from each other. Additionally, 78% of the dysexecutive/mixed, 63% of the amnestic MCI, 42% of the cluster-derived normal, and 34% of the NC group exceeded the amyloid positivity threshold. Finally, a group by APOE genotype interaction demonstrated that APOE ɛ4 carriers within the amnestic MCI, cluster-derived normal, and NC groups showed significantly greater amyloid accumulation compared to non-carriers of their respective group. Such an interaction was not revealed within the dysexecutive/mixed MCI group which was characterized by both greater cognitive impairment and amyloid accumulation compared to the other participant groups. Our results from the ADNI cohort show considerable heterogeneity in Aβ across all groups studied, even within a group of robust NC participants. Findings suggest that conventional criteria for MCI may be susceptible to false positive diagnostic errors, and that onset of Aβ accumulation may occur earlier in APOE ɛ4 carriers compared to non-carriers. PMID:27031472

  14. Depression and frailty in later life: a systematic review.

    PubMed

    Vaughan, Leslie; Corbin, Akeesha L; Goveas, Joseph S

    2015-01-01

    Frailty and depression are important issues affecting older adults. Depressive syndrome may be difficult to clinically disambiguate from frailty in advanced old age. Current reviews on the topic include studies with wide methodological variation. This review examined the published literature on cross-sectional and longitudinal associations between frailty and depressive symptomatology with either syndrome as the outcome, moderators of this relationship, construct overlap, and related medical and behavioral interventions. Prevalence of both was reported. A systematic review of studies published from 2000 to 2015 was conducted in PubMed, the Cochrane Database of Systematic Reviews, and PsychInfo. Key search terms were "frailty", "frail", "frail elderly", "depressive", "depressive disorder", and "depression". Participants of included studies were ≥ 55 years old and community dwelling. Included studies used an explicit biological definition of frailty based on Fried et al's criteria and a screening measure to identify depressive symptomatology. Fourteen studies met the inclusion/exclusion criteria. The prevalence of depressive symptomatology, frailty, or their co-occurrence was greater than 10% in older adults ≥ 55 years old, and these rates varied widely, but less in large epidemiological studies of incident frailty. The prospective relationship between depressive symptomatology and increased risk of incident frailty was robust, while the opposite relationship was less conclusive. The presence of comorbidities that interact with depressive symptomatology increased incident frailty risk. Measurement variability of depressive symptomatology and inclusion of older adults who are severely depressed, have cognitive impairment or dementia, or stroke may confound the frailty syndrome with single disease outcomes, accounting for a substantial proportion of shared variance in the syndromes. Further study is needed to identify medical and behavioral interventions for

  15. Association between mid-life marital status and cognitive function in later life: population based cohort study

    PubMed Central

    Håkansson, Krister; Rovio, Suvi; Helkala, Eeva-Liisa; Vilska, Anna-Riitta; Winblad, Bengt; Soininen, Hilkka; Nissinen, Aulikki; Mohammed, Abdul H

    2009-01-01

    Objectives To evaluate whether mid-life marital status is related to cognitive function in later life. Design Prospective population based study with an average follow-up of 21 years. Setting Kuopio and Joensuu regions in eastern Finland. Participants Participants were derived from random, population based samples previously investigated in 1972, 1977, 1982, or 1987; 1449 individuals (73%), aged 65-79, underwent re-examination in 1998. Main outcome measures Alzheimer’s disease and mild cognitive impairment. Results People cohabiting with a partner in mid-life (mean age 50.4) were less likely than all other categories (single, separated, or widowed) to show cognitive impairment later in life at ages 65-79. Those widowed or divorced in mid-life and still so at follow-up had three times the risk compared with married or cohabiting people. Those widowed both at mid-life and later life had an odds ratio of 7.67 (1.6 to 40.0) for Alzheimer’s disease compared with married or cohabiting people. The highest increased risk for Alzheimer’s disease was in carriers of the apolipoprotein E e4 allele who lost their partner before mid-life and were still widowed or divorced at follow-up. The progressive entering of several adjustment variables from mid-life did not alter these associations. Conclusions Living in a relationship with a partner might imply cognitive and social challenges that have a protective effect against cognitive impairment later in life, consistent with the brain reserve hypothesis. The specific increased risk for widowed and divorced people compared with single people indicates that other factors are needed to explain parts of the results. A sociogenetic disease model might explain the dramatic increase in risk of Alzheimer’s disease for widowed apolipoprotein E e4 carriers. PMID:19574312

  16. Neonatal exposure to lipopolysaccharide enhances vulnerability of nigrostriatal dopaminergic neurons to rotenone neurotoxicity in later life.

    PubMed

    Fan, Lir-Wan; Tien, Lu-Tai; Lin, Rick C S; Simpson, Kimberly L; Rhodes, Philip G; Cai, Zhengwei

    2011-12-01

    Brain inflammation in early life has been proposed to play important roles in the development of neurodegenerative disorders in adult life. To test this hypothesis, we used a neonatal rat model of lipopolysaccharide (LPS) exposure (1000 EU/g body weight, intracerebral injection on P5) to produce brain inflammation. By P70, when LPS-induced behavioral deficits were spontaneously recovered, animals were challenged with rotenone, a commonly used pesticide, through subcutaneous mini-pump infusion at a dose of 1.25 mg/kg per day for 14 days. This rotenone treatment regimen ordinarily does not produce toxic effects on behaviors in normal adult rats. Our results show that neonatal LPS exposure enhanced the vulnerability of nigrostriatal dopaminergic neurons to rotenone neurotoxicity in later life. Rotenone treatment resulted in motor neurobehavioral impairments in rats with the neonatal LPS exposure, but not in those without the neonatal LPS exposure. Rotenone induced losses of tyrosine hydroxylase immunoreactive neurons in the substantia nigra and decreased mitochondrial complex I activity in the striatum of rats with neonatal LPS exposure, but not in those without this exposure. Neonatal LPS exposure with later exposure to rotenone decreased retrogradely labeled nigrostriatal dopaminergic projecting neurons. The current study suggests that perinatal brain inflammation may enhance adult susceptibility to the development of neurodegenerative disorders triggered later on by environmental toxins at an ordinarily non-toxic or sub-toxic dose. Our model may be useful for studying mechanisms involved in the pathogenesis of nonfamilial Parkinson's disease and the development of potential therapeutic treatments.

  17. Decreased prefrontal cortical sensitivity to monetary reward is associated with impaired motivation and self-control in cocaine addiction

    PubMed Central

    Goldstein, Rita Z.; Alia-Klein, Nelly; Tomasi, Dardo; Zhang, Lei; Cottone, Lisa A.; Maloney, Thomas; Telang, Frank; Caparelli, Elisabeth C.; Chang, Linda; Ernst, Thomas; Samaras, Dimitris; Squires, Nancy K.; Volkow, Nora D.

    2008-01-01

    Objective To examine the brain’s sensitivity to monetary rewards of different magnitudes in cocaine abusers and to study its association with motivation and self-control. Method Sixteen cocaine abusers and 13 matched healthy comparison subjects performed a forced-choice task under three monetary value conditions while brain activation was measured with functional magnetic resonance imaging. Objective measures of state motivation were assessed by reaction time and accuracy, and subjective measures were assessed by self-reports of task engagement. Measures of trait motivation and self-control were assessed with the Multidimensional Personality Questionnaire. Results The cocaine abusers demonstrated an overall reduced regional brain responsivity to differences between the monetary value conditions. Also, in comparison subjects but not in cocaine abusers reward-induced improvements in performance were associated with self-reports of task engagement, and money-induced activations in the lateral prefrontal cortex were associated with activations in the orbitofrontal cortex. For cocaine subjects, prefrontal cortex sensitivity to money was instead associated with motivation and self-control. Conclusions These findings suggest that in cocaine addiction (1) activation of the corticolimbic reward circuit to gradations of money is altered; (2) lack of a correlation between objective and subjective measures of state motivation may be indicative of disrupted perception of motivational drive, which could contribute to impairments in self-control; and (3) the lateral prefrontal cortex modulates trait motivation and deficits in self-control, and a possible underlying mechanism may encompass a breakdown in prefrontal-orbitofrontal cortical communication. PMID:17202543

  18. Do early life factors affect the development of knee osteoarthritis in later life: a narrative review.

    PubMed

    Antony, Benny; Jones, Graeme; Jin, Xingzhong; Ding, Changhai

    2016-01-01

    Osteoarthritis (OA) mainly affects older populations; however, it is possible that early life factors contribute to the development of OA in later life. The aim of this review is to describe the association between childhood or early adulthood risk factors and knee pain, structural imaging markers and development of knee OA in later life. A narrative overview of the literature synthesising the findings of literature retrieved from searches of computerised databases and manual searches was conducted. We found that only a few studies have explored the long-term effect of childhood or early adulthood risk factors on the markers of joint health that predispose people to OA or joint symptoms. High body mass index (BMI) and/or overweight status from childhood to adulthood were independently related to knee pain and OA in later life. The findings regarding the association between strenuous physical activity and knee structures in young adults are still conflicting. However, a favourable effect of moderate physical activity and fitness on knee structures is reported. Childhood physical activity and performance measures had independent beneficial effects on knee structures including knee cartilage in children and young adults. Anterior knee pain syndrome in adolescence could lead to the development of patellofemoral knee OA in the late 40s. Furthermore, weak evidence suggests that childhood malalignment, socioeconomic status and physical abuse are associated with OA in later life. The available evidence suggests that early life intervention may prevent OA in later life. PMID:27623622

  19. Parity and parents' health in later life: the gendered case of Ismailia, Egypt.

    PubMed

    Engelman, Michal; Agree, Emily M; Yount, Kathryn M; Bishai, David

    2010-07-01

    We investigate the relationship between reproduction and functional health in later life among women and men in the resource-poor and gender-stratified setting of Ismailia governorate, Egypt. Analyses of survey data collected in 2003 show a statistically significant positive association between parity and difficulty with activities of daily living (ADLs), controlling for demographic and socio-economic factors and other co-morbid conditions. We also find that the number of daughters (but not sons) is associated with worse physical functioning, and this association is more pronounced for older fathers than for older mothers. Our results indicate that both biological and social pathways link fertility and later-life health in this context, and that prescribed familial roles may underlie the differential impact of sons and daughters on the health of mothers and fathers in later life.

  20. The Implications of Unintended Pregnancies for Mental Health in Later Life

    PubMed Central

    Higgins, Jenny; Sicinski, Kamil; Merkurieva, Irina

    2016-01-01

    Despite decades of research on unintended pregnancies, we know little about the health implications for the women who experience them. Moreover, no study has examined the implications for women whose pregnancies occurred before Roe v. Wade was decided—nor whether the mental health consequences of these unintended pregnancies continue into later life. Using the Wisconsin Longitudinal Study, a 60-year ongoing survey, we examined associations between unwanted and mistimed pregnancies and mental health in later life, controlling for factors such as early life socioeconomic conditions, adolescent IQ, and personality. We found that in this cohort of mostly married and White women, who completed their pregnancies before the legalization of abortion, unwanted pregnancies were strongly associated with poorer mental health outcomes in later life. PMID:26691118

  1. The Implications of Unintended Pregnancies for Mental Health in Later Life.

    PubMed

    Herd, Pamela; Higgins, Jenny; Sicinski, Kamil; Merkurieva, Irina

    2016-03-01

    Despite decades of research on unintended pregnancies, we know little about the health implications for the women who experience them. Moreover, no study has examined the implications for women whose pregnancies occurred before Roe v. Wade was decided--nor whether the mental health consequences of these unintended pregnancies continue into later life. Using the Wisconsin Longitudinal Study, a 60-year ongoing survey, we examined associations between unwanted and mistimed pregnancies and mental health in later life, controlling for factors such as early life socioeconomic conditions, adolescent IQ, and personality. We found that in this cohort of mostly married and White women, who completed their pregnancies before the legalization of abortion, unwanted pregnancies were strongly associated with poorer mental health outcomes in later life. PMID:26691118

  2. Cortical Visual Impairment

    MedlinePlus

    ... work? The eyes take a picture of an object. That message is sent to the brain by ... other sensory messages (hearing, proprioceptive (sensing where the object is in relation to the body), etc). The ...

  3. The magnitude of the somatosensory cortical activity is related to the mobility and strength impairments seen in children with cerebral palsy

    PubMed Central

    Heinrichs-Graham, Elizabeth; Becker, Katherine M.; Wilson, Tony W.

    2015-01-01

    The noted disruption of thalamocortical connections and abnormalities in tactile sensory function has resulted in a new definition of cerebral palsy (CP) that recognizes the sensorimotor integration process as central to the motor impairments seen in these children. Despite this updated definition, the connection between a child's motor impairments and somatosensory processing remains almost entirely unknown. In this investigation, we explored the relationship between the magnitude of neural activity within the somatosensory cortices, the strength of the ankle plantarflexors, and the gait spatiotemporal kinematics of a group of children with CP and a typically developing matched cohort. Our results revealed that the magnitude of somatosensory cortical activity in children with CP had a strong positive relationship with the ankle strength, step length, and walking speed. These results suggest that stronger activity within the somatosensory cortices in response to foot somatosensations was related to enhanced ankle plantarflexor strength and improved mobility in the children with CP. These results provide further support for the notion that children with CP exhibit, not only musculoskeletal deficits, but also somatosensory deficits that potentially contribute to their overall functional mobility and strength limitations. PMID:25717160

  4. The magnitude of the somatosensory cortical activity is related to the mobility and strength impairments seen in children with cerebral palsy.

    PubMed

    Kurz, Max J; Heinrichs-Graham, Elizabeth; Becker, Katherine M; Wilson, Tony W

    2015-05-01

    The noted disruption of thalamocortical connections and abnormalities in tactile sensory function has resulted in a new definition of cerebral palsy (CP) that recognizes the sensorimotor integration process as central to the motor impairments seen in these children. Despite this updated definition, the connection between a child's motor impairments and somatosensory processing remains almost entirely unknown. In this investigation, we explored the relationship between the magnitude of neural activity within the somatosensory cortices, the strength of the ankle plantarflexors, and the gait spatiotemporal kinematics of a group of children with CP and a typically developing matched cohort. Our results revealed that the magnitude of somatosensory cortical activity in children with CP had a strong positive relationship with the ankle strength, step length, and walking speed. These results suggest that stronger activity within the somatosensory cortices in response to foot somatosensations was related to enhanced ankle plantarflexor strength and improved mobility in the children with CP. These results provide further support for the notion that children with CP exhibit, not only musculoskeletal deficits, but also somatosensory deficits that potentially contribute to their overall functional mobility and strength limitations.

  5. Gender Transitions in Later Life: The Significance of Time in Queer Aging

    PubMed Central

    Fabbre, Vanessa D.

    2014-01-01

    Concepts of time are ubiquitous in studies of aging. This article integrates an existential perspective on time with a notion of queer time based on the experiences of older transgender persons who contemplate or pursue a gender transition in later life. Interviews were conducted with male-to-female identified persons aged 50 years or older (N=22), along with participant observation at three national transgender conferences (N=170 hours). Interpretive analyses suggest that an awareness of “time left to live” and a feeling of “time served” play a significant role in later life development and help expand gerontological perspectives on time and queer aging. PMID:24798691

  6. Higher Education is Not Associated with Greater Cortical Thickness in Brain Areas Related to Literacy or Intelligence in Normal Aging or Mild Cognitive Impairment

    PubMed Central

    Pillai, Jagan A.; McEvoy, Linda K.; Hagler, Donald J.; Holland, Dominic; Dale, Anders M.; Salmon, David P.; Galasko, Douglas; Fennema-Notestine, Christine

    2012-01-01

    Education may reduce risk of dementia through passive reserve, by increasing neural substrate. We tested the hypotheses that education is associated with thicker cortex and reduced rates of atrophy in brain regions related to literacy and intellectual ability. Healthy older adults and those with mild cognitive impairment were categorized into High (≥18 yrs) and Low (≤13 yrs) education groups. Higher education was associated with thinner cortices in several areas, but one-year atrophy rates in these areas did not differ by education group. These results do not support a passive reserve model in which early life education protects against dementia by increasing cortical thickness. Connectivity and synaptic efficiency, or other lifestyle factors may more directly reflect cognitive reserve. PMID:22905705

  7. Informal Networks and Well-Being in Later Life: A Research Agenda.

    ERIC Educational Resources Information Center

    Ward, Russell A.

    1985-01-01

    Outlines a complex research agenda for understanding the contributions of informal social support to the quality of later life. Suggests a conceptual model for investigating informal support networks and well-being for the elderly and offers suggestions for operationalizing the model. (NRB)

  8. The Role of Musical Possible Selves in Supporting Subjective Well-Being in Later Life

    ERIC Educational Resources Information Center

    Creech, Andrea; Hallam, Susan; Varvarigou, Maria; Gaunt, Helena; McQueen, Hilary; Pincas, Anita

    2014-01-01

    There is now an accepted need for initiatives that support older people's well-being. There is increasing evidence that active engagement with music has the potential to contribute to this. This paper explores the relationship between musical possible selves and subjective well-being in later life. The research reported here formed part of a…

  9. Early-Life Characteristics, Psychiatric History, and Cognition Trajectories in Later Life

    ERIC Educational Resources Information Center

    Brown, Maria Teresa

    2010-01-01

    Purpose of the Study: Although considerable attention has been paid to the relationship between later-life depression and cognitive function, the relationship between a history of psychiatric problems and cognitive function is not very well documented. Few studies of relationships between childhood health, childhood disadvantage, and cognitive…

  10. A Model Community Education Program on Depression and Suicide in Later Life.

    ERIC Educational Resources Information Center

    Pratt, Clara C.; And Others

    1991-01-01

    Describes development and evaluation of three-hour multimedia community education program on depression and suicide in later life. Designed for families, older adults, and service providers, program provides information and teaches skills to recognize and respond to depression and suicidal behavior in elderly. Compared with controls, participants…

  11. The Interplay between Women's Life Course Work Patterns and Financial Planning for Later Life

    ERIC Educational Resources Information Center

    Berger, Ellie D.; Denton, Margaret A.

    2004-01-01

    In order to gain a comprehensive understanding of the interplay between women's life course work patterns and their financial planning for later life, we examined data from semi-structured interviews with retired women (n = 28) aged 59 to 92. The majority of women disrupted their careers at some point in time, for an average of 14 years, primarily…

  12. Sensory Changes in Later Life. A Pacific Northwest Extension Publication. PNW 196. Revised.

    ERIC Educational Resources Information Center

    Schmall, Vicki L.

    This booklet is designed to help persons who have elderly family members or who work with older adults understand and help compensate for the sensory changes that occur in later life. It contains sections on vision, hearing, taste and smell, and touch. Discussed in the section on vision are the following: common age-related changes, eye diseases…

  13. Constructions of sexuality in later life: analyses of Canadian magazine and newspaper portrayals of online dating.

    PubMed

    Wada, Mineko; Hurd Clarke, Laura; Rozanova, Julia

    2015-01-01

    Advertisements as well as contemporary literature and films often depict older adults as sexually undesirable and unattractive, which reinforces the stereotype that they are nonsexual. However, the evolving discourses of successful aging emphasize that active engagement in life is a key element of healthy aging and as such, have been influencing the ways that older adults' sexuality is represented. This paper explores how popular newspapers and magazines in Canada construct and portray later life sexuality within the context of online dating. We retrieved 144 newspaper and magazine articles about later life online dating that were published between 2009 and 2011. Our thematic and discursive analyses of the articles generated six themes. Of 144 articles, 13% idealized sexuality (sexual attractiveness and optimal sexual engagement) for older adults. The articles portrayed sexual interests and functioning as declining in later life (19%) more often than sustaining (15%). Approximately 15% of the articles suggested that older adults should explore new techniques to boost sexual pleasure, thereby medicalizing and ameliorating sexual decline. In addition, the articles challenged the stereotype of older adults as non-sexual and claimed that sexual engagement in later life was valuable as it contributed to successful aging. We address the paradox in the articles' positive portrayals of older adults' sexuality and the tensions that arise between the two distinct ideals of sexuality that they advance. PMID:25661855

  14. Women's Later Life Career Development: Looking through the Lens of the Kaleidoscope Career Model

    ERIC Educational Resources Information Center

    August, Rachel A.

    2011-01-01

    This study explores the relevance of the Kaleidoscope Career Model (KCM) to women's later life career development. Qualitative interview data were gathered from 14 women in both the "truly" late career and bridge employment periods using a longitudinal design. The relevance of authenticity, balance, and challenge--central parameters in the KCM--is…

  15. Deconstructing Positive Affect in Later Life: A Differential Functionalist Analysis of Joy and Interest

    ERIC Educational Resources Information Center

    Consedine, Nathan S.; Magai, Carol; King, Arlene R.

    2004-01-01

    Positive affect, an index of psychological well-being, is a known predictor of functionality and health in later life. Measures typically studied include joy, happiness, and subjective well-being, but less often interest--a positive emotion with functional properties that differ from joy or happiness. Following differential emotions theory, the…

  16. How Old Am I? Perceived Age in Middle and Later Life

    ERIC Educational Resources Information Center

    Ward, Russell A.

    2010-01-01

    Literatures on perceived age and developmental issues in middle and later life are joined in analyzing perceived age and its implications for well-being. Respondents aged 40-74 (N = 2,696) are drawn from the national MIDUS survey, containing developmental variables such as personal growth and insight into past. People generally "feel" ("felt age")…

  17. Constructions of sexuality in later life: analyses of Canadian magazine and newspaper portrayals of online dating.

    PubMed

    Wada, Mineko; Hurd Clarke, Laura; Rozanova, Julia

    2015-01-01

    Advertisements as well as contemporary literature and films often depict older adults as sexually undesirable and unattractive, which reinforces the stereotype that they are nonsexual. However, the evolving discourses of successful aging emphasize that active engagement in life is a key element of healthy aging and as such, have been influencing the ways that older adults' sexuality is represented. This paper explores how popular newspapers and magazines in Canada construct and portray later life sexuality within the context of online dating. We retrieved 144 newspaper and magazine articles about later life online dating that were published between 2009 and 2011. Our thematic and discursive analyses of the articles generated six themes. Of 144 articles, 13% idealized sexuality (sexual attractiveness and optimal sexual engagement) for older adults. The articles portrayed sexual interests and functioning as declining in later life (19%) more often than sustaining (15%). Approximately 15% of the articles suggested that older adults should explore new techniques to boost sexual pleasure, thereby medicalizing and ameliorating sexual decline. In addition, the articles challenged the stereotype of older adults as non-sexual and claimed that sexual engagement in later life was valuable as it contributed to successful aging. We address the paradox in the articles' positive portrayals of older adults' sexuality and the tensions that arise between the two distinct ideals of sexuality that they advance.

  18. Dopaminergic neurotransmission dysfunction induced by amyloid-β transforms cortical long-term potentiation into long-term depression and produces memory impairment.

    PubMed

    Moreno-Castilla, Perla; Rodriguez-Duran, Luis F; Guzman-Ramos, Kioko; Barcenas-Femat, Alejandro; Escobar, Martha L; Bermudez-Rattoni, Federico

    2016-05-01

    Alzheimer's disease (AD) is a neurodegenerative condition manifested by synaptic dysfunction and memory loss, but the mechanisms underlying synaptic failure are not entirely understood. Although dopamine is a key modulator of synaptic plasticity, dopaminergic neurotransmission dysfunction in AD has mostly been associated to noncognitive symptoms. Thus, we aimed to study the relationship between dopaminergic neurotransmission and synaptic plasticity in AD models. We used a transgenic model of AD (triple-transgenic mouse model of AD) and the administration of exogenous amyloid-β (Aβ) oligomers into wild type mice. We found that Aβ decreased cortical dopamine levels and converted in vivo long-term potentiation (LTP) into long-term depression (LTD) after high-frequency stimulation delivered at basolateral amygdaloid nucleus-insular cortex projection, which led to impaired recognition memory. Remarkably, increasing cortical dopamine and norepinephrine levels rescued both high-frequency stimulation -induced LTP and memory, whereas depletion of catecholaminergic levels mimicked the Aβ-induced shift from LTP to LTD. Our results suggest that Aβ-induced dopamine depletion is a core mechanism underlying the early synaptopathy and memory alterations observed in AD models and acts by modifying the threshold for the induction of cortical LTP and/or LTD. PMID:27103531

  19. Dopaminergic neurotransmission dysfunction induced by amyloid-β transforms cortical long-term potentiation into long-term depression and produces memory impairment.

    PubMed

    Moreno-Castilla, Perla; Rodriguez-Duran, Luis F; Guzman-Ramos, Kioko; Barcenas-Femat, Alejandro; Escobar, Martha L; Bermudez-Rattoni, Federico

    2016-05-01

    Alzheimer's disease (AD) is a neurodegenerative condition manifested by synaptic dysfunction and memory loss, but the mechanisms underlying synaptic failure are not entirely understood. Although dopamine is a key modulator of synaptic plasticity, dopaminergic neurotransmission dysfunction in AD has mostly been associated to noncognitive symptoms. Thus, we aimed to study the relationship between dopaminergic neurotransmission and synaptic plasticity in AD models. We used a transgenic model of AD (triple-transgenic mouse model of AD) and the administration of exogenous amyloid-β (Aβ) oligomers into wild type mice. We found that Aβ decreased cortical dopamine levels and converted in vivo long-term potentiation (LTP) into long-term depression (LTD) after high-frequency stimulation delivered at basolateral amygdaloid nucleus-insular cortex projection, which led to impaired recognition memory. Remarkably, increasing cortical dopamine and norepinephrine levels rescued both high-frequency stimulation -induced LTP and memory, whereas depletion of catecholaminergic levels mimicked the Aβ-induced shift from LTP to LTD. Our results suggest that Aβ-induced dopamine depletion is a core mechanism underlying the early synaptopathy and memory alterations observed in AD models and acts by modifying the threshold for the induction of cortical LTP and/or LTD.

  20. Abnormal Changes of Brain Cortical Anatomy and the Association with Plasma MicroRNA107 Level in Amnestic Mild Cognitive Impairment

    PubMed Central

    Wang, Tao; Shi, Feng; Jin, Yan; Jiang, Weixiong; Shen, Dinggang; Xiao, Shifu

    2016-01-01

    MicroRNA107 (Mir107) has been thought to relate to the brain structure phenotype of Alzheimer’s disease. In this study, we evaluated the cortical anatomy in amnestic mild cognitive impairment (aMCI) and the relation between cortical anatomy and plasma levels of Mir107 and beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1). Twenty aMCI (20 aMCI) and 24 cognitively normal control (NC) subjects were recruited, and T1-weighted MR images were acquired. Cortical anatomical measurements, including cortical thickness (CT), surface area (SA), and local gyrification index (LGI), were assessed. Quantitative RT-PCR was used to examine plasma expression of Mir107, BACE1 mRNA. Thinner cortex was found in aMCI in areas associated with episodic memory and language, but with thicker cortex in other areas. SA decreased in aMCI in the areas associated with working memory and emotion. LGI showed a significant reduction in aMCI in the areas involved in language function. Changes in Mir107 and BACE1 messenger RNA plasma expression were correlated with changes in CT and SA. We found alterations in key left brain regions associated with memory, language, and emotion in aMCI that were significantly correlated with plasma expression of Mir107 and BACE1 mRNA. This combination study of brain anatomical alterations and gene information may shed lights on our understanding of the pathology of AD. Clinical Trial Registration: http://www.ClinicalTrials.gov, identifier NCT01819545. PMID:27242521

  1. Personality disorders in later life: questions about the measurement, course, and impact of disorders.

    PubMed

    Oltmanns, Thomas F; Balsis, Steve

    2011-01-01

    Lifespan perspectives have played a crucial role in shaping our understanding of many forms of psychopathology. Unfortunately, little attention has been given to personality disorders in middle adulthood and later life. Several issues are responsible for this deficiency, including difficulty applying the diagnostic criteria for personality disorders to older people and challenges in identifying appropriate samples of older participants. The goal of this review is to explore the benefits of considering older adults in the study of personality disorders. Later life offers a unique opportunity for investigators to consider links between personality pathology and consequential outcomes in people's lives. Many domains are relevant, including health, longevity, social adjustment, marital relationships, and the experience of major life events. We review each domain and consider ways in which the study of middle-aged and older adults challenges researchers to evaluate how personality disorders in general are defined and measured.

  2. Personality Disorders in Later Life: Questions about the Measurement, Course, and Impact of Disorders

    PubMed Central

    Oltmanns, Thomas F.; Balsis, Steve

    2011-01-01

    Lifespan perspectives have played a crucial role in shaping our understanding of many forms of psychopathology. Unfortunately, little attention has been given to personality disorders in middle adulthood and later life. Several issues are responsible for this deficiency, including difficulty applying the diagnostic criteria for personality disorders to older people and challenges in identifying appropriate samples of older participants. The goal of this review is to explore the benefits of considering older adults in the study of personality disorders. Later life offers a unique opportunity for investigators to consider links between personality pathology and consequential outcomes in people’s lives. Many domains are relevant, including health, longevity, social adjustment, marital relationships, and the experience of major life events. We review each domain and consider ways in which the study of middle-aged and older adults challenges researchers to evaluate how personality disorders in general are defined and measured. PMID:21219195

  3. The Enduring Impact of Maladaptive Personality Traits on Relationship Quality and Health in Later Life

    PubMed Central

    Gleason, Marci E. J.; Weinstein, Yana; Balsis, Steve; Oltmanns, Thomas F.

    2013-01-01

    Over the past five years, the St. Louis Personality and Aging Network (SPAN) has been collecting data on personality in later life with an emphasis on maladaptive personality, social integration, and health outcomes in a representative sample of 1630 adults aged 55–64 living in the St. Louis area. This program has confirmed the importance of considering both the normal range of personality and in particular the role of maladaptive traits in order to understand individuals’ relationships, life events, and health outcomes. In the current paper we discuss the explanatory benefits of considering maladaptive traits or traits associated with personality disorders when discussing the role of personality on social and health outcomes with an emphasis on adults in middle to later life, and integrate these findings into the greater literature. PMID:23998798

  4. Physical, Cognitive, Social, and Emotional Mediators of Activity Involvement and Health in Later Life.

    PubMed

    Matz-Costa, Christina; Carr, Dawn C; McNamara, Tay K; James, Jacquelyn Boone

    2016-10-01

    The current study tests the indirect effect of activity-related physical activity, cognitive activity, social interaction, and emotional exchange on the relationship between activity involvement and health (physical and emotional) in later life. Longitudinal data from the Health and Retirement Study (N = 5,442) were used to estimate a series of linear regression models. We found significant indirect effects for social interaction and benefit to others (emotional exchange) on emotional health (depressive symptoms) and indirect effects for use of body and benefit to others (physical) on physical health (frailty). The most potent indirect effect associated with emotional and physical health was experienced by those engaged in all four domains (use of body, use of mind, social interaction, and benefit to others). While effect sizes are small and results should be interpreted with caution, findings shed light on ways in which public health interventions aimed toward increasing role engagement in later life could be improved.

  5. Physical, Cognitive, Social, and Emotional Mediators of Activity Involvement and Health in Later Life.

    PubMed

    Matz-Costa, Christina; Carr, Dawn C; McNamara, Tay K; James, Jacquelyn Boone

    2016-10-01

    The current study tests the indirect effect of activity-related physical activity, cognitive activity, social interaction, and emotional exchange on the relationship between activity involvement and health (physical and emotional) in later life. Longitudinal data from the Health and Retirement Study (N = 5,442) were used to estimate a series of linear regression models. We found significant indirect effects for social interaction and benefit to others (emotional exchange) on emotional health (depressive symptoms) and indirect effects for use of body and benefit to others (physical) on physical health (frailty). The most potent indirect effect associated with emotional and physical health was experienced by those engaged in all four domains (use of body, use of mind, social interaction, and benefit to others). While effect sizes are small and results should be interpreted with caution, findings shed light on ways in which public health interventions aimed toward increasing role engagement in later life could be improved. PMID:26429863

  6. Sex and the (older) single girl: experiences of sex and dating in later life.

    PubMed

    Fileborn, Bianca; Thorpe, Rachel; Hawkes, Gail; Minichiello, Victor; Pitts, Marian

    2015-04-01

    This study explored the sexual subjectivities of older Australian women. In this article we present findings from 15 qualitative interviews with Australian women aged 55-81 who were single at the time of interview. The majority of these women were single following divorce or separation, with a smaller number of women who were widowed or never in a long-term relationship. We found that these women's sexual desire and sexual activity were fluid and diverse across their life course. Although some participants desired a romantic or sexual relationship, they were also protective of their independence and reluctant to re-enter into a relationship in later life. Our findings indicate that these women's sexual subjectivities were shaped by dominant norms of ageing, sex, and gender. At the same time, older women are challenging and resisting these norms, and beginning to renegotiate sexuality in later life. PMID:25841731

  7. Union formation in later life: economic determinants of cohabitation and remarriage among older adults.

    PubMed

    Vespa, Jonathan

    2012-08-01

    This study builds on Becker's and Oppenheimer's theories of union formation to examine the economic determinants of marriage and cohabitation during older adulthood. Based on the 1998-2006 Health and Retirement Study and a sample of previously married Americans who are at least 50 years old, results show that wealthier older adults, regardless of gender, are more likely to repartner than stay single. Wealth has no discernable effect on the likelihood of remarrying versus cohabiting. Among the oldest men, the positive associations between wealth and repartnering are entirely due to housing assets. Results suggest that Oppenheimer's theory of marriage timing may be more applicable to later-life union formation than Becker's independence hypothesis. Further, economic disadvantage does not appear to characterize later-life cohabitation, unlike cohabitation during young adulthood. These findings help illuminate the union formation process during older adulthood and are timely considering demographic changes reshaping the American population.

  8. Later-life planning for older adults with mental retardation: a field experiment.

    PubMed

    Mahon, M J; Goatcher, S

    1999-10-01

    A quasi-experimental design was used to assess the efficacy of a leisure education-based later-life planning model for 10 older adults with mental retardation. Prior to the initiation of the planning process, they were interviewed and completed three standardized scales designed to assess life and leisure satisfaction and leisure constraints. A comparison group completed these scales but did not participate in the planning process. At the completion of the study, both groups completed the same scales. Results demonstrated that the planning-process group had significantly higher life and leisure satisfaction at the end of the study. Many participants also made changes to their lifestyles consistent with plans made during the study. Results suggest that a later-life planning process may contribute to the quality of life of older adults with mental retardation.

  9. Later-life planning: promoting knowledge of options and choice-making.

    PubMed

    Heller, T; Miller, A B; Hsieh, K; Sterns, H

    2000-10-01

    The effectiveness of a person-centered later-life planning training program designed to teach older adults (N = 60) with mental retardation about later-life planning issues and increase their participation in choice-making was examined. Using quantitative data analyses, we assessed the impact of the program on intervention and control groups. Results indicated that the intervention group gained more knowledge of concepts in the curriculum and made more choices over time than did the control group. The wide variety of goals that participants set were examined through qualitative analyses; 87% of the participants met or partially met their goals. Information on the supports and barriers to meeting goals is provided.

  10. Effect of Intensive Exercise in Early Adult Life on Telomere Length in Later Life in Men

    PubMed Central

    Laine, Merja K.; Eriksson, Johan G.; Kujala, Urho M.; Raj, Rahul; Kaprio, Jaakko; Bäckmand, Heli M.; Peltonen, Markku; Sarna, Seppo

    2015-01-01

    A career as an elite-class male athlete seems to improve metabolic heath in later life and is also associated with longer life expectancy. Telomere length is a biomarker of biological cellular ageing and could thus predict morbidity and mortality. The main aim of this study was to assess the association between vigorous elite-class physical activity during young adulthood on later life leukocyte telomere length (LTL). The study participants consist of former male Finnish elite athletes (n = 392) and their age-matched controls (n = 207). Relative telomere length was determined from peripheral blood leukocytes by quantitative real-time polymerase chain reaction. Volume of leisure-time physical activity (LTPA) was self-reported and expressed in metabolic equivalent hours. No significant difference in mean age-adjusted LTL in late life (p = 0.845) was observed when comparing former male elite athletes and their age-matched controls. Current volume of LTPA had no marked influence on mean age-adjusted LTL (p for trend 0.788). LTL was inversely associated with age (p = 0.004).Our study findings suggest that a former elite athlete career is not associated with LTL later in life. Key points A career as an elite-class athlete is associated with improved metabolic health in late life and is associated with longer life expectancy. A career as an elite-class athlete during young adulthood was not associated with leukocyte telomere length in later life. Current volume of leisure-time physical activity did not influence telomere length in later life. PMID:25983570

  11. Negative density dependence regulates two tree species at later life stage in a temperate forest.

    PubMed

    Piao, Tiefeng; Chun, Jung Hwa; Yang, Hee Moon; Cheon, Kwangil

    2014-01-01

    Numerous studies have demonstrated that tree survival is influenced by negative density dependence (NDD) and differences among species in shade tolerance could enhance coexistence via resource partitioning, but it is still unclear how NDD affects tree species with different shade-tolerance guilds at later life stages. In this study, we analyzed the spatial patterns for trees with dbh (diameter at breast height) ≥2 cm using the pair-correlation g(r) function to test for NDD in a temperate forest in South Korea after removing the effects of habitat heterogeneity. The analyses were implemented for the most abundant shade-tolerant (Chamaecyparis obtusa) and shade-intolerant (Quercus serrata) species. We found NDD existed for both species at later life stages. We also found Quercus serrata experienced greater NDD compared with Chamaecyparis obtusa. This study indicates that NDD regulates the two abundant tree species at later life stages and it is important to consider variation in species' shade tolerance in NDD study. PMID:25058660

  12. Maternal nutrition, low nephron number and arterial hypertension in later life.

    PubMed

    Benz, Kerstin; Amann, Kerstin

    2010-12-01

    A potential role of the intrauterine environment in the development of low nephron number and hypertension in later life has been recently recognized in experimental studies and is also postulated in certain conditions in human beings. Nephrogenesis is influenced by genetic as well as by environmental and in particular maternal factors. In man nephrogenesis, i.e. the formation of nephrons during embryogenesis, takes place from weeks 5 to 36 of gestation with the most rapid phase of nephrogenesis occurring from the mid-2nd trimester until 36 weeks. This 16 week period is a very vulnerable phase where genetic and environmental factors such as maternal diet or medication could influence and disturb nephron formation leading to lower nephron number. Given a constant rise in body mass until adulthood lower nephron number may become "nephron underdosing" and result in maladaptive glomerular changes, i.e. glomerular hyperfiltration and glomerular enlargement. These maladaptive changes may then eventually lead to the development of glomerular and systemic hypertension and renal disease in later life. It is the purpose of this review to discuss the currently available experimental and clinical evidence for factors and mechanisms that could interfere with nephrogenesis with particular emphasis on maternal nutrition. In addition, we discuss the emerging concept of low nephron number being a new cardiovascular risk factor in particular for essential hypertension in later life.

  13. Vascular cognitive impairment and dementia.

    PubMed

    Gorelick, Philip B; Counts, Scott E; Nyenhuis, David

    2016-05-01

    Vascular contributions to cognitive impairment are receiving heightened attention as potentially modifiable factors for dementias of later life. These factors have now been linked not only to vascular cognitive disorders but also Alzheimer's disease. In this chapter we review 3 related topics that address vascular contributions to cognitive impairment: 1. vascular pathogenesis and mechanisms; 2. neuropsychological and neuroimaging phenotypic manifestations of cerebrovascular disease; and 3. prospects for prevention of cognitive impairment of later life based on cardiovascular and stroke risk modification. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26704177

  14. Impaired gamma-band activity during perceptual organization in adults with autism spectrum disorders: evidence for dysfunctional network activity in frontal-posterior cortices.

    PubMed

    Sun, Limin; Grützner, Christine; Bölte, Sven; Wibral, Michael; Tozman, Tahmine; Schlitt, Sabine; Poustka, Fritz; Singer, Wolf; Freitag, Christine M; Uhlhaas, Peter J

    2012-07-11

    Current theories of the pathophysiology of autism spectrum disorders (ASD) have focused on abnormal temporal coordination of neural activity in cortical circuits as a core impairment of the disorder. In the current study, we examined the possibility that gamma-band activity may be crucially involved in aberrant brain functioning in ASD. Magneto-encephalographic (MEG) data were recorded from 13 adult human participants with ASD and 16 controls during the presentation of Mooney faces. MEG data were analyzed in the 25-150 Hz frequency range and a beamforming approach was used to identify the sources of spectral power. Participants with ASD showed elevated reaction times and reduced detection rates during the perception of upright Mooney faces, while responses to inverted stimuli were in the normal range. Impaired perceptual organization in the ASD group was accompanied by a reduction in both the amplitude and phase locking of gamma-band activity. A beamforming approach identified distinct networks during perceptual organization in controls and participants with ASD. In controls, perceptual organization of Mooney faces involved increased 60-120 Hz activity in a frontoparietal network, while in the ASD group stronger activation was found in visual regions. These findings highlight the contribution of impaired gamma-band activity toward complex visual processing in ASD, suggesting atypical modulation of high-frequency power in frontoposterior networks.

  15. Predictive timing functions of cortical beta oscillations are impaired in Parkinson's disease and influenced by L-DOPA and deep brain stimulation of the subthalamic nucleus

    PubMed Central

    Gulberti, A.; Moll, C.K.E.; Hamel, W.; Buhmann, C.; Koeppen, J.A.; Boelmans, K.; Zittel, S.; Gerloff, C.; Westphal, M.; Schneider, T.R.; Engel, A.K.

    2015-01-01

    Cortex-basal ganglia circuits participate in motor timing and temporal perception, and are important for the dynamic configuration of sensorimotor networks in response to exogenous demands. In Parkinson's disease (PD) patients, rhythmic auditory stimulation (RAS) induces motor performance benefits. Hitherto, little is known concerning contributions of the basal ganglia to sensory facilitation and cortical responses to RAS in PD. Therefore, we conducted an EEG study in 12 PD patients before and after surgery for subthalamic nucleus deep brain stimulation (STN-DBS) and in 12 age-matched controls. Here we investigated the effects of levodopa and STN-DBS on resting-state EEG and on the cortical-response profile to slow and fast RAS in a passive-listening paradigm focusing on beta-band oscillations, which are important for auditory–motor coupling. The beta-modulation profile to RAS in healthy participants was characterized by local peaks preceding and following auditory stimuli. In PD patients RAS failed to induce pre-stimulus beta increases. The absence of pre-stimulus beta-band modulation may contribute to impaired rhythm perception in PD. Moreover, post-stimulus beta-band responses were highly abnormal during fast RAS in PD patients. Treatment with levodopa and STN-DBS reinstated a post-stimulus beta-modulation profile similar to controls, while STN-DBS reduced beta-band power in the resting-state. The treatment-sensitivity of beta oscillations suggests that STN-DBS may specifically improve timekeeping functions of cortical beta oscillations during fast auditory pacing. PMID:26594626

  16. Survival of offspring who experience early parental death: early life conditions and later-life mortality.

    PubMed

    Smith, Ken R; Hanson, Heidi A; Norton, Maria C; Hollingshaus, Michael S; Mineau, Geraldine P

    2014-10-01

    We examine the influences of a set of early life conditions (ELCs) on all-cause and cause-specific mortality among elderly individuals, with special attention to one of the most dramatic early events in a child's, adolescent's, or even young adult's life, the death of a parent. The foremost question is, once controlling for prevailing (and potentially confounding) conditions early in life (family history of longevity, paternal characteristics (SES, age at time of birth, sibship size, and religious affiliation)), is a parental death associated with enduring mortality risks after age 65? The years following parental death may initiate new circumstances through which the adverse effects of paternal death operate. Here we consider the offspring's marital status (whether married; whether and when widowed), adult socioeconomic status, fertility, and later life health status. Adult health status is based on the Charlson Co-Morbidity Index, a construct that summarizes nearly all serious illnesses afflicting older individuals that relies on Medicare data. The data are based on linkages between the Utah Population Database and Medicare claims that hold medical diagnoses data. We show that offspring whose parents died when they were children, but especially when they were adolescents/young adults, have modest but significant mortality risks after age 65. What are striking are the weak mediating influences of later-life comorbidities, marital status, fertility and adult socioeconomic status since controls for these do little to alter the overall association. No beneficial effects of the surviving parent's remarriage were detected. Overall, we show the persistence of the effects of early life loss on later-life mortality and indicate the difficulties in addressing challenges at young ages.

  17. The Relationship of Childhood Maltreatment and Household Dysfunction and Drug Use in Later Life in Iran

    NASA Astrophysics Data System (ADS)

    Ziaaddini, Hassan; Dastjerdi, Qasem; Nakhaee, Nouzar

    Few studies have examined the relationship between childhood maltreatment and substance use in later life considering household dysfunction variables especially in Eastern Mediterranean countries. The study was conducted to explore the relationship between adverse childhood experiences and substance misuse during later life in an Iranian sample. A case control study was conducted in Kerman, a city located in southern Iran in 2005. Cases were 200 men and women referred to outpatient clinics of the city seeking treatment for substance use disorder. Controls (n = 200) were selected from the general population. With emphasizing the confidentiality and obtaining oral consent the subjects were asked to fill out a questionnaire including demographic variables and 27 questions concerning all types of child abuse/neglect and household dysfunction. Using multivariate logistic regression the associations between baseline characteristics, childhood maltreatment and household dysfunction variables and substance use disorder were analyzed. The mean age of case group was 32.5±8.3 and in control group was 28±9.3 (p< 0.01). Most of subjects in both groups were male. The prevalence of sexual abuse, household substance use and household criminality were higher in substance dependent patients comparing to control group. The highest odds of substance use disorder was associated with household substance abuse (OR: 2.50, 95% CI: 1.53-4.10) and sexual abuse was the only type of childhood maltreatment which showed significant association with substance use disorder in later life (OR: 1.73, 95% CI: 1.03-2.92). The related factors uncovered by the study conduct us to early interventions among dysfunctional families to decrease the maladaptive lives and stressful household environments.

  18. Rescue of Impaired mGluR5-Driven Endocannabinoid Signaling Restores Prefrontal Cortical Output to Inhibit Pain in Arthritic Rats

    PubMed Central

    Kiritoshi, Takaki; Ji, Guangchen

    2016-01-01

    The medial prefrontal cortex (mPFC) serves executive functions that are impaired in neuropsychiatric disorders and pain. Underlying mechanisms remain to be determined. Here we advance the novel concept that metabotropic glutamate receptor 5 (mGluR5) fails to engage endocannabinoid (2-AG) signaling to overcome abnormal synaptic inhibition in pain, but restoring endocannabinoid signaling allows mGluR5 to increase mPFC output hence inhibit pain behaviors and mitigate cognitive deficits. Whole-cell patch-clamp recordings were made from layer V pyramidal cells in the infralimbic mPFC in rat brain slices. Electrical and optogenetic stimulations were used to analyze amygdala-driven mPFC activity. A selective mGluR5 activator (VU0360172) increased pyramidal output through an endocannabinoid-dependent mechanism because intracellular inhibition of the major 2-AG synthesizing enzyme diacylglycerol lipase or blockade of CB1 receptors abolished the facilitatory effect of VU0360172. In an arthritis pain model mGluR5 activation failed to overcome abnormal synaptic inhibition and increase pyramidal output. mGluR5 function was rescued by restoring 2-AG-CB1 signaling with a CB1 agonist (ACEA) or inhibitors of postsynaptic 2-AG hydrolyzing enzyme ABHD6 (intracellular WWL70) and monoacylglycerol lipase MGL (JZL184) or by blocking GABAergic inhibition with intracellular picrotoxin. CB1-mediated depolarization-induced suppression of synaptic inhibition (DSI) was also impaired in the pain model but could be restored by coapplication of VU0360172 and ACEA. Stereotaxic coadministration of VU0360172 and ACEA into the infralimbic, but not anterior cingulate, cortex mitigated decision-making deficits and pain behaviors of arthritic animals. The results suggest that rescue of impaired endocannabinoid-dependent mGluR5 function in the mPFC can restore mPFC output and cognitive functions and inhibit pain. SIGNIFICANCE STATEMENT Dysfunctions in prefrontal cortical interactions with subcortical

  19. The Political Economy of Longevity: Developing New Forms of Solidarity for Later Life

    PubMed Central

    Phillipson, Chris

    2015-01-01

    Aging populations now exert influence on all aspects of social life. This article examines changes to major social and economic institutions linked with old age, taking the period from the mid-20th century to the opening decades of the 21st century. These developments are set within the context of the influence of globalization as well as the impact of the 2008 financial crisis, these restructuring debates around the longevity revolution. The article examines how the basis for a new framework for accommodating longevity can be built, outlining ways of securing new forms of solidarity in later life. PMID:25678722

  20. Immature Cortical Responses to Auditory Stimuli in Specific Language Impairment: Evidence from ERPS to Rapid Tone Sequences

    ERIC Educational Resources Information Center

    Bishop, D. V. M.; McArthur, G. M.

    2004-01-01

    Event-related potentials (ERPs) to tone pairs and single tones were measured for 16 participants with specific language impairment (SLI) and 16 age-matched controls aged from 10 to 19 years. The tone pairs were separated by an inter-stimulus interval (ISI) of 20, 50 or 150 ms. The intraclass correlation (ICC) was computed for each participant…

  1. Forever productive: the discursive shaping of later life workers in contemporary Canadian newspapers.

    PubMed

    Rudman, Debbie Laliberte; Molke, Daniel

    2009-01-01

    Increasingly, ;productive aging' is promoted within government policies and reports in several Western nations, as well as those of international organizations. The ways in which ;productive aging' comes to be shaped within texts, that is, its discursive shaping, influences what aging individuals view as possible and ideal ways to be and do in later life, as well as what collectivities view as required services and programs to support such identities and occupations. Drawing on governmentality theory, in concert with occupational science, a critical discourse analysis of 72 Canadian newspaper articles pertaining to work and retirement published in 2006 was conducted to examine how 'productive aging' is shaped within such print media texts and the possibilities for identity and occupation promoted. This work critically analyzes ways 'later life workers' have come to be discursively shaped within neoliberal sociopolitical contexts, characterized by emphases on fostering individual responsibility, decreasing state dependency, and increasing privatization. The authors raises concerns related to occupational injustice, arguing for continuing vigilance regarding the ways 'productive aging' discourses might be drawn on to justify further state and workplace retreat from policies and programs that support those who face challenges to continued engagement in work or who cannot, or chose not to, be 'forever productive'.

  2. Marital quality, marital dissolution, and mortality risk during the later life course.

    PubMed

    Bulanda, Jennifer Roebuck; Brown, J Scott; Yamashita, Takashi

    2016-09-01

    This study examines the relationship between later-life marital quality, marital dissolution, and mortality using discrete-time event history models with data from nine waves (1992-2008) of the Health and Retirement Study (n = 7388). Results show marital status is more important for men's mortality risk than women's, whereas marital quality is more important for women's survival than men's. Being widowed or divorced more than two years raises mortality risk for men, but later-life marital dissolution is not significantly associated with women's mortality risk, regardless of the type of dissolution or length of time since it occurred. Low-quality marital interaction is negatively related to women's odds of death, but none of the marital quality measures are significantly associated with mortality for men. Marital satisfaction moderates the relationship between widowhood and mortality for women, but the relationship between marital dissolution and mortality is similar for men regardless of marital quality prior to divorce/widowhood. Results suggest the importance of accounting for both marital status and marital quality when examining older individuals' mortality risk. PMID:27509579

  3. Quetiapine attenuates cognitive impairment and decreases seizure susceptibility possibly through promoting myelin development in a rat model of malformations of cortical development.

    PubMed

    Ma, Lei; Yang, Feng; Zhao, Rui; Li, Li; Kang, Xiaogang; Xiao, Lan; Jiang, Wen

    2015-10-01

    Developmental delay, cognitive impairment, and refractory epilepsy are the most frequent consequences found in patients suffering from malformations of cortical development (MCD). However, therapeutic options for these psychiatric and neurological comorbidities are currently limited. The development of white matter undergoes dramatic changes during postnatal brain maturation, thus myelination deficits resulting from MCD contribute to its comorbid diseases. Consequently, drugs specifically targeting white matter are a promising therapeutic option for the treatment of MCD. We have used an in utero irradiation rat model of MCD to investigate the effects of postnatal quetiapine treatment on brain myelination as well as neuropsychological and cognitive performances and seizure susceptibility. Fatally irradiated rats were treated with quetiapine (10mg/kg, i.p.) or saline once daily from postnatal day 0 (P0) to P30. We found that postnatal administration of quetiapine attenuated object recognition memory impairment and improved long-term spatial memory in the irradiated rats. Quetiapine treatment also reduced the susceptibility and severity of pentylenetetrazol-induced seizures. Importantly, quetiapine treatment resulted in an inhibition of irradiation-induced myelin breakdown in the cerebral cortex and corpus callosum. These findings suggest that quetiapine may have beneficial, postnatal effects in the irradiated rats, strongly suggesting that improving MCD-derived white matter pathology is a possible underlying mechanism. Collectively, these results indicate that brain myelination represents an encouraging pharmacological target to improve the prognosis of patients with MCD. PMID:26188240

  4. Quetiapine attenuates cognitive impairment and decreases seizure susceptibility possibly through promoting myelin development in a rat model of malformations of cortical development.

    PubMed

    Ma, Lei; Yang, Feng; Zhao, Rui; Li, Li; Kang, Xiaogang; Xiao, Lan; Jiang, Wen

    2015-10-01

    Developmental delay, cognitive impairment, and refractory epilepsy are the most frequent consequences found in patients suffering from malformations of cortical development (MCD). However, therapeutic options for these psychiatric and neurological comorbidities are currently limited. The development of white matter undergoes dramatic changes during postnatal brain maturation, thus myelination deficits resulting from MCD contribute to its comorbid diseases. Consequently, drugs specifically targeting white matter are a promising therapeutic option for the treatment of MCD. We have used an in utero irradiation rat model of MCD to investigate the effects of postnatal quetiapine treatment on brain myelination as well as neuropsychological and cognitive performances and seizure susceptibility. Fatally irradiated rats were treated with quetiapine (10mg/kg, i.p.) or saline once daily from postnatal day 0 (P0) to P30. We found that postnatal administration of quetiapine attenuated object recognition memory impairment and improved long-term spatial memory in the irradiated rats. Quetiapine treatment also reduced the susceptibility and severity of pentylenetetrazol-induced seizures. Importantly, quetiapine treatment resulted in an inhibition of irradiation-induced myelin breakdown in the cerebral cortex and corpus callosum. These findings suggest that quetiapine may have beneficial, postnatal effects in the irradiated rats, strongly suggesting that improving MCD-derived white matter pathology is a possible underlying mechanism. Collectively, these results indicate that brain myelination represents an encouraging pharmacological target to improve the prognosis of patients with MCD.

  5. Diabetic Goto-Kakizaki rats display pronounced hyperglycemia and longer-lasting cognitive impairments following ischemia induced by cortical compression.

    PubMed

    Moreira, T; Cebers, G; Pickering, C; Ostenson, C-G; Efendic, S; Liljequist, S

    2007-02-23

    Hyperglycemia has been shown to worsen the outcome of brain ischemia in several animal models but few experimental studies have investigated impairments in cognition induced by ischemic brain lesions in hyperglycemic animals. The Goto-Kakizaki (GK) rat naturally develops type 2 diabetes characterized by mild hyperglycemia and insulin resistance. We hypothesized that GK rats would display more severe cerebral damage due to hyperglycemia-aggravated brain injury and, accordingly, more severe cognitive impairments. In this study, recovery of motor and cognitive functions of GK and healthy Wistar rats was examined following extradural compression (EC) of the sensorimotor cortex. For this purpose, tests of vestibulomotor function (beam-walking) and combined tests of motor function and learning (locomotor activity from day (D) 1 to D5, operant lever-pressing from D14 to D25) were used. EC consistently reduced cerebral blood flow in both strains. Anesthesia-challenge and EC resulted in pronounced hyperglycemia in GK but not in Wistar rats. Lower beam-walking scores, increased locomotor activity, impairments in long-term habituation and learning of operant lever-pressing were more pronounced and observed at later time-points in GK rats. Fluoro-Jade, a marker of irreversible neuronal degeneration, revealed consistent degeneration in the ipsilateral cortex, hippocampus and thalamus at 2, 7 and 14 days post-compression. The amount of degeneration in these structures was considerably higher in GK rats. Thus, GK rats exhibited marked hyperglycemia during EC, as well as longer-lasting behavioral deficits and increased neurodegeneration during recovery. The GK rat is thus an attractive model for neuropathologic and cognitive studies after ischemic brain injury in hyperglycemic rats. PMID:17175109

  6. What are the Effects of Severe Visual Impairment on the Cortical Organization and Connectivity of Primary Visual Cortex?

    PubMed Central

    Larsen, DeLaine D.; Luu, Julie D.; Burns, Marie E.; Krubitzer, Leah

    2009-01-01

    The organization and connections of the primary visual area (V1) were examined in mice that lacked functional rods (Gnat−/−), but had normal cone function. Because mice are nocturnal and rely almost exclusively on rod vision for normal behaviors, the Gnat−/− mice used in the present study are considered functionally blind. Our goal was to determine if visual cortex is reorganized in these mice, and to examine the neuroanatomical connections that may subserve reorganization. We found that most neurons in V1 responded to auditory, or some combination of auditory, somatosensory, and/or visual stimulation. We also determined that cortical connections of V1 in Gnat−/− mice were similar to those in normal animals, but even in normal animals, there is sparse input from auditory cortex (AC) to V1. An important observation was that most of the subcortical inputs to V1 were from thalamic nuclei that normally project to V1 such as the lateral geniculate (LG), lateral posterior (LP), and lateral dorsal (LD) nuclei. However, V1 also received some abnormal subcortical inputs from the anterior thalamic nuclei, the ventral posterior, the ventral lateral and the posterior nuclei. While the vision generated from the small number of cones appears to be sufficient to maintain most of the patterns of normal connectivity, the sparse abnormal thalamic inputs to VI, existing inputs from AC, and possibly abnormal inputs to LG and LP may be responsible for generating the alterations in the functional organization of V1. PMID:20057935

  7. Happy Marriage, Happy Life? Marital Quality and Subjective Well-Being in Later Life.

    PubMed

    Carr, Deborah; Freedman, Vicki A; Cornman, Jennifer C; Schwarz, Norbert

    2014-10-01

    The authors examined associations between marital quality and both general life satisfaction and experienced (momentary) well-being among older husbands and wives, the relative importance of own versus spouse's marital appraisals for well-being, and the extent to which the association between own marital appraisals and well-being is moderated by spouse's appraisals. Data are from the 2009 Disability and Use of Time daily diary supplement to the Panel Study of Income Dynamics (N = 722). One's own marital satisfaction is a sizable and significant correlate of life satisfaction and momentary happiness; associations do not differ significantly by gender. The authors did not find a significant association between spouse's marital appraisals and own well-being. However, the association between husband's marital quality and life satisfaction is buoyed when his wife also reports a happy marriage, yet flattened when his wife reports low marital quality. Implications for understanding marital dynamics and well-being in later life are discussed.

  8. Early Life Adversity as a Risk Factor for Fibromyalgia in Later Life

    PubMed Central

    Low, Lucie A.; Schweinhardt, Petra

    2012-01-01

    The impact of early life events is increasingly becoming apparent, as studies investigate how early childhood can shape long-term physiology and behaviour. Fibromyalgia (FM), which is characterised by increased pain sensitivity and a number of affective co-morbidities, has an unclear etiology. This paper discusses risk factors from early life that may increase the occurrence or severity of FM in later life: pain experience during neonatal life causes long-lasting changes in nociceptive circuitry and increases pain sensitivity in the older organism; premature birth and related stressor exposure cause lasting changes in stress responsivity; maternal deprivation affects anxiety-like behaviours that may be partially mediated by epigenetic modulation of the genome—all these adult phenotypes are strikingly similar to symptoms displayed by FM sufferers. In addition, childhood trauma and exposure to substances of abuse may cause lasting changes in developing neurotransmitter and endocrine circuits that are linked to anxiety and stress responses. PMID:22110940

  9. Education is associated with higher later life IQ scores, but not with faster cognitive processing speed.

    PubMed

    Ritchie, Stuart J; Bates, Timothy C; Der, Geoff; Starr, John M; Deary, Ian J

    2013-06-01

    Recent reports suggest a causal relationship between education and IQ, which has implications for cognitive development and aging-education may improve cognitive reserve. In two longitudinal cohorts, we tested the association between education and lifetime cognitive change. We then tested whether education is linked to improved scores on processing-speed variables such as reaction time, which are associated with both IQ and longevity. Controlling for childhood IQ score, we found that education was positively associated with IQ at ages 79 (Sample 1) and 70 (Sample 2), and more strongly for participants with lower initial IQ scores. Education, however, showed no significant association with processing speed, measured at ages 83 and 70. Increased education may enhance important later life cognitive capacities, but does not appear to improve more fundamental aspects of cognitive processing.

  10. In utero exposure to carcinogens: Epigenetics, developmental disruption and consequences in later life.

    PubMed

    Waring, R H; Harris, R M; Mitchell, S C

    2016-04-01

    The uterine environment is often viewed as a relatively safe haven, being guarded by the placenta which acts as a filter, permitting required materials to enter and unwanted products to be removed. However, this defensive barrier is sometimes breached by potential chemical hazards to which the mother may be subjected. Many of these toxins have immediate and recognisable deleterious effects on the embryo, foetus or neonate, but a few are insidious and leave a legacy of health issues that may emerge in later life. Several substances, falling into the categories of metals and metalloids, endocrine disruptors, solvents and other industrial chemicals, have been implicated in the development of long-term health problems in the offspring following maternal and subsequent in utero exposure. The mechanisms involved are complex but often involve epigenetic changes which disrupt normal cell processes leading to the development of cancers and also dysregulation of biochemical pathways. PMID:26921930

  11. Gender Transitions in Later Life: A Queer Perspective on Successful Aging

    PubMed Central

    Fabbre, Vanessa D.

    2015-01-01

    Purpose of the Study: Most understandings of successful aging are developed within a heteronormative cultural framework, leading to a dearth of theoretical and empirical scholarship relevant to lesbian, gay, bisexual, transgender, and queer (LGBTQ) older adults. This study explores the experiences of transgender persons who contemplate or pursue a gender transition in later life in order to develop culturally diverse conceptualizations of health and wellness in older age. Design and Methods: Using the extended case method, in-depth interviews were conducted with male-to-female-identified persons (N = 22) who have seriously contemplated or pursued a gender transition past the age of 50. In addition, 170hr of participant observation was carried out at 3 national transgender conferences generating ethnographic field notes on the topics of aging and gender transitions in later life. Results: Interpretive analyses suggest that many transgender older adults experience challenges to their gender identities that put their emotional and physical well-being at risk. Contemporary queer theory is used to understand these experiences and argue that greater attention to experiences of queer “failure” and negotiating “success on new terms” may be integral aspects of growth and development for transgender older adults. Implications: The Baby Boom generation is aging in a post-Stonewall, LGBTQ civil rights era, yet gerontology’s approach to gender and sexual identity has largely been formulated from a heteronormative perspective. A framework for understanding older transgender persons’ experiences informed by queer theory offers a new orientation for conceptualizing successful aging in the lives of marginalized gender and sexual minorities. PMID:25161264

  12. Ornithine and Homocitrulline Impair Mitochondrial Function, Decrease Antioxidant Defenses and Induce Cell Death in Menadione-Stressed Rat Cortical Astrocytes: Potential Mechanisms of Neurological Dysfunction in HHH Syndrome.

    PubMed

    Zanatta, Ângela; Rodrigues, Marília Danyelle Nunes; Amaral, Alexandre Umpierrez; Souza, Débora Guerini; Quincozes-Santos, André; Wajner, Moacir

    2016-09-01

    Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is caused by deficiency of ornithine translocase leading to predominant tissue accumulation and high urinary excretion of ornithine (Orn), homocitrulline (Hcit) and ammonia. Although affected patients commonly present neurological dysfunction manifested by cognitive deficit, spastic paraplegia, pyramidal and extrapyramidal signs, stroke-like episodes, hypotonia and ataxia, its pathogenesis is still poorly known. Although astrocytes are necessary for neuronal protection. Therefore, in the present study we investigated the effects of Orn and Hcit on cell viability (propidium iodide incorporation), mitochondrial function (thiazolyl blue tetrazolium bromide-MTT-reduction and mitochondrial membrane potential-ΔΨm), antioxidant defenses (GSH) and pro-inflammatory response (NFkB, IL-1β, IL-6 and TNF-α) in unstimulated and menadione-stressed cortical astrocytes that were previously shown to be susceptible to damage by neurotoxins. We first observed that Orn decreased MTT reduction, whereas both amino acids decreased GSH levels, without altering cell viability and the pro-inflammatory factors in unstimulated astrocytes. Furthermore, Orn and Hcit decreased cell viability and ΔΨm in menadione-treated astrocytes. The present data indicate that the major compounds accumulating in HHH syndrome impair mitochondrial function and reduce cell viability and the antioxidant defenses in cultured astrocytes especially when stressed by menadione. It is presumed that these mechanisms may be involved in the neuropathology of this disease. PMID:27161368

  13. Single Dose of a Dopamine Agonist Impairs Reinforcement Learning in Humans: Evidence from Event-related Potentials and Computational Modeling of Striatal-Cortical Function

    PubMed Central

    Santesso, Diane L.; Evins, A. Eden; Frank, Michael J.; Cowman Schetter, Erika M.; Bogdan, Ryan; Pizzagalli, Diego A.

    2011-01-01

    Animal findings have highlighted the modulatory role of phasic dopamine (DA) signaling in incentive learning, particularly in the acquisition of reward-related behavior. In humans, these processes remain largely unknown. In a recent study we demonstrated that a single low dose of a D2/D3 agonist (pramipexole) – assumed to activate DA autoreceptors and thus reduce phasic DA bursts – impaired reward learning in healthy subjects performing a probabilistic reward task. The purpose of the present study was to extend these behavioral findings using event-related potentials and computational modeling. Compared to the placebo group, participants receiving pramipexole showed increased feedback-related negativity to probabilistic rewards and decreased activation in dorsal anterior cingulate regions previously implicated in integrating reinforcement history over time. Additionally, findings of blunted reward learning in participants receiving pramipexole were simulated by reduced presynaptic DA signaling in response to reward in a neural network model of striatal-cortical function. These preliminary findings offer important insights on the role of phasic DA signals on reinforcement learning in humans, and provide initial evidence regarding the spatio-temporal dynamics of brain mechanisms underlying these processes. PMID:18726908

  14. Ornithine and Homocitrulline Impair Mitochondrial Function, Decrease Antioxidant Defenses and Induce Cell Death in Menadione-Stressed Rat Cortical Astrocytes: Potential Mechanisms of Neurological Dysfunction in HHH Syndrome.

    PubMed

    Zanatta, Ângela; Rodrigues, Marília Danyelle Nunes; Amaral, Alexandre Umpierrez; Souza, Débora Guerini; Quincozes-Santos, André; Wajner, Moacir

    2016-09-01

    Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is caused by deficiency of ornithine translocase leading to predominant tissue accumulation and high urinary excretion of ornithine (Orn), homocitrulline (Hcit) and ammonia. Although affected patients commonly present neurological dysfunction manifested by cognitive deficit, spastic paraplegia, pyramidal and extrapyramidal signs, stroke-like episodes, hypotonia and ataxia, its pathogenesis is still poorly known. Although astrocytes are necessary for neuronal protection. Therefore, in the present study we investigated the effects of Orn and Hcit on cell viability (propidium iodide incorporation), mitochondrial function (thiazolyl blue tetrazolium bromide-MTT-reduction and mitochondrial membrane potential-ΔΨm), antioxidant defenses (GSH) and pro-inflammatory response (NFkB, IL-1β, IL-6 and TNF-α) in unstimulated and menadione-stressed cortical astrocytes that were previously shown to be susceptible to damage by neurotoxins. We first observed that Orn decreased MTT reduction, whereas both amino acids decreased GSH levels, without altering cell viability and the pro-inflammatory factors in unstimulated astrocytes. Furthermore, Orn and Hcit decreased cell viability and ΔΨm in menadione-treated astrocytes. The present data indicate that the major compounds accumulating in HHH syndrome impair mitochondrial function and reduce cell viability and the antioxidant defenses in cultured astrocytes especially when stressed by menadione. It is presumed that these mechanisms may be involved in the neuropathology of this disease.

  15. Ethnic inequalities in limiting health and self-reported health in later life revisited

    PubMed Central

    Evandrou, Maria; Falkingham, Jane; Feng, Zhixin; Vlachantoni, Athina

    2016-01-01

    Background It is well established that there are ethnic inequalities in health in the UK; however, such inequalities in later life remain a relatively under-researched area. This paper explores ethnic inequalities in health among older people in the UK, controlling for social and economic disadvantages. Methods This paper analyses the first wave (2009–2011) of Understanding Society to examine differentials in the health of older persons aged 60 years and over. 2 health outcomes are explored: the extent to which one's health limits the ability to undertake typical activities and self-rated health. Logistic regression models are used to control for a range of other factors, including income and deprivation. Results After controlling for social and economic disadvantage, black and minority ethnic (BME) elders are still more likely than white British elders to report limiting health and poor self-rated health. The ‘health disadvantage’ appears most marked among BME elders of South Asian origin, with Pakistani elders exhibiting the poorest health outcomes. Length of time resident in the UK does not have a direct impact on health in models for both genders, but is marginally significant for women. Conclusions Older people from ethnic minorities report poorer health outcomes even after controlling for social and economic disadvantages. This result reflects the complexity of health inequalities among different ethnic groups in the UK, and the need to develop health policies which take into account differences in social and economic resources between different ethnic groups. PMID:26787199

  16. Patterns of intimate partner homicide suicide in later life: Strategies for prevention

    PubMed Central

    Salari, Sonia

    2007-01-01

    Intimate partner homicide suicide (IPHS) constitutes the most violent domestic abuse outcome, devastating individuals, families, neighborhoods and communities. This research used content analysis to analyze 225 murder suicide events (444 deaths) among dyads with at least one member 60 or older. Data were collected from newspaper articles, television news transcripts, police reports and obituaries published between 1999 and 2005. Findings suggest the most dangerous setting was the home and the majority of perpetrators were men. Firearms were most often employed in the violence. Relationship strife was present in some cases, but only slightly higher than the divorce rate for that age group. Illness was cited in just over half of the cases, but 30% of sick elderly couples had only a perpetrator who was ill. Evidence of suicide pacts and mercy killings were very rare and practitioners are encouraged to properly investigate these events. Suicidal men in this age range must be recognized as a potential threat to others, primarily their partner. Homicide was sometimes the primary motive, and the perpetrators in those cases resembled the “intimate terrorist.” Victims in those cases were often terrorized before the murder. Clinicians are educated about the patterns of fatal violence in later life dyads and provided with strategies for prevention. PMID:18044194

  17. What contributes to perceived stress in later life? A recursive partitioning approach

    PubMed Central

    Scott, Stacey B.; Jackson, Brenda R.; Bergeman, C. S.

    2011-01-01

    One possible explanation for the individual differences in outcomes of stress is the diversity of inputs that produce perceptions of being stressed. The current study examines how combinations of contextual features (e.g., social isolation, neighborhood quality, health problems, age discrimination, financial concerns, and recent life events) of later life contribute to overall feelings of stress. Recursive partitioning techniques (regression trees and random forests) were used to examine unique interrelations between predictors of perceived stress in a sample of 282 community-dwelling adults. Trees provided possible examples of equifinality (i.e., subsets of people with similar levels of perceived stress but different predictors) as well as for the identification both of contextual combinations that separated participants with very high and very low perceived stress. Random forest analyses aggregated across many trees based on permuted versions of the data and predictors; loneliness, financial strain, neighborhood strain, ageism, and to some extent life events emerged as important predictors. Interviews with a subsample of participants provided both thick description of the complex relationships identified in the trees, as well as additional risks not appearing in the survey results. Together, the analyses highlight what may be missed when stress is used as a simple unidimensional construct and can guide differential intervention efforts. PMID:21604885

  18. Treatment of major depression in later life: a life cycle perspective.

    PubMed

    Reynolds, C F

    1997-01-01

    The goal of this article is to provide a life-cycle perspective on the treatment of major depressive episodes in later life. Our studies have suggested that older patients appear to benefit as much, though perhaps more slowly, than mid-life patients from acute combined treatment (nortriptyline+interpersonal psychotherapy) of major depression. Given also the apparently higher relapse rate among the elderly, however, continuation treatment needs to be vigorous and closely monitored. The occurrence of severe life events prior to the index episode and the co-existence of an anxiety disorder both appear to prolong treatment response times, while chronic medical burden per se neither compromises response rates nor prolongs time to response. Self-rated perception of health improves with remission of depression in the elderly. As in mid-life patients, both antidepressant medication (nortriptyline) and interpersonal psychotherapy appear to possess chronic efficacy with respect to the prevention of recurrent episodes and prolongation of wellness. Finally, treatment of depression in the elderly results in improved quality of life, especially in domains of well being and coping. Particular challenges in the treatment of elderly patients are noncompliance and the prevention of suicide. The latter is closely linked to feelings of hopelessness, and these may be persistent in some patients. PMID:9237318

  19. Multilingualism and later life: a sociolinguistic perspective on age and aging.

    PubMed

    Divita, David

    2014-08-01

    In this paper, I contribute to subjective accounts of aging by focusing on a population that has been largely overlooked in social gerontology: individuals in later life who are multilingual. How do such individuals experience and make sense of their multilingualism? What role does language play in the way they experience and make sense of their lives? To answer these questions I take a life story approach to three women who experienced similar sociohistorical circumstances but arrived at different linguistic outcomes: born in Spain around the time of the civil war (1936-1939), they migrated to Paris in the 1960s to pursue social and economic mobility. Although they arrived in France as monolingual Spanish speakers, they have since acquired French and now practice their multilingualism in distinct ways. I juxtapose their life stories to illustrate how the acquisition and use of language are informed by a confluence of personal, social, and historical factors. Focusing on the linguistic dimension of the life course I thus introduce a new perspective on the heterogeneity obtained among individuals at this stage of their biographical trajectories. PMID:24984912

  20. Negotiating a moral identity in the context of later life care.

    PubMed

    Breheny, Mary; Stephens, Christine

    2012-12-01

    Strategies to maintain independence for older people have received considerable attention as a social policy solution to the financial and social impact of the ageing population. Critical scholars in gerontology have also highlighted the negative consequences of promoting independence in this way. Understandings of independence have profound implications for caring relationships as people age. To investigate the ways that older people talk about caring we interviewed 48 people aged 55-70 years. A discourse analysis of these data showed that a dominant discourse of 'independence' was drawn upon to value self-sufficiency and construct dependence on others as burdensome. This construction of care provides a comfortable position for those who can afford to purchase professional care; however, those without resources are unable to accept unpaid help without also accepting a position of dependency. An alternative discourse of 'being there' constructs having others to provide personal care as a virtue and obligations to provide such care as based on family duty and affection. This discourse emphasises connections between people and a moral obligation to care which also creates difficulties for those with fewer material resources. The position for a dependent older subject in these two discourses may seem incompatible but can be reconciled by reframing independence as autonomy. Autonomy for those requiring care alongside a wider recognition of caring as the responsibility of all members of the community rather than with individual family members would support a flexible approach to later life care arrangements. PMID:22939540

  1. Comparing the Relationship Between Stature and Later Life Health in Six Low and Middle Income Countries

    PubMed Central

    McGovern, Mark E.

    2014-01-01

    This paper examines the relationship between stature and later life health in 6 emerging economies, each of which are expected to experience significant increases in the mean age of their populations over the coming decades. Using data from the WHO Study on Global Ageing and Adult Health (SAGE) and pilot data from the Longitudinal Ageing Study in India (LASI), I show that various measures of health are associated with height, a commonly used proxy for childhood environment. In the pooled sample, an additional 10cm increase in height is associated with between a 2 and 3 percentage point increase in the probability of being in very good or good self-reported health, a 3 percentage point increase in the probability of reporting no difficulties with activities of daily living or instrumental activities of daily living, and between a fifth and a quarter of a standard deviation increase in grip strength and lung function. Adopting a methodology previously used in the research on inequality, I also summarise the height-grip strength gradient for each country using the concentration index, and provide a decomposition analysis. PMID:25590021

  2. Maternal Differential Treatment in Later Life Families and Within-Family Variations in Adult Sibling Closeness

    PubMed Central

    Suitor, J. Jill; Nam, Sangbo

    2015-01-01

    Objectives. In this article, we explore within-family differences in the closeness of sibling ties in adulthood. Specifically, we consider the sibship as a network and investigate the ways in which perceptions of mothers’ differential treatment play a role in within-family variations in sibling closeness in midlife. Method. Data were analyzed from 2,067 adult sibling dyads nested within 216 later life families, collected as part of the Within-Family Differences Study-II. Results. Respondents reported the greatest closeness to siblings whom they perceived as favored by their mothers when they were not favored themselves, whereas respondents were less likely to choose siblings whom they perceived as disfavored by their mothers when they did not perceive themselves as disfavored. Discussion. Variability in the strength of sibling ties within families suggests that some individuals receive greater benefits from this relationship than do their brothers and sisters. These findings shed new light on such within-family variations in sibling closeness by identifying how specific patterns of maternal differential treatment draw offspring toward some siblings and away from others. PMID:25324293

  3. Leisure Engagement: Medical Conditions, Mobility Difficulties, and Activity Limitations—A Later Life Perspective

    PubMed Central

    Nilsson, Ingeborg; Nyqvist, Fredrica; Gustafson, Yngve; Nygård, Mikael

    2015-01-01

    Objectives. This study aims to investigate the impact of medical conditions, mobility difficulties, and activity limitations on older people's engagement in leisure activities. Methods. The analyses are based on a cross regional survey carried out in 2010 in the Bothnia region (Northern Sweden and Western Finland). A posted questionnaire, which included questions on different aspects of leisure engagement, medical history, and health, was sent out to older persons in the region. The final sample consisted of 5435 persons aged 65, 70, 75, and 80 years. The data was analyzed by using ordinary least squares (OLS) multivariate regression. Results. The most important predictor of leisure engagement abstention among older people is the prevalence of activity limitations, whereas mobility difficulties and medical conditions play less important roles. The strong negative association between activity limitations and leisure engagement remains significant even after we control for individual, sociodemographic characteristics, and country. Discussion. This study provides a window into leisure engagement in later life and factors influencing the magnitude of engagement in leisure activities. PMID:26346706

  4. Preventing Depression in Later Life: Translation From Concept to Experimental Design and Implementation

    PubMed Central

    Sriwattanakomen, Roy; Ford, Angela F.; Thomas, Stephen B.; Miller, Mark D.; Stack, Jacqueline A.; Morse, Jennifer Q.; Kasckow, John; Brown, Charlotte; Reynolds, Charles F.

    2009-01-01

    Objective The authors detail the public health need for depression prevention research and the decisions made in designing an experiment testing problem solving therapy as “indicated” preventive intervention for high-risk older adults with subsyndromal depression. Special attention is given to the recruitment of African Americans because of well-documented inequalities in mental health services and depression treatment outcomes between races. Methods A total of 306 subjects (half white, half African American) with scores of 16 or higher on the Center for Epidemiological Studies of Depression Scale, but with no history of major depressive disorder in the past 12 months, are being recruited and randomly assigned to either problem solving therapy-primary care or to a dietary education control condition. Time to, and rate of, incident episodes of major depressive disorder are to be modeled using survival analysis. Level of depressive symptoms will be analyzed via a mixed models approach. Results Twenty-two subjects have been recruited into the study, and to date eight have completed the randomly assigned intervention and postintervention assessment. Four of 22 have exited after developing major depressive episodes. None have complained about study procedures or demands. Implementation in a variety of community settings is going well. Conclusion The data collected to date support the feasibility of translating from epidemiology to RCT design and implementation of empirical depression prevention research in later life. PMID:18515690

  5. Later Life Learners: A Significant and Receptive Audience for Introductory Astronomy

    NASA Astrophysics Data System (ADS)

    Percy, J. R.; Krstovic, M.

    2001-05-01

    ``Later life learners" (LLL: generally age 65 or older) are a subset of ``life long learners"; both form a large, influential, and receptive audience for courses in introductory astronomy. This year alone, one of us (JRP) has taught two LLL courses of almost 200 ``students" each. In previous years, he has taught several other such courses (as well as courses for life long learners in general). Each course has its own personality, but the students all tend to be interested and highly interactive, bringing a wealth of life experience to the course. They are also influential in that the students provide a strong link with the community, and they tend to have a very positive and supportive attitude to scholarship and research, and to colleges and universities. Yet these courses are rather neglected in terms of educational research, and resources such as textbooks. In this paper, we discuss the nature of LLL courses, and the motivations for teaching them. We present anecdotal comments on the nature of the learners, and results based on questionnaires about their interests and their reactions to the courses. We encourage other astronomy educators to make contact with LLL groups in their community, with a view to offering a course. Thanks to the Ontario Work-Study Program for supporting this project.

  6. Multilingualism and later life: a sociolinguistic perspective on age and aging.

    PubMed

    Divita, David

    2014-08-01

    In this paper, I contribute to subjective accounts of aging by focusing on a population that has been largely overlooked in social gerontology: individuals in later life who are multilingual. How do such individuals experience and make sense of their multilingualism? What role does language play in the way they experience and make sense of their lives? To answer these questions I take a life story approach to three women who experienced similar sociohistorical circumstances but arrived at different linguistic outcomes: born in Spain around the time of the civil war (1936-1939), they migrated to Paris in the 1960s to pursue social and economic mobility. Although they arrived in France as monolingual Spanish speakers, they have since acquired French and now practice their multilingualism in distinct ways. I juxtapose their life stories to illustrate how the acquisition and use of language are informed by a confluence of personal, social, and historical factors. Focusing on the linguistic dimension of the life course I thus introduce a new perspective on the heterogeneity obtained among individuals at this stage of their biographical trajectories.

  7. Improving the rate of Patient Feedback for a Later Life Mental Health Liaison Team.

    PubMed

    Cooper, Daniel

    2016-01-01

    It is well established that patient feedback is key to service development and improvement in the modern NHS. Certain patient groups can be particularly difficult to get feedback from, including those with dementia. The Later Life Mental Health Liaison Team at the Bristol Royal Infirmary were consistently receiving very low levels of patient feedback, such that it was insufficient to properly contribute to future service development and improvement. This QIP aimed to increase this level of feedback to a target of 15% from an existing average of 3%. The intervention centred around getting feedback from patients face to face and was developed over a number of PDSA cycles. The feedback questions were based upon the NHS Friends and Family Test. Over four PDSA cycles levels of feedback increased to 21% which more than achieved the goal set out at the start. This was however achieved at a time cost and involved an increased success rate of existing systems as well as new ones put into place by the QIP.

  8. Combined effects of type 2 diabetes and hypertension associated with cortical thinning and impaired cerebrovascular reactivity relative to hypertension alone in older adults

    PubMed Central

    Tchistiakova, Ekaterina; Anderson, Nicole D.; Greenwood, Carol E.; MacIntosh, Bradley J.

    2014-01-01

    Objective Type 2 diabetes mellitus is characterized by metabolic dysregulation in the form of hyperglycemia and insulin resistance and can have a profound impact on brain structure and vasculature. The primary aim of this study was to identify brain regions where the combined effects of type 2 diabetes and hypertension on brain health exceed those of hypertension alone. A secondary objective was to test whether vascular impairment and structural brain measures in this population are associated with cognitive function. Research design and methods We enrolled 18 diabetic participants with hypertension (HTN + T2DM, 7 women, 71.8 ± 5.6 years) and 22 participants with hypertension only (HTN, 12 women, 73.4 ± 6.2 years). Cerebrovascular reactivity (CVR) was assessed using blood oxygenation level dependent (BOLD) MRI during successive breath holds. Gray matter structure was evaluated using cortical thickness (CThk) measures estimated from T1-weighted images. Analyses of cognitive and blood data were also performed. Results Compared to HTN, HTN + T2DM had decreased CVR and CThk in a spatially overlapping region of the right occipital lobe (P < 0.025); CVR group differences were more expansive and included bilateral occipito-parietal areas (P < 0.025). Whereas CVR showed no significant associations with measures of cognitive function (P > 0.05), CThk in the right lingual gyrus ROI and regions resulting from a vertex-wise analysis (including posterior cingulate, precuneus, superior and middle frontal, and middle and inferior temporal regions (P < 0.025) were associated with executive function. Conclusions Individuals with T2DM and HTN showed decreased CVR and CThk compared to age-matched HTN controls. This study identifies brain regions that are impacted by the combined effects of comorbid T2DM and HTN conditions, with new evidence that the corresponding cortical thinning may contribute to cognitive decline. PMID:24967157

  9. "I'm Sure She Chose Me!" Accuracy of Children's Reports of Mothers' Favoritism in Later Life Families

    ERIC Educational Resources Information Center

    Suitor, J. Jill; Sechrist, Jori; Steinhour, Michael; Pillemer, Karl

    2006-01-01

    We used data from 769 mother-child dyads nested within 300 later life families to explore the accuracy of adult children's perceptions of mothers' patterns of favoritism in terms of closeness and confiding. Adult children were generally accurate regarding whether their mothers preferred a specific child, but often had difficulty identifying whom…

  10. Elevated intracranial dopamine impairs the glutamate-nitric oxide-cyclic guanosine monophosphate pathway in cortical astrocytes in rats with minimal hepatic encephalopathy

    PubMed Central

    DING, SAIDAN; HUANG, WEILONG; YE, YIRU; YANG, JIANJING; HU, JIANGNAN; WANG, XIAOBIN; LIU, LEPING; LU, QIN; LIN, YUANSHAO

    2014-01-01

    In a previous study by our group memory impairment in rats with minimal hepatic encephalopathy (MHE) was associated with the inhibition of the glutamate-nitric oxide-cyclic guanosine monophosphate (Glu-NO-cGMP) pathway due to elevated dopamine (DA). However, the effects of DA on the Glu-NO-cGMP pathway localized in primary cortical astrocytes (PCAs) had not been elucidated in rats with MHE. In the present study, it was identified that when the levels of DA in the cerebral cortex of rats with MHE and high-dose DA (3 mg/kg)-treated rats were increased, the co-localization of N-methyl-d-aspartate receptors subunit 1 (NMDAR1), calmodulin (CaM), nitric oxide synthase (nNOS), soluble guanylyl cyclase (sGC) and cyclic guanine monophosphate (cGMP) with the glial fibrillary acidic protein (GFAP), a marker protein of astrocytes, all significantly decreased, in both the MHE and high-dose DA-treated rats (P<0.01). Furthermore, NMDA-induced augmentation of the expression of NMDAR1, CaM, nNOS, sGC and cGMP localized in PCAs was decreased in MHE and DA-treated rats, as compared with the controls. Chronic exposure of cultured cerebral cortex PCAs to DA treatment induced a dose-dependent decrease in the concentration of intracellular calcium, nitrites and nitrates, the formation of cGMP and the expression of NMDAR1, CaM, nNOS and sGC/cGMP. High doses of DA (50 μM) significantly reduced NMDA-induced augmentation of the formation of cGMP and the contents of NMDAR1, CaM, nNOS, sGC and cGMP (P<0.01). These results suggest that the suppression of DA on the Glu-NO-cGMP pathway localized in PCAs contributes to memory impairment in rats with MHE. PMID:25059564

  11. Developmental cuprizone exposure impairs oligodendrocyte lineages differentially in cortical and white matter tissues and suppresses glutamatergic neurogenesis signals and synaptic plasticity in the hippocampal dentate gyrus of rats.

    PubMed

    Abe, Hajime; Saito, Fumiyo; Tanaka, Takeshi; Mizukami, Sayaka; Hasegawa-Baba, Yasuko; Imatanaka, Nobuya; Akahori, Yumi; Yoshida, Toshinori; Shibutani, Makoto

    2016-01-01

    Developmental cuprizone (CPZ) exposure impairs rat hippocampal neurogenesis. Here, we captured the developmental neurotoxicity profile of CPZ using a region-specific expression microarray analysis in the hippocampal dentate gyrus, corpus callosum, cerebral cortex and cerebellar vermis of rat offspring exposed to 0, 0.1, or 0.4% CPZ in the maternal diet from gestation day 6 to postnatal day (PND) 21. Transcripts of those genes identified as altered were subjected to immunohistochemical analysis on PNDs 21 and 77. Our results showed that transcripts for myelinogenesis-related genes, including Cnp, were selectively downregulated in the cerebral cortex by CPZ at ≥0.1% or 0.4% on PND 21. CPZ at 0.4% decreased immunostaining intensity for 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase) and CNPase(+) and OLIG2(+) oligodendrocyte densities in the cerebral cortex, whereas CNPase immunostaining intensity alone was decreased in the corpus callosum. By contrast, a striking transcript upregulation for Klotho gene and an increased density of Klotho(+) oligodendrocytes were detected in the corpus callosum at ≥0.1%. In the dentate gyrus, CPZ at ≥0.1% or 0.4% decreased the transcript levels for Gria1, Grin2a and Ptgs2, genes related to the synapse and synaptic transmission, and the number of GRIA1(+) and GRIN2A(+) hilar γ-aminobutyric acid (GABA)-ergic interneurons and cyclooxygenase-2(+) granule cells. All changes were reversed at PND 77. Thus, developmental CPZ exposure reversibly decreased mature oligodendrocytes in both cortical and white matter tissues, and Klotho protected white matter oligodendrocyte growth. CPZ also reversibly targeted glutamatergic signals of GABAergic interneuron to affect dentate gyrus neurogenesis and synaptic plasticity in granule cells. PMID:26577399

  12. The Relationship Between Borderline Personality Disorder and Major Depression in Later Life: Acute Versus Temperamental Symptoms

    PubMed Central

    Galione, Janine N.; Oltmanns, Thomas F.

    2012-01-01

    Objective A recent issue in the personality disorder field is the prevalence and course of Axis II symptoms in later life. Focusing on the presentation of personality disorder criteria over time may have some utility in exploring the relationship between borderline personality disorder (BPD) and major depression in older adults. Temperamental personality symptoms are relatively resistant to change but tend to be nonspecific to disorders, while acute symptoms remit relatively quickly. We predicted that temperamental BPD symptoms would be positively correlated with a history of depression and did not expect to find a relationship between major depression and acute BPD symptoms. Method One thousand six hundred and thirty participants between the ages of 55 and 64 were recruited to participate in a community-based longitudinal study representative of the St. Louis area. Participants completed a battery of assessments at baseline, including diagnostic interviews for all ten personality disorders and major depressive disorder. Results Temperamental and acute BPD symptoms were significantly correlated with a history of major depression. After adjustments were made for the effects of temperamental symptoms on depression, acute symptoms were no longer correlated with a history of depression. As predicted, temperamental symptoms remained significantly related to depression, even after controlling for the effects of acute symptoms. BPD acute symptoms showed a unique negative correlation with the amount of time following remission from a depressive episode. Conclusions Overall, this study supports associations between major depression and borderline personality in older adults. The findings indicate that a history of major depression is primarily related to stable BPD symptoms related to emotional distress, which are more prevalent in older adults compared to acute features. PMID:23567384

  13. Maternal Obesity During Pregnancy Associates With Premature Mortality and Major Cardiovascular Events in Later Life.

    PubMed

    Lee, Kuan Ken; Raja, Edwin A; Lee, Amanda J; Bhattacharya, Sohinee; Bhattacharya, Siladitya; Norman, Jane E; Reynolds, Rebecca M

    2015-11-01

    One in 5 pregnant women is obese but the impact on later health is unknown. We aimed to determine whether maternal obesity during pregnancy associates with increased premature mortality and later life major cardiovascular events. Maternity records of women who gave birth to their first child between 1950 and 1976 (n=18 873) from the Aberdeen Maternity and Neonatal databank were linked to the National Register of Deaths, Scotland and Scottish Morbidity Record. The effect of maternal obesity at first antenatal visit on death and hospital admissions for cardiovascular events was tested using time-to-event analysis with Cox proportional hazard regression to compare outcomes of mothers in underweight, overweight, or obese body mass index (BMI) categories compared with normal BMI. Median follow-up was at 73 years. All-cause mortality was increased in women who were obese during pregnancy (BMI>30 kg/m(2)) versus normal BMI after adjustment for socioeconomic status, smoking, gestation at BMI measurement, preeclampsia, and low birth weight (hazard ratio, 1.35; 95% confidence interval, 1.02-1.77). In adjusted models, overweight and obese mothers had increased risk of hospital admission for a cardiovascular event (1.16; 1.06-1.27 and 1.26; 1.01-1.57) compared with normal BMI mothers. Adjustment for parity largely unchanged the hazard ratios (mortality: 1.43, 1.09-1.88; cardiovascular events overweight: 1.17, 1.07-1.29; and obese: 1.30, 1.04-1.62). In conclusion, maternal obesity is associated with increased risk of premature death and cardiovascular disease. Pregnancy and early postpartum could represent an opportunity for interventions to identify obesity and reduce its adverse consequences.

  14. The determinants of transitions into sheltered accommodation in later life in England and Wales

    PubMed Central

    Vlachantoni, Athina; Maslovskaya, Olga; Evandrou, Maria; Falkingham, Jane

    2016-01-01

    Background Population ageing is a global challenge and understanding the dynamics of living arrangements in later life and their implications for the design of appropriate housing and long-term care is a critical policy issue. Existing research has focused on the study of transitions into residential care in the UK. This paper investigates transitions into sheltered accommodation among older people in England and Wales between 1993 and 2008. Methods The study uses longitudinal data constructed from pooled observations across waves 2–18 of the British Household Panel Survey (BHPS) data, focusing on individuals aged 65 and over who lived in private housing at baseline and who were observed for two consecutive time points. A discrete-time logistic regression model was used to examine the association of transitioning into sheltered accommodation with a range of demographic, health and socioeconomic predictors. Results Demographic (age, region), socioeconomic factors (housing tenure, having a washing machine) and contact with health professionals (number of visits to the general practitioner, start in use of health visitor) were significant determinants of an older person's move into sheltered accommodation. Conclusions Transitions into sheltered accommodation are associated with a range of demographic and socioeconomic characteristics as well as service use but not with health. Such results indicate that this type of housing option may be accessible by individuals with relatively good health, but may be limited to those who are referred by gatekeepers. Policymakers could consider making such housing option available to everyone, as well as providing incentives for building lifecourse-sensitive housing in the future. PMID:26896519

  15. Maternal Obesity During Pregnancy Associates With Premature Mortality and Major Cardiovascular Events in Later Life.

    PubMed

    Lee, Kuan Ken; Raja, Edwin A; Lee, Amanda J; Bhattacharya, Sohinee; Bhattacharya, Siladitya; Norman, Jane E; Reynolds, Rebecca M

    2015-11-01

    One in 5 pregnant women is obese but the impact on later health is unknown. We aimed to determine whether maternal obesity during pregnancy associates with increased premature mortality and later life major cardiovascular events. Maternity records of women who gave birth to their first child between 1950 and 1976 (n=18 873) from the Aberdeen Maternity and Neonatal databank were linked to the National Register of Deaths, Scotland and Scottish Morbidity Record. The effect of maternal obesity at first antenatal visit on death and hospital admissions for cardiovascular events was tested using time-to-event analysis with Cox proportional hazard regression to compare outcomes of mothers in underweight, overweight, or obese body mass index (BMI) categories compared with normal BMI. Median follow-up was at 73 years. All-cause mortality was increased in women who were obese during pregnancy (BMI>30 kg/m(2)) versus normal BMI after adjustment for socioeconomic status, smoking, gestation at BMI measurement, preeclampsia, and low birth weight (hazard ratio, 1.35; 95% confidence interval, 1.02-1.77). In adjusted models, overweight and obese mothers had increased risk of hospital admission for a cardiovascular event (1.16; 1.06-1.27 and 1.26; 1.01-1.57) compared with normal BMI mothers. Adjustment for parity largely unchanged the hazard ratios (mortality: 1.43, 1.09-1.88; cardiovascular events overweight: 1.17, 1.07-1.29; and obese: 1.30, 1.04-1.62). In conclusion, maternal obesity is associated with increased risk of premature death and cardiovascular disease. Pregnancy and early postpartum could represent an opportunity for interventions to identify obesity and reduce its adverse consequences. PMID:26370890

  16. Effects of floor eggs on hatchability and later life performance in broiler chickens.

    PubMed

    van den Brand, H; Sosef, M P; Lourens, A; van Harn, J

    2016-05-01

    Two experiments were conducted in which effects of floor eggs, washed floor eggs, and clean nest eggs were investigated on incubation characteristics and performance in later life of broiler chickens. In both experiments, a young and an older breeder flock were used in a 3×2 factorial design during incubation. In the second experiment, male and female chickens were reared separately until d 35 of age in floor pens. During this grow out trial, an extra group was created in which chickens obtained from clean nest eggs were mixed with chickens obtained from floor eggs, meaning that grow out period was set up as a 4×2×2 factorial design with 4 egg types, 2 breeder ages, and 2 sexes. In both experiments, fertility and hatchability of fertile eggs were lower in floor and washed eggs than in clean nest eggs (hatchability: experiment 1: 74.4 vs. 70.6 vs. 92.6% for floor eggs, washed floor eggs and clean nest eggs, respectively, P<0.001; experiment 2: 78.3 vs. 81.7 vs. 90.2%, respectively, P<0.001). In experiment 2, BW at d 0 of chickens obtained from clean nest eggs was higher than that of chickens from floor eggs and washed floor eggs (41.5 vs. 40.4 and 40.3 g, respectively; P<0.001). This difference disappeared during the grow out period and was absent at slaughter age at d 35 of age. Feed intake (FI), feed conversion ratio (FCR), and mortality during the grow out period were not affected by egg type. Incidence and severity of hock burns and footpad dermatitis were not affected by egg type or breeder age. Litter friability at d 35 of age tended to be lower in pens with chickens obtained from washed floor eggs compared to clean nest eggs. We conclude that incubation of floor eggs or washed floor eggs resulted in lower fertility and hatchability compared to clean nest eggs, but that performance during the grow out period was not affected.

  17. Effects of floor eggs on hatchability and later life performance in broiler chickens.

    PubMed

    van den Brand, H; Sosef, M P; Lourens, A; van Harn, J

    2016-05-01

    Two experiments were conducted in which effects of floor eggs, washed floor eggs, and clean nest eggs were investigated on incubation characteristics and performance in later life of broiler chickens. In both experiments, a young and an older breeder flock were used in a 3×2 factorial design during incubation. In the second experiment, male and female chickens were reared separately until d 35 of age in floor pens. During this grow out trial, an extra group was created in which chickens obtained from clean nest eggs were mixed with chickens obtained from floor eggs, meaning that grow out period was set up as a 4×2×2 factorial design with 4 egg types, 2 breeder ages, and 2 sexes. In both experiments, fertility and hatchability of fertile eggs were lower in floor and washed eggs than in clean nest eggs (hatchability: experiment 1: 74.4 vs. 70.6 vs. 92.6% for floor eggs, washed floor eggs and clean nest eggs, respectively, P<0.001; experiment 2: 78.3 vs. 81.7 vs. 90.2%, respectively, P<0.001). In experiment 2, BW at d 0 of chickens obtained from clean nest eggs was higher than that of chickens from floor eggs and washed floor eggs (41.5 vs. 40.4 and 40.3 g, respectively; P<0.001). This difference disappeared during the grow out period and was absent at slaughter age at d 35 of age. Feed intake (FI), feed conversion ratio (FCR), and mortality during the grow out period were not affected by egg type. Incidence and severity of hock burns and footpad dermatitis were not affected by egg type or breeder age. Litter friability at d 35 of age tended to be lower in pens with chickens obtained from washed floor eggs compared to clean nest eggs. We conclude that incubation of floor eggs or washed floor eggs resulted in lower fertility and hatchability compared to clean nest eggs, but that performance during the grow out period was not affected. PMID:26908895

  18. Reproductive History and Later-Life Comorbidity Trajectories: A Medicare-Linked Cohort Study From the Utah Population Database.

    PubMed

    Hanson, Heidi A; Smith, Ken R; Zimmer, Zachary

    2015-12-01

    Reproductive lives of men and women may provide significant insight into later-life morbidity and mortality. Sociological, biological, and evolutionary theories predict a relationship between reproductive history and later-life health; however, current research is lacking consensus on the direction of the relationship. Parity, early age at first birth and last birth, birth weight of offspring, having a child die as an infant, and having a preterm birth may have long-term effects on health for both men and women. In this study, the relationship between these measures of reproductive history and later-life health is examined using the Utah Population Database (a rich source of longitudinal data), and Medicare claims data from 1992-2009. Later-life health is measured using annual Charlson comorbidity index scores, a construct that summarizes most serious illnesses afflicting older individuals. Group-based trajectory modeling that accounts for nonrandom attrition due to death is used to identify the number and types of morbidity trajectories by sex and age for 52,924 individuals aged 65-84 in 1992. For females, early age at first birth, high parity, and having a preterm or high-birth-weight baby are associated with increased risks of comorbidity; later age at last birth is associated with a decreased risk of comorbidity. For males, early age at first birth and having a child with an abnormal birth weight leads to increased risk of comorbidity. The results suggest that both biological and social factors play important roles in the relationships between fertility and morbidity profiles at older ages. PMID:26527471

  19. Mothering alone: cross-national comparisons of later-life disability and health among women who were single mothers

    PubMed Central

    Berkman, Lisa F.; Zheng, Yuhui; Glymour, M. Maria; Avendano, Mauricio; Supan, Axel Börsch; Sabbath, Erika L.

    2016-01-01

    Background Single motherhood is associated with poorer health, but whether this association varies between countries is not known. We examine associations between single motherhood and poor later-life health in the US, England and 13 European countries. Methods Data came from 25,125 women aged 50+ who participated in the US Health and Retirement Study, the English Longitudinal Study of Ageing, and Survey of Health, Ageing and Retirement in Europe. We tested whether single motherhood at ages 16–49 was associated with increased risk of limitations with activities of daily living (ADL), instrumental ADL (IADL) and fair/poor self-rated health in later life. Results 33% of American mothers had experienced single motherhood before age 50, versus 22% in England, 38% in Scandinavia, 22% in Western Europe and 10% in Southern Europe. Single mothers had higher risk of poorer health and disability in later life than married mothers, but associations varied between countries. For example, risk ratios for ADL limitations were 1.51 (95% CI 1.29, 1.98) in England, 1.50 (1.10, 2.05) in Scandinavia and 1.27 (1.17, 1.40) in the US, versus 1.09 (0.80, 1.47) in Western Europe, 1.13 (0.80, 1.60) in Southern Europe, and 0.93 (0.66, 1.31) in Eastern Europe. Women who were single mothers before age 20, for 8+ years, or resulting from divorce or non-marital childbearing, were at particular risk. Conclusion Single motherhood during early- or mid-adulthood is associated with poorer health in later life. Risks were greatest in England, the US, and Scandinavia. Both selection and causation mechanisms might explain between-country variation. PMID:25977123

  20. N-acetylcysteine attenuates lipopolysaccharide-induced impairment in lamination of Ctip2-and Tbr1- expressing cortical neurons in the developing rat fetal brain

    PubMed Central

    Chao, Ming-Wei; Chen, Chie-Pein; Yang, Yu-Hsiu; Chuang, Yu-Chen; Chu, Tzu-Yun; Tseng, Chia-Yi

    2016-01-01

    Oxidative stress and inflammatory insults are the major instigating events of bacterial intrauterine infection that lead to fetal brain injury. The purpose of this study is to investigate the remedial effects of N-acetyl-cysteine (NAC) for inflammation-caused deficits in brain development. We found that lipopolysaccharide (LPS) induced reactive oxygen species (ROS) production by RAW264.7 cells. Macrophage-conditioned medium caused noticeable cortical cell damage, specifically in cortical neurons. LPS at 25 μg/kg caused more than 75% fetal loss in rats. An increase in fetal cortical thickness was noted in the LPS-treated group. In the enlarged fetal cortex, laminar positioning of the early born cortical cells expressing Tbr1 and Ctip2 was disrupted, with a scattered distribution. The effect was similar, but minor, in later born Satb2-expressing cortical cells. NAC protected against LPS-induced neuron toxicity in vitro and counteracted pregnancy loss and alterations in thickness and lamination of the neocortex in vivo. Fetal loss and abnormal fetal brain development were due to LPS-induced ROS production. NAC is an effective protective agent against LPS-induced damage. This finding highlights the key therapeutic impact of NAC in LPS-caused abnormal neuronal laminar distribution during brain development. PMID:27577752

  1. N-acetylcysteine attenuates lipopolysaccharide-induced impairment in lamination of Ctip2-and Tbr1- expressing cortical neurons in the developing rat fetal brain.

    PubMed

    Chao, Ming-Wei; Chen, Chie-Pein; Yang, Yu-Hsiu; Chuang, Yu-Chen; Chu, Tzu-Yun; Tseng, Chia-Yi

    2016-01-01

    Oxidative stress and inflammatory insults are the major instigating events of bacterial intrauterine infection that lead to fetal brain injury. The purpose of this study is to investigate the remedial effects of N-acetyl-cysteine (NAC) for inflammation-caused deficits in brain development. We found that lipopolysaccharide (LPS) induced reactive oxygen species (ROS) production by RAW264.7 cells. Macrophage-conditioned medium caused noticeable cortical cell damage, specifically in cortical neurons. LPS at 25 μg/kg caused more than 75% fetal loss in rats. An increase in fetal cortical thickness was noted in the LPS-treated group. In the enlarged fetal cortex, laminar positioning of the early born cortical cells expressing Tbr1 and Ctip2 was disrupted, with a scattered distribution. The effect was similar, but minor, in later born Satb2-expressing cortical cells. NAC protected against LPS-induced neuron toxicity in vitro and counteracted pregnancy loss and alterations in thickness and lamination of the neocortex in vivo. Fetal loss and abnormal fetal brain development were due to LPS-induced ROS production. NAC is an effective protective agent against LPS-induced damage. This finding highlights the key therapeutic impact of NAC in LPS-caused abnormal neuronal laminar distribution during brain development. PMID:27577752

  2. A window of vulnerability: impaired fear extinction in adolescence.

    PubMed

    Baker, Kathryn D; Den, Miriam L; Graham, Bronwyn M; Richardson, Rick

    2014-09-01

    There have been significant advances made towards understanding the processes mediating extinction of learned fear. However, despite being of clear theoretical and clinical significance, very few studies have examined fear extinction in adolescence, which is often described as a developmental window of vulnerability to psychological disorders. This paper reviews the relatively small body of research examining fear extinction in adolescence. A prominent finding of this work is that adolescents, both humans and rodents, exhibit a marked impairment in extinction relative to both younger (e.g., juvenile) and older (e.g., adult) groups. We then review some potential mechanisms that could produce the striking extinction deficit observed in adolescence. For example, one neurobiological candidate mechanism for impaired extinction in adolescence involves changes in the functional connectivity within the fear extinction circuit, particularly between prefrontal cortical regions and the amygdala. In addition, we review research on emotion regulation and attention processes that suggests that developmental changes in attention bias to threatening cues may be a cognitive mechanism that mediates age-related differences in extinction learning. We also examine how a differential reaction to chronic stress in adolescence impacts upon extinction retention during adolescence as well as in later life. Finally, we consider the findings of several studies illustrating promising approaches that overcome the typically-observed extinction impairments in adolescent rodents and that could be translated to human adolescents.

  3. Selection, optimization, and compensation: strategies to maintain, maximize, and generate resources in later life in the face of chronic illnesses.

    PubMed

    Rozario, Philip A; Kidahashi, Miwako; DeRienzis, Daniel R

    2011-02-01

    This qualitative study of 45 older adults examines how they allocate their resources in the face of chronic health conditions. Participants were recruited from 2 senior centers and interviewed about their repertoire of activities, any changes in those activities in later life, and meanings they ascribed to those changes. The Selection, Optimization, and Compensation model guided our analysis and interpretation of participants' responses. The findings demonstrate the complexity of participants' responses to age-related changes, particularly in how they adapted and negotiated both their perception and life goals when faced with changing social landscapes. We discuss some implications and nuances of our findings.

  4. Childhood school segregation and later life sense of control and physical performance in the African American Health cohort

    PubMed Central

    2012-01-01

    Background The association between childhood school desegregation and later life sense of control and physical performance among African Americans is not clear. We hypothesized that childhood school desegregation adversely affected the sense of control of in later life, and that this reduced sense of control accounts in part for reduced physical performance. Methods In-home follow-up assessments were completed in 2010 with 582 of the 58–74 year old men and women participating in the on-going African American Health cohort. We used these data to examine the relationship between (a) retrospective self-reports of attending segregated schools during one’s 1st-to-12th grade education and one’s current sense of control, as well as (b) the association between current sense of control and physical performance. Multiple linear regression analysis with propensity score re-weighting was used. Results Attending segregated schools for at least half of one’s 1st-to-12th grade education was significantly associated with higher scores on the sense of control. Adjusting for all covariates and potential confounders, those receiving half or more of their 1st-to-12th grade education in segregated schools had sense of control scores that were .886 points higher (p ≤ .01; standardized effect size = .22). Sense of control scores were independently (all p < .01) associated with better systolic blood pressure, grip strength, peak expiratory flow, chair stands, balance tests, and the Short Portable Physical Battery even after adjusting for all covariates and potential confounders. Moreover, sense of control scores either partially or fully mediated the statistically significant beneficial associations between childhood school segregation and physical performance. Conclusions Childhood school desegregation was adversely associated with the sense of control of African Americans in later life, and this reduced sense of control appears, in part, to account for their

  5. Subjective Well-Being In Later Life: 20 years after the Butterworths monograph series on individual and population aging.

    PubMed

    Stones, Michael; Kozma, Albert; McNeil, Kevin; Worobetz, Sarah

    2011-09-01

    This article discusses developments in theory and research on happiness two decades after publication of Psychological Well-Being in Later Life (Butterworths, 1991) by Albert Kozma, Michael Stones, and Kevin McNeil. Major empirical advances include new knowledge about contributions to happiness resulting from genetically related effects and personality. Personality traits have stronger relationships with happiness than was apparent 20 years ago and contribute to covariance between happiness and some of its predictors. Evolving emphases in research include the ways in which genetically related effects influence how people shape, and react to, their environment.

  6. Perinatal BPA exposure induces hyperglycemia, oxidative stress and decreased adiponectin production in later life of male rat offspring.

    PubMed

    Song, Shunzhe; Zhang, Ling; Zhang, Hongyuan; Wei, Wei; Jia, Lihong

    2014-04-01

    The main object of the present study was to explore the effect of perinatal bisphenol A (BPA) exposure on glucose metabolism in early and later life of male rat offspring, and to establish the potential mechanism of BPA-induced dysglycemia. Pregnant rats were treated with either vehicle or BPA by drinking water at concentrations of 1 and 10 µg/mL BPA from gestation day 6 through the end of lactation. We measured the levels of fasting serum glucose, insulin, adiponectin and parameters of oxidative stress on postnatal day (PND) 50 and PND100 in male offspring, and adiponectin mRNA and protein expression in adipose tissue were also examined. Our results showed that perinatal exposure to 1 or 10 µg/mL BPA induced hyperglycemia with insulin resistance on PND100, but only 10 µg/mL BPA exposure had similar effects as early as PND50. In addition, increased oxidative stress and decreased adiponectin production were also observed in BPA exposed male offspring. Our findings indicated that perinatal exposure to BPA resulted in abnormal glucose metabolism in later life of male offspring, with an earlier and more exacerbated effect at higher doses. Down-regulated expression of adiponectin gene and increased oxidative stress induced by BPA may be associated with insulin resistance.

  7. Taking up physical activity in later life and healthy ageing: the English longitudinal study of ageing

    PubMed Central

    Hamer, Mark; Lavoie, Kim L; Bacon, Simon L

    2014-01-01

    Background Physical activity is associated with improved overall health in those people who survive to older ages, otherwise conceptualised as healthy ageing. Previous studies have examined the effects of mid-life physical activity on healthy ageing, but not the effects of taking up activity later in life. We examined the association between physical activity and healthy ageing over 8 years of follow-up. Methods Participants were 3454 initially disease-free men and women (aged 63.7±8.9 years at baseline) from the English Longitudinal Study of Ageing, a prospective study of community dwelling older adults. Self-reported physical activity was assessed at baseline (2002–2003) and through follow-up. Healthy ageing, assessed at 8 years of follow-up (2010-2011), was defined as those participants who survived without developing major chronic disease, depressive symptoms, physical or cognitive impairment. Results At follow-up, 19.3% of the sample was defined as healthy ageing. In comparison with inactive participants, moderate (OR, 2.67, 95% CI 1.95 to 3.64), or vigorous activity (3.53, 2.54 to 4.89) at least once a week was associated with healthy ageing, after adjustment for age, sex, smoking, alcohol, marital status and wealth. Becoming active (multivariate adjusted, 3.37, 1.67 to 6.78) or remaining active (7.68, 4.18 to 14.09) was associated with healthy ageing in comparison with remaining inactive over follow-up. Conclusions Sustained physical activity in older age is associated with improved overall health. Significant health benefits were even seen among participants who became physically active relatively late in life. PMID:24276781

  8. Disconnection Mechanism and Regional Cortical Atrophy Contribute to Impaired Processing of Facial Expressions and Theory of Mind in Multiple Sclerosis: A Structural MRI Study

    PubMed Central

    Mike, Andrea; Strammer, Erzsebet; Aradi, Mihaly; Orsi, Gergely; Perlaki, Gabor; Hajnal, Andras; Sandor, Janos; Banati, Miklos; Illes, Eniko; Zaitsev, Alexander; Herold, Robert; Guttmann, Charles R. G.; Illes, Zsolt

    2013-01-01

    Successful socialization requires the ability of understanding of others’ mental states. This ability called as mentalization (Theory of Mind) may become deficient and contribute to everyday life difficulties in multiple sclerosis. We aimed to explore the impact of brain pathology on mentalization performance in multiple sclerosis. Mentalization performance of 49 patients with multiple sclerosis was compared to 24 age- and gender matched healthy controls. T1- and T2-weighted three-dimensional brain MRI images were acquired at 3Tesla from patients with multiple sclerosis and 18 gender- and age matched healthy controls. We assessed overall brain cortical thickness in patients with multiple sclerosis and the scanned healthy controls, and measured the total and regional T1 and T2 white matter lesion volumes in patients with multiple sclerosis. Performances in tests of recognition of mental states and emotions from facial expressions and eye gazes correlated with both total T1-lesion load and regional T1-lesion load of association fiber tracts interconnecting cortical regions related to visual and emotion processing (genu and splenium of corpus callosum, right inferior longitudinal fasciculus, right inferior fronto-occipital fasciculus, uncinate fasciculus). Both of these tests showed correlations with specific cortical areas involved in emotion recognition from facial expressions (right and left fusiform face area, frontal eye filed), processing of emotions (right entorhinal cortex) and socially relevant information (left temporal pole). Thus, both disconnection mechanism due to white matter lesions and cortical thinning of specific brain areas may result in cognitive deficit in multiple sclerosis affecting emotion and mental state processing from facial expressions and contributing to everyday and social life difficulties of these patients. PMID:24349280

  9. Disconnection mechanism and regional cortical atrophy contribute to impaired processing of facial expressions and theory of mind in multiple sclerosis: a structural MRI study.

    PubMed

    Mike, Andrea; Strammer, Erzsebet; Aradi, Mihaly; Orsi, Gergely; Perlaki, Gabor; Hajnal, Andras; Sandor, Janos; Banati, Miklos; Illes, Eniko; Zaitsev, Alexander; Herold, Robert; Guttmann, Charles R G; Illes, Zsolt

    2013-01-01

    Successful socialization requires the ability of understanding of others' mental states. This ability called as mentalization (Theory of Mind) may become deficient and contribute to everyday life difficulties in multiple sclerosis. We aimed to explore the impact of brain pathology on mentalization performance in multiple sclerosis. Mentalization performance of 49 patients with multiple sclerosis was compared to 24 age- and gender matched healthy controls. T1- and T2-weighted three-dimensional brain MRI images were acquired at 3Tesla from patients with multiple sclerosis and 18 gender- and age matched healthy controls. We assessed overall brain cortical thickness in patients with multiple sclerosis and the scanned healthy controls, and measured the total and regional T1 and T2 white matter lesion volumes in patients with multiple sclerosis. Performances in tests of recognition of mental states and emotions from facial expressions and eye gazes correlated with both total T1-lesion load and regional T1-lesion load of association fiber tracts interconnecting cortical regions related to visual and emotion processing (genu and splenium of corpus callosum, right inferior longitudinal fasciculus, right inferior fronto-occipital fasciculus, uncinate fasciculus). Both of these tests showed correlations with specific cortical areas involved in emotion recognition from facial expressions (right and left fusiform face area, frontal eye filed), processing of emotions (right entorhinal cortex) and socially relevant information (left temporal pole). Thus, both disconnection mechanism due to white matter lesions and cortical thinning of specific brain areas may result in cognitive deficit in multiple sclerosis affecting emotion and mental state processing from facial expressions and contributing to everyday and social life difficulties of these patients.

  10. State policy decisions in the 1990s with implications for the financial well-being of later-life families.

    PubMed

    Hill, Gretchen J

    2006-01-01

    This study explores trends and patterns in states' policy decisions affecting the economic well-being of later-life individuals and families in the United States in recent decades, focusing on the 1990s. Rules were selected from the areas of inheritance, estate taxes, homestead exemptions, Medicaid eligibility, estate recovery, and filial responsibility. Results indicate an increasing use of a broad definition of family, one implying that spouses, the nuclear family, extended kin, step-relations, and sometimes in-laws constitute an ongoing collective whose members share economic resources and risks over their lives and beyond. Despite this global trend, states varied in their rules addressing intrafamilial financial obligations and families' accountability to states. While some seemed interested in facilitating the conservation of familial resources, others seemed willing to minimize public assistance while coercing kin into accepting financial responsibility for one another. Research was suggested to answer questions raised by this study.

  11. The role of family social background and inheritance in later life volunteering: evidence from SHARE-Israel.

    PubMed

    Youssim, Iaroslav; Hank, Karsten; Litwin, Howard

    2015-01-01

    Building on a tripartite model of capitals necessary to perform productive activities and on work suggesting that cumulative (dis-)advantage processes are important mechanisms for life course inequalities, our study set out to investigate the potential role of family social background and inheritance in later life volunteering. We hypothesized that older individuals who inherited work-relevant economic and cultural capitals from their family of origin are more likely to be engaged in voluntary activities than their counterparts with a less advantageous family social background. Our main findings from the analysis of a representative sample of community-dwelling Israelis aged 50 and over provide strong support for this hypothesis: the likelihood to volunteer is significantly higher among those who received substantial financial transfers from their family of origin ("inherited economic capital") and among those having a "white collar" parental background ("inherited cultural capital"). We conclude with perspectives for future research.

  12. [Everyday competencies and learning processes in old age. Results and perspectives of the PIAAC extension study "Competencies in later life"].

    PubMed

    Friebe, J; Knauber, C; Weiß, C; Setzer, B

    2014-11-01

    This article deals with the study "Competencies in later life" (CiLL), a parallel study to the German program for the international assessment of adult competencies (PIAAC) survey which assesses the level and distribution of skills of the adult population in a representative study. Assuming the growing importance of learning and education in a society challenged by demographic changes, the first section of the paper outlines the qualitative research of learning activities of focus groups in the daily life of elderly people. The second section of the paper presents the survey design and exemplary findings of the quantitative CiLL study. Initial results show that basic skills of the elderly are highly influenced by personal and sociodemographic variables, particularly by educational background. The data available indicate that the participation of the elderly in adult education and the options available for competence development have to be increased.

  13. Impaired Memory and Evidence of Histopathology in CA1 Pyramidal Neurons through Injection of Aβ1-42 Peptides into the Frontal Cortices of Rat

    PubMed Central

    Eslamizade, Mohammad Javad; Madjd, Zahra; Rasoolijazi, Homa; Saffarzadeh, Fatemeh; Pirhajati, Vahid; Aligholi, Hadi; Janahmadi, Mahyar; Mehdizadeh, Mehdi

    2016-01-01

    Introduction: Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders, which has much benefited from animal models to find the basics of its pathophysiology. In our previous work (Haghani, Shabani, Javan, Motamedi, & Janahmadi, 2012), a non-transgenic rat model of AD was used in electrophysiological studies. However, we did not investigate the histological aspects in the mentioned study. Methods: An AD model was developed through bilateral injection of amyloid-β peptides (Aβ) into the frontal cortices. Behavioral and histological methods were used to assess alterations in the memory and (ultra)structures. Furthermore, melatonin has been administered to assess its efficacy on this AD model. Results: Passive avoidance showed a progressive decline in the memory following Aβ injection. Furthermore, Nissl staining showed that Aβ neurotoxicity caused shrinkage of the CA1 pyramidal neurons. Neurodegeneration was clearly evident from Fluoro-jade labeled neurons in Aβ treated rats. Moreover, higher NF-κB immunoreactive CA1 pyramidal neurons were remarkably observed in Aβ treated rats. Ultrastructural analysis using electron microscopy also showed the evidence of subcellular abnormalities. Melatonin treatment in this model of AD prevented Aβ-induced increased NF-κB from immunoreaction and neurodegeneration. Discussion: This study suggests that injection of Aβ into the frontal cortices results in the memory decline and histochemical disturbances in CA1 pyramidal neurons. Furthermore, melatonin can prevent several histological changes induced by Aβ. PMID:27303597

  14. Cortical auditory disorders: clinical and psychoacoustic features.

    PubMed Central

    Mendez, M F; Geehan, G R

    1988-01-01

    The symptoms of two patients with bilateral cortical auditory lesions evolved from cortical deafness to other auditory syndromes: generalised auditory agnosia, amusia and/or pure word deafness, and a residual impairment of temporal sequencing. On investigation, both had dysacusis, absent middle latency evoked responses, acoustic errors in sound recognition and matching, inconsistent auditory behaviours, and similarly disturbed psychoacoustic discrimination tasks. These findings indicate that the different clinical syndromes caused by cortical auditory lesions form a spectrum of related auditory processing disorders. Differences between syndromes may depend on the degree of involvement of a primary cortical processing system, the more diffuse accessory system, and possibly the efferent auditory system. Images PMID:2450968

  15. Overexpressed neuroglobin raises threshold for nitric oxide-induced impairment of mitochondrial respiratory activities and stress signaling in primary cortical neurons.

    PubMed

    Singh, Shilpee; Zhuo, Ming; Gorgun, Falih M; Englander, Ella W

    2013-08-01

    Surges of nitric oxide compromise mitochondrial respiration primarily by competitive inhibition of oxygen binding to cytochrome c oxidase (complex IV) and are particularly injurious in neurons, which rely on oxidative phosphorylation for all their energy needs. Here, we show that transgenic overexpression of the neuronal globin protein, neuroglobin, helps diminish protein nitration, preserve mitochondrial function and sustain ATP content of primary cortical neurons challenged by extended nitric oxide exposure. Specifically, in transgenic neurons, elevated neuroglobin curtailed nitric oxide-induced alterations in mitochondrial oxygen consumption rates, including baseline oxygen consumption, consumption coupled with ATP synthesis, proton leak and spare respiratory capacity. Concomitantly, activation of genes involved in sensing and responding to oxidative/nitrosative stress, including the early-immediate c-Fos gene and the phase II antioxidant enzyme, heme oxygenase-1, was diminished in neuroglobin-overexpressing compared to wild-type neurons. Taken together, these differences reflect a lesser insult produced by similar concentrations of nitric oxide in neuroglobin-overexpressing compared to wild-type neurons, suggesting that abundant neuroglobin buffers nitric oxide and raises the threshold of nitric oxide-mediated injury in neurons.

  16. Religiosity is negatively associated with later-life intelligence, but not with age-related cognitive decline.

    PubMed

    Ritchie, Stuart J; Gow, Alan J; Deary, Ian J

    2014-09-01

    A well-replicated finding in the psychological literature is the negative correlation between religiosity and intelligence. However, several studies also conclude that one form of religiosity, church attendance, is protective against later-life cognitive decline. No effects of religious belief per se on cognitive decline have been found, potentially due to the restricted measures of belief used in previous studies. Here, we examined the associations between religiosity, intelligence, and cognitive change in a cohort of individuals (initial n = 550) with high-quality measures of religious belief taken at age 83 and multiple cognitive measures taken in childhood and at four waves between age 79 and 90. We found that religious belief, but not attendance, was negatively related to intelligence. The effect size was smaller than in previous studies of younger participants. Longitudinal analyses showed no effect of either religious belief or attendance on cognitive change either from childhood to old age, or across the ninth decade of life. We discuss differences between our cohort and those in previous studies - including in age and location - that may have led to our non-replication of the association between religious attendance and cognitive decline.

  17. Fetal Hematopoietic Stem Cells Are the Canaries in the Coal Mine That Portend Later Life Immune Deficiency.

    PubMed

    Laiosa, Michael D; Tate, Everett R

    2015-10-01

    Disorders of the blood system are a significant and growing global health concern and include a spectrum of diseases ranging from aplastic anemia and leukemias to immune suppression. This array of hematological disorders is attributed to the fact that the blood system undergoes a perpetual cycle of turn over with aged and exhausted red and white blood cells undergoing daily replacement. The foundational cells of this replenishment process are comprised of rare hematopoietic stem cells (HSCs) located in the bone marrow that possess the dual function of long-term self-renewal and multilineage differentiation. This constant turnover makes the hematopoietic system uniquely vulnerable to changes in the environment that impact multilineage differentiation, self-renewal, or both. Notably, environmental endocrine-disrupting exposures occurring during development, when HSCs are first emerging, can lead to alterations in HSC programming that impacts the blood and immune systems throughout life. In this review, we describe the process of fetal hematopoiesis and provide an overview of the intrauterine environmental and endocrine-disrupting compounds that disrupt this process. Finally, we describe research opportunities for fetal HSCs as potential sentinels of later-life blood and immune system disorders.

  18. Mother's nutritional miRNA legacy: Nutrition during pregnancy and its possible implications to develop cardiometabolic disease in later life.

    PubMed

    Casas-Agustench, Patricia; Iglesias-Gutiérrez, Eduardo; Dávalos, Alberto

    2015-10-01

    Maternal nutrition during pregnancy and lactation influences the offspring's health in the long-term. Indeed, human epidemiological studies and animal model experiments suggest that either an excess or a deficit in maternal nutrition influence offspring development and susceptibility to metabolic disorders. Different epigenetic mechanisms may explain in part the way by which dietary factors in early critical developmental steps might be able to affect the susceptibility to develop metabolic diseases in adulthood. microRNAs are versatile regulators of gene expression and play a major role during tissue homeostasis and disease. Dietary factors have also been shown to modify microRNA expression. However, the role of microRNAs in fetal programming remains largely unstudied. This review evaluates in vivo studies conducted to analyze the effect of maternal diet on the modulation of the microRNA expression in the offspring and their influence to develop metabolic and cardiovascular disease in later life. In overall, the available evidence suggests that nutritional status during pregnancy influence offspring susceptibility to the development of cardiometabolic risk factors, partly through microRNA action. Thus, therapeutic modulation of microRNAs can open up new strategies to combat - later in life - the effects of nutritional insult during critical points of development.

  19. Fetal Hematopoietic Stem Cells Are the Canaries in the Coal Mine That Portend Later Life Immune Deficiency

    PubMed Central

    Tate, Everett R.

    2015-01-01

    Disorders of the blood system are a significant and growing global health concern and include a spectrum of diseases ranging from aplastic anemia and leukemias to immune suppression. This array of hematological disorders is attributed to the fact that the blood system undergoes a perpetual cycle of turn over with aged and exhausted red and white blood cells undergoing daily replacement. The foundational cells of this replenishment process are comprised of rare hematopoietic stem cells (HSCs) located in the bone marrow that possess the dual function of long-term self-renewal and multilineage differentiation. This constant turnover makes the hematopoietic system uniquely vulnerable to changes in the environment that impact multilineage differentiation, self-renewal, or both. Notably, environmental endocrine-disrupting exposures occurring during development, when HSCs are first emerging, can lead to alterations in HSC programming that impacts the blood and immune systems throughout life. In this review, we describe the process of fetal hematopoiesis and provide an overview of the intrauterine environmental and endocrine-disrupting compounds that disrupt this process. Finally, we describe research opportunities for fetal HSCs as potential sentinels of later-life blood and immune system disorders. PMID:26241066

  20. Neonatal immune function and inflammatory illnesses in later life: lessons to be learnt from the developing world?

    PubMed

    Lisciandro, J G; van den Biggelaar, A H J

    2010-12-01

    With the emergence of allergic and autoimmune diseases in populations that have started to transit to a western lifestyle, there has been an increasing interest in the role of environmental factors modulating early immune function. Yet, most of the information concerning neonatal immune function has been derived from studies in westernized countries. We postulate that comparative studies of early immune development in children born under conditions that are typical for a westernized vs. that of a still more traditional setting will provide a crucial insight into the environmental-driven immunological mechanisms that are responsible for the world-wide rise in inflammatory disorders. In this review, we summarize the current understanding of early-life immune function in humans in general and the literature on some major lifestyle factors that may influence neonatal immune function and potentially the risk for disease in later life. An understanding of the mechanisms of 'prenatal/early-life programming' in populations living in traditional compared with modern societies is crucial to develop strategies to prevent a further rise in 'western diseases' such as allergic disorders. Indications exist that prenatal conditioning of the innate immune system by low-grade inflammatory responses is key to inducing more tightly regulated postnatal adaptive immune responses.

  1. Early-Life State-of-Residence Characteristics and Later Life Hypertension, Diabetes, and Ischemic Heart Disease

    PubMed Central

    Eisen, Ellen A.; Modrek, Sepideh; Mokyr Horner, Elizabeth; Goldstein, Benjamin; Costello, Sadie; Cantley, Linda F.; Slade, Martin D.; Cullen, Mark R.

    2015-01-01

    Objectives. We examined how state characteristics in early life are associated with individual chronic disease later in life. Methods. We assessed early-life state of residence using the first 3 digits of social security numbers from blue- and white-collar workers from a US manufacturing company. Longitudinal data were available from 1997 to 2012, with 305 936 person-years of observation. Disease was assessed using medical claims. We modeled associations using pooled logistic regression with inverse probability of censoring weights. Results. We found small but statistically significant associations between early-state-of-residence characteristics and later life hypertension, diabetes, and ischemic heart disease. The most consistent associations were with income inequality, percentage non-White, and education. These associations were similar after statistically controlling for individual socioeconomic and demographic characteristics and current state characteristics. Conclusions. Characteristics of the state in which an individual lives early in life are associated with prevalence of chronic disease later in life, with a strength of association equivalent to genetic associations found for these same health outcomes. PMID:26066927

  2. Fetal Hematopoietic Stem Cells Are the Canaries in the Coal Mine That Portend Later Life Immune Deficiency.

    PubMed

    Laiosa, Michael D; Tate, Everett R

    2015-10-01

    Disorders of the blood system are a significant and growing global health concern and include a spectrum of diseases ranging from aplastic anemia and leukemias to immune suppression. This array of hematological disorders is attributed to the fact that the blood system undergoes a perpetual cycle of turn over with aged and exhausted red and white blood cells undergoing daily replacement. The foundational cells of this replenishment process are comprised of rare hematopoietic stem cells (HSCs) located in the bone marrow that possess the dual function of long-term self-renewal and multilineage differentiation. This constant turnover makes the hematopoietic system uniquely vulnerable to changes in the environment that impact multilineage differentiation, self-renewal, or both. Notably, environmental endocrine-disrupting exposures occurring during development, when HSCs are first emerging, can lead to alterations in HSC programming that impacts the blood and immune systems throughout life. In this review, we describe the process of fetal hematopoiesis and provide an overview of the intrauterine environmental and endocrine-disrupting compounds that disrupt this process. Finally, we describe research opportunities for fetal HSCs as potential sentinels of later-life blood and immune system disorders. PMID:26241066

  3. In Sickness and in Health? Physical Illness as a Risk Factor for Marital Dissolution in Later Life

    PubMed Central

    Karraker, Amelia; Latham, Kenzie

    2016-01-01

    The health consequences of marital dissolution are well-known, but little work has examined the impact of health on the risk of marital dissolution. In this study we use a sample of 2,701 marriages from the Health and Retirement Study (HRS; 1992–2010) to examine the role of serious physical illness onset (i.e., cancer, heart problems, lung disease, and/or stroke) in subsequent marital dissolution due to either divorce or widowhood. We use a series of discrete-time event history models with competing risks to estimate the impact of husband’s and wife’s physical illness onset on risk of divorce and widowhood. We find that only wife’s illness onset is associated with elevated risk of divorce, while either husband’s or wife’s illness onset is associated with elevated risk of widowhood. These findings suggest the importance of health as a determinant of marital dissolution in later life via both biological and gendered social pathways. PMID:26315504

  4. Neonatal immune function and inflammatory illnesses in later life: lessons to be learnt from the developing world?

    PubMed

    Lisciandro, J G; van den Biggelaar, A H J

    2010-12-01

    With the emergence of allergic and autoimmune diseases in populations that have started to transit to a western lifestyle, there has been an increasing interest in the role of environmental factors modulating early immune function. Yet, most of the information concerning neonatal immune function has been derived from studies in westernized countries. We postulate that comparative studies of early immune development in children born under conditions that are typical for a westernized vs. that of a still more traditional setting will provide a crucial insight into the environmental-driven immunological mechanisms that are responsible for the world-wide rise in inflammatory disorders. In this review, we summarize the current understanding of early-life immune function in humans in general and the literature on some major lifestyle factors that may influence neonatal immune function and potentially the risk for disease in later life. An understanding of the mechanisms of 'prenatal/early-life programming' in populations living in traditional compared with modern societies is crucial to develop strategies to prevent a further rise in 'western diseases' such as allergic disorders. Indications exist that prenatal conditioning of the innate immune system by low-grade inflammatory responses is key to inducing more tightly regulated postnatal adaptive immune responses. PMID:20964742

  5. Dose-dependent impairment of inhibitory avoidance retention in rats by immediate post-training infusion of a mitogen-activated protein kinase kinase inhibitor into cortical structures.

    PubMed

    Walz, R; Roesler, R; Quevedo, J; Rockenbach, I C; Amaral, O B; Vianna, M R; Lenz, G; Medina, J H; Izquierdo, I

    1999-11-15

    Mitogen-activated protein kinase (MAPK) is a serine/threonine protein kinase abundantly expressed in postmitotic neurons of the developed nervous system. MAPK is activated in and required for both the induction of long-term potentiation (LTP) in hippocampal slices and the acquisition of fear conditioning training in rats. The present work was performed in order to test the effect of the specific inhibitor of MAPK kinase (MAPKK), PD 098059, on retention of a step-down inhibitory avoidance (IA). Adult male Wistar rats were bilaterally injected (0.5 microl/side) with PD 098059 (at 0.5, 5, or 50 microM) or vehicle into the entorhinal cortex or into the parietal cortex immediately after IA training using a 0.4 mA footshock. Retention testing was carried out 24 h after training. PD 098059 impaired retention when injected into the entorhinal cortex at the dose of 50 microM, but not at the doses of 5 or 0.5 microM. When infused into the parietal cortex, PD 098059 was amnestic at the doses of 5 and 50 microM. The drug had no effect when infused at the highest dose in either structure 6 h after training. Our results suggest that the MAPKK inhibitor impairs IA retention memory in a dose-dependent manner when injected immediately after training into entorhinal cortex or parietal cortex. The effective dose is variable according to the neocortical structure studied.

  6. Computational modeling of stuttering caused by impairments in a basal ganglia thalamo-cortical circuit involved in syllable selection and initiation.

    PubMed

    Civier, Oren; Bullock, Daniel; Max, Ludo; Guenther, Frank H

    2013-09-01

    Atypical white-matter integrity and elevated dopamine levels have been reported for individuals who stutter. We investigated how such abnormalities may lead to speech dysfluencies due to their effects on a syllable-sequencing circuit that consists of basal ganglia (BG), thalamus, and left ventral premotor cortex (vPMC). "Neurally impaired" versions of the neurocomputational speech production model GODIVA were utilized to test two hypotheses: (1) that white-matter abnormalities disturb the circuit via corticostriatal projections carrying copies of executed motor commands and (2) that dopaminergic abnormalities disturb the circuit via the striatum. Simulation results support both hypotheses: in both scenarios, the neural abnormalities delay readout of the next syllable's motor program, leading to dysfluency. The results also account for brain imaging findings during dysfluent speech. It is concluded that each of the two abnormality types can cause stuttering moments, probably by affecting the same BG-thalamus-vPMC circuit.

  7. Time-dependent impairment of inhibitory avoidance retention in rats by posttraining infusion of a mitogen-activated protein kinase kinase inhibitor into cortical and limbic structures.

    PubMed

    Walz, R; Roesler, R; Quevedo, J; Sant'Anna, M K; Madruga, M; Rodrigues, C; Gottfried, C; Medina, J H; Izquierdo, I

    2000-01-01

    Mitogen-activated protein kinase (MAPK) is abundantly expressed in postmitotic neurons of the developed nervous system. MAPK is activated and required for induction of long-term potentiation (LTP) in the CA1 area of the hippocampus, which is blocked by the specific inhibitor of the MAPK kinase, PD 098059. Recently it was demonstrated that MAPK is activated in the hippocampus after training and is necessary for contextual fear conditioning learning. The present work tests the role of the MAPK cascade in step-down inhibitory avoidance (IA) retention. PD 098059 (50 microM) was bilaterally injected (0.5 microl/side) into the CA1 region of the dorsal hippocampus or entorhinal cortex at 0, 90, 180, or 360 min, or into the amygdala or parietal cortex at 0, 180, or 360 min after IA training in rats using a 0.4-mA foot shock. Retention testing was carried out 24 h after training. PD 098059 impaired retention when injected into the dorsal hippocampus at 180 min, but not 0, 90, and 360 min after training. When infused into the entorhinal cortex, PD 098059 was amnestic at 0 and 180 min, but not at 90 and 360 min after training. The MAPKK inhibitor also impairs IA retention when infused into the parietal cortex immediately after training, but not at 180 or 360 min. Infusions performed into amygdala were amnestic at 180 min, but not at 0 and 360 min after training. Our results suggest a time-dependent involvement of the MAPK cascade in the posttraining memory processing of IA; the time dependency is different in the hippocampus, amygdala, entorhinal cortex, or parietal cortex of rats.

  8. In utero exposure to benzo(a)pyrene predisposes offspring to cardiovascular dysfunction in later-life.

    PubMed

    Jules, G E; Pratap, S; Ramesh, A; Hood, D B

    2012-05-16

    In utero exposure of the fetus to benzo(a)pyrene [B(a)P], a polycyclic aromatic hydrocarbon, is thought to dysregulate cardiovascular development. To investigate the effects of in utero B(a)P exposure on cardiovascular development, timed-pregnant Long Evans Hooded (LEH) rats were exposed to diluent or B(a)P (150, 300, 600 and 1200 μg/kg/BW) by oral gavage on embryonic (E) days E14 (the metamorphosing embryo stage) through E17 (the 1st fetal stage). There were no significant effects of in utero exposure to B(a)P on the number of pups born per litter or in pre-weaning growth curves. Pre-weaning profiles for B(a)P metabolite generation from cardiovascular tissue were shown to be dose-dependent and elimination of these metabolites was shown to be time-dependent in exposed offspring. Systolic blood pressure on postnatal day P53 in the middle and high exposure groups of offspring were significantly elevated as compared to controls. Microarray and quantitative real-time PCR results were directly relevant to a biological process pathway in animal models for "regulation of blood pressure". Microarray and quantitative real-time PCR analysis revealed upregulation of mRNA expression for angiotensin (AngII), angiotensinogen (AGT) and endothelial nitric oxide synthase (eNOS) in exposed offspring. Biological network analysis and gene set enrichment analysis subsequently identified potential signaling mechanisms and molecular pathways that might explain the elevated systolic blood pressures observed in B(a)P-exposed offspring. Our findings suggest that in utero exposure to B(a)P predispose offspring to functional deficits in cardiovascular development that may contribute to cardiovascular dysfunction in later life.

  9. Obesity and excess weight in early adulthood and high risks of arsenic-related cancer in later life

    PubMed Central

    Steinmaus, C; Castriota, F; Ferreccio, C; Smith, AH; Yuan, Y; Liaw, J; Acevedo, J; Perez, L; Meza, R; Calcagno, S; Uauy, R; Smith, MT

    2015-01-01

    Background Elevated body mass index (BMI) is a risk factor for cardiovascular disease, diabetes, cancer, and other diseases. Inflammation or oxidative stress induced by high BMI may explain some of these effects. Millions of people drink arsenic-contaminated water worldwide, and ingested arsenic has also been associated with inflammation, oxidative stress, and cancer. Objectives To assess the unique situation of people living in northern Chile exposed to high arsenic concentrations in drinking water and investigate interactions between arsenic and BMI, and associations with lung and bladder cancer risks. Methods Information on self-reported body mass index (BMI) at various life stages, smoking, diet, and lifetime arsenic exposure was collected from 532 cancer cases and 634 population-based controls. Results In subjects with BMIs <90th percentile in early adulthood (27.7 and 28.6 kg/m2 in males and females, respectively), odds ratios (OR) for lung and bladder cancer combined for arsenic concentrations of <100, 100–800 and >800 μg/L were 1.00, 1.64 (95% CI, 1.19–2.27), and 3.12 (2.30–4.22). In subjects with BMIs ≥90th percentile in early adulthood, the corresponding ORs were higher: 1.00, 1.84 (0.75–4.52), and 9.37 (2.88–30.53), respectively (synergy index=4.05, 95% CI, 1.27–12.88). Arsenic-related cancer ORs >20 were seen in those with elevated BMIs in both early adulthood and in later life. Adjustments for smoking, diet, and other factors had little impact. Conclusion These findings provide novel preliminary evidence supporting the notion that environmentally-related cancer risks may be markedly increased in people with elevated BMIs, especially in those with an elevated BMI in early-life. PMID:26301739

  10. In utero exposure to benzo(a)pyrene predisposes offspring to cardiovascular dysfunction in later-life

    PubMed Central

    G.E., Jules; Pratap, S.; Ramesh, A.; Hood, D.B.

    2013-01-01

    In utero exposure of the fetus to benzo(a)pyrene [B(a)P], a polycyclic aromatic hydrocarbon, is thought to dysregulate cardiovascular development. To investigate the effects of in utero B(a)P exposure on cardiovascular development, timed-pregnant Long Evans Hooded (LEH) rats were exposed to diluent or B(a)P (150, 300, 600 and 1200 μg/kg/BW) by oral gavage on embryonic (E) days E14 (the metamorphosing embryo stage) through E17 (the 1st fetal stage). There were no significant effects of in utero exposure to B(a)P on the number of pups born per litter or in pre-weaning growth curves. Pre-weaning profiles for B(a)P metabolite generation from cardiovascular tissue were shown to be dose-dependent and elimination of these metabolites was shown to be time-dependent in exposed offspring. Systolic blood pressure on postnatal day P53 in the middle and high exposure groups of offspring were significantly elevated as compared to controls. Microarray and quantitative real-time PCR results were directly relevant to a biological process pathway in animal models for “regulation of blood pressure”. Microarray and quantitative real-time PCR analysis revealed upregulation of mRNA expression for angiotensin (AngII), angiotensinogen (AGT) and endothelial nitric oxide synthase (eNOS) in exposed offspring. Biological network analysis and gene set enrichment analysis subsequently identified potential signaling mechanisms and molecular pathways that might explain the elevated systolic blood pressures observed in B(a)P-exposed offspring. Our findings suggest that in utero exposure to B(a)P predispose offspring to functional deficits in cardiovascular development that may contribute to cardiovascular dysfunction in later life. PMID:22374506

  11. Cortical and subcortical lesions impair skilled walking in the ladder rung walking test: a new task to evaluate fore- and hindlimb stepping, placing, and co-ordination.

    PubMed

    Metz, Gerlinde A; Whishaw, Ian Q

    2002-04-15

    The ladder rung walking test is a new task to assess skilled walking and measure both forelimb and hindlimb placing, stepping, and inter-limb co-ordination. Rats spontaneously walk from a starting location to a goal along a horizontal ladder. The spacing between the rungs of the ladder is variable and can be changed to prevent the animal from learning either the absolute or relative location of the rungs. The testing procedure requires minimal training and allows detailed quantitative and qualitative analysis using video recording. The utility of the test is described with postoperative data obtained from animals with unilateral neocortical strokes produced by pial stripping over the motor cortex, neonatal and adult unilateral corticospinal tract lesions produced by tract section at the pyramids, and unilateral dopamine depletions produced by injection of 6-hydroxydopamine into the nigrostriatal bundle. In addition, a group of aged rats was examined. Deficits in limb placing, stepping and co-ordination displayed by the animals demonstrate that this test can discriminate between lesions of the motor system or age-associated impairments. The test is useful for assessing loss and recovery of function due to brain or spinal cord injury, the effectiveness of treatment therapies, as well as compensatory processes through which animals adapt to nervous system injury. PMID:11992668

  12. Cortical and Subcortical Grey and White Matter Atrophy in Myotonic Dystrophies Type 1 and 2 Is Associated with Cognitive Impairment, Depression and Daytime Sleepiness

    PubMed Central

    Prehn, Christian; Krogias, Christos; Schneider, Ruth; Klein, Jan; Gold, Ralf; Lukas, Carsten

    2015-01-01

    to cognitive impairment, depression and daytime sleepiness, partly indicating involvement of complex neuronal networks. PMID:26114298

  13. Cognitive impairment and diabetes.

    PubMed

    Dash, Sandip K

    2013-05-01

    The aim of this manuscript is to provide a brief review of the link between diabetes mellitus with cognitive impairment, the possible pathophysiology linking the two, and some possible therapeutic interventions for the treatment of this condition. The prevalence of diabetes increases with age, so also dementia increases in later life. As the population ages, type 2 diabetes and AD are increasing. Both diseases are chronic and are the leading causes of morbidity and mortality. Recent studies showed that older people with type 2 diabetes have a higher risk of cognitive decline. The precise mechanism linking the two remains to be found out. Several hypothetical mechanisms have been postulated. Type 2 diabetes is a risk factor for AD and vascular dementia. The association between diabetes and AD is particularly strong among carriers of the APOE ε4. Several studies have linked dementia to diabetes. Impaired fasting glucose and impaired glucose tolerance and insulin resistance have also been associated with poor cognitive performance and at risk of developing cognitive impairment. Studies have suggested that metabolic syndrome may be linked to vascular dementia, while contrasting findings showed the role of metabolic syndrome to AD. In this review, how diabetes and cognitive impairment and Alzheimer's disease are mutually linked, possible mechanism linking the two and some possible therapeutic interventions with some patents that seem to be good therapeutic targets in future are discussed.

  14. Cortical thickness abnormalities in late adolescence with online gaming addiction.

    PubMed

    Yuan, Kai; Cheng, Ping; Dong, Tao; Bi, Yanzhi; Xing, Lihong; Yu, Dahua; Zhao, Limei; Dong, Minghao; von Deneen, Karen M; Liu, Yijun; Qin, Wei; Tian, Jie

    2013-01-01

    Online gaming addiction, as the most popular subtype of Internet addiction, had gained more and more attention from the whole world. However, the structural differences in cortical thickness of the brain between adolescents with online gaming addiction and healthy controls are not well unknown; neither was its association with the impaired cognitive control ability. High-resolution magnetic resonance imaging scans from late adolescence with online gaming addiction (n = 18) and age-, education- and gender-matched controls (n = 18) were acquired. The cortical thickness measurement method was employed to investigate alterations of cortical thickness in individuals with online gaming addiction. The color-word Stroop task was employed to investigate the functional implications of the cortical thickness abnormalities. Imaging data revealed increased cortical thickness in the left precentral cortex, precuneus, middle frontal cortex, inferior temporal and middle temporal cortices in late adolescence with online gaming addiction; meanwhile, the cortical thicknesses of the left lateral orbitofrontal cortex (OFC), insula, lingual gyrus, the right postcentral gyrus, entorhinal cortex and inferior parietal cortex were decreased. Correlation analysis demonstrated that the cortical thicknesses of the left precentral cortex, precuneus and lingual gyrus correlated with duration of online gaming addiction and the cortical thickness of the OFC correlated with the impaired task performance during the color-word Stroop task in adolescents with online gaming addiction. The findings in the current study suggested that the cortical thickness abnormalities of these regions may be implicated in the underlying pathophysiology of online gaming addiction.

  15. Spatiotemporal SERT expression in cortical map development.

    PubMed

    Chen, Xiaoning; Petit, Emilie I; Dobrenis, Kostantin; Sze, Ji Ying

    2016-09-01

    The cerebral cortex is organized into morphologically distinct areas that provide biological frameworks underlying perception, cognition, and behavior. Profiling mouse and human cortical transcriptomes have revealed temporal-specific differential gene expression modules in distinct neocortical areas during cortical map establishment. However, the biological roles of spatiotemporal gene expression in cortical patterning and how cortical topographic gene expression is regulated are largely unknown. Here, we characterize temporal- and spatial-defined expression of serotonin (5-HT) transporter (SERT) in glutamatergic neurons during sensory map development in mice. SERT is transiently expressed in glutamatergic thalamic neurons projecting to sensory cortices and in pyramidal neurons in the prefrontal cortex (PFC) and hippocampus (HPC) during the period that lays down the basic functional neural circuits. We previously identified that knockout of SERT in the thalamic neurons blocks 5-HT uptake by their thalamocortical axons, resulting in excessive 5-HT signaling that impairs sensory map architecture. In contrast, here we show that selective SERT knockout in the PFC and HPC neurons does not perturb sensory map patterning. These data suggest that transient SERT expression in specific glutamatergic neurons provides area-specific instructions for cortical map patterning. Hence, genetic and pharmacological manipulations of this SERT function could illuminate the fundamental genetic programming of cortex-specific maps and biological roles of temporal-specific cortical topographic gene expression in normal development and mental disorders. PMID:27282696

  16. Proposing interactions between maternal phospholipids and the one carbon cycle: A novel mechanism influencing the risk for cardiovascular diseases in the offspring in later life.

    PubMed

    Khot, Vinita; Chavan-Gautam, Preeti; Joshi, Sadhana

    2015-05-15

    Studies have adequately demonstrated the importance of maternal nutrition, particularly, micronutrients (folic acid, vitamin B12) and long chain polyunsaturated fatty acids (LCPUFAs) in determining pregnancy outcome. Reports indicate that children born preterm or to mothers with preeclampsia are at increased risk of developing cardiovascular diseases (CVD) in later life although mechanisms are unclear. Our earlier studies have established that micronutrients (folic acid, vitamin B12) and LCPUFAs are interlinked in the one carbon cycle and influence methylation reactions. Here, we propose a novel hypothesis that altered phospholipid metabolism and dysregulation in the one carbon cycle will result in altered epigenetic programming of placental genes leading to an adverse pregnancy outcome with increased risk of adult diseases in the offspring. Folic acid and vitamin B12 are involved in S-adenosylmethionine (SAM) synthesis, the major methyl donor for most methyl acceptors. Inadequacy of LCPUFA containing phospholipids, one of the major methyl group acceptors in the one carbon metabolic pathway, may cause diversion of methyl groups toward deoxyribonucleic acid (DNA) eventually resulting in aberrant DNA methylation patterns. These modified DNA methylation patterns lead to alterations in the expression of vital genes e.g. angiogenic factor genes thereby contributing to the dysregulation of angiogenesis/vasculogenesis further affecting placental development. This consequently would adversely "program" the fetus for increased risk of CVD in later life. PMID:25283080

  17. Proposing interactions between maternal phospholipids and the one carbon cycle: A novel mechanism influencing the risk for cardiovascular diseases in the offspring in later life.

    PubMed

    Khot, Vinita; Chavan-Gautam, Preeti; Joshi, Sadhana

    2015-05-15

    Studies have adequately demonstrated the importance of maternal nutrition, particularly, micronutrients (folic acid, vitamin B12) and long chain polyunsaturated fatty acids (LCPUFAs) in determining pregnancy outcome. Reports indicate that children born preterm or to mothers with preeclampsia are at increased risk of developing cardiovascular diseases (CVD) in later life although mechanisms are unclear. Our earlier studies have established that micronutrients (folic acid, vitamin B12) and LCPUFAs are interlinked in the one carbon cycle and influence methylation reactions. Here, we propose a novel hypothesis that altered phospholipid metabolism and dysregulation in the one carbon cycle will result in altered epigenetic programming of placental genes leading to an adverse pregnancy outcome with increased risk of adult diseases in the offspring. Folic acid and vitamin B12 are involved in S-adenosylmethionine (SAM) synthesis, the major methyl donor for most methyl acceptors. Inadequacy of LCPUFA containing phospholipids, one of the major methyl group acceptors in the one carbon metabolic pathway, may cause diversion of methyl groups toward deoxyribonucleic acid (DNA) eventually resulting in aberrant DNA methylation patterns. These modified DNA methylation patterns lead to alterations in the expression of vital genes e.g. angiogenic factor genes thereby contributing to the dysregulation of angiogenesis/vasculogenesis further affecting placental development. This consequently would adversely "program" the fetus for increased risk of CVD in later life.

  18. Neonatal systemic exposure to lipopolysaccharide enhances susceptibility of nigrostriatal dopaminergic neurons to rotenone neurotoxicity in later life

    PubMed Central

    Cai, Zhengwei; Fan, Lir-Wan; Kaizaki, Asuka; Tien, Lu-Tai; Ma, Tangeng; Pang, Yi; Lin, Shuying; Lin, Rick C. S.; Simpson, Kimberly L.

    2013-01-01

    Brain inflammation via intracerebral injection with lipopolysaccharide (LPS) in early life has been shown to increase risks for the development of neurodegenerative disorders in adult rats. To determine if neonatal systemic LPS exposure has the same effects on enhancement of adult dopaminergic neuron susceptibility to rotenone neurotoxicity as centrally-injected LPS does, LPS (2 μg/g body weight) was administered intraperitoneally into post-natal day 5 (P5) rats and when grown to P70, rats were challenged with rotenone, a commonly used pesticide, through subcutaneous mini-pump infusion at a dose of 1.25 mg/kg per day for 14 days. Systemically administered LPS can penetrate into the neonatal rat brain and cause acute and chronic brain inflammation, as evidenced by persistent increases in IL-1β levels, cyclooxygenase-2 expression and microglial activation in the substantia nigra (SN) of P70 rats. Neonatal LPS exposure resulted in suppression of tyrosine hydroxylase (TH) expression, but not actual death of dopaminergic neurons in the SN, as indicated by the reduced number of TH+ cells and unchanged total number of neurons (NeuN+) in the SN. Neonatal LPS exposure also caused motor function deficits, which were spontaneously recoverable by P70. A small dose of rotenone at P70 induced loss of dopaminergic neurons, as indicated by reduced numbers of both TH+ and NeuN+ cells in the SN, and Parkinson’s disease (PD)-like motor impairment in P98 rats that had experienced neonatal LPS exposure, but not in those without the LPS exposure. These results indicate that although neonatal systemic LPS exposure may not necessarily lead to death of dopaminergic neurons in the SN, such an exposure could cause persistent functional alterations in the dopaminergic system and indirectly predispose the nigrostriatal system in the adult brain more vulnerable to be damaged by environmental toxins at an ordinarily non-toxic or sub-toxic dose to develop PD-like pathological features and

  19. Developmental exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin attenuates later-life Notch1-mediated T cell development and leukemogenesis

    SciTech Connect

    Ahrenhoerster, Lori S.; Leuthner, Tess C.; Tate, Everett R.; Lakatos, Peter A.; Laiosa, Michael D.

    2015-03-01

    Over half of T cell acute lymphoblastic leukemia (T-ALL) patients have activating mutations in the Notch gene. Moreover, the contaminant 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) is a known carcinogen that mediates its toxicity through the aryl hydrocarbon receptor (AHR), and crosstalk between activated AHR and Notch signaling pathways has previously been observed. Given the importance of Notch signaling in thymocyte development and T-ALL disease progression, we hypothesized that the activated AHR potentiates disease initiation and progression in an in vivo model of Notch1-induced thymoma. This hypothesis was tested utilizing adult and developmental exposure paradigms to TCDD in mice expressing a constitutively active Notch1 transgene (Notch{sup ICN-TG}). Following exposure of adult Notch{sup ICN-TG} mice to a single high dose of TCDD, we observed a significant increase in the efficiency of CD8 thymocyte generation. We next exposed pregnant mice to 3 μg/kg of TCDD throughout gestation and lactation to elucidate effects of developmental AHR activation on later-life T cell development and T-ALL-like thymoma susceptibility induced by Notch1. We found that the vehicle-exposed Notch{sup ICN-TG} offspring have a peripheral T cell pool heavily biased toward the CD4 lineage, while TCDD-exposed Notch{sup ICN-TG} offspring were biased toward the CD8 lineage. Furthermore, while the vehicle-exposed NotchICN-TG mice showed increased splenomegaly and B to T cell ratios indicative of disease, mice developmentally exposed to TCDD were largely protected from disease. These studies support a model where developmental AHR activation attenuates later-life Notch1-dependent impacts on thymocyte development and disease progression. - Highlights: • Adult mice exposed to 30 μg/kg TCDD have higher efficiency of CD8 thymocyte generation. • Mice carrying a constitutively active Notch transgene were exposed to 3 μg/kg TCDD throughout development. • Progression of Notch

  20. Felt Obligation to Help Others as a Protective Factor Against Losses in Psychological Well-being Following Functional Decline in Middle and Later Life

    PubMed Central

    2009-01-01

    This study examined felt obligation to help others in two domains (close others and society) as protective factors against losses in psychological well-being following functional decline. Lagged-dependent regression models were estimated using data from 849 respondents aged 35–74 years and without any functional limitations at baseline in the 1995–2005 National Survey of Midlife in the United States. Greater felt obligation to help close others protected against declining self-acceptance in the face of more severe functional decline, and greater felt obligation to help society protected against declining personal growth and self-acceptance. Greater felt obligation to help close others and society protected against increasing depressive symptoms at younger ages in adulthood. Findings suggest the importance for additional research on how aspects of altruism can promote psychological adaptation to declining functional health in middle and later life. PMID:19825942

  1. Revising the personality disorder diagnostic criteria for the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-V): consider the later life context.

    PubMed

    Balsis, Steve; Segal, Daniel L; Donahue, Cailin

    2009-10-01

    The categorical measurement approach implemented by the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) personality disorder (PD) diagnostic system is theoretically and pragmatically limited. As a result, many prominent psychologists now advocate for a shift away from this approach in favor of more conceptually sound dimensional measurement. This shift is expected to improve the psychometric properties of the personality disorder (PD) diagnostic system and make it more useful for clinicians and researchers. The current article suggests that despite the probable benefits of such a change, several limitations will remain if the new diagnostic system does not closely consider the context of later life. A failure to address the unique challenges associated with the assessment of personality in older adults likely will result in the continued limited validity, reliability, and utility of the Diagnostic and Statistical Manual of Mental Disorders (DSM) system for this growing population. This article discusses these limitations and their possible implications.

  2. THE ROLE OF PERCEIVED RELIGIOUS SIMILARITY IN THE QUALITY OF MOTHER-CHILD RELATIONS IN LATER-LIFE: DIFFERENCES WITHIN FAMILIES AND BETWEEN RACES

    PubMed Central

    Sechrist, Jori; Suitor, J. Jill; Vargas, Nicholas; Pillemer, Karl

    2010-01-01

    Despite evidence of the importance of value similarity in predicting parent-adult child relations, little attention has been given to the unique role of religious similarity. Using 1,407 dyads nested within 390 families, we examine whether religious similarity predicts the quality of mother-child relations in later life, and whether the strength of this association differs by race. Consistent with our hypotheses, religious similarity was found to be an important factor in predicting both closeness and conflict, particularly in Black families. These findings suggest that it may be important to give greater attention to religion when studying patterns of interaction and support in the later years, especially among Black families. PMID:21221411

  3. Intelligence and socioeconomic position in childhood in relation to frailty and cumulative allostatic load in later life: the Lothian Birth Cohort 1936

    PubMed Central

    Gale, Catharine R; Booth, Tom; Starr, John M; Deary, Ian J

    2016-01-01

    Background Information on childhood determinants of frailty or allostatic load in later life is sparse. We investigated whether lower intelligence and greater socioeconomic disadvantage in childhood increased the risk of frailty and higher allostatic load, and explored the mediating roles of adult socioeconomic position, educational attainment and health behaviours. Methods Participants were 876 members of the Lothian Birth Cohort 1936 whose intelligence was assessed at age 11. At age 70, frailty was assessed using the Fried criteria. Measurements were made of fibrinogen, triglyceride, total and high-density lipoprotein cholesterol, albumin, glycated haemoglobin, C reactive protein, body mass index and blood pressure, from which an allostatic load score was calculated. Results In sex-adjusted analyses, lower intelligence and lower social class in childhood were associated with an increased risk of frailty: relative risks (95% CIs) were 1.57 (1.21 to 2.03) for a SD decrease in intelligence and 1.48 (1.12 to 1.96) for a category decrease in social class. In the fully adjusted model, both associations ceased to be significant: relative risks were 1.13 (0.83 to 1.54) and 1.19 (0.86 to 1.61), respectively. Educational attainment had a significant mediating effect. Lower childhood intelligence in childhood, but not social class, was associated with higher allostatic load. The sex-adjusted coefficient for allostatic load for a SD decrease in intelligence was 0.10 (0.07 to 0.14). In the fully adjusted model, this association was attenuated but remained significant (0.05 (0.01 to 0.09)). Conclusions Further research will need to investigate the mechanisms whereby lower childhood intelligence is linked to higher allostatic load in later life. PMID:26700299

  4. Developmental Exposure To 2,3,7,8 Tetrachlorodibenzo-p-Dioxin Attenuates Later-Life Notch1-Mediated T Cell Development and Leukemogenesis

    PubMed Central

    Ahrenhoerster, Lori S.; Leuthner, Tess C.; Tate, Everett R.; Lakatos, Peter A.; Laiosa, Michael D.

    2015-01-01

    Over half of T-cell acute lymphoblastic leukemia (T-ALL) patients have activating mutations in the Notch gene. Moreover, the contaminant 2,3,7,8 Tetrachlorodibenzo-p-dioxin (TCDD) is a known carcinogen that mediates its toxicity through the aryl hydrocarbon receptor (AHR), and crosstalk between activated AHR and Notch signaling pathways has previously been observed. Given the importance of Notch signaling in thymocyte development and T-ALL disease progression, we hypothesized that the activated AHR potentiates disease initiation and progression in an in vivo model of Notch1-induced thymoma. This hypothesis was tested utilizing adult and developmental exposure paradigms to TCDD in mice expressing a constitutively active Notch1 transgene (NotchICN-TG). Following exposure of adult NotchICN-TG mice to a single high dose of TCDD, we observed a significant increase in the efficiency of CD8 thymocyte generation. We next exposed pregnant mice to 3μg/kg of TCDD throughout gestation and lactation to elucidate effects of developmental AHR activation on later-life T cell development and T-ALL-like thymoma susceptibility induced by Notch1. We found that the vehicle-exposed NotchICN-TG offspring have a peripheral T-cell pool heavily biased toward the CD4 lineage, while TCDD-exposed NotchICN-TG offspring were biased toward the CD8 lineage. Furthermore, while the vehicle-exposed NotchICN-TG mice showed increased splenomegaly and B to T cell ratios indicative of disease, mice developmentally exposed to TCDD were largely protected from disease. These studies support a model where developmental AHR activation attenuates later-life Notch1-dependent impacts on thymocyte development and disease progression. PMID:25585350

  5. Bilingual aphasia and subcortical-cortical lesions.

    PubMed

    Moretti, R; Bava, A; Torre, P; Antonello, R M; Zorzon, M; Zivadinov, R; Cazzato, G

    2001-06-01

    The use of the mother tongue relies on implicit memory procedures that are mainly controlled by subcortical structures. A second language depends on the integrity of the explicit memory system, largely subserved by cortical areas. Therefore, bilinguals can be considered as neurolinguistic models which contribute to the understanding of how the cortical and subcortical language systems communicate while maintaining independent functions. We describe a patient who developed an impairment of the mother tongue after an infarct of the caudate. During follow-up, a dramatic improvement of the mother tongue accompanied by worsening of the second language became evident after the extension of the ischemic lesion to the cortex.

  6. Basic visual function and cortical thickness patterns in posterior cortical atrophy.

    PubMed

    Lehmann, Manja; Barnes, Josephine; Ridgway, Gerard R; Wattam-Bell, John; Warrington, Elizabeth K; Fox, Nick C; Crutch, Sebastian J

    2011-09-01

    Posterior cortical atrophy (PCA) is characterized by a progressive decline in higher-visual object and space processing, but the extent to which these deficits are underpinned by basic visual impairments is unknown. This study aimed to assess basic and higher-order visual deficits in 21 PCA patients. Basic visual skills including form detection and discrimination, color discrimination, motion coherence, and point localization were measured, and associations and dissociations between specific basic visual functions and measures of higher-order object and space perception were identified. All participants showed impairment in at least one aspect of basic visual processing. However, a number of dissociations between basic visual skills indicated a heterogeneous pattern of visual impairment among the PCA patients. Furthermore, basic visual impairments were associated with particular higher-order object and space perception deficits, but not with nonvisual parietal tasks, suggesting the specific involvement of visual networks in PCA. Cortical thickness analysis revealed trends toward lower cortical thickness in occipitotemporal (ventral) and occipitoparietal (dorsal) regions in patients with visuoperceptual and visuospatial deficits, respectively. However, there was also a lot of overlap in their patterns of cortical thinning. These findings suggest that different presentations of PCA represent points in a continuum of phenotypical variation.

  7. Future talk in later life.

    PubMed

    Paoletti, Isabella; Gomes, Sandra

    2014-04-01

    This article focuses on the relevance that the dimension of the future has for promoting healthy and active aging. Older people generally have difficulties in talking about the future and when they do they generally express very negative perspectives on it. The data analyzed in this paper are part of an on-going interdisciplinary research project: "Aging, poverty and social exclusion: an interdisciplinary study on innovative support services" (https://apseclunl.wordpress.com/). The project aims at documenting good practices in social intervention with older people who are at risk of exclusion. This study describes and critically discusses an activity carried out in Portugal among older women in a poor area in the suburb of Lisbon entitled "self-awareness workshop on the future". Through a detailed discourse analysis within an ethnomethodological framework the study shows age membership categorizations in use and categorization processes, examining the workshop interaction. In particular, the article describes how the psychologist works at deconstructing and problematizing the negative connotations related to age membership categories. Taking into consideration the interactionally constructed nature of aging and the material consequences that different attitudes towards aging can imply is very important in particular in relation to the provision of services to older people. PMID:24655681

  8. Household Disbandment in Later Life

    PubMed Central

    Sergeant, Julie F.; Dingel, Molly; Bowen, Mary Elizabeth

    2005-01-01

    Objectives. This study described activities that older people undertake to reduce the volume of their possessions in the course of a residential move to smaller quarters, a process with practical, cognitive, emotional, and social dimensions. Methods. Qualitative interviews were conducted with members of 30 households who had moved in the prior year. The disbandment period, typically lasting about 2 months, was a particular focus of the interview. Results. The interviews suggested nine reasons why people had accumulated and kept things, which now became problematic for the impending move. The initial steps of disbandment entailed decisions about major furniture and meaningful gifts to family and friends, followed by evaluation of the remaining belongings for retention, sale, further gifts, donation, or discard. Things not divested by one means were reassigned to another strategy. People took pleasure in dispositions that saw their things used, cared for, and valued as they had done, thus fulfilling a responsibility to their belongings. Discussion. Disbandment is an acute episode of a more general, lifelong process of possession management. It is an encounter with things that are meaningful to the self, but as it unfolds, it also makes new meaning for things. PMID:15358801

  9. Can a nudge keep you warm? Using nudges to reduce excess winter deaths: insight from the Keeping Warm in Later Life Project (KWILLT)

    PubMed Central

    Allmark, Peter; Tod, Angela M.

    2014-01-01

    Nudges are interventions that aim to change people's behaviour through changing the environment in which they choose rather than appealing to their reasoning. Nudges have been proposed as of possible use in relation to health-related behaviour. However, nudges have been criticized as ethically dubious because they bypass peoples reasoning and (anyway) are of little help in relation to affecting ill-health that results from social determinants, such as poverty. Reducing the rate of excess winter deaths (EWDs) is a public health priority; however, EWD seems clearly to be socially determined such that nudges arguably have little role. This article defends two claims: (i) nudges could have a place in tackling even the heavily socially determined problem of EWD. We draw on evidence from an empirical study, the Keeping Warm in Later Life Project (KWILLT), to argue that in some cases the risk of cold is within the person’s control to some extent such that environmental modifications to influence behaviour such as nudges are possible. (ii) Some uses of behavioural insights in the form of nudges are acceptable, including some in the area of EWD. We suggest a question-based framework by which to judge the ethical acceptability of nudges. PMID:23873728

  10. Race/Ethnic and Nativity Disparities in Later Life Physical Performance: The Role of Health and Socioeconomic Status Over the Life Course

    PubMed Central

    Krueger, Patrick M.; Rohlfsen, Leah

    2012-01-01

    Objectives. We examine race/ethnic and nativity differences in objective measures of physical performance (i.e., peak expiratory flow, grip strength, and gait speed) in a nationally representative sample of older Whites, Blacks, and Hispanics. We also examine whether detailed measures of childhood and adult health and socioeconomic status (SES) mediate race/ethnic differences in physical performance. Method. We use data from the Health and Retirement Study, a population-based sample of older Americans born before 1947, and 3 measures of physical performance. Nested ordinary least squares models examine whether childhood and adult health and SES mediate race/ethnic differences in performance. Results. We find large and significant race/ethnic and nativity differences in lung function, grip strength, and gait speed. Adjusting for childhood and current adult health and SES reduces race/ethnic differences in physical performance but does not eliminate them entirely. Childhood health and SES as well as more proximal levels of SES are important determinants of race/ethnic disparities in later life physical performance. Discussion. The analysis highlights that a large proportion of race/ethnic and nativity disparities result from health and socioeconomic disadvantages in both early life and adulthood and thus suggests multiple intervention points at which disparities can be reduced. PMID:22391749

  11. Early-Life Social Origins of Later-Life Body Weight: The Role of Socioeconomic Status and Health Behaviors over the Life Course

    PubMed Central

    Logan, Ellis Scott; Richman, Aliza

    2014-01-01

    Using the 1957-2004 data from the Wisconsin Longitudinal Study, we apply structural equation modeling to examine gender-specific effects of family socioeconomic status (SES) at age 18 on body weight at age 65. We further explore SES and health behaviors over the life course as mechanisms linking family background and later-life body weight. We find that early-life socioeconomic disadvantage is related to higher body weight at age 65 and a steeper weight increase between midlife and late life. These adverse effects are stronger among women than men. Significant mediators of the effect of parents' SES include adolescent body mass (especially among women) as well as exercise and SES in midlife. Yet, consistent with the critical period mechanism, the effect of early-life SES on late-life body weight persists net of all mediating variables. This study expands current understanding of life-course mechanisms that contribute to obesity and increase biological vulnerability to social disadvantage. PMID:24767590

  12. Holding on and letting go: the perspectives of pre-seniors and seniors on driving self-regulation in later life.

    PubMed

    Rudman, Deborah Laliberte; Friedland, Judith; Chipman, Mary; Sciortino, Paola

    2006-01-01

    Although decisions related to driving are vital to well-being in later life, little is known about how aging drivers who do not experience a medical condition that requires driving cessation regulate their driving. This exploratory, qualitative study used focus groups with 79 such community-dwelling individuals to examine driving self-regulation from the perspective of pre-senior (aged 55-64) drivers, senior (aged 65 years or over) drivers, and senior ex-drivers. Themes resulting from inductive analysis addressed the importance of driving, mechanisms of self-monitoring and self-regulation, people who influenced decision making, and opinions regarding licensing regulations. A preliminary model of the process of self-regulation that highlights intrapersonal, interpersonal, and environmental influences on why, how, and when aging drivers adapt or cease driving is presented. The model identifies areas for future research to enhance understanding of this process, including the effectiveness of self-regulation. Findings suggest that increased public awareness of issues related to driving and aging could assist aging drivers, their families, and their family physicians in optimizing driving safety for this population. Since a near accident or accident was seen as the only factor that would lead many informants to stop driving and few informants planned for driving cessation, there is a need for interventions that help aging drivers make the transition to ex-driver in a timely and personally acceptable way. PMID:16770749

  13. Can a nudge keep you warm? Using nudges to reduce excess winter deaths: insight from the Keeping Warm in Later Life Project (KWILLT).

    PubMed

    Allmark, Peter; Tod, Angela M

    2014-03-01

    Nudges are interventions that aim to change people's behaviour through changing the environment in which they choose rather than appealing to their reasoning. Nudges have been proposed as of possible use in relation to health-related behaviour. However, nudges have been criticized as ethically dubious because they bypass peoples reasoning and (anyway) are of little help in relation to affecting ill-health that results from social determinants, such as poverty. Reducing the rate of excess winter deaths (EWDs) is a public health priority; however, EWD seems clearly to be socially determined such that nudges arguably have little role. This article defends two claims: (i) nudges could have a place in tackling even the heavily socially determined problem of EWD. We draw on evidence from an empirical study, the Keeping Warm in Later Life Project (KWILLT), to argue that in some cases the risk of cold is within the person's control to some extent such that environmental modifications to influence behaviour such as nudges are possible. (ii) Some uses of behavioural insights in the form of nudges are acceptable, including some in the area of EWD. We suggest a question-based framework by which to judge the ethical acceptability of nudges. PMID:23873728

  14. Sleep and olfactory cortical plasticity

    PubMed Central

    Barnes, Dylan C.; Wilson, Donald A.

    2014-01-01

    In many systems, sleep plays a vital role in memory consolidation and synaptic homeostasis. These processes together help store information of biological significance and reset synaptic circuits to facilitate acquisition of information in the future. In this review, we describe recent evidence of sleep-dependent changes in olfactory system structure and function which contribute to odor memory and perception. During slow-wave sleep, the piriform cortex becomes hypo-responsive to odor stimulation and instead displays sharp-wave activity similar to that observed within the hippocampal formation. Furthermore, the functional connectivity between the piriform cortex and other cortical and limbic regions is enhanced during slow-wave sleep compared to waking. This combination of conditions may allow odor memory consolidation to occur during a state of reduced external interference and facilitate association of odor memories with stored hedonic and contextual cues. Evidence consistent with sleep-dependent odor replay within olfactory cortical circuits is presented. These data suggest that both the strength and precision of odor memories is sleep-dependent. The work further emphasizes the critical role of synaptic plasticity and memory in not only odor memory but also basic odor perception. The work also suggests a possible link between sleep disturbances that are frequently co-morbid with a wide range of pathologies including Alzheimer’s disease, schizophrenia and depression and the known olfactory impairments associated with those disorders. PMID:24795585

  15. Chronic methamphetamine self-administration disrupts cortical control of cognition.

    PubMed

    Bernheim, Aurelien; See, Ronald E; Reichel, Carmela M

    2016-10-01

    Methamphetamine (meth) is one of the most abused substances worldwide. Chronic use has been associated with repeated relapse episodes that may be exacerbated by cognitive impairments during drug abstinence. Growing evidence demonstrates that meth compromises prefrontal cortex activity, resulting in persisting attentional and memory impairments. After summarizing recent studies of meth-induced cognitive dysfunction using a translationally relevant model of self-administered meth, this review emphasizes the cortical brain changes contributing to cognitive dysregulation during abstinence. Finally, we propose the use of cognitive enhancers during abstinence that may promote a drug-free state by reversing cortical dysfunction linked with prolonged meth abuse. PMID:27450578

  16. Behavioural Risk Factors in Mid-Life Associated with Successful Ageing, Disability, Dementia and Frailty in Later Life: A Rapid Systematic Review

    PubMed Central

    Lafortune, Louise; Martin, Steven; Kelly, Sarah; Kuhn, Isla; Remes, Olivia; Cowan, Andy; Brayne, Carol

    2016-01-01

    Background Smoking, alcohol consumption, poor diet and low levels of physical activity significantly contribute to the burden of illness in developed countries. Whilst the links between specific and multiple risk behaviours and individual chronic conditions are well documented, the impact of these behaviours in mid-life across a range of later life outcomes has yet to be comprehensively assessed. This review aimed to provide an overview of behavioural risk factors in mid-life that are associated with successful ageing and the primary prevention or delay of disability, dementia, frailty and non-communicable chronic conditions. Methods A literature search was conducted to identify cohort studies published in English since 2000 up to Dec 2014. Multivariate analyses and a minimum follow-up of five years were required for inclusion. Two reviewers screened titles, abstracts and papers independently. Studies were assessed for quality. Evidence was synthesised by mid-life behavioural risk for a range of late life outcomes. Findings This search located 10,338 individual references, of which 164 are included in this review. Follow-up data ranged from five years to 36 years. Outcomes include dementia, frailty, disability and cardiovascular disease. There is consistent evidence of beneficial associations between mid-life physical activity, healthy ageing and disease outcomes. Across all populations studied there is consistent evidence that mid-life smoking has a detrimental effect on health. Evidence specific to alcohol consumption was mixed. Limited, but supportive, evidence was available relating specifically to mid-life diet, leisure and social activities or health inequalities. Conclusions There is consistent evidence of associations between mid-life behaviours and a range of late life outcomes. The promotion of physical activity, healthy diet and smoking cessation in all mid-life populations should be encouraged for successful ageing and the prevention of disability and

  17. Relation of Childhood Home Environment to Cortical Thickness in Late Adolescence: Specificity of Experience and Timing

    PubMed Central

    Avants, Brian B.; Hackman, Daniel A.; Betancourt, Laura M.; Lawson, Gwendolyn M.; Hurt, Hallam; Farah, Martha J.

    2015-01-01

    What are the long-term effects of childhood experience on brain development? Research with animals shows that the quality of environmental stimulation and parental nurturance both play important roles in shaping lifelong brain structure and function. Human research has so far been limited to the effects of abnormal experience and pathological development. Using a unique longitudinal dataset of in-home measures of childhood experience at ages 4 and 8 and MRI acquired in late adolescence, we were able to relate normal variation in childhood experience to later life cortical thickness. Environmental stimulation at age 4 predicted cortical thickness in a set of automatically derived regions in temporal and prefrontal cortex. In contrast, age 8 experience was not predictive. Parental nurturance was not predictive at either age. This work reveals an association between childhood experience and later brain structure that is specific relative to aspects of experience, regions of brain, and timing. PMID:26509809

  18. Modulation of Cortical Oscillations by Low-Frequency Direct Cortical Stimulation Is State-Dependent

    PubMed Central

    Alagapan, Sankaraleengam; Schmidt, Stephen L.; Lefebvre, Jérémie; Hadar, Eldad; Shin, Hae Won; Frӧhlich, Flavio

    2016-01-01

    Cortical oscillations play a fundamental role in organizing large-scale functional brain networks. Noninvasive brain stimulation with temporally patterned waveforms such as repetitive transcranial magnetic stimulation (rTMS) and transcranial alternating current stimulation (tACS) have been proposed to modulate these oscillations. Thus, these stimulation modalities represent promising new approaches for the treatment of psychiatric illnesses in which these oscillations are impaired. However, the mechanism by which periodic brain stimulation alters endogenous oscillation dynamics is debated and appears to depend on brain state. Here, we demonstrate with a static model and a neural oscillator model that recurrent excitation in the thalamo-cortical circuit, together with recruitment of cortico-cortical connections, can explain the enhancement of oscillations by brain stimulation as a function of brain state. We then performed concurrent invasive recording and stimulation of the human cortical surface to elucidate the response of cortical oscillations to periodic stimulation and support the findings from the computational models. We found that (1) stimulation enhanced the targeted oscillation power, (2) this enhancement outlasted stimulation, and (3) the effect of stimulation depended on behavioral state. Together, our results show successful target engagement of oscillations by periodic brain stimulation and highlight the role of nonlinear interaction between endogenous network oscillations and stimulation. These mechanistic insights will contribute to the design of adaptive, more targeted stimulation paradigms. PMID:27023427

  19. Cortical State and Attention

    PubMed Central

    Harris, Kenneth D.; Thiele, Alexander

    2012-01-01

    Preface The brain continuously adapts its processing machinery to behavioural demands. To achieve this it rapidly modulates the operating mode of cortical circuits, controlling the way information is transformed and routed. This article will focus on two experimental approaches by which the control of cortical information processing has been investigated: the study of state-dependent cortical processing in rodents, and attention in the primate visual system. Both processes involve a modulation of low-frequency activity fluctuations and spiking correlation, and are mediated by common receptor systems. We suggest that selective attention involves processes similar to state change, operating at a local columnar level to enhance the representation of otherwise nonsalient features while suppressing internally generated activity patterns. PMID:21829219

  20. Bidirectional plasticity of cortical pattern recognition and behavioral sensory acuity

    PubMed Central

    Chapuis, Julie; Wilson, Donald A.

    2011-01-01

    Learning to adapt to a complex and fluctuating environment requires the ability to adjust neural representations of sensory stimuli. Through pattern completion processes, cortical networks can reconstruct familiar patterns from degraded input patterns, while pattern separation processes allow discrimination of even highly overlapping inputs. Here we show that the balance between pattern separation and completion is experience-dependent. Rats given extensive training with overlapping complex odorant mixtures show improved behavioral discrimination ability and enhanced cortical ensemble pattern separation. In contrast, behavioral training to disregard normally detectable differences between overlapping mixtures results in impaired cortical ensemble pattern separation (enhanced pattern completion) and impaired discrimination. This bidirectional effect was not found in the olfactory bulb, and may be due to plasticity within olfactory cortex itself. Thus pattern recognition, and the balance between pattern separation and completion, is highly malleable based on task demands and occurs in concert with changes in perceptual performance. PMID:22101640

  1. Cortical dynamics revisited.

    PubMed

    Singer, Wolf

    2013-12-01

    Recent discoveries on the organisation of the cortical connectome together with novel data on the dynamics of neuronal interactions require an extension of classical concepts on information processing in the cerebral cortex. These new insights justify considering the brain as a complex, self-organised system with nonlinear dynamics in which principles of distributed, parallel processing coexist with serial operations within highly interconnected networks. The observed dynamics suggest that cortical networks are capable of providing an extremely high-dimensional state space in which a large amount of evolutionary and ontogenetically acquired information can coexist and be accessible to rapid parallel search.

  2. Cortical Thinning and Altered Cortico-Cortical Structural Covariance of the Default Mode Network in Patients with Persistent Insomnia Symptoms

    PubMed Central

    Suh, Sooyeon; Kim, Hosung; Dang-Vu, Thien Thanh; Joo, Eunyeon; Shin, Chol

    2016-01-01

    Study Objectives: Recent studies have suggested that structural abnormalities in insomnia may be linked with alterations in the default-mode network (DMN). This study compared cortical thickness and structural connectivity linked to the DMN in patients with persistent insomnia (PI) and good sleepers (GS). Methods: The current study used a clinical subsample from the longitudinal community-based Korean Genome and Epidemiology Study (KoGES). Cortical thickness and structural connectivity linked to the DMN in patients with persistent insomnia symptoms (PIS; n = 57) were compared to good sleepers (GS; n = 40). All participants underwent MRI acquisition. Based on literature review, we selected cortical regions corresponding to the DMN. A seed-based structural covariance analysis measured cortical thickness correlation between each seed region of the DMN and other cortical areas. Association of cortical thickness and covariance with sleep quality and neuropsychological assessments were further assessed. Results: Compared to GS, cortical thinning was found in PIS in the anterior cingulate cortex, precentral cortex, and lateral prefrontal cortex. Decreased structural connectivity between anterior and posterior regions of the DMN was observed in the PIS group. Decreased structural covariance within the DMN was associated with higher PSQI scores. Cortical thinning in the lateral frontal lobe was related to poor performance in executive function in PIS. Conclusion: Disrupted structural covariance network in PIS might reflect malfunctioning of antero-posterior disconnection of the DMN during the wake to sleep transition that is commonly found during normal sleep. The observed structural network alteration may further implicate commonly observed sustained sleep difficulties and cognitive impairment in insomnia. Citation: Suh S, Kim H, Dang-Vu TT, Joo E, Shin C. Cortical thinning and altered cortico-cortical structural covariance of the default mode network in patients with

  3. Visualization of Cortical Dynamics

    NASA Astrophysics Data System (ADS)

    Grinvald, Amiram

    2003-03-01

    Recent progress in studies of cortical dynamics will be reviewed including the combination of real time optical imaging based on voltage sensitive dyes, single and multi- unit recordings, LFP, intracellular recordings and microstimulation. To image the flow of neuronal activity from one cortical site to the next, in real time, we have used optical imaging based on newly designed voltage sensitive dyes and a Fuji 128x 128 fast camera which we modified. A factor of 20-40 fold improvement in the signal to noise ratio was obtained with the new dye during in vivo imaging experiments. This improvements has facilitates the exploration of cortical dynamics without signal averaging in the millisecond time domain. We confirmed that the voltage sensitive dye signal indeed reflects membrane potential changes in populations of neurons by showing that the time course of the intracellular activity recorded intracellularly from a single neuron was highly correlated in many cases with the optical signal from a small patch of cortex recorded nearby. We showed that the firing of single cortical neurons is not a random process but occurs when the on-going pattern of million of neurons is similar to the functional architecture map which correspond to the tuning properties of that neuron. Chronic optical imaging, combined with electrical recordings and microstimulation, over a long period of times of more than a year, was successfully applied also to the study of higher brain functions in the behaving macaque monkey.

  4. Cortical thinning in psychopathy

    PubMed Central

    Ly, Martina; Motzkin, Julian C.; Philippi, Carissa L.; Kirk, Gregory R.; Newman, Joseph P.; Kiehl, Kent A.; Koenigs, Michael

    2013-01-01

    Objective Psychopathy is a personality disorder associated with severely antisocial behavior and a host of cognitive and affective deficits. The neuropathological basis of the disorder has not been clearly established. Cortical thickness is a sensitive measure of brain structure that has been used to identify neurobiological abnormalities in a number of psychiatric disorders. The purpose of this study is to evaluate cortical thickness and corresponding functional connectivity in criminal psychopaths. Method Using T1 MRI data, we computed cortical thickness maps in a sample of adult male prison inmates selected based on psychopathy diagnosis (n=21 psychopathic inmates, n=31 non-psychopathic inmates). Using rest-fMRI data from a subset of these inmates (n=20 psychopathic inmates, n=20 non-psychopathic inmates), we then computed functional connectivity within networks exhibiting significant thinning among psychopaths. Results Relative to non-psychopaths, psychopaths exhibited significantly thinner cortex in a number of regions, including left insula and dorsal anterior cingulate cortex, bilateral precentral gyrus, bilateral anterior temporal cortex, and right inferior frontal gyrus. These neurostructural differences were not due to differences in age, IQ, or substance abuse. Psychopaths also exhibited a corresponding reduction in functional connectivity between left insula and left dorsal anterior cingulate cortex. Conclusions Psychopathy is associated with a distinct pattern of cortical thinning and reduced functional connectivity. PMID:22581200

  5. Impaired consciousness in epilepsy.

    PubMed

    Blumenfeld, Hal

    2012-09-01

    Consciousness is essential to normal human life. In epileptic seizures consciousness is often transiently lost, which makes it impossible for the individual to experience or respond. These effects have huge consequences for safety, productivity, emotional health, and quality of life. To prevent impaired consciousness in epilepsy, it is necessary to understand the mechanisms that lead to brain dysfunction during seizures. Normally the consciousness system-a specialised set of cortical-subcortical structures-maintains alertness, attention, and awareness. Advances in neuroimaging, electrophysiology, and prospective behavioural testing have shed light on how epileptic seizures disrupt the consciousness system. Diverse seizure types, including absence, generalised tonic-clonic, and complex partial seizures, converge on the same set of anatomical structures through different mechanisms to disrupt consciousness. Understanding of these mechanisms could lead to improved treatment strategies to prevent impairment of consciousness and improve the quality of life of people with epilepsy.

  6. Patterns of cortical thinning in nondemented Parkinson's disease patients

    PubMed Central

    Uribe, Carme; Segura, Barbara; Baggio, Hugo Cesar; Abos, Alexandra; Marti, Maria Jose; Valldeoriola, Francesc; Compta, Yaroslau; Bargallo, Nuria

    2016-01-01

    ABSTRACT Background Clinical variability in the Parkinson's disease phenotype suggests the existence of disease subtypes. We investigated whether distinct anatomical patterns of atrophy can be identified in Parkinson's disease using a hypothesis‐free, data‐driven approach based on cortical thickness data. Methods T1‐weighted 3‐tesla MRI and a comprehensive neuropsychological assessment were performed in a sample of 88 nondemented Parkinson's disease patients and 31 healthy controls. We performed a hierarchical cluster analysis of imaging data using Ward's linkage method. A general linear model with cortical thickness data was used to compare clustering groups. Results We observed 3 patterns of cortical thinning in patients when compared with healthy controls. Pattern 1 (n = 30, 34.09%) consisted of cortical atrophy in bilateral precentral gyrus, inferior and superior parietal lobules, cuneus, posterior cingulate, and parahippocampal gyrus. These patients showed worse cognitive performance when compared with controls and the other 2 patterns. Pattern 2 (n = 29, 32.95%) consisted of cortical atrophy involving occipital and frontal as well as superior parietal areas and included patients with younger age at onset. Finally, in pattern 3 (n = 29, 32.95%), there was no detectable cortical thinning. Patients in the 3 patterns did not differ in disease duration, motor severity, dopaminergic medication doses, or presence of mild cognitive impairment. Conclusions Three cortical atrophy subtypes were identified in nondemented Parkinson's disease patients: (1) parieto‐temporal pattern of atrophy with worse cognitive performance, (2) occipital and frontal cortical atrophy and younger disease onset, and (3) patients without detectable cortical atrophy. These findings may help identify prognosis markers in Parkinson's disease. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement

  7. Prefrontal cortical dopamine transmission is decreased in alcoholism

    PubMed Central

    Narendran, Rajesh; Mason, Neale Scott; Paris, Jennifer; Himes, Michael L.; Douaihy, Antoine B.; Frankle, W. Gordon

    2014-01-01

    Objective Basic studies have demonstrated that optimal levels of prefrontal cortical dopamine are critical to various executive functions such working memory, attention, inhibitory control and risk/reward decisions--all of which are impaired in addictive disorders such as alcoholism. Based on this and imaging studies in alcoholics that have demonstrated less dopamine in the striatum, we hypothesized decreased dopamine transmission in the prefrontal cortex in alcoholism. To test this hypothesis, we used amphetamine and [11C]FLB 457 positron emission tomography (PET) to measure cortical dopamine transmission in a group of 21 recently abstinent alcoholics and matched healthy controls. Methods [11C]FLB 457 binding potential (BPND) was measured in subjects with kinetic analysis using the arterial input function both before and after 0.5 mg kg−1 of d-amphetamine. Results Amphetamine-induced displacement of [11C]FLB 457 binding potential (Δ BPND) was significantly smaller in the cortical regions in alcoholics compared to healthy controls. Cortical regions that demonstrated lower dopamine transmission in alcoholics included the dorsolateral prefrontal cortex, medial prefrontal cortex, orbital frontal cortex, temporal cortex and medial temporal lobe. Conclusions The results of this study for the first time unambiguously demonstrate decreased dopamine transmission in the cortex in alcoholism. Further research is necessary to understand the clinical relevance of decreased cortical dopamine as to whether it is related to impaired executive function, relapse, and outcome in alcoholism. PMID:24874293

  8. Purely Cortical Anaplastic Ependymoma

    PubMed Central

    Romero, Flávio Ramalho; Zanini, Marco Antônio; Ducati, Luis Gustavo; Vital, Roberto Bezerra; de Lima Neto, Newton Moreira; Gabarra, Roberto Colichio

    2012-01-01

    Ependymomas are glial tumors derived from ependymal cells lining the ventricles and the central canal of the spinal cord. It may occur outside the ventricular structures, representing the extraventicular form, or without any relationship of ventricular system, called ectopic ependymona. Less than fifteen cases of ectopic ependymomas were reported and less than five were anaplastic. We report a rare case of pure cortical ectopic anaplastic ependymoma. PMID:23119204

  9. Purely cortical anaplastic ependymoma.

    PubMed

    Romero, Flávio Ramalho; Zanini, Marco Antônio; Ducati, Luis Gustavo; Vital, Roberto Bezerra; de Lima Neto, Newton Moreira; Gabarra, Roberto Colichio

    2012-01-01

    Ependymomas are glial tumors derived from ependymal cells lining the ventricles and the central canal of the spinal cord. It may occur outside the ventricular structures, representing the extraventicular form, or without any relationship of ventricular system, called ectopic ependymona. Less than fifteen cases of ectopic ependymomas were reported and less than five were anaplastic. We report a rare case of pure cortical ectopic anaplastic ependymoma.

  10. Posterior Cortical Atrophy

    PubMed Central

    Crutch, Sebastian J; Lehmann, Manja; Schott, Jonathan M; Rabinovici, Gil D; Rossor, Martin N; Fox, Nick C

    2013-01-01

    Posterior cortical atrophy (PCA) is a neurodegenerative syndrome that is characterized by a progressive decline in visuospatial, visuoperceptual, literacy and praxic skills. The progressive neurodegeneration affecting parietal, occipital and occipito-temporal cortices which underlies PCA is attributable to Alzheimer's disease (AD) in the majority of patients. However, alternative underlying aetiologies including Dementia with Lewy Bodies (DLB), corticobasal degeneration (CBD) and prion disease have also been identified, and not all PCA patients have atrophy on clinical imaging. This heterogeneity has led to diagnostic and terminological inconsistencies, caused difficulty comparing studies from different centres, and limited the generalizability of clinical trials and investigations of factors driving phenotypic variability. Significant challenges remain in identifying the factors associated with both the selective vulnerability of posterior cortical regions and the young age of onset seen in PCA. Greater awareness of the syndrome and agreement over the correspondence between syndrome-and disease-level classifications are required in order to improve diagnostic accuracy, research study design and clinical management. PMID:22265212

  11. Cortical dopamine dysfunction in symptomatic and premanifest Huntington's disease gene carriers.

    PubMed

    Pavese, Nicola; Politis, Marios; Tai, Yen F; Barker, Roger A; Tabrizi, Sarah J; Mason, Sarah L; Brooks, David J; Piccini, Paola

    2010-02-01

    We used (11)C-raclopride PET, a marker of D(2) dopamine receptor binding, and statistical parametric mapping (SPM) to localise cortical D(2) receptor dysfunction in individual Huntington's disease (HD) gene carriers (16 symptomatic and 11 premanifest subjects) and assess its clinical significance. 62.5% of symptomatic HD patients and 54.5% of premanifest carriers showed cortical reductions in D(2) binding. The most frequent decreases in cortical binding in individual HD subjects were seen in temporal and frontal areas. Symptomatic HD subjects with decreased cortical D(2) binding had worse scores on neuropsychological tests assessing attention and executive functions than subjects without cortical dopamine dysfunction, notwithstanding comparable reduction in striatal D(2) binding and motor disability. Our results indicate that cortical dopaminergic dysfunction is common in both symptomatic and premanifest HD gene carriers. It is an early event in HD pathophysiology and could contribute to the impairment in neuropsychological performance in these patients.

  12. Posterior cortical atrophy: an atypical variant of Alzheimer disease.

    PubMed

    Suárez-González, Aida; Henley, Susie M; Walton, Jill; Crutch, Sebastian J

    2015-06-01

    Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by striking progressive visual impairment and a pattern of atrophy mainly involving posterior cortices. PCA is the most frequent atypical presentation of Alzheimer disease. The purpose of this article is to provide a summary of PCA's neuropsychiatric manifestations. Emotional and psychotic symptoms are discussed in the context of signal characteristic features of the PCA syndrome (the early onset, focal loss of visual perception, focal posterior brain atrophy) and the underlying cause of the disease. The authors' experience with psychotherapeutic intervention and PCA support groups is shared in detail.

  13. Regional Cortical Thinning Associated with Detectable Levels of HIV DNA

    PubMed Central

    Kirk, Gregory R.; Sailasuta, Napapon; Valcour, Victor; Shiramizu, Bruce; Nakamoto, Beau K.; Shikuma, Cecilia

    2012-01-01

    High levels of human immunodeficiency virus (HIV) DNA in peripheral blood mononuclear cells (PBMCs), and specifically within CD14+ blood monocytes, have been found in HIV-infected individuals with neurocognitive impairment and dementia. The failure of highly active antiretroviral therapy (HAART) to eliminate cognitive dysfunction in HIV may be secondary to persistence of HIV-infected PBMCs which cross the blood-brain barrier, leading to perivascular inflammation and neuronal injury. This study assessed brain cortical thickness relative to HIV DNA levels and identified, we believe for the first time, a neuroimaging correlate of detectable PBMC HIV DNA in subjects with undetectable HIV RNA. Cortical thickness was compared between age- and education-matched groups of older (>40 years) HIV-seropositive subjects on HAART who had detectable (N = 9) and undetectable (N = 10) PBMC HIV DNA. Statistical testing revealed highly significant (P < 0.001) cortical thinning associated with detectable HIV DNA. The largest regions affected were in bilateral insula, orbitofrontal and temporal cortices, right superior frontal cortex, and right caudal anterior cingulate. Cortical thinning correlated significantly with a measure of psychomotor speed. The areas of reduced cortical thickness are key nodes in cognitive and emotional processing networks and may be etiologically important in HIV-related neurological deficits. PMID:22016479

  14. Can Ketones Help Rescue Brain Fuel Supply in Later Life? Implications for Cognitive Health during Aging and the Treatment of Alzheimer’s Disease

    PubMed Central

    Cunnane, Stephen C.; Courchesne-Loyer, Alexandre; Vandenberghe, Camille; St-Pierre, Valérie; Fortier, Mélanie; Hennebelle, Marie; Croteau, Etienne; Bocti, Christian; Fulop, Tamas; Castellano, Christian-Alexandre

    2016-01-01

    We propose that brain energy deficit is an important pre-symptomatic feature of Alzheimer’s disease (AD) that requires closer attention in the development of AD therapeutics. Our rationale is fourfold: (i) Glucose uptake is lower in the frontal cortex of people >65 years-old despite cognitive scores that are normal for age. (ii) The regional deficit in brain glucose uptake is present in adults <40 years-old who have genetic or lifestyle risk factors for AD but in whom cognitive decline has not yet started. Examples include young adult carriers of presenilin-1 or apolipoprotein E4, and young adults with mild insulin resistance or with a maternal family history of AD. (iii) Regional brain glucose uptake is impaired in AD and mild cognitive impairment (MCI), but brain uptake of ketones (beta-hydroxybutyrate and acetoacetate), remains the same in AD and MCI as in cognitively healthy age-matched controls. These observations point to a brain fuel deficit which appears to be specific to glucose, precedes cognitive decline associated with AD, and becomes more severe as MCI progresses toward AD. Since glucose is the brain’s main fuel, we suggest that gradual brain glucose exhaustion is contributing significantly to the onset or progression of AD. (iv) Interventions that raise ketone availability to the brain improve cognitive outcomes in both MCI and AD as well as in acute experimental hypoglycemia. Ketones are the brain’s main alternative fuel to glucose and brain ketone uptake is still normal in MCI and in early AD, which would help explain why ketogenic interventions improve some cognitive outcomes in MCI and AD. We suggest that the brain energy deficit needs to be overcome in order to successfully develop more effective therapeutics for AD. At present, oral ketogenic supplements are the most promising means of achieving this goal. PMID:27458340

  15. 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

  16. Explaining health differences between men and women in later life: a cross-city comparison in Latin America and the Caribbean.

    PubMed

    Zunzunegui, Maria-Victoria; Alvarado, Beatriz-Eugenia; Béland, François; Vissandjee, Bilkis

    2009-01-01

    This paper describes differences in health and functional status among older men and women and attempts to anchor the explanations for these differences within a lifecourse perspective. Seven health outcomes for men and women 60 years and older from seven Latin American and Caribbean cities are examined, using data from the 2000 SABE survey (Salud, Bienestar y Envejecimiento-n=10,587). Age-adjusted as well as city- and sex-specific prevalence was estimated for poor self-rated health, comorbidity, mobility limitations, cognitive impairment, depressive symptoms and disability in basic and instrumental activities of daily living. Logistic regressions were fitted to determine if the differences between men and women in each outcome could be explained by differential exposures in childhood (hunger, poverty), adulthood (education, occupation) and old age (income) and/or by differential vulnerability of men and women to these exposures. Sao Paulo, Santiago and Mexico, cities in countries with a high level of income inequalities, presented the highest prevalence of disability, functional limitations and poor physical health for both women and men. Women showed poorer health outcomes as compared with men for all health indicators and in all cities. Controlling for lifecourse exposures in childhood, adulthood and old age did not attenuate these differences. Women's unadjusted and adjusted odds of reporting poor self-rated health, cognitive impairment and basic activities of daily living disability were approximately 50% higher than for men, twice as high for number of comorbidities, depressive symptoms and instrumental activities of daily living disability, and almost three times as high for mobility limitations. Higher vulnerability to lifecourse exposures in women as compared with men was not found, meaning that lifecourse exposures have similar odds of poor health outcomes for men and women. A more integrated understanding of how sex and gender act together to influence

  17. Cortical Clefts and Cortical Bumps: A Continuous Spectrum

    PubMed Central

    Furruqh, Farha; Thirunavukarasu, Suresh; Vivekandan, Ravichandran

    2016-01-01

    Cortical ‘clefts’ (schizencephaly) and cortical ‘bumps’ (polymicrogyria) are malformations arising due to defects in postmigrational development of neurons. They are frequently encountered together, with schizencephalic clefts being lined by polymicrogyria. We present the case of an eight-year-old boy who presented with seizures. Imaging revealed closed lip schizencephaly, polymicrogyria and a deep ‘incomplete’ cleft lined by polymicrogyria not communicating with the lateral ventricle. We speculate that hypoperfusion or ischaemic cortical injury during neuronal development may lead to a spectrum of malformations ranging from polymicrogyria to incomplete cortical clefts to schizencephaly. PMID:27630923

  18. Cortical Clefts and Cortical Bumps: A Continuous Spectrum.

    PubMed

    Biswas, Asthik; Furruqh, Farha; Thirunavukarasu, Suresh; Vivekandan, Ravichandran

    2016-07-01

    Cortical 'clefts' (schizencephaly) and cortical 'bumps' (polymicrogyria) are malformations arising due to defects in postmigrational development of neurons. They are frequently encountered together, with schizencephalic clefts being lined by polymicrogyria. We present the case of an eight-year-old boy who presented with seizures. Imaging revealed closed lip schizencephaly, polymicrogyria and a deep 'incomplete' cleft lined by polymicrogyria not communicating with the lateral ventricle. We speculate that hypoperfusion or ischaemic cortical injury during neuronal development may lead to a spectrum of malformations ranging from polymicrogyria to incomplete cortical clefts to schizencephaly. PMID:27630923

  19. Cortical Basal Ganglionic Degeneration

    PubMed Central

    Scarmeas, Nikolaos; Chin, Steven S.; Marder, Karen

    2011-01-01

    In this case study, we describe the symptoms, neuropsychological testing, and brain pathology of a retired mason's assistant with cortical basal ganglionic degeneration (CBGD). CBGD is an extremely rare neurodegenerative disease that is categorized under both Parkinsonian syndromes and frontal lobe dementias. It affects men and women nearly equally, and the age of onset is usually in the sixth decade of life. CBGD is characterized by Parkinson's-like motor symptoms and by deficits of movement and cognition, indicating focal brain pathology. Neuronal cell loss is ultimately responsible for the neurological symptoms. PMID:14602941

  20. Impact of prenatal environmental stress on cortical development

    PubMed Central

    Ishii, Seiji; Hashimoto-Torii, Kazue

    2015-01-01

    Prenatal exposure of the developing brain to various types of environmental stress increases susceptibility to neuropsychiatric disorders such as autism, attention deficit hyperactivity disorder and schizophrenia. Given that even subtle perturbations by prenatal environmental stress in the cerebral cortex impair the cognitive and memory functions, this review focuses on underlying molecular mechanisms of pathological cortical development. We especially highlight recent works that utilized animal exposure models, human specimens or/and induced Pluripotent Stem (iPS) cells to demonstrate: (1) molecular mechanisms shared by various types of environmental stressors, (2) the mechanisms by which the affected extracortical tissues indirectly impact the cortical development and function, and (3) interaction between prenatal environmental stress and the genetic predisposition of neuropsychiatric disorders. Finally, we discuss current challenges for achieving a comprehensive understanding of the role of environmentally disturbed molecular expressions in cortical maldevelopment, knowledge of which may eventually facilitate discovery of interventions for prenatal environment-linked neuropsychiatric disorders. PMID:26074774

  1. Time in Cortical Circuits

    PubMed Central

    Shadlen, Michael N.; Jazayeri, Mehrdad; Nobre, Anna C.; Buonomano, Dean V.

    2015-01-01

    Time is central to cognition. However, the neural basis for time-dependent cognition remains poorly understood. We explore how the temporal features of neural activity in cortical circuits and their capacity for plasticity can contribute to time-dependent cognition over short time scales. This neural activity is linked to cognition that operates in the present or anticipates events or stimuli in the near future. We focus on deliberation and planning in the context of decision making as a cognitive process that integrates information across time. We progress to consider how temporal expectations of the future modulate perception. We propose that understanding the neural basis for how the brain tells time and operates in time will be necessary to develop general models of cognition. SIGNIFICANCE STATEMENT Time is central to cognition. However, the neural basis for time-dependent cognition remains poorly understood. We explore how the temporal features of neural activity in cortical circuits and their capacity for plasticity can contribute to time-dependent cognition over short time scales. We propose that understanding the neural basis for how the brain tells time and operates in time will be necessary to develop general models of cognition. PMID:26468192

  2. Cortical thickness abnormalities associated with dyslexia, independent of remediation status.

    PubMed

    Ma, Yizhou; Koyama, Maki S; Milham, Michael P; Castellanos, F Xavier; Quinn, Brian T; Pardoe, Heath; Wang, Xiuyuan; Kuzniecky, Ruben; Devinsky, Orrin; Thesen, Thomas; Blackmon, Karen

    2015-01-01

    Abnormalities in cortical structure are commonly observed in children with dyslexia in key regions of the "reading network." Whether alteration in cortical features reflects pathology inherent to dyslexia or environmental influence (e.g., impoverished reading experience) remains unclear. To address this question, we compared MRI-derived metrics of cortical thickness (CT), surface area (SA), gray matter volume (GMV), and their lateralization across three different groups of children with a historical diagnosis of dyslexia, who varied in current reading level. We compared three dyslexia subgroups with: (1) persistent reading and spelling impairment; (2) remediated reading impairment (normal reading scores), and (3) remediated reading and spelling impairments (normal reading and spelling scores); and a control group of (4) typically developing children. All groups were matched for age, gender, handedness, and IQ. We hypothesized that the dyslexia group would show cortical abnormalities in regions of the reading network relative to controls, irrespective of remediation status. Such a finding would support that cortical abnormalities are inherent to dyslexia and are not a consequence of abnormal reading experience. Results revealed increased CT of the left fusiform gyrus in the dyslexia group relative to controls. Similarly, the dyslexia group showed CT increase of the right superior temporal gyrus, extending into the planum temporale, which resulted in a rightward CT asymmetry on lateralization indices. There were no group differences in SA, GMV, or their lateralization. These findings held true regardless of remediation status. Each reading level group showed the same "double hit" of atypically increased left fusiform CT and rightward superior temporal CT asymmetry. Thus, findings provide evidence that a developmental history of dyslexia is associated with CT abnormalities, independent of remediation status.

  3. Cortical thickness abnormalities associated with dyslexia, independent of remediation status

    PubMed Central

    Ma, Yizhou; Koyama, Maki S.; Milham, Michael P.; Castellanos, F. Xavier; Quinn, Brian T.; Pardoe, Heath; Wang, Xiuyuan; Kuzniecky, Ruben; Devinsky, Orrin; Thesen, Thomas; Blackmon, Karen

    2014-01-01

    Abnormalities in cortical structure are commonly observed in children with dyslexia in key regions of the “reading network.” Whether alteration in cortical features reflects pathology inherent to dyslexia or environmental influence (e.g., impoverished reading experience) remains unclear. To address this question, we compared MRI-derived metrics of cortical thickness (CT), surface area (SA), gray matter volume (GMV), and their lateralization across three different groups of children with a historical diagnosis of dyslexia, who varied in current reading level. We compared three dyslexia subgroups with: (1) persistent reading and spelling impairment; (2) remediated reading impairment (normal reading scores), and (3) remediated reading and spelling impairments (normal reading and spelling scores); and a control group of (4) typically developing children. All groups were matched for age, gender, handedness, and IQ. We hypothesized that the dyslexia group would show cortical abnormalities in regions of the reading network relative to controls, irrespective of remediation status. Such a finding would support that cortical abnormalities are inherent to dyslexia and are not a consequence of abnormal reading experience. Results revealed increased CT of the left fusiform gyrus in the dyslexia group relative to controls. Similarly, the dyslexia group showed CT increase of the right superior temporal gyrus, extending into the planum temporale, which resulted in a rightward CT asymmetry on lateralization indices. There were no group differences in SA, GMV, or their lateralization. These findings held true regardless of remediation status. Each reading level group showed the same “double hit” of atypically increased left fusiform CT and rightward superior temporal CT asymmetry. Thus, findings provide evidence that a developmental history of dyslexia is associated with CT abnormalities, independent of remediation status. PMID:25610779

  4. Regional vulnerability of longitudinal cortical association connectivity

    PubMed Central

    Ceschin, Rafael; Lee, Vince K.; Schmithorst, Vince; Panigrahy, Ashok

    2015-01-01

    Preterm born children with spastic diplegia type of cerebral palsy and white matter injury or periventricular leukomalacia (PVL), are known to have motor, visual and cognitive impairments. Most diffusion tensor imaging (DTI) studies performed in this group have demonstrated widespread abnormalities using averaged deterministic tractography and voxel-based DTI measurements. Little is known about structural network correlates of white matter topography and reorganization in preterm cerebral palsy, despite the availability of new therapies and the need for brain imaging biomarkers. Here, we combined novel post-processing methodology of probabilistic tractography data in this preterm cohort to improve spatial and regional delineation of longitudinal cortical association tract abnormalities using an along-tract approach, and compared these data to structural DTI cortical network topology analysis. DTI images were acquired on 16 preterm children with cerebral palsy (mean age 5.6 ± 4) and 75 healthy controls (mean age 5.7 ± 3.4). Despite mean tract analysis, Tract-Based Spatial Statistics (TBSS) and voxel-based morphometry (VBM) demonstrating diffusely reduced fractional anisotropy (FA) reduction in all white matter tracts, the along-tract analysis improved the detection of regional tract vulnerability. The along-tract map-structural network topology correlates revealed two associations: (1) reduced regional posterior–anterior gradient in FA of the longitudinal visual cortical association tracts (inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, optic radiation, posterior thalamic radiation) correlated with reduced posterior–anterior gradient of intra-regional (nodal efficiency) metrics with relative sparing of frontal and temporal regions; and (2) reduced regional FA within frontal–thalamic–striatal white matter pathways (anterior limb/anterior thalamic radiation, superior longitudinal fasciculus and cortical spinal tract) correlated

  5. Cortico-cortical communication dynamics

    PubMed Central

    Roland, Per E.; Hilgetag, Claus C.; Deco, Gustavo

    2014-01-01

    In principle, cortico-cortical communication dynamics is simple: neurons in one cortical area communicate by sending action potentials that release glutamate and excite their target neurons in other cortical areas. In practice, knowledge about cortico-cortical communication dynamics is minute. One reason is that no current technique can capture the fast spatio-temporal cortico-cortical evolution of action potential transmission and membrane conductances with sufficient spatial resolution. A combination of optogenetics and monosynaptic tracing with virus can reveal the spatio-temporal cortico-cortical dynamics of specific neurons and their targets, but does not reveal how the dynamics evolves under natural conditions. Spontaneous ongoing action potentials also spread across cortical areas and are difficult to separate from structured evoked and intrinsic brain activity such as thinking. At a certain state of evolution, the dynamics may engage larger populations of neurons to drive the brain to decisions, percepts and behaviors. For example, successfully evolving dynamics to sensory transients can appear at the mesoscopic scale revealing how the transient is perceived. As a consequence of these methodological and conceptual difficulties, studies in this field comprise a wide range of computational models, large-scale measurements (e.g., by MEG, EEG), and a combination of invasive measurements in animal experiments. Further obstacles and challenges of studying cortico-cortical communication dynamics are outlined in this critical review. PMID:24847217

  6. Visual cortical contributions to associative cerebellar learning

    PubMed Central

    Steinmetz, Adam B.; Harmon, Thomas C.; Freeman, John H.

    2013-01-01

    Eye-blink conditioning (EBC) is a form of associative learning that depends on the cerebellum. Previous reports suggested that sensory cortex is necessary for trace EBC but not for delay EBC. The trace and delay EBC procedures used in these studies differed by the presence or absence of a temporal gap between the end of the conditioned stimulus and the onset of the unconditioned stimulus (trace interval) and in the interval between the onset of the CS and the US (inter-stimulus interval, ISI). The current study examined the role of the visual cortex in delay, long-delay, and trace EBC, matching CS duration and inter-stimulus interval between groups. In Experiment 1, extensive removal of the visual cortex impaired acquisition of long-delay and trace EBC but had no effect on delay EBC. In Experiment 2, bilateral inactivation of the visual cortex impaired acquisition and retention of long-delay and trace EBC, but had no effect on delay EBC. In Experiment 3, unilateral inactivation of the visual cortex impaired long-delay EBC but had no effect on trace EBC. The results indicate that the visual cortex facilitates EBC with relatively long ISIs, regardless of whether there is a trace interval or not. Moreover, the ipsilateral projections from the visual cortex to the pontine nuclei are sufficient for modulating long-delay EBC, whereas trace EBC involves bilateral visual cortical interactions with forebrain systems including the hippocampus and prefrontal cortex. PMID:23791556

  7. Modeling cortical circuits.

    SciTech Connect

    Rohrer, Brandon Robinson; Rothganger, Fredrick H.; Verzi, Stephen J.; Xavier, Patrick Gordon

    2010-09-01

    The neocortex is perhaps the highest region of the human brain, where audio and visual perception takes place along with many important cognitive functions. An important research goal is to describe the mechanisms implemented by the neocortex. There is an apparent regularity in the structure of the neocortex [Brodmann 1909, Mountcastle 1957] which may help simplify this task. The work reported here addresses the problem of how to describe the putative repeated units ('cortical circuits') in a manner that is easily understood and manipulated, with the long-term goal of developing a mathematical and algorithmic description of their function. The approach is to reduce each algorithm to an enhanced perceptron-like structure and describe its computation using difference equations. We organize this algorithmic processing into larger structures based on physiological observations, and implement key modeling concepts in software which runs on parallel computing hardware.

  8. Cortical plasticity and rehabilitation.

    PubMed

    Moucha, Raluca; Kilgard, Michael P

    2006-01-01

    The brain is constantly adapting to environmental and endogenous changes (including injury) that occur at every stage of life. The mechanisms that regulate neural plasticity have been refined over millions of years. Motivation and sensory experience directly shape the rewiring that makes learning and neurological recovery possible. Guiding neural reorganization in a manner that facilitates recovery of function is a primary goal of neurological rehabilitation. As the rules that govern neural plasticity become better understood, it will be possible to manipulate the sensory and motor experience of patients to induce specific forms of plasticity. This review summarizes our current knowledge regarding factors that regulate cortical plasticity, illustrates specific forms of reorganization induced by control of each factor, and suggests how to exploit these factors for clinical benefit.

  9. Decoding of Covert Vowel Articulation Using Electroencephalography Cortical Currents

    PubMed Central

    Yoshimura, Natsue; Nishimoto, Atsushi; Belkacem, Abdelkader Nasreddine; Shin, Duk; Kambara, Hiroyuki; Hanakawa, Takashi; Koike, Yasuharu

    2016-01-01

    With the goal of providing assistive technology for the communication impaired, we proposed electroencephalography (EEG) cortical currents as a new approach for EEG-based brain-computer interface spellers. EEG cortical currents were estimated with a variational Bayesian method that uses functional magnetic resonance imaging (fMRI) data as a hierarchical prior. EEG and fMRI data were recorded from ten healthy participants during covert articulation of Japanese vowels /a/ and /i/, as well as during a no-imagery control task. Applying a sparse logistic regression (SLR) method to classify the three tasks, mean classification accuracy using EEG cortical currents was significantly higher than that using EEG sensor signals and was also comparable to accuracies in previous studies using electrocorticography. SLR weight analysis revealed vertices of EEG cortical currents that were highly contributive to classification for each participant, and the vertices showed discriminative time series signals according to the three tasks. Furthermore, functional connectivity analysis focusing on the highly contributive vertices revealed positive and negative correlations among areas related to speech processing. As the same findings were not observed using EEG sensor signals, our results demonstrate the potential utility of EEG cortical currents not only for engineering purposes such as brain-computer interfaces but also for neuroscientific purposes such as the identification of neural signaling related to language processing. PMID:27199638

  10. Taste - impaired

    MedlinePlus

    ... longer. Causes of impaired taste include: Bell's palsy Common cold Flu and other viral infections Nasal infection, nasal ... your diet. For taste problems due to the common cold or flu, normal taste should return when the ...

  11. Cortical overgrowth in fetuses with isolated ventriculomegaly.

    PubMed

    Kyriakopoulou, Vanessa; Vatansever, Deniz; Elkommos, Samia; Dawson, Sarah; McGuinness, Amy; Allsop, Joanna; Molnár, Zoltán; Hajnal, Joseph; Rutherford, Mary

    2014-08-01

    Mild cerebral ventricular enlargement is associated with schizophrenia, autism, epilepsy, and attention-deficit/hyperactivity disorder. Fetal ventriculomegaly is the most common central nervous system (CNS) abnormality affecting 1% of fetuses and is associated with cognitive, language, and behavioral impairments in childhood. Neurodevelopmental outcome is partially predictable by the 2-dimensional size of the ventricles in the absence of other abnormalities. We hypothesized that isolated fetal ventriculomegaly is a marker of altered brain development characterized by relative overgrowth and aimed to quantify brain growth using volumetric magnetic resonance imaging (MRI) in fetuses with isolated ventriculomegaly. Fetal brain MRI (1.5 T) was performed in 60 normal fetuses and 65 with isolated ventriculomegaly, across a gestational age range of 22-38 weeks. Volumetric analysis of the ventricles and supratentorial brain structures was performed on 3-dimensional reconstructed datasets. Fetuses with isolated ventriculomegaly had increased brain parenchyma volumes when compared with the control cohort (9.6%, P < 0.0001) with enlargement restricted to the cortical gray matter (17.2%, P = 0.002). The extracerebral cerebrospinal fluid and third and fourth ventricles were also enlarged. White matter, basal ganglia, and thalamic volumes were not significantly different between cohorts. The presence of relative cortical overgrowth in fetuses with ventriculomegaly may represent the neurobiological substrate for cognitive, language, and behavioral deficits in these children.

  12. Cognitive impairment in multiple sclerosis.

    PubMed

    Jongen, P J; Ter Horst, A T; Brands, A M

    2012-04-01

    Cognitive impairment occurs in 40-65% of multiple sclerosis (MS) patients, typically involving complex attention, information processing speed, (episodic) memory and executive functions. It is seen in the subclinical radiologically isolated syndrome, clinically isolated syndrome, and all phases of clinical MS. In pediatric-onset MS cognition is frequently impaired and worsens relatively rapidly. Cognitive impairment often affects personal life and vocational status. Depression, anxiety and fatigue aggravate symptoms, whereas cognitive reserve partially protects. Cognitive dysfunction correlates to brain magnetic resonance imaging (MRI) lesion volumes and (regional) atrophy, and degree of and increase in MRI abnormalities predict further worsening. Experimental MRI indicates a crucial role for (focal) cortical lesions and atrophy, abnormal cortical integrity, and early changes in normal appearing brain tissue. Functional MRI suggests compensatory reorganization and adaptation changes in neural activities. Screening tools are the Brief Repeatable Neuropsychological Battery, Symbol Digit Modalities Test and Audio Recorded Cognitive Screen. The Minimal Assessment of Cognitive Function in Multiple Sclerosis (MS) is used for formal neuropsychological evaluation. What constitutes a clinically relevant change and how to optimally monitor cognition are issues to be settled. In relapsing-remitting MS timely and adequate disease modifying drug treatment may stabilize or possibly improve cognition. There is no evidence-based symptomatic drug treatment, nor are there optimal non-pharmacological approaches. Leisure activities enhance cognitive reserve. Cognitive rehabilitation in MS patients is still in its infancy. Cognitive behavioral therapy, exercise, and education programs are promising psychosocial interventions to improve coping and lessen cognitive symptoms.

  13. Analysis of Cortical Flow Models In Vivo

    PubMed Central

    Benink, Hélène A.; Mandato, Craig A.; Bement, William M.

    2000-01-01

    Cortical flow, the directed movement of cortical F-actin and cortical organelles, is a basic cellular motility process. Microtubules are thought to somehow direct cortical flow, but whether they do so by stimulating or inhibiting contraction of the cortical actin cytoskeleton is the subject of debate. Treatment of Xenopus oocytes with phorbol 12-myristate 13-acetate (PMA) triggers cortical flow toward the animal pole of the oocyte; this flow is suppressed by microtubules. To determine how this suppression occurs and whether it can control the direction of cortical flow, oocytes were subjected to localized manipulation of either the contractile stimulus (PMA) or microtubules. Localized PMA application resulted in redirection of cortical flow toward the site of application, as judged by movement of cortical pigment granules, cortical F-actin, and cortical myosin-2A. Such redirected flow was accelerated by microtubule depolymerization, showing that the suppression of cortical flow by microtubules is independent of the direction of flow. Direct observation of cortical F-actin by time-lapse confocal analysis in combination with photobleaching showed that cortical flow is driven by contraction of the cortical F-actin network and that microtubules suppress this contraction. The oocyte germinal vesicle serves as a microtubule organizing center in Xenopus oocytes; experimental displacement of the germinal vesicle toward the animal pole resulted in localized flow away from the animal pole. The results show that 1) cortical flow is directed toward areas of localized contraction of the cortical F-actin cytoskeleton; 2) microtubules suppress cortical flow by inhibiting contraction of the cortical F-actin cytoskeleton; and 3) localized, microtubule-dependent suppression of actomyosin-based contraction can control the direction of cortical flow. We discuss these findings in light of current models of cortical flow. PMID:10930453

  14. Spatial integration and cortical dynamics.

    PubMed Central

    Gilbert, C D; Das, A; Ito, M; Kapadia, M; Westheimer, G

    1996-01-01

    Cells in adult primary visual cortex are capable of integrating information over much larger portions of the visual field than was originally thought. Moreover, their receptive field properties can be altered by the context within which local features are presented and by changes in visual experience. The substrate for both spatial integration and cortical plasticity is likely to be found in a plexus of long-range horizontal connections, formed by cortical pyramidal cells, which link cells within each cortical area over distances of 6-8 mm. The relationship between horizontal connections and cortical functional architecture suggests a role in visual segmentation and spatial integration. The distribution of lateral interactions within striate cortex was visualized with optical recording, and their functional consequences were explored by using comparable stimuli in human psychophysical experiments and in recordings from alert monkeys. They may represent the substrate for perceptual phenomena such as illusory contours, surface fill-in, and contour saliency. The dynamic nature of receptive field properties and cortical architecture has been seen over time scales ranging from seconds to months. One can induce a remapping of the topography of visual cortex by making focal binocular retinal lesions. Shorter-term plasticity of cortical receptive fields was observed following brief periods of visual stimulation. The mechanisms involved entailed, for the short-term changes, altering the effectiveness of existing cortical connections, and for the long-term changes, sprouting of axon collaterals and synaptogenesis. The mutability of cortical function implies a continual process of calibration and normalization of the perception of visual attributes that is dependent on sensory experience throughout adulthood and might further represent the mechanism of perceptual learning. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8570604

  15. Visual impairment.

    PubMed

    Ellenberger, Carl

    2016-01-01

    This chapter can guide the use of imaging in the evaluation of common visual syndromes: transient visual disturbance, including migraine and amaurosis fugax; acute optic neuropathy complicating multiple sclerosis, neuromyelitis optica spectrum disorder, Leber hereditary optic neuropathy, and Susac syndrome; papilledema and pseudotumor cerebri syndrome; cerebral disturbances of vision, including posterior cerebral arterial occlusion, posterior reversible encephalopathy, hemianopia after anterior temporal lobe resection, posterior cortical atrophy, and conversion blindness. Finally, practical efforts in visual rehabilitation by sensory substitution for blind patients can improve their lives and disclose new information about the brain. PMID:27430448

  16. Models of cortical malformation--Chemical and physical.

    PubMed

    Luhmann, Heiko J

    2016-02-15

    Pharmaco-resistant epilepsies, and also some neuropsychiatric disorders, are often associated with malformations in hippocampal and neocortical structures. The mechanisms leading to these cortical malformations causing an imbalance between the excitatory and inhibitory system are largely unknown. Animal models using chemical or physical manipulations reproduce different human pathologies by interfering with cell generation and neuronal migration. The model of in utero injection of methylazoxymethanol (MAM) acetate mimics periventricular nodular heterotopia. The freeze lesion model reproduces (poly)microgyria, focal heterotopia and schizencephaly. The in utero irradiation model causes microgyria and heterotopia. Intraperitoneal injections of carmustine 1-3-bis-chloroethyl-nitrosurea (BCNU) to pregnant rats produces laminar disorganization, heterotopias and cytomegalic neurons. The ibotenic acid model induces focal cortical malformations, which resemble human microgyria and ulegyria. Cortical dysplasia can be also observed following prenatal exposure to ethanol, cocaine or antiepileptic drugs. All these models of cortical malformations are characterized by a pronounced hyperexcitability, few of them also produce spontaneous epileptic seizures. This dysfunction results from an impairment in GABAergic inhibition and/or an increase in glutamatergic synaptic transmission. The cortical region initiating or contributing to this hyperexcitability may not necessarily correspond to the site of the focal malformation. In some models wide-spread molecular and functional changes can be observed in remote regions of the brain, where they cause pathophysiological activities. This paper gives an overview on different animal models of cortical malformations, which are mostly used in rodents and which mimic the pathology and to some extent the pathophysiology of neuronal migration disorders associated with epilepsy in humans.

  17. Alterations in cortical thickness development in preterm-born individuals: Implications for high-order cognitive functions

    PubMed Central

    Nam, Kie Woo; Castellanos, Nazareth; Simmons, Andrew; Froudist-Walsh, Seán; Allin, Matthew P.; Walshe, Muriel; Murray, Robin M.; Evans, Alan; Muehlboeck, J-Sebastian; Nosarti, Chiara

    2015-01-01

    Very preterm birth (gestational age < 33 weeks) is associated with alterations in cortical thickness and with neuropsychological/behavioural impairments. Here we studied cortical thickness in very preterm born individuals and controls in mid-adolescence (mean age 15 years) and beginning of adulthood (mean age 20 years), as well as longitudinal changes between the two time points. Using univariate approaches, we showed both increases and decreases in cortical thickness in very preterm born individuals compared to controls. Specifically (1) very preterm born adolescents displayed extensive areas of greater cortical thickness, especially in occipitotemporal and prefrontal cortices, differences which decreased substantially by early adulthood; (2) at both time points, very preterm-born participants showed smaller cortical thickness, especially in parahippocampal and insular regions. We then employed a multivariate approach (support vector machine) to study spatially discriminating features between the two groups, which achieved a mean accuracy of 86.5%. The spatially distributed regions in which cortical thickness best discriminated between the groups (top 5%) included temporal, occipitotemporal, parietal and prefrontal cortices. Within these spatially distributed regions (top 1%), longitudinal changes in cortical thickness in left temporal pole, right occipitotemporal gyrus and left superior parietal lobe were significantly associated with scores on language-based tests of executive function. These results describe alterations in cortical thickness development in preterm-born individuals in their second decade of life, with implications for high-order cognitive processing. PMID:25871628

  18. Alterations in cortical thickness development in preterm-born individuals: Implications for high-order cognitive functions.

    PubMed

    Nam, Kie Woo; Castellanos, Nazareth; Simmons, Andrew; Froudist-Walsh, Seán; Allin, Matthew P; Walshe, Muriel; Murray, Robin M; Evans, Alan; Muehlboeck, J-Sebastian; Nosarti, Chiara

    2015-07-15

    Very preterm birth (gestational age <33 weeks) is associated with alterations in cortical thickness and with neuropsychological/behavioural impairments. Here we studied cortical thickness in very preterm born individuals and controls in mid-adolescence (mean age 15 years) and beginning of adulthood (mean age 20 years), as well as longitudinal changes between the two time points. Using univariate approaches, we showed both increases and decreases in cortical thickness in very preterm born individuals compared to controls. Specifically (1) very preterm born adolescents displayed extensive areas of greater cortical thickness, especially in occipitotemporal and prefrontal cortices, differences which decreased substantially by early adulthood; (2) at both time points, very preterm-born participants showed smaller cortical thickness, especially in parahippocampal and insular regions. We then employed a multivariate approach (support vector machine) to study spatially discriminating features between the two groups, which achieved a mean accuracy of 86.5%. The spatially distributed regions in which cortical thickness best discriminated between the groups (top 5%) included temporal, occipitotemporal, parietal and prefrontal cortices. Within these spatially distributed regions (top 1%), longitudinal changes in cortical thickness in left temporal pole, right occipitotemporal gyrus and left superior parietal lobe were significantly associated with scores on language-based tests of executive function. These results describe alterations in cortical thickness development in preterm-born individuals in their second decade of life, with implications for high-order cognitive processing. PMID:25871628

  19. The evolution of alexia and simultanagnosia in posterior cortical atrophy.

    PubMed

    Mendez, M F; Cherrier, M M

    1998-04-01

    Early alexia and higher visual impairments characterize Posterior cortical atrophy (PCA), a progressive dementing syndrome most often caused by Alzheimer disease. Posterior cortical atrophy is rare, and the nature of the visual impairments in PCA are unclear. The authors observed two patients who had an insidiously progressive reading difficulty characterized by letter-by-letter reading and otherwise intact cognitive functions. Over time, these patients developed "ventral simultanagnosia" with preserved detection of multiple stimuli but inability to interpret whole scenes. Subsequently, they progressed to Balint syndrome with "dorsal simultanagnosia," optic ataxia, and oculomotor apraxia. Structural imaging was normal, but functional imaging revealed posterior cortical dysfunction. On a letter reading task, both patients had a word superiority effect, and on a whole word reading task, they could not read most words with missing or crosshatched letters. An inability to assess whole scenes progressed to an inability to detect more than one stimulus in an array. These findings suggest an evolution of PCA with progressive difficulty in visual integration beginning with letters, progressing to whole scenes, and culminating in Balint syndrome. These changes may reflect an extension of the pathophysiology of PCA from the extrastriate visual cortex to its occipitotemporal and occipitoparietal connections. PMID:9652488

  20. Early Adolescent Affect Predicts Later Life Outcomes

    PubMed Central

    Kansky, Jessica; Allen, Joseph P.; Diener, Ed

    2016-01-01

    Background Subjective well-being as a predictor for later behavior and health has highlighted its relationship to health, work performance, and social relationships. However, the majority of such studies neglect the developmental nature of well-being in contributing to important changes across the transition to adulthood. Methods To examine the potential role of subjective well-being as a long-term predictor of critical life outcomes, we examined indicators of positive and negative affect at age 14 as a predictor of relationship, adjustment, self worth, and career outcomes a decade later at ages 23 to 25, controlling for family income and gender. We utilized multi-informant methods including reports from the target participant, close friends, and romantic partners in a demographically diverse community sample of 184 participants. Results Early adolescent positive affect predicted less relationship problems (less self-reported and partner-reported conflict, greater friendship attachment as rated by close peers), healthy adjustment to adulthood (lower levels of depression, anxiety, and loneliness). It also predicted positive work functioning (higher levels of career satisfaction and job competence) and increased self-worth. Negative affect did not significantly predict any of these important life outcomes. In addition to predicting desirable mean levels of later outcomes, early positive affect predicted beneficial changes across time in many outcomes. Conclusions The findings extend early research on the beneficial outcomes of subjective well-being by having an earlier assessment of well-being, including informant reports in measuring a large variety of outcome variables, and by extending the findings to a lower socioeconomic group of a diverse and younger sample. The results highlight the importance of considering positive affect as an important component of subjective well-being distinct from negative affect. PMID:27075545

  1. Fructose, pregnancy and later life impacts.

    PubMed

    Regnault, Timothy R H; Gentili, Sheridan; Sarr, Ousseynou; Toop, Carla R; Sloboda, Deborah M

    2013-11-01

    Fructose is an increasingly common constituent of the Westernized diet due to cost and production efficiencies. Although an integral component of our pre-industrial revolution diet, over the past two decades human and animal studies have highlighted that excessive fructose intake appears to be associated with adverse metabolic effects. Excessive intake of fructose is the combined result of increased total energy consumption and increased portion sizes of foods, which often incorporate the fructose-containing sugars sucrose and high-fructose corn-syrup (HFCS). The adverse metabolic effects following excessive fructose consumption have become a hot topic in mainstream media and there is now rigorous scientific debate regarding periods of exposure, dosage levels, interactive effects with other sugars and fats and mechanisms underlying the actions of fructose. There is still a degree of controversy regarding the extent to which sugars such as sucrose and HFCS have contributed to the current epidemic of obesity and diabetes. Furthermore, an increasing number of infants are being exposed to sugar-sweetened food and beverages before birth and during early postnatal life, highlighting the importance of determining the long-term effects of this perinatal exposure on the developing offspring. There are limited human observational and controlled studies identifying associations of excessive sweetened food and beverage consumption with poor pregnancy outcomes. Animal research has demonstrated an increased incidence of gestational diabetes as well as altered maternal, fetal and offspring metabolic function, although the long-term effects and the mechanism underlying these perturbations are ill defined. This review aims to understand the role of early life fructose exposure in modifying postnatal risk of disease in the offspring, focusing on fructose intake during pregnancy and in early postnatal life.

  2. Stress and Adaptation in Later Life.

    ERIC Educational Resources Information Center

    Palmore, Erdman; And Others

    1979-01-01

    Effects of major life events, and of types of resources, on the physical and social-psychological adaptation of participants in a longitudinal study were examined. Medical events had the most impact on physical adaptation but had little impact on social-psychological adaptation. Retirement had the most negative social-psychological effects.…

  3. MOTIVES FOR RESIDENTIAL MOBILITY IN LATER LIFE

    PubMed Central

    SERGEANT, JULIE F.; EKERDT, DAVID J.

    2008-01-01

    This qualitative study delineates motives for residential mobility, describes dynamics between the elder and family members during the move decision process, and locates the move decision within ecological layers of the aging context. Interviews were conducted with 30 individuals and couples (ages 60-87) who experienced a community-based move within the past year, and with 14 extended family members. Reasons for moving (from perspectives of both elders who moved and their family members) were grouped into four themes and eleven issues that influenced the move decision. These themes parallel the ecological context of individual health and functioning, beliefs and attitudes, physical environment, and social pressures. Late-life mobility is a significant life transition that is the outcome of an ongoing appraisal and reappraisal of housing fit with individual functioning, needs, and aspirations. Family members are an integral part of these decision and residential mobility processes. Well, she moved because my sister and I decided she was going to move. But she wanted to move. It wouldn’t have happened if we hadn’t decided that she was gonna move. It was a little complicated . . . - Linda Brierton’s daughter, Karen PMID:18453180

  4. Isolation of the Unmarried in Later Life.

    ERIC Educational Resources Information Center

    Keith, Pat M.

    1986-01-01

    Reports longitudinal research which examined isolation among the unmarried aged and assessed personal characteristics associated with isolation from family and friends. Men and women were more isolated from neighbors and friends than from family, although the never-married maintained more ties with friends. (Author/BL)

  5. Fructose, pregnancy and later life impacts.

    PubMed

    Regnault, Timothy R H; Gentili, Sheridan; Sarr, Ousseynou; Toop, Carla R; Sloboda, Deborah M

    2013-11-01

    Fructose is an increasingly common constituent of the Westernized diet due to cost and production efficiencies. Although an integral component of our pre-industrial revolution diet, over the past two decades human and animal studies have highlighted that excessive fructose intake appears to be associated with adverse metabolic effects. Excessive intake of fructose is the combined result of increased total energy consumption and increased portion sizes of foods, which often incorporate the fructose-containing sugars sucrose and high-fructose corn-syrup (HFCS). The adverse metabolic effects following excessive fructose consumption have become a hot topic in mainstream media and there is now rigorous scientific debate regarding periods of exposure, dosage levels, interactive effects with other sugars and fats and mechanisms underlying the actions of fructose. There is still a degree of controversy regarding the extent to which sugars such as sucrose and HFCS have contributed to the current epidemic of obesity and diabetes. Furthermore, an increasing number of infants are being exposed to sugar-sweetened food and beverages before birth and during early postnatal life, highlighting the importance of determining the long-term effects of this perinatal exposure on the developing offspring. There are limited human observational and controlled studies identifying associations of excessive sweetened food and beverage consumption with poor pregnancy outcomes. Animal research has demonstrated an increased incidence of gestational diabetes as well as altered maternal, fetal and offspring metabolic function, although the long-term effects and the mechanism underlying these perturbations are ill defined. This review aims to understand the role of early life fructose exposure in modifying postnatal risk of disease in the offspring, focusing on fructose intake during pregnancy and in early postnatal life. PMID:24033459

  6. Measuring the quality of later life.

    PubMed Central

    O'Boyle, C A

    1997-01-01

    This paper examines quality of life as a scientific construct with a wide range of applications. The assessment of patients' quality of life is assuming increasing importance in medicine and health care. Illnesses, diseases and their treatments can have significant impacts on such areas of functioning as mobility, mood, life satisfaction, sexuality, cognition and ability to fulfil occupational, social and family roles. The emerging quality of life construct may be viewed as a paradigm shift in outcome measurement since it shifts the focus of attention from symptoms to functioning. This holistic approach more clearly establishes the patient as the centre of attention and subsumes many of the traditional measures of outcome. Quality of life assessment is particularly relevant to ageing populations both for healthy elderly and for those who develop chronic diseases where maintenance of quality of life rather than cure may be the primary goal of treatment. This paper introduces the concept of quality of life and describes the significant difficulties in definition, measurement and interpretation that must be addressed before such measures can be used as reliable and valid indicators of disease impact and treatment outcomes. It is argued that approaches to quality of life assessment in the elderly should incorporate advances in knowledge about the psychological adaptation to ageing. Consequently, the unique perspective of the individual on his or her own quality of life must be incorporated into outcome assessments aimed at improving the quality of health care. Incorporating measures of subjective outcome such as quality of life into policy decisions on resource allocation in health care will prove one of the major challenges for health services over the next decade. PMID:9460072

  7. Wisdom and Psychosocial Functioning in Later Life.

    PubMed

    Wink, Paul; Staudinger, Ursula M

    2016-06-01

    We investigated the connection between wisdom-related performance, personality, and generativity to further the understanding of how they are interrelated. Our sample consisted of 163 men and women 68-77 years of age, mostly White, and predominantly middle class. Wisdom was assessed with the performance-based Berlin Wisdom Paradigm, with the remaining measures being mostly self-report. As hypothesized, on the zero-order level, wisdom-related performance (WRP) was positively associated with (a) growth, a personality component indexed by Openness to Experience, psychological mindedness, and a sense of well-being derived from growth, purpose in life, and autonomy; (b) adjustment, a personality component associated with life satisfaction, high levels of Agreeableness and Conscientiousness, low Neuroticism, a sense of well-being derived from positive relations with others, self-acceptance, and environmental mastery; and (c) a generative concern for the welfare of others. Latent path analysis indicated that the bivariate associations between adjustment and wisdom and between generativity and wisdom were mediated by growth. Wise individuals are characterized by their ability to balance different personal strengths and interests, an integration that occurs, however, within the context of a dominant personality style marked by the pursuit of maturity through personal growth.

  8. Increased visual cortical thickness in sight-recovery individuals.

    PubMed

    Guerreiro, Maria J S; Erfort, Maria V; Henssler, Jonathan; Putzar, Lisa; Röder, Brigitte

    2015-12-01

    Individuals who are born blind due to dense bilateral cataracts and who later regain vision due to cataract surgery provide a unique model to evaluate the effect of early sensory experience in humans. In recent years, several studies have started to assess the functional consequences of early visual deprivation in these individuals, revealing a number of behavioral impairments in visual and multisensory functions. In contrast, the extent to which a transient period of congenital visual deprivation impacts brain structure has not yet been investigated. The present study investigated this by assessing cortical thickness of occipital areas in a group of six cataract-reversal individuals and a group of six age-matched normally sighted controls. This analysis revealed higher cortical thickness in cataract-reversal individuals in the left calcarine sulcus, in the superior occipital gyrus and in the transverse occipital sulcus bilaterally. In addition, occipital cortical thickness correlated negatively with behavioral performance in an audio-visual task for which visual input was critical, and positively with behavioral performance in auditory tasks. Together, these results underscore the critical role of early sensory experience in shaping brain structure and suggest that increased occipital cortical thickness, while potentially compensatory for auditory sensory processing, might be maladaptive for visual recovery in cases of sight restoration.

  9. Homeostatic responses by surviving cortical pyramidal cells in neurodegenerative tauopathy.

    PubMed

    Crimins, Johanna L; Rocher, Anne B; Peters, Alan; Shultz, Penny; Lewis, Jada; Luebke, Jennifer I

    2011-11-01

    Cortical neuron death is prevalent by 9 months in rTg(tau(P301L))4510 tau mutant mice (TG) and surviving pyramidal cells exhibit dendritic regression and spine loss. We used whole-cell patch-clamp recordings to investigate the impact of these marked structural changes on spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) of layer 3 pyramidal cells in frontal cortical slices from behaviorally characterized TG and non-transgenic (NT) mice at this age. Frontal lobe function of TG mice was intact following a short delay interval but impaired following a long delay interval in an object recognition test, and cortical atrophy and cell loss were pronounced. Surviving TG cells had significantly reduced dendritic diameters, total spine density, and mushroom spines, yet sEPSCs were increased and sIPSCs were unchanged in frequency. Thus, despite significant regressive structural changes, synaptic responses were not reduced in TG cells, indicating that homeostatic compensatory mechanisms occur during progressive tauopathy. Consistent with this idea, surviving TG cells were more intrinsically excitable than NT cells, and exhibited sprouting of filopodia and axonal boutons. Moreover, the neuropil in TG mice showed an increased density of asymmetric synapses, although their mean size was reduced. Taken together, these data indicate that during progressive tauopathy, cortical pyramidal cells compensate for loss of afferent input by increased excitability and establishment of new synapses. These compensatory homeostatic mechanisms may play an important role in slowing the progression of neuronal network dysfunction during neurodegenerative tauopathies.

  10. Prefrontal atrophy, disrupted NREM slow waves and impaired hippocampal-dependent memory in aging.

    PubMed

    Mander, Bryce A; Rao, Vikram; Lu, Brandon; Saletin, Jared M; Lindquist, John R; Ancoli-Israel, Sonia; Jagust, William; Walker, Matthew P

    2013-03-01

    Aging has independently been associated with regional brain atrophy, reduced slow wave activity (SWA) during non-rapid eye movement (NREM) sleep and impaired long-term retention of episodic memories. However, whether the interaction of these factors represents a neuropatholgical pathway associated with cognitive decline in later life remains unknown. We found that age-related medial prefrontal cortex (mPFC) gray-matter atrophy was associated with reduced NREM SWA in older adults, the extent to which statistically mediated the impairment of overnight sleep-dependent memory retention. Moreover, this memory impairment was further associated with persistent hippocampal activation and reduced task-related hippocampal-prefrontal cortex functional connectivity, potentially representing impoverished hippocampal-neocortical memory transformation. Together, these data support a model in which age-related mPFC atrophy diminishes SWA, the functional consequence of which is impaired long-term memory. Such findings suggest that sleep disruption in the elderly, mediated by structural brain changes, represents a contributing factor to age-related cognitive decline in later life.

  11. Contralesional neglect in monkeys with small unilateral parietal cortical ablations.

    PubMed

    Marshall, J W B; Baker, H F; Ridley, R M

    2002-10-17

    Transient contralesional spatial neglect, in addition to motor impairment in the contralesional arm, is sometimes seen in patients following cerebral infarction in the right hemisphere and is seen following experimental occlusion of the right middle cerebral artery in primates. To test whether contralesional visuospatial neglect arises from a disruption of the forward flow of information from the striate cortex through the dorsal territory of the middle cerebral artery, we made a small strip suction ablation in the right parietal cortex from the medial edge of the dorsal cortical surface to the posterior ventral edge of the superior temporal gyrus in marmoset monkeys. These monkeys did not exhibit a motor impairment, or misreaching, with the contralesional arm. When they were unrestrained and free to use either arm, they were impaired at finding rewards in their contralesional space and in choosing the nearer of two rewards hidden in ipsilesional space (i.e. they had an ultra-ipsilesional bias in ipsilesional space). Comparison of performance under four conditions in a task in which the monkeys were constrained to reach into each hemispace with each arm separately indicated that they were impaired at reaching into contralesional, but not ipsilesional, space with either arm but they did not exhibit any impairment confined to the contralesional arm. These impairments in contralesional space were transient suggesting that the monkeys were able to re-align their egocentric spatial coordinates to obviate these deficits.

  12. A circuit for motor cortical modulation of auditory cortical activity.

    PubMed

    Nelson, Anders; Schneider, David M; Takatoh, Jun; Sakurai, Katsuyasu; Wang, Fan; Mooney, Richard

    2013-09-01

    Normal hearing depends on the ability to distinguish self-generated sounds from other sounds, and this ability is thought to involve neural circuits that convey copies of motor command signals to various levels of the auditory system. Although such interactions at the cortical level are believed to facilitate auditory comprehension during movements and drive auditory hallucinations in pathological states, the synaptic organization and function of circuitry linking the motor and auditory cortices remain unclear. Here we describe experiments in the mouse that characterize circuitry well suited to transmit motor-related signals to the auditory cortex. Using retrograde viral tracing, we established that neurons in superficial and deep layers of the medial agranular motor cortex (M2) project directly to the auditory cortex and that the axons of some of these deep-layer cells also target brainstem motor regions. Using in vitro whole-cell physiology, optogenetics, and pharmacology, we determined that M2 axons make excitatory synapses in the auditory cortex but exert a primarily suppressive effect on auditory cortical neuron activity mediated in part by feedforward inhibition involving parvalbumin-positive interneurons. Using in vivo intracellular physiology, optogenetics, and sound playback, we also found that directly activating M2 axon terminals in the auditory cortex suppresses spontaneous and stimulus-evoked synaptic activity in auditory cortical neurons and that this effect depends on the relative timing of motor cortical activity and auditory stimulation. These experiments delineate the structural and functional properties of a corticocortical circuit that could enable movement-related suppression of auditory cortical activity. PMID:24005287

  13. Effects of cortical damage on binocular depth perception.

    PubMed

    Bridge, Holly

    2016-06-19

    Stereoscopic depth perception requires considerable neural computation, including the initial correspondence of the two retinal images, comparison across the local regions of the visual field and integration with other cues to depth. The most common cause for loss of stereoscopic vision is amblyopia, in which one eye has failed to form an adequate input to the visual cortex, usually due to strabismus (deviating eye) or anisometropia. However, the significant cortical processing required to produce the percept of depth means that, even when the retinal input is intact from both eyes, brain damage or dysfunction can interfere with stereoscopic vision. In this review, I examine the evidence for impairment of binocular vision and depth perception that can result from insults to the brain, including both discrete damage, temporal lobectomy and more systemic diseases such as posterior cortical atrophy.This article is part of the themed issue 'Vision in our three-dimensional world'.

  14. Effects of cortical damage on binocular depth perception

    PubMed Central

    2016-01-01

    Stereoscopic depth perception requires considerable neural computation, including the initial correspondence of the two retinal images, comparison across the local regions of the visual field and integration with other cues to depth. The most common cause for loss of stereoscopic vision is amblyopia, in which one eye has failed to form an adequate input to the visual cortex, usually due to strabismus (deviating eye) or anisometropia. However, the significant cortical processing required to produce the percept of depth means that, even when the retinal input is intact from both eyes, brain damage or dysfunction can interfere with stereoscopic vision. In this review, I examine the evidence for impairment of binocular vision and depth perception that can result from insults to the brain, including both discrete damage, temporal lobectomy and more systemic diseases such as posterior cortical atrophy. This article is part of the themed issue ‘Vision in our three-dimensional world’. PMID:27269597

  15. Effects of cortical damage on binocular depth perception.

    PubMed

    Bridge, Holly

    2016-06-19

    Stereoscopic depth perception requires considerable neural computation, including the initial correspondence of the two retinal images, comparison across the local regions of the visual field and integration with other cues to depth. The most common cause for loss of stereoscopic vision is amblyopia, in which one eye has failed to form an adequate input to the visual cortex, usually due to strabismus (deviating eye) or anisometropia. However, the significant cortical processing required to produce the percept of depth means that, even when the retinal input is intact from both eyes, brain damage or dysfunction can interfere with stereoscopic vision. In this review, I examine the evidence for impairment of binocular vision and depth perception that can result from insults to the brain, including both discrete damage, temporal lobectomy and more systemic diseases such as posterior cortical atrophy.This article is part of the themed issue 'Vision in our three-dimensional world'. PMID:27269597

  16. Isolated executive impairment and associated frontal neuropathology.

    PubMed

    Johnson, Julene K; Vogt, Brent A; Kim, Ronald; Cotman, Carl W; Head, Elizabeth

    2004-01-01

    Cognitive impairment in the absence of dementia is common in elderly individuals and is most often studied in the context of an isolated impairment in memory. In the current study, we report the neuropsychological and neuropathological features of a nondemented elderly individual with isolated impairment on a test of executive function (i.e., Trail Making Test) and preserved memory, language, and visuospatial function. Postmortem studies indicated that cortical neurofibrillary tangles (NFT) varied considerably, and some regions contained large numbers of neuritic senile plaques. Semiquantitative immunohistochemistry showed higher NFT and amyloid-beta (Abeta) loads in the frontal cortex relative to the temporal, entorhinal, occipital, and parietal cortices. A survey of the entire cingulate gyrus showed a wide dispersion of Abeta42 with the highest concentration in the perigenual part of the anterior cingulate cortex; Abeta appeared to be linked with neuron loss and did not overlap with the heaviest neuritic degeneration. The current case may represent a nonmemory presentation of mild cognitive impairment (executive mild cognitive impairment) that is associated with frontal and anterior cingulate pathology and may be an early stage of the frontal variant of Alzheimer disease.

  17. Evaluating long-latency auditory evoked potentials in the diagnosis of cortical hearing loss in children

    PubMed Central

    Lopez-Soto, Teresa; Postigo-Madueno, Amparo; Nunez-Abades, Pedro

    2016-01-01

    In centrally related hearing loss, there is no apparent damage in the auditory system, but the patient is unable to hear sounds. In patients with cortical hearing loss (and in the absence of communication deficit, either total or partial, as in agnosia or aphasia), some attention-related or language-based disorders may lead to a wrong diagnosis of hearing impairment. The authors present two patients (8 and 11 years old) with no anatomical damage to the ear, the absence of neurological damage or trauma, but immature cortical auditory evoked potentials. Both patients presented a clinical history of multiple diagnoses over several years. Because the most visible symptom was moderate hearing loss, the patients were recurrently referred to audiological testing, with no improvement. This report describes the use of long-latency evoked potentials to determine cases of cortical hearing loss, where hearing impairment is a consequence of underdevelopment at the central nervous system. PMID:27006780

  18. Imprinting and recalling cortical ensembles.

    PubMed

    Carrillo-Reid, Luis; Yang, Weijian; Bando, Yuki; Peterka, Darcy S; Yuste, Rafael

    2016-08-12

    Neuronal ensembles are coactive groups of neurons that may represent building blocks of cortical circuits. These ensembles could be formed by Hebbian plasticity, whereby synapses between coactive neurons are strengthened. Here we report that repetitive activation with two-photon optogenetics of neuronal populations from ensembles in the visual cortex of awake mice builds neuronal ensembles that recur spontaneously after being imprinted and do not disrupt preexisting ones. Moreover, imprinted ensembles can be recalled by single- cell stimulation and remain coactive on consecutive days. Our results demonstrate the persistent reconfiguration of cortical circuits by two-photon optogenetics into neuronal ensembles that can perform pattern completion. PMID:27516599

  19. Grid cells and cortical representation.

    PubMed

    Moser, Edvard I; Roudi, Yasser; Witter, Menno P; Kentros, Clifford; Bonhoeffer, Tobias; Moser, May-Britt

    2014-07-01

    One of the grand challenges in neuroscience is to comprehend neural computation in the association cortices, the parts of the cortex that have shown the largest expansion and differentiation during mammalian evolution and that are thought to contribute profoundly to the emergence of advanced cognition in humans. In this Review, we use grid cells in the medial entorhinal cortex as a gateway to understand network computation at a stage of cortical processing in which firing patterns are shaped not primarily by incoming sensory signals but to a large extent by the intrinsic properties of the local circuit.

  20. Horizontal integration and cortical dynamics.

    PubMed

    Gilbert, C D

    1992-07-01

    We have discussed several results that lead to a view that cells in the visual system are endowed with dynamic properties, influenced by context, expectation, and long-term modifications of the cortical network. These observations will be important for understanding how neuronal ensembles produce a system that perceives, remembers, and adapts to injury. The advantage to being able to observe changes at early stages in a sensory pathway is that one may be able to understand the way in which neuronal ensembles encode and represent images at the level of their receptive field properties, of cortical topographies, and of the patterns of connections between cells participating in a network.

  1. Apraxia in a patient with lesion located in right sub-cortical area. Analysis of errors.

    PubMed

    Mozaz, M; Marti, J F; Carrera, E; De la Puente, E

    1990-12-01

    This report describes a case of apraxia caused by a right sided sub-cortical lesion. Performance on test for apraxia was impaired. A new type of error which involved demonstrating the use of objects on one's own body is reported. Some theoretical interpretations of the findings are discussed.

  2. Neural Correlates of Impaired Vision in Adolescents Born Extremely Preterm and/or Extremely Low Birthweight

    PubMed Central

    Kelly, Claire E.; Cheong, Jeanie L. Y.; Molloy, Carly; Anderson, Peter J.; Lee, Katherine J.; Burnett, Alice C.; Connelly, Alan; Doyle, Lex W.; Thompson, Deanne K.

    2014-01-01

    Background Adolescents born extremely preterm (EP; <28 weeks' gestation) and/or extremely low birthweight (ELBW; <1000 g) experience high rates of visual impairments, however the potential neural correlates of visual impairments in EP/ELBW adolescents require further investigation. This study aimed to: 1) compare optic radiation and primary visual cortical structure between EP/ELBW adolescents and normal birthweight controls; 2) investigate associations between perinatal factors and optic radiation and primary visual cortical structure in EP/ELBW adolescents; 3) investigate associations between optic radiation and primary visual cortical structure in EP/ELBW adolescents and the odds of impaired vision. Methods 196 EP/ELBW adolescents and 143 controls underwent magnetic resonance imaging at a mean age of 18 years. Optic radiations were delineated using constrained spherical deconvolution based probabilistic tractography. Primary visual cortices were segmented using FreeSurfer software. Diffusion tensor variables and tract volume of the optic radiations, as well as volume, surface area and thickness of the primary visual cortices, were estimated. Results Axial, radial and mean diffusivities within the optic radiations, and primary visual cortical thickness, were higher in the EP/ELBW adolescents than controls. Within EP/ELBW adolescents, postnatal corticosteroid exposure was associated with altered optic radiation diffusion values and lower tract volume, while decreasing gestational age at birth was associated with increased primary visual cortical volume, area and thickness. Furthermore, decreasing optic radiation fractional anisotropy and tract volume, and increasing optic radiation diffusivity in EP/ELBW adolescents were associated with increased odds of impaired vision, whereas primary visual cortical measures were not associated with the odds of impaired vision. Conclusions Optic radiation and primary visual cortical structure are altered in EP/ELBW adolescents

  3. [Cognitive impairment in Parkinson's disease].

    PubMed

    Tachibana, Hisao

    2013-01-01

    Cognitive impairment is a common finding in Parkinson's disease (PD), even in the early stages. The concept of mild cognitive impairment (MCI) in PD was recently formalized with diagnosis being reached after impairments in neuropsychological tasks become significant in at least one domain. The brain profile of cognitive deficits involves executive functions (e. g., planning, set shifting, set maintenance, problem solving), attention and memory function. Memory deficits are characterized by impairments in delayed recall, temporal ordering and conditional associate learning. PD patients demonstrate relatively preserved recognition. Visuospatial dysfunctions have also been reported, while language is largely preserved. The existence of two distinct mild cognitive syndromes has also been suggested. One of these affects mainly the frontostriatal executive deficits that are modulated by dopaminergic medications and by a genetically determined level of prefrontal cortex dopamine release. The other affects the more-posterior cortical abilities, such as visuospatial and memory functions, and is suggested to be associated with an increased risk for conversion to dementia. Cross-sectional studies have commonly reported dementia in 20-30% of PD patients, although the 8-year cumulative incidence of dementia may be as high as 78%. Factors associated with dementia in PD are age at onset, age at the time of examination, akinetic-rigid form PD, depression, hallucination, rapid eye movement sleep behavioral disorder and severe olfactory deficits. Clinical features generally involve the same type of deficits as those found in MCI patients, which are more severe and more extensive. The phenomenology of the dementia syndrome is similar to that seen in dementia with Lewy bodies, and clinicopathological correlation studies have revealed varying results with regard to neurochemical deficits and the pathological substrate underlying cognitive impairment and dementia. Early cognitive

  4. Pitch-Responsive Cortical Regions in Congenital Amusia.

    PubMed

    Norman-Haignere, Sam V; Albouy, Philippe; Caclin, Anne; McDermott, Josh H; Kanwisher, Nancy G; Tillmann, Barbara

    2016-03-01

    Congenital amusia is a lifelong deficit in music perception thought to reflect an underlying impairment in the perception and memory of pitch. The neural basis of amusic impairments is actively debated. Some prior studies have suggested that amusia stems from impaired connectivity between auditory and frontal cortex. However, it remains possible that impairments in pitch coding within auditory cortex also contribute to the disorder, in part because prior studies have not measured responses from the cortical regions most implicated in pitch perception in normal individuals. We addressed this question by measuring fMRI responses in 11 subjects with amusia and 11 age- and education-matched controls to a stimulus contrast that reliably identifies pitch-responsive regions in normal individuals: harmonic tones versus frequency-matched noise. Our findings demonstrate that amusic individuals with a substantial pitch perception deficit exhibit clusters of pitch-responsive voxels that are comparable in extent, selectivity, and anatomical location to those of control participants. We discuss possible explanations for why amusics might be impaired at perceiving pitch relations despite exhibiting normal fMRI responses to pitch in their auditory cortex: (1) individual neurons within the pitch-responsive region might exhibit abnormal tuning or temporal coding not detectable with fMRI, (2) anatomical tracts that link pitch-responsive regions to other brain areas (e.g., frontal cortex) might be altered, and (3) cortical regions outside of pitch-responsive cortex might be abnormal. The ability to identify pitch-responsive regions in individual amusic subjects will make it possible to ask more precise questions about their role in amusia in future work. PMID:26961952

  5. An essential role of SVZ progenitors in cortical folding in gyrencephalic mammals

    PubMed Central

    Toda, Tomohisa; Shinmyo, Yohei; Dinh Duong, Tung Anh; Masuda, Kosuke; Kawasaki, Hiroshi

    2016-01-01

    Because folding of the cerebral cortex in the mammalian brain is believed to be crucial for higher brain functions, the mechanisms underlying its formation during development and evolution are of great interest. Although it has been proposed that increased neural progenitors in the subventricular zone (SVZ) are responsible for making cortical folds, their roles in cortical folding are still largely unclear, mainly because genetic methods for gyrencephalic mammals had been poorly available. Here, by taking an advantage of our newly developed in utero electroporation technique for the gyrencephalic brain of ferrets, we investigated the role of SVZ progenitors in cortical folding. We found regional differences in the abundance of SVZ progenitors in the developing ferret brain even before cortical folds began to be formed. When Tbr2 transcription factor was inhibited, intermediate progenitor cells were markedly reduced in the ferret cerebral cortex. Interestingly, outer radial glial cells were also reduced by inhibiting Tbr2. We uncovered that reduced numbers of SVZ progenitors resulted in impaired cortical folding. When Tbr2 was inhibited, upper cortical layers were preferentially reduced in gyri compared to those in sulci. Our findings indicate the biological importance of SVZ progenitors in cortical folding in the gyrencephalic brain. PMID:27403992

  6. Early detection of AD using cortical thickness measurements

    NASA Astrophysics Data System (ADS)

    Spjuth, M.; Gravesen, F.; Eskildsen, S. F.; Østergaard, L. R.

    2007-03-01

    Alzheimer's disease (AD) is a neurodegenerative disorder that causes cortical atrophy and impaired cognitive functions. The diagnosis is difficult to make and is often made over a longer period of time using a combination of neuropsychological tests, and structural and functional imaging. Due to the impact of early intervention the challenge of distinguishing early AD from normal ageing has received increasing attention. This study uses cortical thickness measurements to characterize the atrophy in nine mild AD patients (mean MMSE-score 23.3 (std: 2.6)) compared to five healthy middle-aged subjects. A fully automated method based on deformable models is used for delineation of the inner and outer boundaries of the cerebral cortex from Magnetic Resonance Images. This allows observer independent high-resolution quantification of the cortical thickness. The cortex analysis facilitates detection of alterations throughout the entire cortical mantle. To perform inter-subject thickness comparison in which the spatial information is retained, a feature-based registration algorithm is developed which uses local cortical curvature, normal vector, and a distance measure. A comparison of the two study groups reveals that the lateral side of the hemispheres shows diffuse thinner areas in the mild AD group but especially the medial side shows a pronounced thinner area which can be explained by early limbic changes in AD. For classification principal component analysis is applied to reduce the high number of thickness measurements (>200,000) into fewer features. All mild AD and healthy middle-aged subjects are classified correctly (sensitivity and specificity 100%).

  7. Biomechanics of Single Cortical Neurons

    PubMed Central

    Bernick, Kristin B.; Prevost, Thibault P.; Suresh, Subra; Socrate, Simona

    2011-01-01

    This study presents experimental results and computational analysis of the large strain dynamic behavior of single neurons in vitro with the objective of formulating a novel quantitative framework for the biomechanics of cortical neurons. Relying on the atomic force microscopy (AFM) technique, novel testing protocols are developed to enable the characterization of neural soma deformability over a range of indentation rates spanning three orders of magnitude – 10, 1, and 0.1 μm/s. Modified spherical AFM probes were utilized to compress the cell bodies of neonatal rat cortical neurons in load, unload, reload and relaxation conditions. The cell response showed marked hysteretic features, strong non-linearities, and substantial time/rate dependencies. The rheological data were complemented with geometrical measurements of cell body morphology, i.e. cross-diameter and height estimates. A constitutive model, validated by the present experiments, is proposed to quantify the mechanical behavior of cortical neurons. The model aimed to correlate empirical findings with measurable degrees of (hyper-) elastic resilience and viscosity at the cell level. The proposed formulation, predicated upon previous constitutive model developments undertaken at the cortical tissue level, was implemented into a three-dimensional finite element framework. The simulated cell response was calibrated to the experimental measurements under the selected test conditions, providing a novel single cell model that could form the basis for further refinements. PMID:20971217

  8. Role of perinatal long-chain omega-3 fatty acids in cortical circuit maturation: Mechanisms and implications for psychopathology.

    PubMed

    McNamara, Robert K; Vannest, Jennifer J; Valentine, Christina J

    2015-03-22

    Accumulating translational evidence suggests that the long-chain omega-3 fatty acid docosahexaenoic acid (DHA) plays a role in the maturation and stability of cortical circuits that are impaired in different recurrent psychiatric disorders. Specifically, rodent and cell culture studies find that DHA preferentially accumulates in synaptic and growth cone membranes and promotes neurite outgrowth, dendritic spine stability, and synaptogenesis. Additional evidence suggests that DHA may play a role in microglia-mediated synaptic pruning, as well as myelin development and resilience. In non-human primates n-3 fatty acid insufficiency during perinatal development leads to widespread deficits in functional connectivity in adult frontal cortical networks compared to primates raised on DHA-fortified diet. Preterm delivery in non-human primates and humans is associated with early deficits in cortical DHA accrual. Human preterm birth is associated with long-standing deficits in myelin integrity and cortical circuit connectivity and increased risk for attention deficit/hyperactivity disorder (ADHD), mood, and psychotic disorders. In general, ADHD and mood and psychotic disorders initially emerge during rapid periods of cortical circuit maturation and are characterized by DHA deficits, myelin pathology, and impaired cortical circuit connectivity. Together these associations suggest that early and uncorrected deficits in fetal brain DHA accrual may represent a modifiable risk factor for cortical circuit maturation deficits in psychiatric disorders, and could therefore have significant implications for informing early intervention and prevention strategies.

  9. Role of perinatal long-chain omega-3 fatty acids in cortical circuit maturation: Mechanisms and implications for psychopathology

    PubMed Central

    McNamara, Robert K; Vannest, Jennifer J; Valentine, Christina J

    2015-01-01

    Accumulating translational evidence suggests that the long-chain omega-3 fatty acid docosahexaenoic acid (DHA) plays a role in the maturation and stability of cortical circuits that are impaired in different recurrent psychiatric disorders. Specifically, rodent and cell culture studies find that DHA preferentially accumulates in synaptic and growth cone membranes and promotes neurite outgrowth, dendritic spine stability, and synaptogenesis. Additional evidence suggests that DHA may play a role in microglia-mediated synaptic pruning, as well as myelin development and resilience. In non-human primates n-3 fatty acid insufficiency during perinatal development leads to widespread deficits in functional connectivity in adult frontal cortical networks compared to primates raised on DHA-fortified diet. Preterm delivery in non-human primates and humans is associated with early deficits in cortical DHA accrual. Human preterm birth is associated with long-standing deficits in myelin integrity and cortical circuit connectivity and increased risk for attention deficit/hyperactivity disorder (ADHD), mood, and psychotic disorders. In general, ADHD and mood and psychotic disorders initially emerge during rapid periods of cortical circuit maturation and are characterized by DHA deficits, myelin pathology, and impaired cortical circuit connectivity. Together these associations suggest that early and uncorrected deficits in fetal brain DHA accrual may represent a modifiable risk factor for cortical circuit maturation deficits in psychiatric disorders, and could therefore have significant implications for informing early intervention and prevention strategies. PMID:25815252

  10. Hearing Loss Severity: Impaired Processing of Formant Transition Duration

    ERIC Educational Resources Information Center

    Coez, A.; Belin, P.; Bizaguet, E.; Ferrary, E.; Zilbovicius, M.; Samson, Y.

    2010-01-01

    Normal hearing listeners exploit the formant transition (FT) detection to identify place of articulation for stop consonants. Neuro-imaging studies revealed that short FT induced less cortical activation than long FT. To determine the ability of hearing impaired listeners to distinguish short and long formant transitions (FT) from vowels of the…

  11. Cortical hyperexcitability and sensitivity to discomfort glare.

    PubMed

    Bargary, Gary; Furlan, Michele; Raynham, Peter J; Barbur, John L; Smith, Andrew T

    2015-03-01

    It is well established that there are two main aspects to glare, the visual impairment and the discomfort, known as disability and discomfort glare, respectively. In contrast to the case of disability glare we understand very little about the underlying mechanisms or physiology of discomfort glare. This study attempts to elucidate the neural mechanisms involved using fMRI and glare sources with controlled levels of retinal illuminance. Prior to carrying out the fMRI experiment, we determined each participant's discomfort glare threshold. The participants were then divided into two groups of equal size based on their ranked sensitivity to discomfort glare, a low and high sensitivity group. In the fMRI experiment each participant was presented with three levels of glare intensity whilst simultaneously required to carry out a simple behavioral task. We compared BOLD responses between the two groups and found that the group more sensitive to glare had an increased response that was localized at three discrete, bilateral cortical locations: one in the cunei, one in the lingual gyri and one in the superior parietal lobules. This increased response was present for all light levels tested, whether or not they were intense enough to cause discomfort glare. Based on the results, we present the case that discomfort glare may be a response to hyperexcitability or saturation of visual neurons. PMID:25659503

  12. Anatomical imbalance between cortical networks in autism.

    PubMed

    Watanabe, Takamitsu; Rees, Geraint

    2016-01-01

    Influential psychological models of autism spectrum disorder (ASD) have proposed that this prevalent developmental disorder results from impairment of global (integrative) information processing and overload of local (sensory) information. However, little neuroanatomical evidence consistent with this account has been reported. Here, we examined relative grey matter volumes (rGMVs) between three cortical networks, how they changed with age, and their relationship with core symptomatology. Using public neuroimaging data of high-functioning ASD males and age-/sex-/IQ-matched controls, we first identified age-associated atypical increases in rGMVs of the regions of two sensory systems (auditory and visual networks), and an age-related aberrant decrease in rGMV of a task-control system (fronto-parietal network, FPN) in ASD children. While the enlarged rGMV of the auditory network in ASD adults was associated with the severity of autistic socio-communicational core symptom, that of the visual network was instead correlated with the severity of restricted and repetitive behaviours in ASD. Notably, the atypically decreased rGMV of FPN predicted both of the two core symptoms. These findings suggest that disproportionate undergrowth of a task-control system (FPN) may be a common anatomical basis for the two ASD core symptoms, and relative overgrowth of the two different sensory systems selectively compounds the distinct symptoms.

  13. Anatomical imbalance between cortical networks in autism

    PubMed Central

    Watanabe, Takamitsu; Rees, Geraint

    2016-01-01

    Influential psychological models of autism spectrum disorder (ASD) have proposed that this prevalent developmental disorder results from impairment of global (integrative) information processing and overload of local (sensory) information. However, little neuroanatomical evidence consistent with this account has been reported. Here, we examined relative grey matter volumes (rGMVs) between three cortical networks, how they changed with age, and their relationship with core symptomatology. Using public neuroimaging data of high-functioning ASD males and age-/sex-/IQ-matched controls, we first identified age-associated atypical increases in rGMVs of the regions of two sensory systems (auditory and visual networks), and an age-related aberrant decrease in rGMV of a task-control system (fronto-parietal network, FPN) in ASD children. While the enlarged rGMV of the auditory network in ASD adults was associated with the severity of autistic socio-communicational core symptom, that of the visual network was instead correlated with the severity of restricted and repetitive behaviours in ASD. Notably, the atypically decreased rGMV of FPN predicted both of the two core symptoms. These findings suggest that disproportionate undergrowth of a task-control system (FPN) may be a common anatomical basis for the two ASD core symptoms, and relative overgrowth of the two different sensory systems selectively compounds the distinct symptoms. PMID:27484308

  14. Anatomical imbalance between cortical networks in autism.

    PubMed

    Watanabe, Takamitsu; Rees, Geraint

    2016-01-01

    Influential psychological models of autism spectrum disorder (ASD) have proposed that this prevalent developmental disorder results from impairment of global (integrative) information processing and overload of local (sensory) information. However, little neuroanatomical evidence consistent with this account has been reported. Here, we examined relative grey matter volumes (rGMVs) between three cortical networks, how they changed with age, and their relationship with core symptomatology. Using public neuroimaging data of high-functioning ASD males and age-/sex-/IQ-matched controls, we first identified age-associated atypical increases in rGMVs of the regions of two sensory systems (auditory and visual networks), and an age-related aberrant decrease in rGMV of a task-control system (fronto-parietal network, FPN) in ASD children. While the enlarged rGMV of the auditory network in ASD adults was associated with the severity of autistic socio-communicational core symptom, that of the visual network was instead correlated with the severity of restricted and repetitive behaviours in ASD. Notably, the atypically decreased rGMV of FPN predicted both of the two core symptoms. These findings suggest that disproportionate undergrowth of a task-control system (FPN) may be a common anatomical basis for the two ASD core symptoms, and relative overgrowth of the two different sensory systems selectively compounds the distinct symptoms. PMID:27484308

  15. Slower postnatal growth is associated with delayed cerebral cortical maturation in preterm newborns.

    PubMed

    Vinall, Jillian; Grunau, Ruth E; Brant, Rollin; Chau, Vann; Poskitt, Kenneth J; Synnes, Anne R; Miller, Steven P

    2013-01-16

    Slower postnatal growth is an important predictor of adverse neurodevelopmental outcomes in infants born preterm. However, the relationship between postnatal growth and cortical development remains largely unknown. Therefore, we examined the association between neonatal growth and diffusion tensor imaging measures of microstructural cortical development in infants born very preterm. Participants were 95 neonates born between 24 and 32 weeks gestational age studied twice with diffusion tensor imaging: scan 1 at a median of 32.1 weeks (interquartile range, 30.4 to 33.6) and scan 2 at a median of 40.3 weeks (interquartile range, 38.7 to 42.7). Fractional anisotropy and eigenvalues were recorded from 15 anatomically defined cortical regions. Weight, head circumference, and length were recorded at birth and at the time of each scan. Growth between scans was examined in relation to diffusion tensor imaging measures at scans 1 and 2, accounting for gestational age, birth weight, sex, postmenstrual age, known brain injury (white matter injury, intraventricular hemorrhage, and cerebellar hemorrhage), and neonatal illness (patent ductus arteriosus, days intubated, infection, and necrotizing enterocolitis). Impaired weight, length, and head growth were associated with delayed microstructural development of the cortical gray matter (fractional anisotropy: P < 0.001), but not white matter (fractional anisotropy: P = 0.529), after accounting for prenatal growth, neonatal illness, and brain injury. Avoiding growth impairment during neonatal care may allow cortical development to proceed optimally and, ultimately, may provide an opportunity to reduce neurological disabilities related to preterm birth.

  16. Examining cortical thickness in male and female DWI offenders.

    PubMed

    Dedovic, Katarina; Pruessner, Jens; Tremblay, Jacques; Nadeau, Louise; Ouimet, Marie Claude; Lepage, Martin; Brown, Thomas G

    2016-04-21

    Some sex differences have been detected in driving while impaired by alcohol (DWI) offenders. However, understanding of the key factors contributing to DWI among male and female drivers remains elusive, limiting development of targeted interventions. Sex-based neurocognitive analyses could provide the much-needed insight. We examined whether male DWI offenders show cortical thickness anomalies that differ from those in female DWI offenders, when compared to their respective controls. Moderating role of sex and alcohol use on DWI status was also investigated. Sixty-one DWI offenders (29 male; 32 female) and 58 controls (29 male; 29 female) completed an anatomical brain scan and assessments on other relevant characteristics. Only male DWI offenders had reduced cortical thickness in the right dorsal posterior cingulate cortex (PCC), a region involved in cognitive control. Lower cortical thickness was associated with increased odds of DWI status only among males who have not engaged in very hazardous pattern of alcohol misuse in the previous 12 months. Thus, for these male DWI drivers, interventions that could impact PCC could be most advantageous. Continued multidimensional sex analysis of the neural characteristics of male and female DWI offenders is warranted. PMID:27016386

  17. Cortical networks of procedural learning: evidence from cerebellar damage.

    PubMed

    Torriero, Sara; Oliveri, Massimiliano; Koch, Giacomo; Lo Gerfo, Emanuele; Salerno, Silvia; Petrosini, Laura; Caltagirone, Carlo

    2007-03-25

    The lateral cerebellum plays a critical role in procedural learning that goes beyond the strict motor control functions attributed to it. Patients with cerebellar damage show marked impairment in the acquisition of procedures, as revealed by their performance on the serial reaction time task (SRTT). Here we present the case of a patient affected by ischemic damage involving the left cerebellum who showed a selective deficit in procedural learning while performing the SRTT with the left hand. The deficit recovered when the cortical excitability of an extensive network involving both cerebellar hemispheres and the dorsolateral prefrontal cortex (DLPFC) was decreased by low-frequency repetitive transcranial magnetic stimulation (rTMS). Although inhibition of the right DLPFC or a control fronto-parietal region did not modify the patient's performance, inhibition of the right (unaffected) cerebellum and the left DLPFC markedly improved task performance. These findings could be explained by the modulation of a set of inhibitory and excitatory connections between the lateral cerebellum and the contralateral prefrontal area induced by rTMS. The presence of left cerebellar damage is likely associated with a reduced excitatory drive from sub-cortical left cerebellar nuclei towards the right DLPFC, causing reduced excitability of the right DLPFC and, conversely, unbalanced activation of the left DLPFC. Inhibition of the left DLPFC would reduce the unbalancing of cortical activation, thus explaining the observed selective recovery of procedural memory. PMID:17166525

  18. Examining cortical thickness in male and female DWI offenders.

    PubMed

    Dedovic, Katarina; Pruessner, Jens; Tremblay, Jacques; Nadeau, Louise; Ouimet, Marie Claude; Lepage, Martin; Brown, Thomas G

    2016-04-21

    Some sex differences have been detected in driving while impaired by alcohol (DWI) offenders. However, understanding of the key factors contributing to DWI among male and female drivers remains elusive, limiting development of targeted interventions. Sex-based neurocognitive analyses could provide the much-needed insight. We examined whether male DWI offenders show cortical thickness anomalies that differ from those in female DWI offenders, when compared to their respective controls. Moderating role of sex and alcohol use on DWI status was also investigated. Sixty-one DWI offenders (29 male; 32 female) and 58 controls (29 male; 29 female) completed an anatomical brain scan and assessments on other relevant characteristics. Only male DWI offenders had reduced cortical thickness in the right dorsal posterior cingulate cortex (PCC), a region involved in cognitive control. Lower cortical thickness was associated with increased odds of DWI status only among males who have not engaged in very hazardous pattern of alcohol misuse in the previous 12 months. Thus, for these male DWI drivers, interventions that could impact PCC could be most advantageous. Continued multidimensional sex analysis of the neural characteristics of male and female DWI offenders is warranted.

  19. Reconstitution of cortical Dynein function.

    PubMed

    Roth, Sophie; Laan, Liedewij; Dogterom, Marileen

    2014-01-01

    Cytoplasmic dynein is a major microtubule (MT)-associated motor in nearly all eukaryotic cells. A subpopulation of dyneins associates with the cell cortex and the interaction of this cortical dynein with MTs helps to drive processes such as nuclear migration, mitotic spindle orientation, and cytoskeletal reorientation during wound healing. In this chapter, we describe three types of assays in which interactions between cortical dynein and MTs are reconstituted in vitro at increasing levels of complexity. In the first 1D assay, MTs, nucleated from a centrosome attached to a surface, grow against dynein-coated gold barriers. In this assay configuration, the interactions between MTs and dynein attached to a barrier can be studied in great detail. In the second and third assays, a freely moving dynamic aster is placed in either a 2D microfabricated chamber or a 3D water-in-oil emulsion droplet, with dynein-coated boundaries. These assays can be used to study how cortical dynein positions centrosomes. Finally, we discuss future possibilities for increasing the complexity of these reconstituted systems.

  20. Cortical Control of Affective Networks

    PubMed Central

    Kumar, Sunil; Black, Sherilynn J.; Hultman, Rainbo; Szabo, Steven T.; DeMaio, Kristine D.; Du, Jeanette; Katz, Brittany M.; Feng, Guoping; Covington, Herbert E.; Dzirasa, Kafui

    2013-01-01

    Transcranial magnetic stimulation and deep brain stimulation have emerged as therapeutic modalities for treatment refractory depression; however, little remains known regarding the circuitry that mediates the therapeutic effect of these approaches. Here we show that direct optogenetic stimulation of prefrontal cortex (PFC) descending projection neurons in mice engineered to express Chr2 in layer V pyramidal neurons (Thy1–Chr2 mice) models an antidepressant-like effect in mice subjected to a forced-swim test. Furthermore, we show that this PFC stimulation induces a long-lasting suppression of anxiety-like behavior (but not conditioned social avoidance) in socially stressed Thy1–Chr2 mice: an effect that is observed >10 d after the last stimulation. Finally, we use optogenetic stimulation and multicircuit recording techniques concurrently in Thy1–Chr2 mice to demonstrate that activation of cortical projection neurons entrains neural oscillatory activity and drives synchrony across limbic brain areas that regulate affect. Importantly, these neural oscillatory changes directly correlate with the temporally precise activation and suppression of limbic unit activity. Together, our findings show that the direct activation of cortical projection systems is sufficient to modulate activity across networks underlying affective regulation. They also suggest that optogenetic stimulation of cortical projection systems may serve as a viable therapeutic strategy for treating affective disorders. PMID:23325249

  1. Cognitive Impairment in Multiple Sclerosis

    PubMed Central

    Lovera, Jesus; Kovner, Blake

    2012-01-01

    Cognitive Impairment (CI) is a serious complication of MS, and the domains affected are well established but new affected domains such as theory of mind are still being identified. The evidence that some disease modifying therapies (DMTs) may improve and prevent the development of CI in MS is not solid. Recent studies on the prevalence CI in MS, although not as solid as studies completed prior to DMT introduction, suggest that CI remains a problem even among people on DMTs and even at the very earliest stages of MS. Functional MRI studies and studies using diffusion tractography show that the impact of lesions on cognition depends on the particular cortical networks affected and their plasticity. Cognitive rehabilitation and L-amphetamine appear promising treatments, cholinesterase inhibitors and memantine have failed, and data on Ginkgo and exercise are limited. We need more work to understand and develop treatment for CI in MS. PMID:22791241

  2. Differential impact of partial cortical blindness on gaze strategies when sitting and walking - an immersive virtual reality study

    PubMed Central

    Iorizzo, Dana B.; Riley, Meghan E.; Hayhoe, Mary; Huxlin, Krystel R.

    2011-01-01

    The present experiments aimed to characterize the visual performance of subjects with long-standing, unilateral cortical blindness when walking in a naturalistic, virtual environment. Under static, seated testing conditions, cortically blind subjects are known to exhibit compensatory eye movement strategies. However, they still complain of significant impairment in visual detection during navigation. To assess whether this is due to a change in compensatory eye movement strategy between sitting and walking, we measured eye and head movements in subjects asked to detect peripherally-presented, moving basketballs. When seated, cortically blind subjects detected ~80% of balls, while controls detected almost all balls. Seated blind subjects did not make larger head movements than controls, but they consistently biased their fixation distribution towards their blind hemifield. When walking, head movements were similar in the two groups, but the fixation bias decreased to the point that fixation distribution in cortically blind subjects became similar to that in controls - with one major exception: at the time of basketball appearance, walking controls looked primarily at the far ground, in upper quadrants of the virtual field of view; cortically blind subjects looked significantly more at the near ground, in lower quadrants of the virtual field. Cortically blind subjects detected only 58% of the balls when walking while controls detected ~90%. Thus, the adaptive gaze strategies adopted by cortically blind individuals as a compensation for their visual loss are strongest and most effective when seated and stationary. Walking significantly alters these gaze strategies in a way that seems to favor walking performance, but impairs peripheral target detection. It is possible that this impairment underlies the experienced difficulty of those with cortical blindness when navigating in real life. PMID:21414339

  3. Differential impact of partial cortical blindness on gaze strategies when sitting and walking - an immersive virtual reality study.

    PubMed

    Iorizzo, Dana B; Riley, Meghan E; Hayhoe, Mary; Huxlin, Krystel R

    2011-05-25

    The present experiments aimed to characterize the visual performance of subjects with long-standing, unilateral cortical blindness when walking in a naturalistic, virtual environment. Under static, seated testing conditions, cortically blind subjects are known to exhibit compensatory eye movement strategies. However, they still complain of significant impairment in visual detection during navigation. To assess whether this is due to a change in compensatory eye movement strategy between sitting and walking, we measured eye and head movements in subjects asked to detect peripherally-presented, moving basketballs. When seated, cortically blind subjects detected ∼80% of balls, while controls detected almost all balls. Seated blind subjects did not make larger head movements than controls, but they consistently biased their fixation distribution towards their blind hemifield. When walking, head movements were similar in the two groups, but the fixation bias decreased to the point that fixation distribution in cortically blind subjects became similar to that in controls - with one major exception: at the time of basketball appearance, walking controls looked primarily at the far ground, in upper quadrants of the virtual field of view; cortically blind subjects looked significantly more at the near ground, in lower quadrants of the virtual field. Cortically blind subjects detected only 58% of the balls when walking while controls detected ∼90%. Thus, the adaptive gaze strategies adopted by cortically blind individuals as a compensation for their visual loss are strongest and most effective when seated and stationary. Walking significantly alters these gaze strategies in a way that seems to favor walking performance, but impairs peripheral target detection. It is possible that this impairment underlies the experienced difficulty of those with cortical blindness when navigating in real life.

  4. Plasticity of spatial hearing: behavioural effects of cortical inactivation

    PubMed Central

    Nodal, Fernando R; Bajo, Victoria M; King, Andrew J

    2012-01-01

    The contribution of auditory cortex to spatial information processing was explored behaviourally in adult ferrets by reversibly deactivating different cortical areas by subdural placement of a polymer that released the GABAA agonist muscimol over a period of weeks. The spatial extent and time course of cortical inactivation were determined electrophysiologically. Muscimol-Elvax was placed bilaterally over the anterior (AEG), middle (MEG) or posterior ectosylvian gyrus (PEG), so that different regions of the auditory cortex could be deactivated in different cases. Sound localization accuracy in the horizontal plane was assessed by measuring both the initial head orienting and approach-to-target responses made by the animals. Head orienting behaviour was unaffected by silencing any region of the auditory cortex, whereas the accuracy of approach-to-target responses to brief sounds (40 ms noise bursts) was reduced by muscimol-Elvax but not by drug-free implants. Modest but significant localization impairments were observed after deactivating the MEG, AEG or PEG, although the largest deficits were produced in animals in which the MEG, where the primary auditory fields are located, was silenced. We also examined experience-induced spatial plasticity by reversibly plugging one ear. In control animals, localization accuracy for both approach-to-target and head orienting responses was initially impaired by monaural occlusion, but recovered with training over the next few days. Deactivating any part of the auditory cortex resulted in less complete recovery than in controls, with the largest deficits observed after silencing the higher-level cortical areas in the AEG and PEG. Although suggesting that each region of auditory cortex contributes to spatial learning, differences in the localization deficits and degree of adaptation between groups imply a regional specialization in the processing of spatial information across the auditory cortex. PMID:22547635

  5. Numerosity Impairment in Corticobasal Syndrome

    PubMed Central

    Koss, Shira; Clark, Robin; Vesely, Luisa; Weinstein, Jessica; Anderson, Chivon; Richmond, Lauren; Farag, Christine; Gross, Rachel; Liang, Tsao-Wei; Grossman, Murray

    2010-01-01

    OBJECTIVE We assessed the representation of numerosity in corticobasal syndrome (CBS), a neurodegenerative condition affecting the parietal lobe. METHOD Patients judged whether a target numerosity (e.g., “3”) falls between two bounding numerosities (e.g., “1” and “5”). We manipulated the format for representing numerosity (Arabic numerals or dot arrays), the size of the gap between the two bounding numerosities, the absolute magnitude of the numerosities, and the order for presenting the bounding numerosities. In a subset of patients with available imaging, we related performance to cortical atrophy using voxel-based morphometry (VBM). RESULTS CBS patients were significantly impaired overall (65.7% ±16.2 correct) compared to healthy seniors (96.6% ± 2.4 correct), and required three times longer than controls to judge correct stimuli. This deficit was equally evident for Arabic numeral and dot array formats. Controls were significantly slower with smaller gaps than larger gaps, consistent with the greater challenge distinguishing between numerosities that are more similar to each other than very different numerosities. However, CBS patients were equally slow and inaccurate for all gap sizes. Controls also were significantly slower with larger numerosities than smaller numerosities, but CBS patients were equally slow and inaccurate with all numerosity magnitudes. VBM revealed significant cortical atrophy in parietal and frontal regions in CBS compared to controls, including the intraparietal sulcus. CONCLUSIONS These observations are consistent with the claim that the representation of numerosity is degraded in CBS. PMID:20604622

  6. Interictal epileptiform discharges induce hippocampal-cortical coupling in temporal lobe epilepsy

    PubMed Central

    Gelinas, Jennifer N.; Khodagholy, Dion; Thesen, Thomas; Devinsky, Orrin; Buzsáki, György

    2016-01-01

    Interactions between the hippocampus and cortex are critical for memory. Interictal epileptiform discharges (IEDs) identify epileptic brain regions and can impair memory, but how they interact with physiological patterns of network activity is mostly undefined. We show in a rat model of temporal lobe epilepsy that spontaneous hippocampal IEDs correlate with impaired memory consolidation and are precisely coordinated with spindle oscillations in the prefrontal cortex during NREM sleep. This coordination surpasses the normal physiological ripple-spindle coupling and is accompanied by decreased ripple occurrence. IEDs also induce spindles during REM sleep and wakefulness, behavioral states that do not naturally express these oscillations, by generating a cortical ‘DOWN’ state. We confirm a similar correlation of temporofrontal IEDs with spindles over anatomically restricted cortical regions in a pilot clinical examination of four subjects with focal epilepsy. These findings imply that IEDs may impair memory via misappropriation of physiological mechanisms for hippocampal-cortical coupling, suggesting a target to treat memory impairment in epilepsy. PMID:27111281

  7. The effect of blur on cortical responses to global form and motion

    PubMed Central

    Burton, Eliza A.; Wattam-Bell, John; Rubin, Gary S.; Atkinson, Janette; Braddick, Oliver; Nardini, Marko

    2015-01-01

    Global form and motion sensitivity undergo long development in childhood with motion sensitivity rather than form being impaired in a number of childhood disorders and both impaired in adult clinical populations. This suggests extended development and vulnerability of extrastriate cortical areas associated with global processing. However, in some developmental and clinical populations, it remains unclear to what extent impairments might reflect deficits at earlier stages of visual processing, such as reduced visual acuity and contrast sensitivity. To address this, we investigated the impact of degraded spatial vision on cortical global form and motion processing in healthy adults. Loss of high spatial frequencies was simulated using a diffuser to blur the stimuli. Participants completed behavioral and EEG tests of global form and motion perception under three levels of blur. For the behavioral tests, participants' form and motion coherence thresholds were measured using a two-alternative, forced-choice procedure. Steady-state visual evoked potentials were used to measure cortical responses to changes in the coherence of global form and motion stimuli. Both global form and global motion perception were impaired with increasing blur as measured by elevated behavioral thresholds and reduced cortical responses. However, form thresholds showed greater impairment in both behavioral and EEG measures than motion thresholds at the highest levels of blur. The results suggest that high spatial frequencies play an important role in the perception of both global form and motion but are especially significant for global form. Overall, the results reveal complex interactions between low-level factors and global visual processing, highlighting the importance of taking these factors into account when investigating extrastriate function in low vision populations. PMID:26605841

  8. Cortical microtubule rearrangements and cell wall patterning

    PubMed Central

    Oda, Yoshihisa

    2015-01-01

    Plant cortical microtubules, which form a highly ordered array beneath the plasma membrane, play essential roles in determining cell shape and function by directing the arrangement of cellulosic and non-cellulosic compounds on the cell surface. Interphase transverse arrays of cortical microtubules self-organize through their dynamic instability and inter-microtubule interactions, and by branch-form microtubule nucleation and severing. Recent studies revealed that distinct spatial signals including ROP GTPase, cellular geometry, and mechanical stress regulate the behavior of cortical microtubules at the subcellular and supercellular levels, giving rise to dramatic rearrangements in the cortical microtubule array in response to internal and external cues. Increasing evidence indicates that negative regulators of microtubules also contribute to the rearrangement of the cortical microtubule array. In this review, I summarize recent insights into how the rearrangement of the cortical microtubule array leads to proper, flexible cell wall patterning. PMID:25904930

  9. Circadian regulation of human cortical excitability

    PubMed Central

    Ly, Julien Q. M.; Gaggioni, Giulia; Chellappa, Sarah L.; Papachilleos, Soterios; Brzozowski, Alexandre; Borsu, Chloé; Rosanova, Mario; Sarasso, Simone; Middleton, Benita; Luxen, André; Archer, Simon N.; Phillips, Christophe; Dijk, Derk-Jan; Maquet, Pierre; Massimini, Marcello; Vandewalle, Gilles

    2016-01-01

    Prolonged wakefulness alters cortical excitability, which is essential for proper brain function and cognition. However, besides prior wakefulness, brain function and cognition are also affected by circadian rhythmicity. Whether the regulation of cognition involves a circadian impact on cortical excitability is unknown. Here, we assessed cortical excitability from scalp electroencephalography (EEG) responses to transcranial magnetic stimulation in 22 participants during 29 h of wakefulness under constant conditions. Data reveal robust circadian dynamics of cortical excitability that are strongest in those individuals with highest endocrine markers of circadian amplitude. In addition, the time course of cortical excitability correlates with changes in EEG synchronization and cognitive performance. These results demonstrate that the crucial factor for cortical excitability, and basic brain function in general, is the balance between circadian rhythmicity and sleep need, rather than sleep homoeostasis alone. These findings have implications for clinical applications such as non-invasive brain stimulation in neurorehabilitation. PMID:27339884

  10. Inhibitory Circuits in Cortical Layer 5

    PubMed Central

    Naka, Alexander; Adesnik, Hillel

    2016-01-01

    Inhibitory neurons play a fundamental role in cortical computation and behavior. Recent technological advances, such as two photon imaging, targeted in vivo recording, and molecular profiling, have improved our understanding of the function and diversity of cortical interneurons, but for technical reasons most work has been directed towards inhibitory neurons in the superficial cortical layers. Here we review current knowledge specifically on layer 5 (L5) inhibitory microcircuits, which play a critical role in controlling cortical output. We focus on recent work from the well-studied rodent barrel cortex, but also draw on evidence from studies in primary visual cortex and other cortical areas. The diversity of both deep inhibitory neurons and their pyramidal cell targets make this a challenging but essential area of study in cortical computation and sensory processing. PMID:27199675

  11. Hamilton-Jacobi skeleton on cortical surfaces.

    PubMed

    Shi, Y; Thompson, P M; Dinov, I; Toga, A W

    2008-05-01

    In this paper, we propose a new method to construct graphical representations of cortical folding patterns by computing skeletons on triangulated cortical surfaces. In our approach, a cortical surface is first partitioned into sulcal and gyral regions via the solution of a variational problem using graph cuts, which can guarantee global optimality. After that, we extend the method of Hamilton-Jacobi skeleton [1] to subsets of triangulated surfaces, together with a geometrically intuitive pruning process that can trade off between skeleton complexity and the completeness of representing folding patterns. Compared with previous work that uses skeletons of 3-D volumes to represent sulcal patterns, the skeletons on cortical surfaces can be easily decomposed into branches and provide a simpler way to construct graphical representations of cortical morphometry. In our experiments, we demonstrate our method on two different cortical surface models, its ability of capturing major sulcal patterns and its application to compute skeletons of gyral regions. PMID:18450539

  12. Circadian regulation of human cortical excitability.

    PubMed

    Ly, Julien Q M; Gaggioni, Giulia; Chellappa, Sarah L; Papachilleos, Soterios; Brzozowski, Alexandre; Borsu, Chloé; Rosanova, Mario; Sarasso, Simone; Middleton, Benita; Luxen, André; Archer, Simon N; Phillips, Christophe; Dijk, Derk-Jan; Maquet, Pierre; Massimini, Marcello; Vandewalle, Gilles

    2016-06-24

    Prolonged wakefulness alters cortical excitability, which is essential for proper brain function and cognition. However, besides prior wakefulness, brain function and cognition are also affected by circadian rhythmicity. Whether the regulation of cognition involves a circadian impact on cortical excitability is unknown. Here, we assessed cortical excitability from scalp electroencephalography (EEG) responses to transcranial magnetic stimulation in 22 participants during 29 h of wakefulness under constant conditions. Data reveal robust circadian dynamics of cortical excitability that are strongest in those individuals with highest endocrine markers of circadian amplitude. In addition, the time course of cortical excitability correlates with changes in EEG synchronization and cognitive performance. These results demonstrate that the crucial factor for cortical excitability, and basic brain function in general, is the balance between circadian rhythmicity and sleep need, rather than sleep homoeostasis alone. These findings have implications for clinical applications such as non-invasive brain stimulation in neurorehabilitation.

  13. A Rare Hydrocephalus Complication: Cortical Blindness.

    PubMed

    Ünal, Emre; Göçmen, Rahşan; Işıkay, Ayşe İlksen; Tekşam, Özlem

    2015-01-01

    Cortical blindness related to bilateral occipital lobe infarction is an extremely rare complication of hydrocephalus. Compression of the posterior cerebral artery, secondary to tentorial herniation, is the cause of occipital infarction. Particularly in children and mentally ill patients, cortical blindness may be missed. Therefore, early diagnosis and treatment of hydrocephalus is important. We present herein a child of ventricular shunt malfunction complicated by cortical blindness. PMID:27411424

  14. Communication and wiring in the cortical connectome

    PubMed Central

    Budd, Julian M. L.; Kisvárday, Zoltán F.

    2012-01-01

    In cerebral cortex, the huge mass of axonal wiring that carries information between near and distant neurons is thought to provide the neural substrate for cognitive and perceptual function. The goal of mapping the connectivity of cortical axons at different spatial scales, the cortical connectome, is to trace the paths of information flow in cerebral cortex. To appreciate the relationship between the connectome and cortical function, we need to discover the nature and purpose of the wiring principles underlying cortical connectivity. A popular explanation has been that axonal length is strictly minimized both within and between cortical regions. In contrast, we have hypothesized the existence of a multi-scale principle of cortical wiring where to optimize communication there is a trade-off between spatial (construction) and temporal (routing) costs. Here, using recent evidence concerning cortical spatial networks we critically evaluate this hypothesis at neuron, local circuit, and pathway scales. We report three main conclusions. First, the axonal and dendritic arbor morphology of single neocortical neurons may be governed by a similar wiring principle, one that balances the conservation of cellular material and conduction delay. Second, the same principle may be observed for fiber tracts connecting cortical regions. Third, the absence of sufficient local circuit data currently prohibits any meaningful assessment of the hypothesis at this scale of cortical organization. To avoid neglecting neuron and microcircuit levels of cortical organization, the connectome framework should incorporate more morphological description. In addition, structural analyses of temporal cost for cortical circuits should take account of both axonal conduction and neuronal integration delays, which appear mostly of the same order of magnitude. We conclude the hypothesized trade-off between spatial and temporal costs may potentially offer a powerful explanation for cortical wiring patterns

  15. Cortical Tremor (CT) with coincident orthostatic movements.

    PubMed

    Termsarasab, Pichet; Frucht, Steven J

    2015-01-01

    Cortical tremor (CT) is a form of cortical reflex myoclonus that can mimic essential tremor (ET). Clinical features that are helpful in distinguishing CT from ET are the irregular and jerky appearance of the movements. We report two patients with CT with coexisting orthostatic movements, either orthostatic tremor (OT) or myoclonus, who experienced functional improvement in both cortical myoclonus and orthostatic movements when treated with levetiracetam. PMID:26788343

  16. A Rare Hydrocephalus Complication: Cortical Blindness.

    PubMed

    Ünal, Emre; Göçmen, Rahşan; Işıkay, Ayşe İlksen; Tekşam, Özlem

    2015-01-01

    Cortical blindness related to bilateral occipital lobe infarction is an extremely rare complication of hydrocephalus. Compression of the posterior cerebral artery, secondary to tentorial herniation, is the cause of occipital infarction. Particularly in children and mentally ill patients, cortical blindness may be missed. Therefore, early diagnosis and treatment of hydrocephalus is important. We present herein a child of ventricular shunt malfunction complicated by cortical blindness.

  17. Prefrontal cortical volume reduction associated with frontal cortex function deficit in 6-week abstinent crack-cocaine dependent men

    PubMed Central

    Fein, George; Di Sclafani, Victoria; Meyerhoff, Dieter J.

    2010-01-01

    Background This study examined regional cortical volumes in 6-week abstinent men dependent on crack-cocaine only (Cr) or on both crack-cocaine and alcohol (CrA). Our goal was to test the a priori hypothesis of prefrontal cortical volume reduction, along with associated impairments in frontal mediated functions, and to look for differences between the Cr and CrA groups. Methods Structural magnetic resonance imaging (MRI) of the brain and neuropsychological assessment were performed on 17 6-week abstinent Cr subjects, 29 six-week abstinent CrA subjects, and 20 normal controls. Cortical volume was quantified in the prefrontal, parietal, temporal and occipital regions. Results Cr and CrA subjects showed comparable reductions in prefrontal gray matter volume compared to controls; this reduction was negatively associated with performance impairments in the executive function domain. Conclusions Dependence on Cr (with or without concomitant alcohol dependence) was associated with reduced prefrontal cortical volume. Cr dependence with concomitant alcohol dependence was not associated with greater prefrontal volume reductions than Cr dependence alone. The existence of these findings at 6-week abstinence indicates that they are not a result of acute cocaine or alcohol exposure. The association of reduced prefrontal cortical volume with cognitive impairments in frontal cortex mediated abilities suggests that this reduced cerebral volume has functional consequences. PMID:12167554

  18. A Causal Role for the Cortical Frontal Eye Fields in Microsaccade Deployment

    PubMed Central

    Dash, Suryadeep; Lomber, Stephen G.

    2016-01-01

    Microsaccades aid vision by helping to strategically sample visual scenes. Despite the importance of these small eye movements, no cortical area has ever been implicated in their generation. Here, we used unilateral and bilateral reversible inactivation of the frontal eye fields (FEF) to identify a cortical drive for microsaccades. Unexpectedly, FEF inactivation altered microsaccade metrics and kinematics. Such inactivation also impaired microsaccade deployment following peripheral cue onset, regardless of cue side or inactivation configuration. Our results demonstrate that the FEF provides critical top-down drive for microsaccade generation, particularly during the recovery of microsaccades after disruption by sensory transients. Our results constitute the first direct evidence, to our knowledge, for the contribution of any cortical area to microsaccade generation, and they provide a possible substrate for how cognitive processes can influence the strategic deployment of microsaccades. PMID:27509130

  19. Asymmetrical effects of unilateral right or left amygdala damage on auditory cortical processing of vocal emotions

    PubMed Central

    Frühholz, Sascha; Hofstetter, Christoph; Cristinzio, Chiara; Saj, Arnaud; Seeck, Margitta; Vuilleumier, Patrik; Grandjean, Didier

    2015-01-01

    We tested whether human amygdala lesions impair vocal processing in intact cortical networks. In two functional MRI experiments, patients with unilateral amygdala resection either listened to voices and nonvocal sounds or heard binaural vocalizations with attention directed toward or away from emotional information on one side. In experiment 1, all patients showed reduced activation to voices in the ipsilesional auditory cortex. In experiment 2, emotional voices evoked increased activity in both the auditory cortex and the intact amygdala for right-damaged patients, whereas no such effects were found for left-damaged amygdala patients. Furthermore, the left inferior frontal cortex was functionally connected with the intact amygdala in right-damaged patients, but only with homologous right frontal areas and not with the amygdala in left-damaged patients. Thus, unilateral amygdala damage leads to globally reduced ipsilesional cortical voice processing, but only left amygdala lesions are sufficient to suppress the enhanced auditory cortical processing of vocal emotions. PMID:25605886

  20. Altered Theta Oscillations and Aberrant Cortical Excitatory Activity in the 5XFAD Model of Alzheimer's Disease

    PubMed Central

    Siwek, Magdalena Elisabeth; Müller, Ralf; Henseler, Christina; Trog, Astrid; Lundt, Andreas; Wormuth, Carola; Broich, Karl; Weiergräber, Marco; Papazoglou, Anna

    2015-01-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by impairment of memory function. The 5XFAD mouse model was analyzed and compared with wild-type (WT) controls for aberrant cortical excitability and hippocampal theta oscillations by using simultaneous video-electroencephalogram (EEG) monitoring. Seizure staging revealed that 5XFAD mice exhibited cortical hyperexcitability whereas controls did not. In addition, 5XFAD mice displayed a significant increase in hippocampal theta activity from the light to dark phase during nonmotor activity. We also observed a reduction in mean theta frequency in 5XFAD mice compared to controls that was again most prominent during nonmotor activity. Transcriptome analysis of hippocampal probes and subsequent qPCR validation revealed an upregulation of Plcd4 that might be indicative of enhanced muscarinic signalling. Our results suggest that 5XFAD mice exhibit altered cortical excitability, hippocampal dysrhythmicity, and potential changes in muscarinic signaling. PMID:25922768

  1. A Causal Role for the Cortical Frontal Eye Fields in Microsaccade Deployment.

    PubMed

    Peel, Tyler R; Hafed, Ziad M; Dash, Suryadeep; Lomber, Stephen G; Corneil, Brian D

    2016-08-01

    Microsaccades aid vision by helping to strategically sample visual scenes. Despite the importance of these small eye movements, no cortical area has ever been implicated in their generation. Here, we used unilateral and bilateral reversible inactivation of the frontal eye fields (FEF) to identify a cortical drive for microsaccades. Unexpectedly, FEF inactivation altered microsaccade metrics and kinematics. Such inactivation also impaired microsaccade deployment following peripheral cue onset, regardless of cue side or inactivation configuration. Our results demonstrate that the FEF provides critical top-down drive for microsaccade generation, particularly during the recovery of microsaccades after disruption by sensory transients. Our results constitute the first direct evidence, to our knowledge, for the contribution of any cortical area to microsaccade generation, and they provide a possible substrate for how cognitive processes can influence the strategic deployment of microsaccades. PMID:27509130

  2. Myosin VI small insert isoform maintains exocytosis by tethering secretory granules to the cortical actin

    PubMed Central

    Tomatis, Vanesa M.; Papadopulos, Andreas; Malintan, Nancy T.; Martin, Sally; Wallis, Tristan; Gormal, Rachel S.; Kendrick-Jones, John; Buss, Folma

    2013-01-01

    Before undergoing neuroexocytosis, secretory granules (SGs) are mobilized and tethered to the cortical actin network by an unknown mechanism. Using an SG pull-down assay and mass spectrometry, we found that myosin VI was recruited to SGs in a Ca2+-dependent manner. Interfering with myosin VI function in PC12 cells reduced the density of SGs near the plasma membrane without affecting their biogenesis. Myosin VI knockdown selectively impaired a late phase of exocytosis, consistent with a replenishment defect. This exocytic defect was selectively rescued by expression of the myosin VI small insert (SI) isoform, which efficiently tethered SGs to the cortical actin network. These myosin VI SI–specific effects were prevented by deletion of a c-Src kinase phosphorylation DYD motif, identified in silico. Myosin VI SI thus recruits SGs to the cortical actin network, potentially via c-Src phosphorylation, thereby maintaining an active pool of SGs near the plasma membrane. PMID:23382463

  3. Cortical Specializations Underlying Fast Computations

    PubMed Central

    Volgushev, Maxim

    2016-01-01

    The time course of behaviorally relevant environmental events sets temporal constraints on neuronal processing. How does the mammalian brain make use of the increasingly complex networks of the neocortex, while making decisions and executing behavioral reactions within a reasonable time? The key parameter determining the speed of computations in neuronal networks is a time interval that neuronal ensembles need to process changes at their input and communicate results of this processing to downstream neurons. Theoretical analysis identified basic requirements for fast processing: use of neuronal populations for encoding, background activity, and fast onset dynamics of action potentials in neurons. Experimental evidence shows that populations of neocortical neurons fulfil these requirements. Indeed, they can change firing rate in response to input perturbations very quickly, within 1 to 3 ms, and encode high-frequency components of the input by phase-locking their spiking to frequencies up to 300 to 1000 Hz. This implies that time unit of computations by cortical ensembles is only few, 1 to 3 ms, which is considerably faster than the membrane time constant of individual neurons. The ability of cortical neuronal ensembles to communicate on a millisecond time scale allows for complex, multiple-step processing and precise coordination of neuronal activity in parallel processing streams, while keeping the speed of behavioral reactions within environmentally set temporal constraints. PMID:25689988

  4. Cortical control of facial expression.

    PubMed

    Müri, René M

    2016-06-01

    The present Review deals with the motor control of facial expressions in humans. Facial expressions are a central part of human communication. Emotional face expressions have a crucial role in human nonverbal behavior, allowing a rapid transfer of information between individuals. Facial expressions can be either voluntarily or emotionally controlled. Recent studies in nonhuman primates and humans have revealed that the motor control of facial expressions has a distributed neural representation. At least five cortical regions on the medial and lateral aspects of each hemisphere are involved: the primary motor cortex, the ventral lateral premotor cortex, the supplementary motor area on the medial wall, and the rostral and caudal cingulate cortex. The results of studies in humans and nonhuman primates suggest that the innervation of the face is bilaterally controlled for the upper part and mainly contralaterally controlled for the lower part. Furthermore, the primary motor cortex, the ventral lateral premotor cortex, and the supplementary motor area are essential for the voluntary control of facial expressions. In contrast, the cingulate cortical areas are important for emotional expression, because they receive input from different structures of the limbic system. PMID:26418049

  5. Gyrification from constrained cortical expansion

    PubMed Central

    Tallinen, Tuomas; Chung, Jun Young; Biggins, John S.; Mahadevan, L.

    2014-01-01

    The exterior of the mammalian brain—the cerebral cortex—has a conserved layered structure whose thickness varies little across species. However, selection pressures over evolutionary time scales have led to cortices that have a large surface area to volume ratio in some organisms, with the result that the brain is strongly convoluted into sulci and gyri. Here we show that the gyrification can arise as a nonlinear consequence of a simple mechanical instability driven by tangential expansion of the gray matter constrained by the white matter. A physical mimic of the process using a layered swelling gel captures the essence of the mechanism, and numerical simulations of the brain treated as a soft solid lead to the formation of cusped sulci and smooth gyri similar to those in the brain. The resulting gyrification patterns are a function of relative cortical expansion and relative thickness (compared with brain size), and are consistent with observations of a wide range of brains, ranging from smooth to highly convoluted. Furthermore, this dependence on two simple geometric parameters that characterize the brain also allows us to qualitatively explain how variations in these parameters lead to anatomical anomalies in such situations as polymicrogyria, pachygyria, and lissencephalia. PMID:25136099

  6. Acetaminophen Induces Apoptosis in Rat Cortical Neurons

    PubMed Central

    Posadas, Inmaculada; Santos, Pablo; Blanco, Almudena; Muñoz-Fernández, Maríangeles; Ceña, Valentín

    2010-01-01

    Background Acetaminophen (AAP) is widely prescribed for treatment of mild pain and fever in western countries. It is generally considered a safe drug and the most frequently reported adverse effect associated with acetaminophen is hepatotoxicity, which generally occurs after acute overdose. During AAP overdose, encephalopathy might develop and contribute to morbidity and mortality. Our hypothesis is that AAP causes direct neuronal toxicity contributing to the general AAP toxicity syndrome. Methodology/Principal Findings We report that AAP causes direct toxicity on rat cortical neurons both in vitro and in vivo as measured by LDH release. We have found that AAP causes concentration-dependent neuronal death in vitro at concentrations (1 and 2 mM) that are reached in human plasma during AAP overdose, and that are also reached in the cerebrospinal fluid of rats for 3 hours following i.p injection of AAP doses (250 and 500 mg/Kg) that are below those required to induce acute hepatic failure in rats. AAP also increases both neuronal cytochrome P450 isoform CYP2E1 enzymatic activity and protein levels as determined by Western blot, leading to neuronal death through mitochondrial–mediated mechanisms that involve cytochrome c release and caspase 3 activation. In addition, in vivo experiments show that i.p. AAP (250 and 500 mg/Kg) injection induces neuronal death in the rat cortex as measured by TUNEL, validating the in vitro data. Conclusions/Significance The data presented here establish, for the first time, a direct neurotoxic action by AAP both in vivo and in vitro in rats at doses below those required to produce hepatotoxicity and suggest that this neurotoxicity might be involved in the general toxic syndrome observed during patient APP overdose and, possibly, also when AAP doses in the upper dosing schedule are used, especially if other risk factors (moderate drinking, fasting, nutritional impairment) are present. PMID:21170329

  7. Cholinesterase inhibitors affect brain potentials in amnestic mild cognitive impairment

    PubMed Central

    Irimajiri, Rie; Michalewski, Henry J; Golob, Edward J; Starr, Arnold

    2007-01-01

    Amnestic mild cognitive impairment (MCI) is an isolated episodic memory disorder that has a high likelihood of progressing to Alzheimer’s disease. Auditory sensory cortical responses (P50, N100) have been shown to be increased in amplitude in MCI compared to older controls. We tested whether (1) cortical potentials to other sensory modalities (somatosensory and visual) were also affected in MCI and (2) cholinesterase inhibitors (ChEIs), one of the therapies used in this disorder, modulated sensory cortical potentials in MCI. Somatosensory cortical potentials to median nerve stimulation and visual cortical potentials to reversing checkerboard stimulation were recorded from 15 older controls and 15 amnestic MCI subjects (single domain). Results were analyzed as a function of diagnosis (Control, MCI) and ChEIs treatment (Treated MCI, Untreated MCI). Somatosensory and visual potentials did not differ significantly in amplitude in MCI subjects compared to controls. When ChEIs use was considered, somatosensory potentials (N20, P50) but not visual potentials (N70, P100, N150) were of larger amplitude in untreated MCI subjects compared to treated MCI subjects. Three individual MCI subjects showed increased N20 amplitude while off ChEIs compared to while on ChEIs. An enhancement of N20 somatosensory cortical activity occurs in amnestic single domain MCI and is sensitive to modulation by ChEIs. PMID:17320833

  8. Cortical and Subcortical Contributions to Short-Term Memory for Orienting Movements.

    PubMed

    Kopec, Charles D; Erlich, Jeffrey C; Brunton, Bingni W; Deisseroth, Karl; Brody, Carlos D

    2015-10-21

    Neural activity in frontal cortical areas has been causally linked to short-term memory (STM), but whether this activity is necessary for forming, maintaining, or reading out STM remains unclear. In rats performing a memory-guided orienting task, the frontal orienting fields in cortex (FOF) are considered critical for STM maintenance, and during each trial display a monotonically increasing neural encoding for STM. Here, we transiently inactivated either the FOF or the superior colliculus and found that the resulting impairments in memory-guided orienting performance followed a monotonically decreasing time course, surprisingly opposite to the neural encoding. A dynamical attractor model in which STM relies equally on cortical and subcortical regions reconciled the encoding and inactivation data. We confirmed key predictions of the model, including a time-dependent relationship between trial difficulty and perturbability, and substantial, supralinear, impairment following simultaneous inactivation of the FOF and superior colliculus during memory maintenance.

  9. Aberrant synchrony in the somatosensory cortices predicts motor performance errors in children with cerebral palsy.

    PubMed

    Kurz, Max J; Heinrichs-Graham, Elizabeth; Arpin, David J; Becker, Katherine M; Wilson, Tony W

    2014-02-01

    Cerebral palsy (CP) results from a perinatal brain injury that often results in sensory impairments and greater errors in motor performance. Although these impairments have been well catalogued, the relationship between sensory processing networks and errors in motor performance has not been well explored. Children with CP and typically developing age-matched controls participated in this investigation. We used high-density magnetoencephalography to measure event-related oscillatory changes in the somatosensory cortices following tactile stimulation to the bottom of the foot. In addition, we quantified the amount of variability or errors in the isometric ankle joint torques as these children attempted to match a target. Our results showed that neural populations in the somatosensory cortices of children with CP were desynchronized by the tactile stimulus, whereas those of typically developing children were clearly synchronized. Such desynchronization suggests that children with CP were unable to fully integrate the external stimulus into ongoing sensorimotor computations. Our results also indicated that children with CP had a greater amount of errors in their motor output when they attempted to match the target force, and this amount of error was negatively correlated with the degree of synchronization present in the somatosensory cortices. These results are the first to show that the motor performance errors of children with CP are linked with neural synchronization within the somatosensory cortices.

  10. Cortical thickness gradients in structural hierarchies

    PubMed Central

    Wagstyl, Konrad; Ronan, Lisa; Goodyer, Ian M.; Fletcher, Paul C.

    2015-01-01

    MRI, enabling in vivo analysis of cortical morphology, offers a powerful tool in the assessment of brain development and pathology. One of the most ubiquitous measures used—the thickness of the cortex—shows abnormalities in a number of diseases and conditions, but the functional and biological correlates of such alterations are unclear. If the functional connotations of structural MRI measures are to be understood, we must strive to clarify the relationship between measures such as cortical thickness and their cytoarchitectural determinants. We therefore sought to determine whether patterns of cortical thickness mirror a key motif of the cortex, specifically its structural hierarchical organisation. We delineated three sensory hierarchies (visual, somatosensory and auditory) in two species—macaque and human—and explored whether cortical thickness was correlated with specific cytoarchitectural characteristics. Importantly, we controlled for cortical folding which impacts upon thickness and may obscure regional differences. Our results suggest that an easily measurable macroscopic brain parameter, namely, cortical thickness, is systematically related to cytoarchitecture and to the structural hierarchical organisation of the cortex. We argue that the measurement of cortical thickness gradients may become an important way to develop our understanding of brain structure–function relationships. The identification of alterations in such gradients may complement the observation of regionally localised cortical thickness changes in our understanding of normal development and neuropsychiatric illnesses. PMID:25725468

  11. Cortical Correspondence with Probabilistic Fiber Connectivity

    PubMed Central

    Oguz, Ipek; Niethammer, Marc; Cates, Josh; Whitaker, Ross; Fletcher, Thomas; Vachet, Clement; Styner, Martin

    2009-01-01

    This paper presents a novel method of optimizing point-based correspondence among populations of human cortical surfaces by combining structural cues with probabilistic connectivity maps. The proposed method establishes a tradeoff between an even sampling of the cortical surfaces (a low surface entropy) and the similarity of corresponding points across the population (a low ensemble entropy). The similarity metric, however, isn’t constrained to be just spatial proximity, but uses local sulcal depth measurements as well as probabilistic connectivity maps, computed from DWI scans via a stochastic tractography algorithm, to enhance the correspondence definition. We propose a novel method for projecting this fiber connectivity information on the cortical surface, using a surface evolution technique. Our cortical correspondence method does not require a spherical parameterization. Experimental results are presented, showing improved correspondence quality demonstrated by a cortical thickness analysis, as compared to correspondence methods using spatial metrics as the sole correspondence criterion. PMID:19694301

  12. Cortical Cartography and Caret Software

    PubMed Central

    Van Essen, David C.

    2011-01-01

    Caret software is widely used for analyzing and visualizing many types of fMRI data, often in conjunction with experimental data from other modalities. This article places Caret’s development in a historical context that spans three decades of brain mapping – from the early days of manually generated flat maps to the nascent field of human connectomics. It also highlights some of Caret’s distinctive capabilities. This includes the ease of visualizing data on surfaces and/or volumes and on atlases as well as individual subjects. Caret can display many types of experimental data using various combinations of overlays (e.g., fMRI activation maps, cortical parcellations, areal boundaries), and it has other features that facilitate the analysis and visualization of complex neuroimaging datasets. PMID:22062192

  13. Gyrification from constrained cortical expansion

    NASA Astrophysics Data System (ADS)

    Tallinen, Tuomas

    The convolutions of the human brain are a symbol of its functional complexity. But how does the outer surface of the brain, the layered cortex of neuronal gray matter get its folds? In this talk, we ask to which extent folding of the brain can be explained as a purely mechanical consequence of unpatterned growth of the cortical layer relative to the sublayers. Modeling the growing brain as a soft layered solid leads to elastic instabilities and the formation of cusped sulci and smooth gyri consistent with observations across species in both normal and pathological situations. Furthermore, we apply initial geometries obtained from fetal brain MRI to address the question of how the brain geometry and folding patterns may be coupled via mechanics.

  14. Cortical cartography and Caret software.

    PubMed

    Van Essen, David C

    2012-08-15

    Caret software is widely used for analyzing and visualizing many types of fMRI data, often in conjunction with experimental data from other modalities. This article places Caret's development in a historical context that spans three decades of brain mapping--from the early days of manually generated flat maps to the nascent field of human connectomics. It also highlights some of Caret's distinctive capabilities. This includes the ease of visualizing data on surfaces and/or volumes and on atlases as well as individual subjects. Caret can display many types of experimental data using various combinations of overlays (e.g., fMRI activation maps, cortical parcellations, areal boundaries), and it has other features that facilitate the analysis and visualization of complex neuroimaging datasets.

  15. Nicotinic modulation of cortical circuits

    PubMed Central

    Arroyo, Sergio; Bennett, Corbett; Hestrin, Shaul

    2014-01-01

    The ascending cholinergic neuromodulatory system sends projections throughout cortex and has been shown to play an important role in a number of cognitive functions including arousal, working memory, and attention. However, despite a wealth of behavioral and anatomical data, understanding how cholinergic synapses modulate cortical function has been limited by the inability to selectively activate cholinergic axons. Now, with the development of optogenetic tools and cell-type specific Cre-driver mouse lines, it has become possible to stimulate cholinergic axons from the basal forebrain (BF) and probe cholinergic synapses in the cortex for the first time. Here we review recent work studying the cell-type specificity of nicotinic signaling in the cortex, synaptic mechanisms mediating cholinergic transmission, and the potential functional role of nicotinic modulation. PMID:24734005

  16. N-Methyl D-Aspartate Receptor Antagonist Kynurenic Acid Affects Human Cortical Development

    PubMed Central

    Bagasrawala, Inseyah; Zecevic, Nada; Radonjić, Nevena V.

    2016-01-01

    Kynurenic acid (KYNA), a neuroactive metabolite of tryptophan degradation, acts as an endogenous N-methyl-D-aspartate receptor (NMDAR) antagonist. Elevated levels of KYNA have been observed in pregnant women after viral infections and are considered to play a role in neurodevelopmental disorders. However, the consequences of KYNA-induced NMDAR blockade in human cortical development still remain elusive. To study the potential impact of KYNA on human neurodevelopment, we used an in vitro system of multipotent cortical progenitors, i.e., radial glia cells (RGCs), enriched from human cerebral cortex at mid-gestation (16–19 gestational weeks). KYNA treatment significantly decreased RGCs proliferation and survival by antagonizing NMDAR. This alteration resulted in a reduced number of cortical progenitors and neurons while number and activation of astrocytes increased. KYNA treatment reduced differentiation of RGCs into GABAergic neurons, while differentiation into glutamatergic neurons was relatively spared. Furthermore, in mixed cortical cultures KYNA triggered an inflammatory response as evidenced by increased levels of the pro-inflammatory cytokine IL-6. In conclusion, elevated levels of KYNA play a significant role in human RGC fate determination by antagonizing NMDARs and by activating an inflammatory response. The altered cell composition observed in cell culture following exposure to elevated KYNA levels suggests a mechanism for impairment of cortical circuitry formation in the fetal brain after viral infection, as seen in neurodevelopmental disorders such as schizophrenia. PMID:27746712

  17. Caloric restriction stimulates autophagy in rat cortical neurons through neuropeptide Y and ghrelin receptors activation

    PubMed Central

    Carmo-Silva, Sara; Botelho, Mariana; de Almeida, Luís Pereira; Cavadas, Cláudia

    2016-01-01

    Caloric restriction is an anti-aging intervention known to extend lifespan in several experimental models, at least in part, by stimulating autophagy. Caloric restriction increases neuropeptide Y (NPY) in the hypothalamus and plasma ghrelin, a peripheral gut hormone that acts in hypothalamus to modulate energy homeostasis. NPY and ghrelin have been shown to be neuroprotective in different brain areas and to induce several physiological modifications similar to those induced by caloric restriction. However, the effect of NPY and ghrelin in autophagy in cortical neurons is currently not known. Using a cell culture of rat cortical neurons we investigate the involvement of NPY and ghrelin in caloric restriction-induced autophagy. We observed that a caloric restriction mimetic cell culture medium stimulates autophagy in rat cortical neurons and NPY or ghrelin receptor antagonists blocked this effect. On the other hand, exogenous NPY or ghrelin stimulate autophagy in rat cortical neurons. Moreover, NPY mediates the stimulatory effect of ghrelin on autophagy in rat cortical neurons. Since autophagy impairment occurs in aging and age-related neurodegenerative diseases, NPY and ghrelin synergistic effect on autophagy stimulation may suggest a new strategy to delay aging process. PMID:27441412

  18. Unsupervised fetal cortical surface parcellation

    NASA Astrophysics Data System (ADS)

    Dahdouh, Sonia; Limperopoulos, Catherine

    2016-03-01

    At the core of many neuro-imaging studies, atlas-based brain parcellations are used for example to study normal brain evolution across the lifespan. These atlases rely on the assumption that the same anatomical features are present on all subjects to be studied and that these features are stable enough to allow meaningful comparisons between different brain surfaces and structures These methods, however, often fail when applied to fetal MRI data, due to the lack of consistent anatomical features present across gestation. This paper presents a novel surface-based fetal cortical parcellation framework which attempts to circumvent the lack of consistent anatomical features by proposing a brain parcellation scheme that is based solely on learned geometrical features. A mesh signature incorporating both extrinsic and intrinsic geometrical features is proposed and used in a clustering scheme to define a parcellation of the fetal brain. This parcellation is then learned using a Random Forest (RF) based learning approach and then further refined in an alpha-expansion graph-cut scheme. Based on the votes obtained by the RF inference procedure, a probability map is computed and used as a data term in the graph-cut procedure. The smoothness term is defined by learning a transition matrix based on the dihedral angles of the faces. Qualitative and quantitative results on a cohort of both healthy and high-risk fetuses are presented. Both visual and quantitative assessments show good results demonstrating a reliable method for fetal brain data and the possibility of obtaining a parcellation of the fetal cortical surfaces using only geometrical features.

  19. Cortical spreading depression: An enigma

    NASA Astrophysics Data System (ADS)

    Miura, R. M.; Huang, H.; Wylie, J. J.

    2007-08-01

    The brain is a complex organ with active components composed largely of neurons, glial cells, and blood vessels. There exists an enormous experimental and theoretical literature on the mechanisms involved in the functioning of the brain, but we still do not have a good understanding of how it works on a gross mechanistic level. In general, the brain maintains a homeostatic state with relatively small ion concentration changes, the major ions being sodium, potassium, and chloride. Calcium ions are present in smaller quantities but still play an important role in many phenomena. Cortical spreading depression (CSD for short) was discovered over 60 years ago by A.A.P. Leão, a Brazilian physiologist doing his doctoral research on epilepsy at Harvard University, “Spreading depression of activity in the cerebral cortex," J. Neurophysiol., 7 (1944), pp. 359-390. Cortical spreading depression is characterized by massive changes in ionic concentrations and slow nonlinear chemical waves, with speeds on the order of mm/min, in the cortex of different brain structures in various experimental animals. In humans, CSD is associated with migraine with aura, where a light scintillation in the visual field propagates, then disappears, and is followed by a sustained headache. To date, CSD remains an enigma, and further detailed experimental and theoretical investigations are needed to develop a comprehensive picture of the diverse mechanisms involved in producing CSD. A number of mechanisms have been hypothesized to be important for CSD wave propagation. In this paper, we briefly describe several characteristics of CSD wave propagation, and examine some of the mechanisms that are believed to be important, including ion diffusion, membrane ionic currents, osmotic effects, spatial buffering, neurotransmitter substances, gap junctions, metabolic pumps, and synaptic connections. Continuum models of CSD, consisting of coupled nonlinear diffusion equations for the ion concentrations, and

  20. Cortical thickness, volume and surface area in patients with bipolar disorder types I and II

    PubMed Central

    Abé, Christoph; Ekman, Carl-Johan; Sellgren, Carl; Petrovic, Predrag; Ingvar, Martin; Landén, Mikael

    2016-01-01

    Background Bipolar disorder (BD) is a common chronic psychiatric disorder mainly characterized by episodes of mania, hypomania and depression. The disorder is associated with cognitive impairments and structural brain abnormalities, such as lower cortical volumes in primarily frontal brain regions than healthy controls. Although bipolar disorder types I (BDI) and II (BDII) exhibit different symptoms and severity, previous studies have focused on BDI. Furthermore, the most frequently investigated measure in this population is cortical volume. The aim of our study was to investigate abnormalities in patients with BDI and BDII by simultaneously analyzing cortical volume, thickness and surface area, which yields more information about disease- and symptom-related neurobiology. Methods We used MRI to measure cortical volume, thickness and area in patients with BDI and BDII as well as in healthy controls. The large study cohort enabled us to adjust for important confounding factors. Results We included 81 patients with BDI, 59 with BDII and 85 controls in our analyses. Cortical volume, thickness and surface area abnormalities were present in frontal, temporal and medial occipital regions in patients with BD. Lithium and antiepileptic drug use had an effect on the observed differences in medial occipital regions. Patients with the subtypes BDI and BDII displayed common cortical abnormalities, such as lower volume, thickness and surface area than healthy controls in frontal brain regions but differed in temporal and medial prefrontal regions, where only those with BDI had abnormally low cortical volume and thickness. Limitations The group differences can be explained by progressive changes, but also by premorbid conditions. They could also have been influenced by unknown factors, such as social, environmental or genetic factors. Conclusion Our findings suggest diagnosis-related neurobiological differences between the BD subtypes, which could explain distinct symptoms and

  1. Regional brain differences in cortical thickness, surface area and subcortical volume in individuals with Williams syndrome.

    PubMed

    Meda, Shashwath A; Pryweller, Jennifer R; Thornton-Wells, Tricia A

    2012-01-01

    Williams syndrome (WS) is a rare genetic neurodevelopmental disorder characterized by increased non-social anxiety, sensitivity to sounds and hypersociability. Previous studies have reported contradictory findings with regard to regional brain variation in WS, relying on only one type of morphological measure (usually volume) in each study. The present study aims to contribute to this body of literature and perhaps elucidate some of these discrepancies by examining concurrent measures of cortical thickness, surface area and subcortical volume between WS subjects and typically-developing (TD) controls. High resolution MRI scans were obtained on 31 WS subjects and 50 typically developing control subjects. We derived quantitative regional estimates of cortical thickness, cortical surface area, and subcortical volume using FreeSurfer software. We evaluated between-group ROI differences while controlling for total intracranial volume. In post-hoc exploratory analyses within the WS group, we tested for correlations between regional brain variation and Beck Anxiety Inventory scores. Consistent with our hypothesis, we detected complex patterns of between-group cortical variation, which included lower surface area in combination with greater thickness in the following cortical regions: post central gyrus, cuneus, lateral orbitofrontal cortex and lingual gyrus. Additional cortical regions showed between-group differences in one (but not both) morphological measures. Subcortical volume was lower in the basal ganglia and the hippocampus in WS versus TD controls. Exploratory correlations revealed that anxiety scores were negatively correlated with gray matter surface area in insula, OFC, rostral middle frontal, superior temporal and lingual gyrus. Our results were consistent with previous reports showing structural alterations in regions supporting the socio-affective and visuospatial impairments in WS. However, we also were able to effectively capture novel and complex

  2. Cytoskeletal proteins in cortical development and disease: actin associated proteins in periventricular heterotopia

    PubMed Central

    Lian, Gewei; Sheen, Volney L.

    2015-01-01

    The actin cytoskeleton regulates many important cellular processes in the brain, including cell division and proliferation, migration, and cytokinesis and differentiation. These developmental processes can be regulated through actin dependent vesicle and organelle movement, cell signaling, and the establishment and maintenance of cell junctions and cell shape. Many of these processes are mediated by extensive and intimate interactions of actin with cellular membranes and proteins. Disruption in the actin cytoskeleton in the brain gives rise to periventricular heterotopia (PH), a malformation of cortical development, characterized by abnormal neurons clustered deep in the brain along the lateral ventricles. This disorder can give rise to seizures, dyslexia and psychiatric disturbances. Anatomically, PH is characterized by a smaller brain (impaired proliferation), heterotopia (impaired initial migration) and disruption along the neuroependymal lining (impaired cell-cell adhesion). Genes causal for PH have also been implicated in actin-dependent processes. The current review provides mechanistic insight into actin cytoskeletal regulation of cortical development in the context of this malformation of cortical development. PMID:25883548

  3. Evidence for a role of the reticulospinal system in recovery of skilled reaching after cortical stroke: initial results from a model of ischemic cortical injury.

    PubMed

    Herbert, Wendy J; Powell, Kimerly; Buford, John A

    2015-11-01

    The purposes of this pilot study were to create a model of focal cortical ischemia in Macaca fascicularis and to explore contributions of the reticulospinal system in recovery of reaching. Endothelin-1 was used to create a focal lesion in the shoulder/elbow representation of left primary motor cortex (M1) of two adult female macaques. Repetitive microstimulation was used to map upper limb motor outputs from right and left cortical motor areas and from the pontomedullary reticular formation (PMRF). In subject 1 with a small lesion and spontaneous recovery, reaching was mildly impaired. Changes were evident in the shoulder/elbow representations of both the lesioned and contralesional M1, and there appeared to be fewer than expected upper limb responses from the left (ipsilesional) PMRF. In subject 2 with a substantial lesion, reaching was severely impaired immediately after the lesion. After 12 weeks of intensive rehabilitative training, reach performance recovered to near-baseline levels, but movement times remained about 50% slower. Surprisingly, the shoulder/elbow representation in the lesioned M1 remained completely absent after recovery, and there was a little change in the contralesional M1. There was a definite difference in motor output patterns for left versus right PMRF for this subject, with an increase in right arm responses from right PMRF and a paucity of left arm responses from left PMRF. The results are consistent with increased reliance on PMRF motor outputs for recovery of voluntary upper limb motor control after significant cortical ischemic injury. PMID:26231990

  4. Alteration of Electro-Cortical Activity in Microgravity

    NASA Astrophysics Data System (ADS)

    Schneider, Stefan; Brummer, Vera; Carnahan, Heather; Askew, Christopher D.; Guardiera, Simon; Struder, Heiko K.

    2008-06-01

    There is growing interest in the effects of weightlessness on central nervous system (CNS) activity. Due to technical and logistical limitations it presently seems impossible to apply imaging techniques as fMRI or PET in weightless environments e.g. on ISS or during parabolic flights. Within this study we evaluated changes in brain cortical activity using low resolution brain electromagnetic tomography (LORETA) during parabolic flights. Results showed a distinct inhibition of right frontal area activity >12Hz during phases of microgravity compared to normal gravity. We conclude that the inhibition of high frequency frontal activity during microgravity may serve as a marker of emotional anxiety and/or indisposition associated with weightlessness. This puts a new light on the debate as to whether cognitive and sensorimotor impairments are attributable to primary physiological effects or secondary psychological effects of a weightless environment.

  5. Synaptic unreliability facilitates information transmission in balanced cortical populations

    NASA Astrophysics Data System (ADS)

    Gatys, Leon A.; Ecker, Alexander S.; Tchumatchenko, Tatjana; Bethge, Matthias

    2015-06-01

    Synaptic unreliability is one of the major sources of biophysical noise in the brain. In the context of neural information processing, it is a central question how neural systems can afford this unreliability. Here we examine how synaptic noise affects signal transmission in cortical circuits, where excitation and inhibition are thought to be tightly balanced. Surprisingly, we find that in this balanced state synaptic response variability actually facilitates information transmission, rather than impairing it. In particular, the transmission of fast-varying signals benefits from synaptic noise, as it instantaneously increases the amount of information shared between presynaptic signal and postsynaptic current. Furthermore we show that the beneficial effect of noise is based on a very general mechanism which contrary to stochastic resonance does not reach an optimum at a finite noise level.

  6. Acute cortical deafness in a child with MELAS syndrome.

    PubMed

    Pittet, Marie P; Idan, Roni B; Kern, Ilse; Guinand, Nils; Van, Hélène Cao; Toso, Seema; Fluss, Joël

    2016-05-01

    Auditory impairment in mitochondrial disorders are usually due to peripheral sensorineural dysfunction. Central deafness is only rarely reported. We report here an 11-year-old boy with MELAS syndrome who presented with subacute deafness after waking up from sleep. Peripheral hearing loss was rapidly excluded. A brain MRI documented bilateral stroke-like lesions predominantly affecting the superior temporal lobe, including the primary auditory cortex, confirming the central nature of deafness. Slow recovery was observed in the following weeks. This case serves to illustrate the numerous challenges caused by MELAS and the unusual occurrence of acute cortical deafness, that to our knowledge has not be described so far in a child in this setting.

  7. Degraded attentional modulation of cortical neural populations in strabismic amblyopia

    PubMed Central

    Hou, Chuan; Kim, Yee-Joon; Lai, Xin Jie; Verghese, Preeti

    2016-01-01

    Behavioral studies have reported reduced spatial attention in amblyopia, a developmental disorder of spatial vision. However, the neural populations in the visual cortex linked with these behavioral spatial attention deficits have not been identified. Here, we use functional MRI–informed electroencephalography source imaging to measure the effect of attention on neural population activity in the visual cortex of human adult strabismic amblyopes who were stereoblind. We show that compared with controls, the modulatory effects of selective visual attention on the input from the amblyopic eye are substantially reduced in the primary visual cortex (V1) as well as in extrastriate visual areas hV4 and hMT+. Degraded attentional modulation is also found in the normal-acuity fellow eye in areas hV4 and hMT+ but not in V1. These results provide electrophysiological evidence that abnormal binocular input during a developmental critical period may impact cortical connections between the visual cortex and higher level cortices beyond the known amblyopic losses in V1 and V2, suggesting that a deficit of attentional modulation in the visual cortex is an important component of the functional impairment in amblyopia. Furthermore, we find that degraded attentional modulation in V1 is correlated with the magnitude of interocular suppression and the depth of amblyopia. These results support the view that the visual suppression often seen in strabismic amblyopia might be a form of attentional neglect of the visual input to the amblyopic eye. PMID:26885628

  8. Motor-cortical oscillations in early stages of Parkinson's disease

    PubMed Central

    Pollok, B; Krause, V; Martsch, W; Wach, C; Schnitzler, A; Südmeyer, M

    2012-01-01

    Pathophysiological changes in basal ganglia-thalamo-cortical circuits are well established in idiopathic Parkinson's disease (PD). However, it remains open whether such alterations already occur at early stages representing a characteristic neurophysiological marker of PD. Therefore, the present study aims at elucidating changes of synchronised oscillatory activity in early PD patients. In this study, we performed whole-head magnetoencephalography (MEG) in a resting condition and during steady state contraction of the more severely affected forearm in 10 drug–naive, de novo patients, in 10 early-stage patients with chronic medication and in 10 age-matched control subjects. While cortico-muscular coherence (CMC) did not differ between groups, patients showed increased sensori-motor cortical power at beta frequency (13–30 Hz) during rest as well as during isometric contraction compared to controls. In healthy control subjects the power of the contralateral hemisphere was significantly suppressed during isometric contraction. By contrast, both hemispheres were activated equally strongly in de novo patients. In medicated patients, the pattern was found to be reversed. Contralateral beta power was significantly correlated with motor impairment during isometric contraction but not during rest. The present results suggest that the reduced ability of the primary motor cortex to disengage from increased beta band oscillations during the execution of movements is an early marker of PD. PMID:22547636

  9. A Turing Reaction-Diffusion Model for Human Cortical Folding Patterns and Cortical Pattern Malformations

    NASA Astrophysics Data System (ADS)

    Hurdal, Monica K.; Striegel, Deborah A.

    2011-11-01

    Modeling and understanding cortical folding pattern formation is important for quantifying cortical development. We present a biomathematical model for cortical folding pattern formation in the human brain and apply this model to study diseases involving cortical pattern malformations associated with neural migration disorders. Polymicrogyria is a cortical malformation disease resulting in an excessive number of small gyri. Our mathematical model uses a Turing reaction-diffusion system to model cortical folding. The lateral ventricle (LV) and ventricular zone (VZ) of the brain are critical components in the formation of cortical patterning. In early cortical development the shape of the LV can be modeled with a prolate spheroid and the VZ with a prolate spheroid surface. We use our model to study how global cortex characteristics, such as size and shape of the LV, affect cortical pattern formation. We demonstrate increasing domain scale can increase the number of gyri and sulci formed. Changes in LV shape can account for sulcus directionality. By incorporating LV size and shape, our model is able to elucidate which parameters can lead to excessive cortical folding.

  10. Cortical astrocytes rewire somatosensory cortical circuits for peripheral neuropathic pain.

    PubMed

    Kim, Sun Kwang; Hayashi, Hideaki; Ishikawa, Tatsuya; Shibata, Keisuke; Shigetomi, Eiji; Shinozaki, Youichi; Inada, Hiroyuki; Roh, Seung Eon; Kim, Sang Jeong; Lee, Gihyun; Bae, Hyunsu; Moorhouse, Andrew J; Mikoshiba, Katsuhiko; Fukazawa, Yugo; Koizumi, Schuichi; Nabekura, Junichi

    2016-05-01

    Long-term treatments to ameliorate peripheral neuropathic pain that includes mechanical allodynia are limited. While glial activation and altered nociceptive transmission within the spinal cord are associated with the pathogenesis of mechanical allodynia, changes in cortical circuits also accompany peripheral nerve injury and may represent additional therapeutic targets. Dendritic spine plasticity in the S1 cortex appears within days following nerve injury; however, the underlying cellular mechanisms of this plasticity and whether it has a causal relationship to allodynia remain unsolved. Furthermore, it is not known whether glial activation occurs within the S1 cortex following injury or whether it contributes to this S1 synaptic plasticity. Using in vivo 2-photon imaging with genetic and pharmacological manipulations of murine models, we have shown that sciatic nerve ligation induces a re-emergence of immature metabotropic glutamate receptor 5 (mGluR5) signaling in S1 astroglia, which elicits spontaneous somatic Ca2+ transients, synaptogenic thrombospondin 1 (TSP-1) release, and synapse formation. This S1 astrocyte reactivation was evident only during the first week after injury and correlated with the temporal changes in S1 extracellular glutamate levels and dendritic spine turnover. Blocking the astrocytic mGluR5-signaling pathway suppressed mechanical allodynia, while activating this pathway in the absence of any peripheral injury induced long-lasting (>1 month) allodynia. We conclude that reawakened astrocytes are a key trigger for S1 circuit rewiring and that this contributes to neuropathic mechanical allodynia. PMID:27064281

  11. Cortical astrocytes rewire somatosensory cortical circuits for peripheral neuropathic pain

    PubMed Central

    Hayashi, Hideaki; Ishikawa, Tatsuya; Shibata, Keisuke; Inada, Hiroyuki; Roh, Seung Eon; Kim, Sang Jeong; Moorhouse, Andrew J.

    2016-01-01

    Long-term treatments to ameliorate peripheral neuropathic pain that includes mechanical allodynia are limited. While glial activation and altered nociceptive transmission within the spinal cord are associated with the pathogenesis of mechanical allodynia, changes in cortical circuits also accompany peripheral nerve injury and may represent additional therapeutic targets. Dendritic spine plasticity in the S1 cortex appears within days following nerve injury; however, the underlying cellular mechanisms of this plasticity and whether it has a causal relationship to allodynia remain unsolved. Furthermore, it is not known whether glial activation occurs within the S1 cortex following injury or whether it contributes to this S1 synaptic plasticity. Using in vivo 2-photon imaging with genetic and pharmacological manipulations of murine models, we have shown that sciatic nerve ligation induces a re-emergence of immature metabotropic glutamate receptor 5 (mGluR5) signaling in S1 astroglia, which elicits spontaneous somatic Ca2+ transients, synaptogenic thrombospondin 1 (TSP-1) release, and synapse formation. This S1 astrocyte reactivation was evident only during the first week after injury and correlated with the temporal changes in S1 extracellular glutamate levels and dendritic spine turnover. Blocking the astrocytic mGluR5-signaling pathway suppressed mechanical allodynia, while activating this pathway in the absence of any peripheral injury induced long-lasting (>1 month) allodynia. We conclude that reawakened astrocytes are a key trigger for S1 circuit rewiring and that this contributes to neuropathic mechanical allodynia. PMID:27064281

  12. [Preoperative direct cortical and sub-cortical electric stimulation during cerebral surgery in functional areas].

    PubMed

    Duffau, H; Capelle, L; Sichez, J P; Bitar, A; Faillot, T; Arthuis, F; Van Effenterre, R; Fohanno, D

    1999-09-01

    Indications of surgical treatment for lesions in functional cerebral areas depend on the ratio between the definitive neurological deficit and the beneficial effect of resection. Detection of eloquent cortex is difficult because of important individual variability. Peroperative direct cortical and subcortical electrical stimulations (DCS) provide the most precise and reliable method currently available allowing identification and preservation of neurons essential for motricity, sensitivity++ and language. We report our preliminary experience with DCS in surgery of intracerebral infiltrative tumors with a consecutive series of 15 patients operated from November 96 through September 97 in our institution. Presenting symptoms in the 15 patients (8 males, 7 females, mean age 43 years) were seizures in 11 cases (73%) and neurological deficit in 4 cases (27%). Clinical examination was normal in 11 patients and revealed hemiparesia in 4. Magnetic resonance imaging (MRI) with three-dimensional reconstruction showed a precentral tumor in 10 cases, central lesion in one patient, postcentral lesion in two cases, right insular tumor (non-dominant hemisphere) in one case. All patients underwent surgical resection using DCS with detection in 13 cases of motor cortex and subcortical pathways under genera anesthesia, in one case of somatosensory area under local anesthesia, and in one case of language areas also under local anesthesia. The tumor was recurrent in two patients had been operated earlier but without DCS. Resection, verified by postoperative MRI, was total in 12 cases (80%) and estimated at 80% in 3 patients. Histological examination revealed an infiltrative glioma in 12 cases (8 low grade astrocytomas, 3 low grade oligodendrogliomas, and one anaplastic oligodendroglioma), and metastases in 3 cases. Eight patients had no postoperative deficit, while the other 7 patients were impaired, with, in all cases except one, complete recovery in 15 days to 2 months. Direct

  13. Linking cortical network synchrony and excitability

    PubMed Central

    Meisel, Christian

    2016-01-01

    ABSTRACT Theoretical approaches based on dynamical systems theory can provide useful frameworks to guide experiments and analysis techniques when investigating cortical network activity. The notion of phase transitions between qualitatively different kinds of network dynamics has been such a framework inspiring novel approaches to neurophysiological data analysis over the recent years. One particular intriguing hypothesis has been that cortical networks reside in the vicinity of a phase transition. Although the final verdict on this hypothesis is still out, trying to understand cortex dynamics from this viewpoint has recently led to interesting insights on cortical network function with relevance for clinical practice. PMID:27065159

  14. Focal Cortical Dysplasia in Childhood Epilepsy.

    PubMed

    Shaker, Tarek; Bernier, Anne; Carmant, Lionel

    2016-05-01

    Focal cortical dysplasia is a common cause of medication resistant epilepsy. A better understanding of its presentation, pathophysiology and consequences have helped us improved its treatment and outcome. This paper reviews the most recent classification, pathophysiology and imaging findings in clinical research as well as the knowledge gained from studying genetic and lesional animal models of focal cortical dysplasia. This review of this recently gained knowledge will most likely help develop new research models and new therapeutic targets for patients with epilepsy associated with focal cortical dysplasia. PMID:27544467

  15. Apaf1-deficient cortical neurons exhibit defects in axonal outgrowth.

    PubMed

    De Zio, Daniela; Molinari, Francesca; Rizza, Salvatore; Gatta, Lucia; Ciotti, Maria Teresa; Salvatore, Anna Maria; Mathiassen, Søs Grønbæk; Cwetsch, Andrzej W; Filomeni, Giuseppe; Rosano, Giuseppe; Ferraro, Elisabetta

    2015-11-01

    The establishment of neuronal polarity and axonal outgrowth are key processes affecting neuronal migration and synapse formation, their impairment likely leading to cognitive deficits. Here we have found that the apoptotic protease activating factor 1 (Apaf1), apart from its canonical role in apoptosis, plays an additional function in cortical neurons, where its deficiency specifically impairs axonal growth. Given the central role played by centrosomes and microtubules in the polarized extension of the axon, our data suggest that Apaf1-deletion affects axonal outgrowth through an impairment of centrosome organization. In line with this, centrosomal protein expression, as well as their centrosomal localization proved to be altered upon Apaf1-deletion. Strikingly, we also found that Apaf1-loss affects trans-Golgi components and leads to a robust activation of AMP-dependent protein kinase (AMPK), this confirming the stressful conditions induced by Apaf1-deficiency. Since AMPK hyper-phosphorylation is known to impair a proper axon elongation, our finding contributes to explain the effect of Apaf1-deficiency on axogenesis. We also discovered that the signaling pathways mediating axonal growth and involving glycogen synthase kinase-3β, liver kinase B1, and collapsing-response mediator protein-2 are altered in Apaf1-KO neurons. Overall, our results reveal a novel non-apoptotic role for Apaf1 in axonal outgrowth, suggesting that the neuronal phenotype due to Apaf1-deletion could not only be fully ascribed to apoptosis inhibition, but might also be the result of defects in axogenesis. The discovery of new molecules involved in axonal elongation has a clinical relevance since it might help to explain neurological abnormalities occurring during early brain development. PMID:25975226

  16. Speech impairment (adult)

    MedlinePlus

    Language impairment; Impairment of speech; Inability to speak; Aphasia; Dysarthria; Slurred speech; Dysphonia voice disorders ... environment and keep external stimuli to a minimum. Speak in a normal tone of voice (this condition ...

  17. Neuropsychological evidence of impaired cognitive empathy in euthymic bipolar disorder.

    PubMed

    Shamay-Tsoory, Simone; Harari, Hagai; Szepsenwol, Ohad; Levkovitz, Yechiel

    2009-01-01

    The empathic abilities have never been examined in bipolar disorder patients, despite frequent observations of impaired social behavior. To examine the neuropsychological processes that underlie the affective and cognitive empathic ability in bipolar disorder, the authors compared affective and cognitive empathic abilities, as well as theory of mind and executive functions, of euthymic bipolar disorder patients and healthy comparison subjects. Significant deficits in cognitive empathy and theory of mind were observed, while affective empathy was elevated in bipolar disorder. Patients showed impaired cognitive flexibility (shifting and reversal learning) but intact planning behavior. Impaired cognitive empathy was related with performance in neurocognitive tasks of cognitive flexibility, suggesting that prefrontal cortical dysfunction may account for impaired cognitive empathy in bipolar disorder. PMID:19359453

  18. Maternal obesity impairs specific regulatory pathways in human myometrial arteries.

    PubMed

    Hayward, Christina E; Cowley, Elizabeth J; Mills, Tracey A; Sibley, Colin P; Wareing, Mark

    2014-03-01

    Obese women (body mass index ≥30 kg/m(2)) are at greater risk than normal weight women of pregnancy complications associated with maternal and infant morbidity, particularly the development of cardiovascular disease and metabolic disorders in later life; why this occurs is unknown. Nonpregnant, obese individuals exhibit systemic vascular endothelial dysfunction. We tested the hypothesis that obese pregnant women have altered myometrial arterial function compared to pregnant women of normal (18-24 kg/m(2)) and overweight (25-29 kg/m(2)) body mass index. Responses to vasoconstrictors, U46619 (thromboxane mimetic) and arginine vasopressin, and vasodilators, bradykinin and the nitric oxide donor sodium nitroprusside, were assessed by wire myography in myometrial arteries from normal weight (n = 18), overweight (n = 18), and obese (n = 20) women with uncomplicated pregnancies. Thromboxane-prostanoid receptor expression was assessed using immunostaining in myometrial arteries of normal weight and obese women. Vasoconstriction and vasodilatation were impaired in myometrial arteries from obese women with otherwise uncomplicated pregnancies. Disparate agonist responses suggest that vascular function in obese women is not globally dysregulated but may be specific to thromboxane and nitric oxide pathways. Because obesity rates are escalating, it is important to identify the mechanisms underlying impaired vascular function and establish why some obese women compensate for vascular dysfunction and some do not. Future studies are needed to determine whether central adiposity results in an altered endocrine milieu that may promote vascular dysfunction by altering the function of perivascular adipose tissue.

  19. Grey matter volumetric changes related to recovery from hand paresis after cortical sensorimotor stroke.

    PubMed

    Abela, E; Seiler, A; Missimer, J H; Federspiel, A; Hess, C W; Sturzenegger, M; Weder, B J; Wiest, R

    2015-09-01

    Preclinical studies using animal models have shown that grey matter plasticity in both perilesional and distant neural networks contributes to behavioural recovery of sensorimotor functions after ischaemic cortical stroke. Whether such morphological changes can be detected after human cortical stroke is not yet known, but this would be essential to better understand post-stroke brain architecture and its impact on recovery. Using serial behavioural and high-resolution magnetic resonance imaging (MRI) measurements, we tracked recovery of dexterous hand function in 28 patients with ischaemic stroke involving the primary sensorimotor cortices. We were able to classify three recovery subgroups (fast, slow, and poor) using response feature analysis of individual recovery curves. To detect areas with significant longitudinal grey matter volume (GMV) change, we performed tensor-based morphometry of MRI data acquired in the subacute phase, i.e. after the stage compromised by acute oedema and inflammation. We found significant GMV expansion in the perilesional premotor cortex, ipsilesional mediodorsal thalamus, and caudate nucleus, and GMV contraction in the contralesional cerebellum. According to an interaction model, patients with fast recovery had more perilesional than subcortical expansion, whereas the contrary was true for patients with impaired recovery. Also, there were significant voxel-wise correlations between motor performance and ipsilesional GMV contraction in the posterior parietal lobes and expansion in dorsolateral prefrontal cortex. In sum, perilesional GMV expansion is associated with successful recovery after cortical stroke, possibly reflecting the restructuring of local cortical networks. Distant changes within the prefrontal-striato-thalamic network are related to impaired recovery, probably indicating higher demands on cognitive control of motor behaviour.

  20. Prefrontal cognitive deficits in mice with altered cerebral cortical GABAergic interneurons

    PubMed Central

    Bissonette, Gregory B.; Bae, Mihyun H.; Suresh, Tejas; Jaffe, David E.; Powell, Elizabeth M.

    2013-01-01

    Alterations of inhibitory GABAergic neurons are implicated in multiple psychiatric and neurological disorders, including schizophrenia, autism and epilepsy. In particular, interneuron deficits in prefrontal areas, along with presumed decreased inhibition, have been reported in several human patients. The majority of forebrain GABAergic interneurons arise from a single subcortical source before migrating to their final regional destination. Factors that govern the interneuron populations have been identified, demonstrating that a single gene mutation may globally affect forebrain structures or a single area. In particular, mice lacking the urokinase plasminogen activator receptor (Plaur) gene have decreased GABAergic interneurons in frontal and parietal, but not caudal, cortical regions. Plaur assists in the activation of hepatocyte growth factor/scatter factor (HGF/SF), and several of the interneuron deficits are correlated with decreased levels of HGF/SF. In some cortical regions, the interneuron deficit can be remediated by endogenous overexpression of HGF/SF. In this study, we demonstrate decreased parvalbumin-expressing interneurons in the medial frontal cortex, but not in the hippocampus or basal lateral amygdala in the Plaur null mouse. The Plaur null mouse demonstrates impaired medial frontal cortical function in extinction of cued fear conditioning and the inability to form attentional sets. Endogenous HGF/SF overexpression increased the number of PV-expressing cells in medial frontal cortical areas to levels greater than found in wildtype mice, but did not remediate the behavioral deficits. These data suggest that proper medial frontal cortical function is dependent upon optimum levels of inhibition and that a deficit or excess of interneuron numbers impairs normal cognition. PMID:24211452

  1. Cortical circuits for perceptual inference.

    PubMed

    Friston, Karl; Kiebel, Stefan

    2009-10-01

    This paper assumes that cortical circuits have evolved to enable inference about the causes of sensory input received by the brain. This provides a principled specification of what neural circuits have to achieve. Here, we attempt to address how the brain makes inferences by casting inference as an optimisation problem. We look at how the ensuing recognition dynamics could be supported by directed connections and message-passing among neuronal populations, given our knowledge of intrinsic and extrinsic neuronal connections. We assume that the brain models the world as a dynamic system, which imposes causal structure on the sensorium. Perception is equated with the optimisation or inversion of this internal model, to explain sensory input. Given a model of how sensory data are generated, we use a generic variational approach to model inversion to furnish equations that prescribe recognition; i.e., the dynamics of neuronal activity that represents the causes of sensory input. Here, we focus on a model whose hierarchical and dynamical structure enables simulated brains to recognise and predict sequences of sensory states. We first review these models and their inversion under a variational free-energy formulation. We then show that the brain has the necessary infrastructure to implement this inversion and present stimulations using synthetic birds that generate and recognise birdsongs.

  2. Cortical circuits for perceptual inference.

    PubMed

    Friston, Karl; Kiebel, Stefan

    2009-10-01

    This paper assumes that cortical circuits have evolved to enable inference about the causes of sensory input received by the brain. This provides a principled specification of what neural circuits have to achieve. Here, we attempt to address how the brain makes inferences by casting inference as an optimisation problem. We look at how the ensuing recognition dynamics could be supported by directed connections and message-passing among neuronal populations, given our knowledge of intrinsic and extrinsic neuronal connections. We assume that the brain models the world as a dynamic system, which imposes causal structure on the sensorium. Perception is equated with the optimisation or inversion of this internal model, to explain sensory input. Given a model of how sensory data are generated, we use a generic variational approach to model inversion to furnish equations that prescribe recognition; i.e., the dynamics of neuronal activity that represents the causes of sensory input. Here, we focus on a model whose hierarchical and dynamical structure enables simulated brains to recognise and predict sequences of sensory states. We first review these models and their inversion under a variational free-energy formulation. We then show that the brain has the necessary infrastructure to implement this inversion and present stimulations using synthetic birds that generate and recognise birdsongs. PMID:19635656

  3. 21 CFR 882.1310 - Cortical electrode.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...) Identification. A cortical electrode is an electrode which is temporarily placed on the surface of the brain for stimulating the brain or recording the brain's electrical activity. (b) Classification. Class II...

  4. 21 CFR 882.1310 - Cortical electrode.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) Identification. A cortical electrode is an electrode which is temporarily placed on the surface of the brain for stimulating the brain or recording the brain's electrical activity. (b) Classification. Class II...

  5. 21 CFR 882.1310 - Cortical electrode.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...) Identification. A cortical electrode is an electrode which is temporarily placed on the surface of the brain for stimulating the brain or recording the brain's electrical activity. (b) Classification. Class II...

  6. 21 CFR 882.1310 - Cortical electrode.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) Identification. A cortical electrode is an electrode which is temporarily placed on the surface of the brain for stimulating the brain or recording the brain's electrical activity. (b) Classification. Class II...

  7. 21 CFR 882.1310 - Cortical electrode.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) Identification. A cortical electrode is an electrode which is temporarily placed on the surface of the brain for stimulating the brain or recording the brain's electrical activity. (b) Classification. Class II...

  8. Left anterior temporal cortex actively engages in speech perception: A direct cortical stimulation study.

    PubMed

    Matsumoto, Riki; Imamura, Hisaji; Inouchi, Morito; Nakagawa, Tomokazu; Yokoyama, Yohei; Matsuhashi, Masao; Mikuni, Nobuhiro; Miyamoto, Susumu; Fukuyama, Hidenao; Takahashi, Ryosuke; Ikeda, Akio

    2011-04-01

    Recent neuroimaging studies proposed the importance of the anterior auditory pathway for speech comprehension. Its clinical significance is implicated by semantic dementia or pure word deafness. Neurodegenerative or cerebrovascular nature, however, precluded precise localization of the cortex responsible for speech perception. Electrical cortical stimulation could delineate such localization by producing transient, functional impairment. We investigated engagement of the left anterior temporal cortex in speech perception by means of direct electrical cortical stimulation. Subjects were two partial epilepsy patients, who underwent direct cortical stimulation as a part of invasive presurgical evaluations. Stimulus sites were coregistered to presurgical 3D-MRI, and then to MNI standard space for anatomical localization. Separate from the posterior temporal language area, electrical cortical stimulation revealed a well-restricted language area in the anterior part of the superior temporal sulcus and gyrus (aSTS/STG) in both patients. Auditory sentence comprehension was impaired upon electrical stimulation of aSTS/STG. In one patient, additional investigation revealed that the functional impairment was restricted to auditory sentence comprehension with preserved visual sentence comprehension and perception of music and environmental sounds. Both patients reported that they could hear the voice but not understand the sentence well (e.g., heard as a series of meaningless utterance). The standard coordinates of this restricted area at left aSTS/STG well corresponded with the coordinates of speech perception reported in neuroimaging activation studies in healthy subjects. The present combined anatomo-functional case study, for the first time, demonstrated that aSTS/STG in the language dominant hemisphere actively engages in speech perception.

  9. Reduced cortical thickness, surface area in patients with chronic obstructive pulmonary disease: a surface-based morphometry and neuropsychological study.

    PubMed

    Chen, Ji; Lin, In-Tsang; Zhang, Haiyan; Lin, Jianzhong; Zheng, Shili; Fan, Ming; Zhang, Jiaxing

    2016-06-01

    Neural impairments accompanying chronic obstructive pulmonary disease (COPD) have received growing research attention. Previous neuroimaging studies exclusively used volumetric methods to measure cortical volume as a whole rather than focusing on anatomical and neuropathological distinct indices. Here we decomposed the cortical architecture into cortical thickness (CTh), surface area (SA), and gyrification, for the first time, to provide a more integrative profile of brain damage in COPD. Clinical T1-weighted MRI scans were acquired in 25 stable COPD patients (mean age 69) and 25 age-matched controls. Images were processed using surface-based morphometry to obtain cortical parameters enabling more accurate measurement in deep sulci and localized regional mapping. Demographic, physiological, and cognitive assessments were made and correlated with cortical indices. Compared to controls, COPD patients showed significantly reduced CTh broadly distributed in motor, parietal, and prefrontal cortices, together with more circumscribed SA reduction in dorsomedial prefrontal cortex and Broca's area (cluster-level P < 0.05 corrected). No abnormal gyrification was detected. Decreased CTh in parietofrontal networks strongly correlated with visuospatial construction impairment in COPD patients. Furthermore, thinner dorsolateral prefrontal cortex (DLPFC) best predicted poorer performance (r (2)  = 0.315, P = 0.004), and was associated with lower arterial oxygen saturation. These data indicate that cortical thinning is a key morphologic feature associated with COPD that could be partly attributed to oxygen desaturation and contributes to COPD visual memory and drawing deficits. Surface-based morphometry provides valuable information concerning COPD, and could ultimately help us to characterize the neurodegenerative pattern and to clarify neurologic mechanisms underlying cognitive dysfunction in COPD patients. PMID:25986304

  10. Striatal GABAergic and cortical glutamatergic neurons mediate contrasting effects of cannabinoids on cortical network synchrony.

    PubMed

    Sales-Carbonell, Carola; Rueda-Orozco, Pavel E; Soria-Gómez, Edgar; Buzsáki, György; Marsicano, Giovanni; Robbe, David

    2013-01-01

    Activation of type 1 cannabinoid receptors (CB1R) decreases GABA and glutamate release in cortical and subcortical regions, with complex outcomes on cortical network activity. To date there have been few attempts to disentangle the region- and cell-specific mechanisms underlying the effects of cannabinoids on cortical network activity in vivo. Here we addressed this issue by combining in vivo electrophysiological recordings with local and systemic pharmacological manipulations in conditional mutant mice lacking CB1R expression in different neuronal populations. First we report that cannabinoids induce hypersynchronous thalamocortical oscillations while decreasing the amplitude of faster cortical oscillations. Then we demonstrate that CB1R at striatonigral synapses (basal ganglia direct pathway) mediate the thalamocortical hypersynchrony, whereas activation of CB1R expressed in cortical glutamatergic neurons decreases cortical synchrony. Finally we show that activation of CB1 expressed in cortical glutamatergic neurons limits the cannabinoid-induced thalamocortical hypersynchrony. By reporting that CB1R activations in cortical and subcortical regions have contrasting effects on cortical synchrony, our study bridges the gap between cellular and in vivo network effects of cannabinoids. Incidentally, the thalamocortical hypersynchrony we report suggests a potential mechanism to explain the sensory "high" experienced during recreational consumption of marijuana.

  11. Striatal GABAergic and cortical glutamatergic neurons mediate contrasting effects of cannabinoids on cortical network synchrony

    PubMed Central

    Sales-Carbonell, Carola; Rueda-Orozco, Pavel E.; Soria-Gómez, Edgar; Buzsáki, György; Marsicano, Giovanni; Robbe, David

    2013-01-01

    Activation of type 1 cannabinoid receptors (CB1R) decreases GABA and glutamate release in cortical and subcortical regions, with complex outcomes on cortical network activity. To date there have been few attempts to disentangle the region- and cell-specific mechanisms underlying the effects of cannabinoids on cortical network activity in vivo. Here we addressed this issue by combining in vivo electrophysiological recordings with local and systemic pharmacological manipulations in conditional mutant mice lacking CB1R expression in different neuronal populations. First we report that cannabinoids induce hypersynchronous thalamocortical oscillations while decreasing the amplitude of faster cortical oscillations. Then we demonstrate that CB1R at striatonigral synapses (basal ganglia direct pathway) mediate the thalamocortical hypersynchrony, whereas activation of CB1R expressed in cortical glutamatergic neurons decreases cortical synchrony. Finally we show that activation of CB1 expressed in cortical glutamatergic neurons limits the cannabinoid-induced thalamocortical hypersynchrony. By reporting that CB1R activations in cortical and subcortical regions have contrasting effects on cortical synchrony, our study bridges the gap between cellular and in vivo network effects of cannabinoids. Incidentally, the thalamocortical hypersynchrony we report suggests a potential mechanism to explain the sensory “high” experienced during recreational consumption of marijuana. PMID:23269835

  12. Cortical Neural Computation by Discrete Results Hypothesis

    PubMed Central

    Castejon, Carlos; Nuñez, Angel

    2016-01-01

    One of the most challenging problems we face in neuroscience is to understand how the cortex performs computations. There is increasing evidence that the power of the cortical processing is produced by populations of neurons forming dynamic neuronal ensembles. Theoretical proposals and multineuronal experimental studies have revealed that ensembles of neurons can form emergent functional units. However, how these ensembles are implicated in cortical computations is still a mystery. Although cell ensembles have been associated with brain rhythms, the functional interaction remains largely unclear. It is still unknown how spatially distributed neuronal activity can be temporally integrated to contribute to cortical computations. A theoretical explanation integrating spatial and temporal aspects of cortical processing is still lacking. In this Hypothesis and Theory article, we propose a new functional theoretical framework to explain the computational roles of these ensembles in cortical processing. We suggest that complex neural computations underlying cortical processing could be temporally discrete and that sensory information would need to be quantized to be computed by the cerebral cortex. Accordingly, we propose that cortical processing is produced by the computation of discrete spatio-temporal functional units that we have called “Discrete Results” (Discrete Results Hypothesis). This hypothesis represents a novel functional mechanism by which information processing is computed in the cortex. Furthermore, we propose that precise dynamic sequences of “Discrete Results” is the mechanism used by the cortex to extract, code, memorize and transmit neural information. The novel “Discrete Results” concept has the ability to match the spatial and temporal aspects of cortical processing. We discuss the possible neural underpinnings of these functional computational units and describe the empirical evidence supporting our hypothesis. We propose that fast

  13. Development and evolution of cortical fields.

    PubMed

    Arai, Yoko; Pierani, Alessandra

    2014-09-01

    The neocortex is the brain structure that has been subjected to a major size expansion, in its relative size, during mammalian evolution. It arises from the cortical primordium through coordinated growth of neural progenitor cells along both the tangential and radial axes and their patterning providing spatial coordinates. Functional neocortical areas are ultimately consolidated by environmental influences such as peripheral sensory inputs. Throughout neocortical evolution, cortical areas have become more sophisticated and numerous. This increase in number is possibly involved in the complexification of neocortical function in primates. Whereas extensive divergence of functional cortical fields is observed during evolution, the fundamental mechanisms supporting the allocation of cortical areas and their wiring are conserved, suggesting the presence of core genetic mechanisms operating in different species. We will discuss some of the basic molecular mechanisms including morphogen-dependent ones involved in the precise orchestration of neurogenesis in different cortical areas, elucidated from studies in rodents. Attention will be paid to the role of Cajal-Retzius neurons, which were recently proposed to be migrating signaling units also involved in arealization, will be addressed. We will further review recent works on molecular mechanisms of cortical patterning resulting from comparative analyses between different species during evolution.

  14. Awake vs. anesthetized: layer-specific sensory processing in visual cortex and functional connectivity between cortical areas.

    PubMed

    Sellers, Kristin K; Bennett, Davis V; Hutt, Axel; Williams, James H; Fröhlich, Flavio

    2015-06-01

    During general anesthesia, global brain activity and behavioral state are profoundly altered. Yet it remains mostly unknown how anesthetics alter sensory processing across cortical layers and modulate functional cortico-cortical connectivity. To address this gap in knowledge of the micro- and mesoscale effects of anesthetics on sensory processing in the cortical microcircuit, we recorded multiunit activity and local field potential in awake and anesthetized ferrets (Mustela putoris furo) during sensory stimulation. To understand how anesthetics alter sensory processing in a primary sensory area and the representation of sensory input in higher-order association areas, we studied the local sensory responses and long-range functional connectivity of primary visual cortex (V1) and prefrontal cortex (PFC). Isoflurane combined with xylazine provided general anesthesia for all anesthetized recordings. We found that anesthetics altered the duration of sensory-evoked responses, disrupted the response dynamics across cortical layers, suppressed both multimodal interactions in V1 and sensory responses in PFC, and reduced functional cortico-cortical connectivity between V1 and PFC. Together, the present findings demonstrate altered sensory responses and impaired functional network connectivity during anesthesia at the level of multiunit activity and local field potential across cortical layers.

  15. Awake vs. anesthetized: layer-specific sensory processing in visual cortex and functional connectivity between cortical areas

    PubMed Central

    Sellers, Kristin K.; Bennett, Davis V.; Hutt, Axel; Williams, James H.

    2015-01-01

    During general anesthesia, global brain activity and behavioral state are profoundly altered. Yet it remains mostly unknown how anesthetics alter sensory processing across cortical layers and modulate functional cortico-cortical connectivity. To address this gap in knowledge of the micro- and mesoscale effects of anesthetics on sensory processing in the cortical microcircuit, we recorded multiunit activity and local field potential in awake and anesthetized ferrets (Mustela putoris furo) during sensory stimulation. To understand how anesthetics alter sensory processing in a primary sensory area and the representation of sensory input in higher-order association areas, we studied the local sensory responses and long-range functional connectivity of primary visual cortex (V1) and prefrontal cortex (PFC). Isoflurane combined with xylazine provided general anesthesia for all anesthetized recordings. We found that anesthetics altered the duration of sensory-evoked responses, disrupted the response dynamics across cortical layers, suppressed both multimodal interactions in V1 and sensory responses in PFC, and reduced functional cortico-cortical connectivity between V1 and PFC. Together, the present findings demonstrate altered sensory responses and impaired functional network connectivity during anesthesia at the level of multiunit activity and local field potential across cortical layers. PMID:25833839

  16. Memory Impairment in Children with Language Impairment

    ERIC Educational Resources Information Center

    Baird, Gillian; Dworzynski, Katharina; Slonims, Vicky; Simonoff, Emily

    2010-01-01

    Aim: The aim of this study was to assess whether any memory impairment co-occurring with language impairment is global, affecting both verbal and visual domains, or domain specific. Method: Visual and verbal memory, learning, and processing speed were assessed in children aged 6 years to 16 years 11 months (mean 9y 9m, SD 2y 6mo) with current,…

  17. Euchromatin histone methyltransferase 1 regulates cortical neuronal network development

    PubMed Central

    Bart Martens, Marijn; Frega, Monica; Classen, Jessica; Epping, Lisa; Bijvank, Elske; Benevento, Marco; van Bokhoven, Hans; Tiesinga, Paul; Schubert, Dirk; Nadif Kasri, Nael

    2016-01-01

    Heterozygous mutations or deletions in the human Euchromatin histone methyltransferase 1 (EHMT1) gene cause Kleefstra syndrome, a neurodevelopmental disorder that is characterized by autistic-like features and severe intellectual disability (ID). Neurodevelopmental disorders including ID and autism may be related to deficits in activity-dependent wiring of brain circuits during development. Although Kleefstra syndrome has been associated with dendritic and synaptic defects in mice and Drosophila, little is known about the role of EHMT1 in the development of cortical neuronal networks. Here we used micro-electrode arrays and whole-cell patch-clamp recordings to investigate the impact of EHMT1 deficiency at the network and single cell level. We show that EHMT1 deficiency impaired neural network activity during the transition from uncorrelated background action potential firing to synchronized network bursting. Spontaneous bursting and excitatory synaptic currents were transiently reduced, whereas miniature excitatory postsynaptic currents were not affected. Finally, we show that loss of function of EHMT1 ultimately resulted in less regular network bursting patterns later in development. These data suggest that the developmental impairments observed in EHMT1-deficient networks may result in a temporal misalignment between activity-dependent developmental processes thereby contributing to the pathophysiology of Kleefstra syndrome. PMID:27767173

  18. Enrichment and training improve cognition in rats with cortical malformations.

    PubMed

    Jenks, Kyle R; Lucas, Marcella M; Duffy, Ben A; Robbins, Ashlee A; Gimi, Barjor; Barry, Jeremy M; Scott, Rod C

    2013-01-01

    Children with malformations of cortical development (MCD) frequently have associated cognitive impairments which reduce quality of life. We hypothesized that cognitive deficits associated with MCD can be improved with environmental manipulation or additional training. The E17 methylazoxymethanol acetate (MAM) exposure model bears many anatomical hallmarks seen in human MCDs as well as similar behavioral and cognitive deficits. We divided control and MAM exposed Sprague-Dawley rats into enriched and non-enriched groups and tested performance in the Morris water maze. Another group similarly divided underwent sociability testing and also underwent Magnetic Resonance Imaging (MRI) scans pre and post enrichment. A third group of control and MAM rats without enrichment were trained until they reached criterion on the place avoidance task. MAM rats had impaired performance on spatial tasks and enrichment improved performance of both control and MAM animals. Although MAM rats did not have a deficit in sociability they showed similar improvement with enrichment as controls. MRI revealed a whole brain volume decrease with MAM exposure, and an increase in both MAM and control enriched volumes in comparison to non-enriched animals. In the place avoidance task, MAM rats required approximately 3 times as long to reach criterion as control animals, but with additional training were able to reach control performance. Environmental manipulation and additional training can improve cognition in a rodent MCD model. We therefore suggest that patients with MCD may benefit from appropriate alterations in educational strategies, social interaction and environment. These factors should be considered in therapeutic strategies.

  19. Cortical thinning of parahippocampal subregions in very early Alzheimer's disease.

    PubMed

    Krumm, Sabine; Kivisaari, Sasa L; Probst, Alphonse; Monsch, Andreas U; Reinhardt, Julia; Ulmer, Stephan; Stippich, Christoph; Kressig, Reto W; Taylor, Kirsten I

    2016-02-01

    The stereotypical pattern of neurofibrillary tangle spreading in the earliest stages of typical Alzheimer's dementia (AD) predicts that medial perirhinal cortex (mPRC) atrophy precedes entorhinal cortex (ERC) atrophy, whereas the status of the parahippocampal cortex (PHC) remains unclear. Atrophy studies have focused on more advanced rather than early AD patients, and usually segment the entire PRC as opposed to the mPRC versus lateral PRC (lPRC). The present study therefore determined the extent of ERC, mPRC, lPRC, and PHC atrophy in very early AD (mean Mini-Mental State Examination score = 26) patients and its presumed prodrome amnestic mild cognitive impairment (mean Mini-Mental State Examination score = 28) compared to demographically matched controls. PHG structures were manually segmented (blinded rater) and cortical thicknesses extracted. ERC and mPRC were similarly atrophied in both patient groups. The lPRC was atrophied in the AD group only. Thus, atrophic changes in very early AD broadly map onto the pattern of neurofibrillary tangle spreading and suggest that mPRC, ERC, and lPRC, but not PHC-associated functional impairments, characterize very early-stage AD. PMID:26827657

  20. Dynamic cortical lateralization during olfactory discrimination learning

    PubMed Central

    Cohen, Yaniv; Putrino, David; Wilson, Donald A

    2015-01-01

    Key points Odour discrimination and memory involve changes in the primary olfactory (piriform) cortex. The results obtained in the present study suggest that there is an asymmetry in piriform cortical change, with learning-related changes in cortical oscillations emerging with different time courses over the course of multiday training in the left and right piriform cortices in rats. There is an initial decrease in coherence between the left and right piriform cortices during the early stages of the odour discrimination task, which recovers as the animals approach criterion performance. This decreased coherence is expressed when the animals are performing the task relative to when they are in their home cage. The results suggest a transient cortical asymmetry during learning and raise new questions about the functions and mechanisms of cerebral lateralization. Abstract Bilateral cortical circuits are not necessarily symmetrical. Asymmetry, or cerebral lateralization, allows functional specialization of bilateral brain regions and has been described in humans for such diverse functions as perception, memory and emotion. There is also evidence for asymmetry in the human olfactory system, although evidence in non-human animal models is lacking. In the present study, we took advantage of the known changes in olfactory cortical local field potentials that occur over the course of odour discrimination training to test for functional asymmetry in piriform cortical activity during learning. Both right and left piriform cortex local field potential activities were recorded. The results obtained demonstrate a robust interhemispheric asymmetry in anterior piriform cortex activity that emerges during specific stages of odour discrimination learning, with a transient bias toward the left hemisphere. This asymmetry is not apparent during error trials. Furthermore, functional connectivity (coherence) between the bilateral anterior piriform cortices is learning- and context

  1. Disrupted cortical connectivity theory as an explanatory model for autism spectrum disorders

    NASA Astrophysics Data System (ADS)

    Kana, Rajesh K.; Libero, Lauren E.; Moore, Marie S.

    2011-12-01

    Recent findings of neurological functioning in autism spectrum disorder (ASD) point to altered brain connectivity as a key feature of its pathophysiology. The cortical underconnectivity theory of ASD (Just et al., 2004) provides an integrated framework for addressing these new findings. This theory suggests that weaker functional connections among brain areas in those with ASD hamper their ability to accomplish complex cognitive and social tasks successfully. We will discuss this theory, but will modify the term underconnectivity to ‘disrupted cortical connectivity’ to capture patterns of both under- and over-connectivity in the brain. In this paper, we will review the existing literature on ASD to marshal supporting evidence for hypotheses formulated on the disrupted cortical connectivity theory. These hypotheses are: 1) underconnectivity in ASD is manifested mainly in long-distance cortical as well as subcortical connections rather than in short-distance cortical connections; 2) underconnectivity in ASD is manifested only in complex cognitive and social functions and not in low-level sensory and perceptual tasks; 3) functional underconnectivity in ASD may be the result of underlying anatomical abnormalities, such as problems in the integrity of white matter; 4) the ASD brain adapts to underconnectivity through compensatory strategies such as overconnectivity mainly in frontal and in posterior brain areas. This may be manifested as deficits in tasks that require frontal-parietal integration. While overconnectivity can be tested by examining the cortical minicolumn organization, long-distance underconnectivity can be tested by cognitively demanding tasks; and 5) functional underconnectivity in brain areas in ASD will be seen not only during complex tasks but also during task-free resting states. We will also discuss some empirical predictions that can be tested in future studies, such as: 1) how disrupted connectivity relates to cognitive impairments in skills

  2. Multimodal neuroimaging evidence of alterations in cortical structure and function in HIV-infected older adults

    PubMed Central

    Wilson, Tony W.; Heinrichs-Graham, Elizabeth; Becker, Katherine M.; Aloi, Joey; Robertson, Kevin R.; Sandkovsky, Uriel; White, Matthew L.; O’Neill, Jennifer; Knott, Nichole L.; Fox, Howard S.; Swindells, Susan

    2015-01-01

    Combination antiretroviral therapy transformed HIV-infection from a terminal illness to a manageable condition, but these patients remain at a significantly elevated risk of developing cognitive impairments and the mechanisms are not understood. Some previous neuroimaging studies have found hyperactivation in fronto-parietal networks of HIV-infected patients, whereas others reported aberrations restricted to sensory cortices. In this study, we utilize high-resolution structural and neurophysiological imaging to determine whether alterations in brain structure, function, or both contribute to HIV-related cognitive impairments. HIV-infected adults and individually-matched controls completed 3-Tesla structural magnetic-resonance imaging (sMRI) and a mechanoreception task during magnetoencephalography (MEG). MEG data was examined using advanced beamforming methods, and sMRI data was analyzed using the latest voxel-based morphometry methods with DARTEL. We found significantly reduced theta responses in the postcentral gyrus and increased alpha activity in the prefrontal cortices of HIV-infected patients compared with controls. Patients also had reduced gray matter volume in the postcentral gyrus, parahippocampal gyrus, and other regions. Importantly, reduced gray matter volume in the left postcentral gyrus was spatially-coincident with abnormal MEG responses in HIV-infected patients. Finally, left prefrontal and postcentral gyrus activity was correlated with neuropsychological performance and, when used in conjunction, these two MEG findings had a sensitivity and specificity of over 87.5% for HIV-associated cognitive impairment. This study is the first to demonstrate abnormally increased activity in association cortices with simultaneously decreased activity in sensory areas. These MEG findings had excellent sensitivity and specificity for HIV-associated cognitive impairment, and may hold promise as a potential disease marker. PMID:25376125

  3. Multimodal neuroimaging evidence of alterations in cortical structure and function in HIV-infected older adults.

    PubMed

    Wilson, Tony W; Heinrichs-Graham, Elizabeth; Becker, Katherine M; Aloi, Joseph; Robertson, Kevin R; Sandkovsky, Uriel; White, Matthew L; O'Neill, Jennifer; Knott, Nichole L; Fox, Howard S; Swindells, Susan

    2015-03-01

    Combination antiretroviral therapy transformed human immunodeficiency virus (HIV)-infection from a terminal illness to a manageable condition, but these patients remain at a significantly elevated risk of developing cognitive impairments and the mechanisms are not understood. Some previous neuroimaging studies have found hyperactivation in frontoparietal networks of HIV-infected patients, whereas others reported aberrations restricted to sensory cortices. In this study, we utilize high-resolution structural and neurophysiological imaging to determine whether alterations in brain structure, function, or both contribute to HIV-related cognitive impairments. HIV-infected adults and individually matched controls completed 3-Tesla structural magnetic resonance imaging (sMRI) and a mechanoreception task during magnetoencephalography (MEG). MEG data were examined using advanced beamforming methods, and sMRI data were analyzed using the latest voxel-based morphometry methods with DARTEL. We found significantly reduced theta responses in the postcentral gyrus and increased alpha activity in the prefrontal cortices of HIV-infected patients compared with controls. Patients also had reduced gray matter volume in the postcentral gyrus, parahippocampal gyrus, and other regions. Importantly, reduced gray matter volume in the left postcentral gyrus was spatially coincident with abnormal MEG responses in HIV-infected patients. Finally, left prefrontal and postcentral gyrus activity was correlated with neuropsychological performance and, when used in conjunction, these two MEG findings had a sensitivity and specificity of over 87.5% for HIV-associated cognitive impairment. This study is the first to demonstrate abnormally increased activity in association cortices with simultaneously decreased activity in sensory areas. These MEG findings had excellent sensitivity and specificity for HIV-associated cognitive impairment, and may hold promise as a potential disease marker.

  4. Recent advancements in diffusion MRI for investigating cortical development after preterm birth—potential and pitfalls

    PubMed Central

    Dudink, J.; Pieterman, K.; Leemans, A.; Kleinnijenhuis, M.; van Cappellen van Walsum, A. M.; Hoebeek, F. E.

    2015-01-01

    Preterm infants are born during a critical period of brain maturation, in which even subtle events can result in substantial behavioral, motor and cognitive deficits, as well as psychiatric diseases. Recent evidence shows that the main source for these devastating disabilities is not necessarily white matter (WM) damage but could also be disruptions of cortical microstructure. Animal studies showed how moderate hypoxic-ischemic conditions did not result in significant neuronal loss in the developing brain, but did cause significantly impaired dendritic growth and synapse formation alongside a disturbed development of neuronal connectivity as measured using diffusion magnetic resonance imaging (dMRI). When using more advanced acquisition settings such as high-angular resolution diffusion imaging (HARDI), more advanced reconstruction methods can be applied to investigate the cortical microstructure with higher levels of detail. Recent advances in dMRI acquisition and analysis have great potential to contribute to a better understanding of neuronal connectivity impairment in preterm birth. We will review the current understanding of abnormal preterm cortical development, novel approaches in dMRI, and the pitfalls in scanning vulnerable preterm infants. PMID:25653607

  5. Evidence of temporal cortical dysfunction in rhesus monkeys following chronic cocaine self-administration.

    PubMed

    Liu, S; Heitz, R P; Sampson, A R; Zhang, W; Bradberry, C W

    2008-09-01

    Cocaine abusers show impaired performance on cognitive tasks that engage prefrontal cortex. These deficits may contribute to impaired control and relapse in abusers. Understanding the neuronal substrates that lead to these deficits requires animal models that are relevant to the human condition. However, to date, models have mostly focused on behaviors mediated by subcortical systems. Here we evaluated the impact of long-term self-administration of cocaine in the rhesus monkey on cognitive performance. Tests included stimulus discrimination (SD)/reversal and delayed alternation tasks. The chronic cocaine animals showed marked deficits in ability to organize their behavior for maximal reward. This was demonstrated by an increased time needed to acquire SDs. Deficits were also indicated by an increased time to initially learn the delayed alternation task, and to adapt strategies for bypassing a reliance on working memory to respond accurately. Working memory per se (delay dependent performance) was not affected by chronic self-administration. This pattern of cognitive deficits suggests dysfunction that extends beyond localized prefrontal cortical areas. In particular, it appears that temporal cortical function is also compromised. This agrees with other recent clinical and preclinical findings, and suggests further study into addiction related dysfunction across more widespread cortical networks is warranted. PMID:18096561

  6. Disembodied Mind: Cortical Changes Following Brainstem Injury in Patients with Locked-in Syndrome

    PubMed Central

    Pistoia, Francesca; Cornia, Riccardo; Conson, Massimiliano; Gosseries, Olivia; Carolei, Antonio; Sacco, Simona; Quattrocchi, Carlo C.; Mallio, Carlo A.; Iani, Cristina; Mambro, Debora Di; Sarà, Marco

    2016-01-01

    Locked-in syndrome (LIS) following ventral brainstem damage is the most severe form of motor disability. Patients are completely entrapped in an unresponsive body despite consciousness is preserved. Although the main feature of LIS is this extreme motor impairment, minor non-motor dysfunctions such as motor imagery defects and impaired emotional recognition have been reported suggesting an alteration of embodied cognition, defined as the effects that the body and its performances may have on cognitive domains. We investigated the presence of structural cortical changes in LIS, which may account for the reported cognitive dysfunctions. For this aim, magnetic resonance imaging scans were acquired in 11 patients with LIS (6 males and 5 females; mean age: 52.3±5.2SD years; mean time interval from injury to evaluation: 9±1.2SD months) and 44 healthy control subjects matching patients for age, sex and education. Freesurfer software was used to process data and to estimate cortical volumes in LIS patients as compared to healthy subjects. Results showed a selective cortical volume loss in patients involving the superior frontal gyrus, the pars opercularis and the insular cortex in the left hemisphere, and the superior and medium frontal gyrus, the pars opercularis, the insular cortex, and the superior parietal lobule in the right hemisphere. As these structures are typically associated with the mirror neuron system, which represents the neural substrate for embodied simulation processes, our results provide neuroanatomical support for potential disembodiment in LIS. PMID:27347263

  7. Periventricular Heterotopia: Shuttling of Proteins through Vesicles and Actin in Cortical Development and Disease

    PubMed Central

    Sheen, Volney L.

    2012-01-01

    During cortical development, proliferating neural progenitors exhibit polarized apical and basolateral membranes that are maintained by tightly controlled and membrane-specific vesicular trafficking pathways. Disruption of polarity through impaired delivery of proteins can alter cell fate decisions and consequent expansion of the progenitor pool, as well as impact the integrity of the neuroependymal lining. Loss of neuroependymal integrity disrupts radial glial scaffolding and alters initial neuronal migration from the ventricular zone. Vesicle trafficking is also required for maintenance of lipid and protein cycling within the leading and trailing edge of migratory neurons, as well as dendrites and synapses of mature neurons. Defects in this transport machinery disrupt neuronal identity, migration, and connectivity and give rise to a malformation of cortical development termed as periventricular heterotopia (PH). PH is characterized by a reduction in brain size, ectopic clusters of neurons localized along the lateral ventricle, and epilepsy and dyslexia. These anatomical anomalies correlate with developmental impairments in neural progenitor proliferation and specification, migration from loss of neuroependymal integrity and neuronal motility, and aberrant neuronal process extension. Genes causal for PH regulate vesicle-mediated endocytosis along an actin cytoskeletal network. This paper explores the role of these dynamic processes in cortical development and disease. PMID:24278701

  8. ERBB4 Polymorphism and Family History of Psychiatric Disorders on Age-Related Cortical Changes in Healthy Children

    PubMed Central

    Douet, Vanessa; Chang, Linda; Lee, Kristin; Ernst, Thomas

    2015-01-01

    Background Genetic variations in ERBB4 were associated with increased susceptibility for schizophrenia (SCZ) and bipolar disorders (BPD). Structural imaging studies showed cortical abnormalities in adolescents and adults with SCZ or BPD. However, less is known about subclinical cortical changes or the influence of ERBB4 on cortical development. Methods 971 healthy children (ages 3–20 years old; 462 girls and 509 boys) were genotyped for the ERBB4-rs7598440 variants, had structural MRI, and cognitive evaluation (NIH Toolbox ®). We investigated the effects of ERBB4 variants and family history of SCZ and/or BPD (FH) on cortical measures and cognitive performances across ages 3–20 years using a general additive model. Results Variations in ERBB4 and FH impact differentially the age-related cortical changes in regions often affected by SCZ and BPD. The ERBB4-TT-risk genotype children with no FH had subtle cortical changes across the age span, primarily located in the left temporal lobe and superior parietal cortex. In contrast, the TT-risk genotype children with FH had more pronounced age-related changes, mainly in the frontal lobes compared to the non-risk genotype children. Interactive effects of age, FH and ERBB4 variations were also found on episodic memory and working memory, which are often impaired in SCZ and BPD. Conclusions Healthy children carrying the risk-genotype in ERBB4 and/or with FH had cortical measures resembling those reported in SCZ or BPD. These subclinical cortical variations may provide early indicators for increased risk of psychiatric disorders and improve our understanding of the effect of the NRG1–ERBB4 pathway on brain development. PMID:25744101

  9. High-spatial-resolution mapping of the oxygen concentration in cortical tissue (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Jaswal, Rajeshwer S.; Yaseen, Mohammad A.; Fu, Buyin; Boas, David A.; Sakadžic, Sava

    2016-03-01

    Due to a lack of imaging tools for high-resolution imaging of cortical tissue oxygenation, the detailed maps of the oxygen partial pressure (PO2) around arterioles, venules, and capillaries remain largely unknown. Therefore, we have limited knowledge about the mechanisms that secure sufficient oxygen delivery in microvascular domains during brain activation, and provide some metabolic reserve capacity in diseases that affect either microvascular networks or the regulation of cerebral blood flow (CBF). To address this challenge, we applied a Two-Photon PO2 Microscopy to map PO2 at different depths in mice cortices. Measurements were performed through the cranial window in the anesthetized healthy mice as well as in the mouse models of microvascular dysfunctions. In addition, microvascular morphology was recorded by the two-photon microscopy at the end of each experiment and subsequently segmented. Co-registration of the PO2 measurements and exact microvascular morphology enabled quantification of the tissue PO2 dependence on distance from the arterioles, capillaries, and venules at various depths. Our measurements reveal significant spatial heterogeneity of the cortical tissue PO2 distribution that is dominated by the high oxygenation in periarteriolar spaces. In cases of impaired oxygen delivery due to microvascular dysfunction, significant reduction in tissue oxygenation away from the arterioles was observed. These tissue domains may be the initial sites of cortical injury that can further exacerbate the progression of the disease.

  10. Systematic assessment of BDNF and its receptor levels in human cortices affected by Huntington's disease.

    PubMed

    Zuccato, Chiara; Marullo, Manuela; Conforti, Paola; MacDonald, Marcy E; Tartari, Marzia; Cattaneo, Elena

    2008-04-01

    One cardinal feature of Huntington's disease (HD) is the degeneration of striatal neurons, whose survival greatly depends on the binding of cortical brain-derived neurotrophic factor (BDNF) with high-affinity (TrkB) and low-affinity neurotrophin receptors [p75 pan-neurotrophin receptor (p75(NTR))]. With a few exceptions, results obtained in HD mouse models demonstrate a reduction in cortical BDNF mRNA and protein, although autopsy data from a limited number of human HD cortices are conflicting. These studies indicate the presence of defects in cortical BDNF gene transcription and transport to striatum. We provide new evidence indicating a significant reduction in BDNF mRNA and protein in the cortex of 20 HD subjects in comparison with 17 controls, which supports the hypothesis of impaired BDNF production in human HD cortex. Analyses of the BDNF isoforms show that transcription from BDNF promoter II and IV is down-regulated in human HD cortex from an early symptomatic stage. We also found that TrkB mRNA levels are reduced in caudate tissue but not in the cortex, whereas the mRNA levels of T-Shc (a truncated TrkB isoform) and p75(NTR) are increased in the caudate. This indicates that, in addition to the reduction in BDNF mRNA, there is also unbalanced neurotrophic receptor signaling in HD. PMID:18093249

  11. Simulating Cortical Feedback Modulation as Changes in Excitation and Inhibition in a Cortical Circuit Model.

    PubMed

    Zagha, Edward; Murray, John D; McCormick, David A

    2016-01-01

    Cortical feedback pathways are hypothesized to distribute context-dependent signals during flexible behavior. Recent experimental work has attempted to understand the mechanisms by which cortical feedback inputs modulate their target regions. Within the mouse whisker sensorimotor system, cortical feedback stimulation modulates spontaneous activity and sensory responsiveness, leading to enhanced sensory representations. However, the cellular mechanisms underlying these effects are currently unknown. In this study we use a simplified neural circuit model, which includes two recurrent excitatory populations and global inhibition, to simulate cortical modulation. First, we demonstrate how changes in the strengths of excitation and inhibition alter the input-output processing responses of our model. Second, we compare these responses with experimental findings from cortical feedback stimulation. Our analyses predict that enhanced inhibition underlies the changes in spontaneous and sensory evoked activity observed experimentally. More generally, these analyses provide a framework for relating cellular and synaptic properties to emergent circuit function and dynamic modulation. PMID:27595137

  12. Simulating Cortical Feedback Modulation as Changes in Excitation and Inhibition in a Cortical Circuit Model

    PubMed Central

    Murray, John D.; McCormick, David A.

    2016-01-01

    Abstract Cortical feedback pathways are hypothesized to distribute context-dependent signals during flexible behavior. Recent experimental work has attempted to understand the mechanisms by which cortical feedback inputs modulate their target regions. Within the mouse whisker sensorimotor system, cortical feedback stimulation modulates spontaneous activity and sensory responsiveness, leading to enhanced sensory representations. However, the cellular mechanisms underlying these effects are currently unknown. In this study we use a simplified neural circuit model, which includes two recurrent excitatory populations and global inhibition, to simulate cortical modulation. First, we demonstrate how changes in the strengths of excitation and inhibition alter the input–output processing responses of our model. Second, we compare these responses with experimental findings from cortical feedback stimulation. Our analyses predict that enhanced inhibition underlies the changes in spontaneous and sensory evoked activity observed experimentally. More generally, these analyses provide a framework for relating cellular and synaptic properties to emergent circuit function and dynamic modulation.

  13. Simulating Cortical Feedback Modulation as Changes in Excitation and Inhibition in a Cortical Circuit Model.

    PubMed

    Zagha, Edward; Murray, John D; McCormick, David A

    2016-01-01

    Cortical feedback pathways are hypothesized to distribute context-dependent signals during flexible behavior. Recent experimental work has attempted to understand the mechanisms by which cortical feedback inputs modulate their target regions. Within the mouse whisker sensorimotor system, cortical feedback stimulation modulates spontaneous activity and sensory responsiveness, leading to enhanced sensory representations. However, the cellular mechanisms underlying these effects are currently unknown. In this study we use a simplified neural circuit model, which includes two recurrent excitatory populations and global inhibition, to simulate cortical modulation. First, we demonstrate how changes in the strengths of excitation and inhibition alter the input-output processing responses of our model. Second, we compare these responses with experimental findings from cortical feedback stimulation. Our analyses predict that enhanced inhibition underlies the changes in spontaneous and sensory evoked activity observed experimentally. More generally, these analyses provide a framework for relating cellular and synaptic properties to emergent circuit function and dynamic modulation.

  14. Simulating Cortical Feedback Modulation as Changes in Excitation and Inhibition in a Cortical Circuit Model

    PubMed Central

    Murray, John D.; McCormick, David A.

    2016-01-01

    Abstract Cortical feedback pathways are hypothesized to distribute context-dependent signals during flexible behavior. Recent experimental work has attempted to understand the mechanisms by which cortical feedback inputs modulate their target regions. Within the mouse whisker sensorimotor system, cortical feedback stimulation modulates spontaneous activity and sensory responsiveness, leading to enhanced sensory representations. However, the cellular mechanisms underlying these effects are currently unknown. In this study we use a simplified neural circuit model, which includes two recurrent excitatory populations and global inhibition, to simulate cortical modulation. First, we demonstrate how changes in the strengths of excitation and inhibition alter the input–output processing responses of our model. Second, we compare these responses with experimental findings from cortical feedback stimulation. Our analyses predict that enhanced inhibition underlies the changes in spontaneous and sensory evoked activity observed experimentally. More generally, these analyses provide a framework for relating cellular and synaptic properties to emergent circuit function and dynamic modulation. PMID:27595137

  15. Cortical thinning in bipolar disorder and schizophrenia.

    PubMed

    Knöchel, Christian; Reuter, Johanna; Reinke, Britta; Stäblein, Michael; Marbach, Katharina; Feddern, Richard; Kuhlmann, Kristina; Alves, Gilberto; Prvulovic, David; Wenzler, Sofia; Linden, David E J; Oertel-Knöchel, Viola

    2016-04-01

    Although schizophrenia (SZ) and bipolar disorder (BD) share some clinical features such as psychotic symptoms and cognitive dysfunctions, little is known about possible pathophysiological similarities between both diseases. Therefore, we investigated the potential topographical overlap and segregation of cortical thickness abnormalities in SZ and BD patients. We analyzed 3D-anatomical magnetic resonance imaging datasets with the FreeSurfer 5.1.0 software to examine cortical thickness and volumes in three groups of participants: n=34 BD patients, n=32 SZ patients and n=38 healthy controls. We observed similar bilateral cortical thickness reductions in BD and SZ patients predominantly in the pars opercularis of the inferior frontal gyrus and in the anterior and posterior cingulate. We also found disease-specific cortical reductions in the orbitofrontal cortex for BD patients and in dorsal frontal and temporal areas for SZ. Furthermore, inferior frontal gyrus cortical thinning was associated with deficits in psychomotor speed and executive functioning in SZ patients and with age at onset in both groups. Our findings support the hypothesis that thinning of the frontal cortex may represent a biological feature shared by both disease groups. The associations between cognitive deficits and the reported findings in SZ and to a lesser degree in BD patients add to the functional relevance of our results. However, further studies are needed to corroborate a model of shared pathophysiological disease features across BD and SZ. PMID:26876312

  16. Automatic parcellation of longitudinal cortical surfaces

    NASA Astrophysics Data System (ADS)

    Alassaf, Manal H.; Hahn, James K.

    2015-03-01

    We present a novel automatic method to parcellate the cortical surfaces of the neonatal brain longitudinal atlas at different stages of development. A labeled brain atlas of newborn at 41 weeks gestational age (GA) is used to propagate labels of anatomical regions of interest to an unlabeled spatio-temporal atlas, which provides a dynamic model of brain development at each week between 28-44 GA weeks. First, labels from the cortical volume of the labeled newborn brain are propagated to an age-matched cortical surface from the spatio-temporal atlas. Then, labels are propagated across the cortical surfaces of each week of the spatio-temporal atlas by registering successive cortical surfaces using a novel approach and an energy optimization function. This procedure incorporates local and global, spatial and temporal information when assigning the labels to each surface. The result is a complete parcellation of 17 neonatal brain surfaces of the spatio-temporal atlas with similar points per labels distributions across weeks.

  17. Malformations of cortical development and epilepsy.

    PubMed

    Leventer, Richard J; Guerrini, Renzo; Dobyns, William B

    2008-01-01

    Malformations of cortical development (MCDs) are macroscopic or microscopic abnormalities of the cerebral cortex that arise as a consequence of an interruption to the normal steps of formation of the cortical plate. The human cortex develops its basic structure during the first two trimesters of pregnancy as a series of overlapping steps, beginning with proliferation and differentiation of neurons, which then migrate before finally organizing themselves in the developing cortex. Abnormalities at any of these stages, be they environmental or genetic in origin, may cause disruption of neuronal circuitry and predispose to a variety of clinical consequences, the most common of which is epileptic seizures. A large number of MCDs have now been described, each with characteristic pathological, clinical, and imaging features. The causes of many of these MCDs have been determined through the study of affected individuals, with many MCDs now established as being secondary to mutations in cortical development genes. This review will highlight the best-known of the human cortical malformations associated with epilepsy. The pathological, clinical, imaging, and etiologic features of each MCD will be summarized, with representative magnetic resonance imaging (MRI) images shown for each MCD. The malformations tuberous sclerosis, focal cortical dysplasia, hemimegalencephaly, classical lissencephaly, subcortical band heterotopia, periventricular nodular heterotopia, polymicrogyria, and schizencephaly will be presented. PMID:18472484

  18. Intraoperative determination and display of cortical function

    NASA Astrophysics Data System (ADS)

    Bass, W. Andrew; Galloway, Robert L., Jr.; Dawant, Benoit M.; Maciunas, Robert J.

    1997-05-01

    One of the most important issues in neurosurgical lesion resection is margin definition. And while there is still some effort required to exactly determine lesion boundaries from tomographic images, the lesions are at least perceptible on the scans. What is not visible is the location of function. Functional imaging such as PET and fMRI hold some promise for cortical function localization; however, intraoperative cortical mapping can provide exact localization of function without ambiguity. Since tomographic images can provide lesion margin definition and cortical mapping can provide functional information we have developed a system for combining the two in our Interactive, Image-Guided system. For cortical surface mapping we need a surface description. Brain contours are extracted from a MRI volume using a deformable model approach and rendered from multiple angular positions. As the surgeon moves a probe, its position is displayed on the view closes to the angular position of the probe. During functional mapping, positive response to stimulation result in a color overlay 'dot' added to the cortical surface display. Different colored dots are used to distinguish between motor function and language function. And a third color is used to display overlapping functionality. This information is used to guide the resection around functionally eloquent areas of the cortex.

  19. Cortical reorganization in the aging brain.

    PubMed

    Dinse, Hubert R

    2006-01-01

    Aging exerts major reorganization and remodeling at all levels of brain structure and function. Studies in aged animals and in human elderly individuals demonstrate that sensorimotor cortical representational maps undergo significant alterations. Because cortical reorganization is paralleled by a decline in perceptual and behavioral performance, this type of cortical remodeling differs from the plastic reorganization observed during learning processes in young individuals where map changes are associated with a gain in performance. It is now clear that brain plasticity is operational into old age; therefore, protocols for interventions such as training, exercising, practicing, and stimulation, which make use of neuroplasticity principles, are effective to ameliorate some forms of cortical and behavioral age-related changes, indicating that aging effects are not irreversible but treatable. However, old individuals cannot be rejuvenated, but restoration of function is possible through the emergence of new processing strategies. This implies that cortical reorganization in the aging brain occurs twice: during aging, and during treatment of age-related changes.

  20. Human Cortical Excitability Increases with Time Awake

    PubMed Central

    Huber, Reto; Mäki, Hanna; Rosanova, Mario; Casarotto, Silvia; Canali, Paola; Casali, Adenauer G.; Tononi, Giulio

    2013-01-01

    Prolonged wakefulness is associated not only with obvious changes in the way we feel and perform but also with well-known clinical effects, such as increased susceptibility to seizures, to hallucinations, and relief of depressive symptoms. These clinical effects suggest that prolonged wakefulness may be associated with significant changes in the state of cortical circuits. While recent animal experiments have reported a progressive increase of cortical excitability with time awake, no conclusive evidence could be gathered in humans. In this study, we combine transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to monitor cortical excitability in healthy individuals as a function of time awake. We observed that the excitability of the human frontal cortex, measured as the immediate (0–20 ms) EEG reaction to TMS, progressively increases with time awake, from morning to evening and after one night of total sleep deprivation, and that it decreases after recovery sleep. By continuously monitoring vigilance, we also found that this modulation in cortical responsiveness is tonic and not attributable to transient fluctuations of the level of arousal. The present results provide noninvasive electrophysiological evidence that wakefulness is associated with a steady increase in the excitability of human cortical circuits that is rebalanced during sleep. PMID:22314045

  1. Depression in Cognitive Impairment

    PubMed Central

    Pellegrino, Laurel D.; Lyketsos, Constantine G.; Marano, Christopher M.

    2014-01-01

    Depression and cognitive disorders, including dementia and mild cognitive impairment, are common in the elderly. Depression is also a common feature of cognitive impairment although the symptoms of depression in cognitive impairment differ from depression without cognitive impairment. Pre-morbid depression approximately doubles the risk of subsequent dementia. There are two predominant, though not mutually exclusive, constructs linking pre-morbid depression to subsequent cognitive impairment: Alzheimer’s pathology and the vascular depression hypothesis. When evaluating a patient with depression and cognitive impairment, it is important to obtain caregiver input and to evaluate for alternative etiologies for depressive symptoms such as delirium. We recommend a sequential approach to the treatment of depression in dementia patients: (1) a period of watchful waiting for milder symptoms, (2) psychosocial treatment program, (3) a medication trial for more severe symptoms or failure of psychosocial interventions, and (4) possible ECT for refractory symptoms. PMID:23933974

  2. Impaired Inhibition of Prepotent Motor Tendencies in Friedreich Ataxia Demonstrated by the Simon Interference Task

    ERIC Educational Resources Information Center

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

    2011-01-01

    Friedreich ataxia (FRDA) is the most common of the genetically inherited ataxias. We recently demonstrated that people with FRDA have impairment in motor planning--most likely because of pathology affecting the cerebral cortex and/or cerebello-cortical projections. We used the Simon interference task to examine how effective 13 individuals with…

  3. Functional Cortical and Cerebellar Reorganization in a Case of Moyamoya Disease

    PubMed Central

    Calabrò, Rocco S.; Bramanti, Placido; Baglieri, Annalisa; Corallo, Francesco; De Luca, Rosaria; De Salvo, Simona

    2015-01-01

    Background: Functional studies have been previous reported in stroke patients, but no studies of functional magnetic resonance imaging have been performed in Moyamoya disease. Objective: To assess the cortical and cerebellar reorganization in a moyamoya patient. Methods: We reported a case of a patient suffering from moyamoya disease, undergoing a neuropsychological assessment, a neurocognitive rehabilitative treatment, an electroencephalogram evaluation, and a functional magnetic resonance imaging examination. Results: The subject showed a cognitive impairment, a slow electroencephalogram activity, and the ipsi- and controlateral motor cortex and cerebellar functional magnetic resonance imaging activation. Conclusions: This is the first functional magnetic resonance imaging case study reported in moyamoya disease. We showed a cortical reorganization, which could play an important role in clinical evaluation and motor recovery. The cerebellar activation, showed after cognitive and motor rehabilitation, could support the idea that the cerebellum contains several cognitive-related subregions involved in different functional networks in moyamoya disease. PMID:25852976

  4. Evolving Models of Pavlovian Conditioning: Cerebellar Cortical Dynamics in Awake Behaving Mice

    PubMed Central

    ten Brinke, Michiel M.; Boele, Henk-Jan; Spanke, Jochen K.; Potters, Jan-Willem; Kornysheva, Katja; Wulff, Peer; IJpelaar, Anna C.H.G.; Koekkoek, Sebastiaan K.E.; De Zeeuw, Chris I.

    2015-01-01

    Summary Three decades of electrophysiological research on cerebellar cortical activity underlying Pavlovian conditioning have expanded our understanding of motor learning in the brain. Purkinje cell simple spike suppression is considered to be crucial in the expression of conditional blink responses (CRs). However, trial-by-trial quantification of this link in awake behaving animals is lacking, and current hypotheses regarding the underlying plasticity mechanisms have diverged from the classical parallel fiber one to the Purkinje cell synapse LTD hypothesis. Here, we establish that acquired simple spike suppression, acquired conditioned stimulus (CS)-related complex spike responses, and molecular layer interneuron (MLI) activity predict the expression of CRs on a trial-by-trial basis using awake behaving mice. Additionally, we show that two independent transgenic mouse mutants with impaired MLI function exhibit motor learning deficits. Our findings suggest multiple cerebellar cortical plasticity mechanisms underlying simple spike suppression, and they implicate the broader involvement of the olivocerebellar module within the interstimulus interval. PMID:26655909

  5. Role of secondary sensory cortices in emotional memory storage and retrieval in rats.

    PubMed

    Sacco, Tiziana; Sacchetti, Benedetto

    2010-08-01

    Visual, acoustic, and olfactory stimuli associated with a highly charged emotional situation take on the affective qualities of that situation. Where the emotional meaning of a given sensory experience is stored is a matter of debate. We found that excitotoxic lesions of auditory, visual, or olfactory secondary sensory cortices impaired remote, but not recent, fear memories in rats. Amnesia was modality-specific and not due to an interference with sensory or emotional processes. In these sites, memory persistence was dependent on ongoing protein kinase Mzeta activity and was associated with an increased activity of layers II-IV, thus suggesting a synaptic strengthening of corticocortical connections. Lesions of the same areas left intact the memory of sensory stimuli not associated with any emotional charge. We propose that secondary sensory cortices support memory storage and retrieval of sensory stimuli that have acquired a behavioral salience with the experience.

  6. Convulsive seizures from experimental focal cortical dysplasia occur independently of cell misplacement

    PubMed Central

    Hsieh, Lawrence S.; Wen, John H.; Claycomb, Kumiko; Huang, Yuegao; Harrsch, Felicia A.; Naegele, Janice R.; Hyder, Fahmeed; Buchanan, Gordon F.; Bordey, Angelique

    2016-01-01

    Focal cortical dysplasia (FCD), a local malformation of cortical development, is the most common cause of pharmacoresistant epilepsy associated with life-long neurocognitive impairments. It remains unclear whether neuronal misplacement is required for seizure activity. Here we show that dyslamination and white matter heterotopia are not necessary for seizure generation in a murine model of type II FCDs. These experimental FCDs generated by increasing mTOR activity in layer 2/3 neurons of the medial prefrontal cortex are associated with tonic-clonic seizures and a normal survival rate. Preventing all FCD-related defects, including neuronal misplacement and dysmorphogenesis, with rapamycin treatments from birth eliminates seizures, but seizures recur after rapamycin withdrawal. In addition, bypassing neuronal misplacement and heterotopia using inducible vectors do not prevent seizure occurrence. Collectively, data obtained using our new experimental FCD-associated epilepsy suggest that life-long treatment to reduce neuronal dysmorphogenesis is required to suppress seizures in individuals with FCD. PMID:27249187

  7. Lateralization of observational fear learning at the cortical but not thalamic level in mice.

    PubMed

    Kim, Sangwoo; Mátyás, Ferenc; Lee, Sukchan; Acsády, László; Shin, Hee-Sup

    2012-09-18

    Major cognitive and emotional faculties are dominantly lateralized in the human cerebral cortex. The mechanism of this lateralization has remained elusive owing to the inaccessibility of human brains to many experimental manipulations. In this study we demonstrate the hemispheric lateralization of observational fear learning in mice. Using unilateral inactivation as well as electrical stimulation of the anterior cingulate cortex (ACC), we show that observational fear learning is controlled by the right but not the left ACC. In contrast to the cortex, inactivation of either left or right thalamic nuclei, both of which are in reciprocal connection to ACC, induced similar impairment of this behavior. The data suggest that lateralization of negative emotions is an evolutionarily conserved trait and mainly involves cortical operations. Lateralization of the observational fear learning behavior in a rodent model will allow detailed analysis of cortical asymmetry in cognitive functions.

  8. Autonomic cardiovascular regulation and cortical tone.

    PubMed

    Duschek, Stefan; Wörsching, Jana; Reyes Del Paso, Gustavo A

    2015-09-01

    This study aimed to investigate interactions between tonic cortical arousal and features of autonomic cardiovascular regulation. In 50 healthy subjects, the power spectrum of the spontaneous EEG was obtained at resting state. Concurrently, respiratory sinus arrhythmia (RSA), baroreflex sensitivity (BRS) and R-wave to pulse interval (RPI) were recorded as indices of cardiovascular control. At the bivariate level, only a negative correlation between beta power recorded at frontal electrode positions and RPI was found. However, when common variance of BRS and RSA was controlled for in multiple regression analyses, a positive association between alpha power and RSA, and an inverse relationship with BRS, also arose. The findings concerning RPI and RSA are suggestive of a relationship between higher levels of cortical tone and increased sympathetic and reduced vagal cardiac influences. The inverse association between BRS and alpha activity may reflect bottom-up modulation of cortical arousal by baroreceptor afferents. PMID:25080269

  9. Decision by division: making cortical maps.

    PubMed

    Rakic, Pasko; Ayoub, Albert E; Breunig, Joshua J; Dominguez, Martin H

    2009-05-01

    In the past three decades, mounting evidence has revealed that specification of the basic cortical neuronal classes starts at the time of their final mitotic divisions in the embryonic proliferative zones. This early cell determination continues during the migration of the newborn neurons across the widening cerebral wall, and it is in the cortical plate that they attain their final positions and establish species-specific cytoarchitectonic areas. Here, the development and evolutionary expansion of the neocortex is viewed in the context of the radial unit and protomap hypotheses. A broad spectrum of findings gave insight into the pathogenesis of cortical malformations and the biological bases for the evolution of the modern human neocortex. We examine the history and evidence behind the concept of early specification of neurons and provide the latest compendium of genes and signaling molecules involved in neuronal fate determination and specification.

  10. The pain and suffering of a Mexican American woman with mobility impairment.

    PubMed

    Walker, Janiece L; Harrison, Tracie C; Hendrickson, Sherry G

    2013-01-01

    There is a dearth of literature examining how adversity shapes the experiences of pain and/or suffering in middle-aged Mexican American women. The purpose of this qualitative descriptive study was to understand pain and suffering from a life course perspective as described by a Mexican American woman aging with early-onset mobility impairment. This Hispanic woman experienced episodes of abuse and rejection over the life course, which may have significantly influenced her pain and suffering experience in adulthood. This adds to the literature on how adversity influences later life pain experience and provides insight on why pharmacological treatment alone may not be as successful as a holistic intervention. PMID:24830728

  11. The ontogeny of the cortical language network.

    PubMed

    Skeide, Michael A; Friederici, Angela D

    2016-05-01

    Language-processing functions follow heterogeneous developmental trajectories. The human embryo can already distinguish vowels in utero, but grammatical complexity is usually not fully mastered until at least 7 years of age. Examining the current literature, we propose that the ontogeny of the cortical language network can be roughly subdivided into two main developmental stages. In the first stage extending over the first 3 years of life, the infant rapidly acquires bottom-up processing capacities, which are primarily implemented bilaterally in the temporal cortices. In the second stage continuing into adolescence, top-down processes emerge gradually with the increasing functional selectivity and structural connectivity of the left inferior frontal cortex.

  12. Rasmussen's encephalitis presenting as focal cortical dysplasia.

    PubMed

    O'Rourke, D J; Bergin, A; Rotenberg, A; Peters, J; Gorman, M; Poduri, A; Cryan, J; Lidov, H; Madsen, J; Harini, C

    2014-01-01

    Rasmussen's encephalitis is a rare syndrome characterized by intractable seizures, often associated with epilepsia partialis continua and symptoms of progressive hemispheric dysfunction. Seizures are usually the hallmark of presentation, but antiepileptic drug treatment fails in most patients and is ineffective against epilepsia partialis continua, which often requires surgical intervention. Co-occurrence of focal cortical dysplasia has only rarely been described and may have implications regarding pathophysiology and management. We describe a rare case of dual pathology of Rasmussen's encephalitis presenting as a focal cortical dysplasia (FCD) and discuss the literature on this topic. PMID:25667877

  13. Cortical Networks for Visual Self-Recognition

    NASA Astrophysics Data System (ADS)

    Sugiura, Motoaki

    This paper briefly reviews recent developments regarding the brain mechanisms of visual self-recognition. A special cognitive mechanism for visual self-recognition has been postulated based on behavioral and neuropsychological evidence, but its neural substrate remains controversial. Recent functional imaging studies suggest that multiple cortical mechanisms play self-specific roles during visual self-recognition, reconciling the existing controversy. Respective roles for the left occipitotemporal, right parietal, and frontal cortices in symbolic, visuospatial, and conceptual aspects of self-representation have been proposed.

  14. Amyloid beta-peptide disrupts carbachol-induced muscarinic cholinergic signal transduction in cortical neurons.

    PubMed

    Kelly, J F; Furukawa, K; Barger, S W; Rengen, M R; Mark, R J; Blanc, E M; Roth, G S; Mattson, M P

    1996-06-25

    Cholinergic pathways serve important functions in learning and memory processes, and deficits in cholinergic transmission occur in Alzheimer disease (AD). A subset of muscarinic cholinergic receptors are linked to G-proteins that activate phospholipase C, resulting in the liberation of inositol trisphosphate and Ca2+ release from intracellular stores. We now report that amyloid beta-peptide (Abeta), which forms plaques in the brain in AD, impairs muscarinic receptor activation of G proteins in cultured rat cortical neurons. Exposure of rodent fetal cortical neurons to Abeta25-35 and Abeta1-40 resulted in a concentration and time-dependent attenuation of carbachol-induced GTPase activity without affecting muscarinic receptor ligand binding parameters. Downstream events in the signal transduction cascade were similarly attenuated by Abeta. Carbachol-induced accumulation of inositol phosphates (IP, IP2, IP3, and IP4) was decreased and calcium imaging studies revealed that carbachol-induced release of calcium was severely impaired in neurons pretreated with Abeta. Muscarinic cholinergic signal transduction was disrupted with subtoxic levels of exposure to AP. The effects of Abeta on carbachol-induced GTPase activity and calcium release were attenuated by antioxidants, implicating free radicals in the mechanism whereby Abeta induced uncoupling of muscarinic receptors. These data demonstrate that Abeta disrupts muscarinic receptor coupling to G proteins that mediate induction of phosphoinositide accumulation and calcium release, findings that implicate Abeta in the impairment of cholinergic transmission that occurs in AD. PMID:8692890

  15. Number processing in posterior cortical atrophy--a neuropsycholgical case study.

    PubMed

    Delazer, M; Karner, E; Zamarian, L; Donnemiller, E; Benke, Th

    2006-01-01

    Posterior cortical atrophy (PCA) is an uncommon syndrome of dementia with early onset, characterised by disorders of higher visual function, variable symptoms of Balint's syndrome, visual agnosia, alexia, agraphia, finger agnosia, right-left disorientation and dyscalculia [Benson D. F., Davis R. J., & Snyder B. D. (1988). Posterior cortical atrophy. Archives of Neurology, 45, 789-793]. In a single case study specific numerical deficits were observed which may be predicted by parietal neurodegeneration (more pronounced on the right side; verified by SPECT). Besides impairments in all tasks involving visuo-spatial abilities (e.g., dot counting, analog number scale task), deficits appeared in tasks requiring access to an internal representation of numbers such as mental number bisection, approximation, estimation and semantic facts. In number comparison an increased distance effect was found. In simple arithmetic, a striking dissociation between operations was found-multiplication and addition facts being preserved at a superficial level, subtraction and division being severely impaired. The study confirms the close relation between spatial and numerical processing and highlights the modular organisation of the semantic system (number semantics impaired). Moreover, the study adds evidence about the clinical manifestation of the particular degenerative syndrome. PMID:15936044

  16. Self-Related Processing and Deactivation of Cortical Midline Regions in Disorders of Consciousness

    PubMed Central

    Crone, Julia Sophia; Höller, Yvonne; Bergmann, Jürgen; Golaszewski, Stefan; Trinka, Eugen; Kronbichler, Martin

    2013-01-01

    Self-related stimuli activate anterior parts of cortical midline regions, which normally show task-induced deactivation. Deactivation in medial posterior and frontal regions is associated with the ability to focus attention on the demands of the task, and therefore, with consciousness. Studies investigating patients with impaired consciousness, that is, patients in minimally conscious state and patients with unresponsive wakefulness syndrome (formerly vegetative state), demonstrate that these patients show responses to self-related content in the anterior cingulate cortex. However, it remains unclear if these responses are an indication for conscious processing of stimuli or are due to automatic processing. To shed further light on this issue, we investigated responses of cortical midline regions to the own and another name in 27 patients with a disorder of consciousness and compared them to task-induced deactivation. While almost all of the control subjects responding to the own name demonstrated higher activation due to the self-related content in anterior midline regions and additional deactivation, none of the responding patients did so. Differences between groups showed a similar pattern of findings. Despite the relation between behavioral responsiveness in patients and activation in response to the own name, the findings of this study do not provide evidence for a direct association of activation in anterior midline regions and conscious processing. The deficits in processing of self-referential content in anterior midline regions may rather be due to general impairments in cognitive processing and not particularly linked to impaired consciousness. PMID:23986685

  17. Cortically projecting basal forebrain parvalbumin neurons regulate cortical gamma band oscillations

    PubMed Central

    Kim, Tae; Thankachan, Stephen; McKenna, James T.; McNally, James M.; Yang, Chun; Choi, Jee Hyun; Chen, Lichao; Kocsis, Bernat; Deisseroth, Karl; Strecker, Robert E.; Basheer, Radhika; McCarley, Robert W.

    2015-01-01

    Cortical gamma band oscillations (GBO, 30–80 Hz, typically ∼40 Hz) are involved in higher cognitive functions such as feature binding, attention, and working memory. GBO abnormalities are a feature of several neuropsychiatric disorders associated with dysfunction of cortical fast-spiking interneurons containing the calcium-binding protein parvalbumin (PV). GBO vary according to the state of arousal, are modulated by attention, and are correlated with conscious awareness. However, the subcortical cell types underlying the state-dependent control of GBO are not well understood. Here we tested the role of one cell type in the wakefulness-promoting basal forebrain (BF) region, cortically projecting GABAergic neurons containing PV, whose virally transduced fibers we found apposed cortical PV interneurons involved in generating GBO. Optogenetic stimulation of BF PV neurons in mice preferentially increased cortical GBO power by entraining a cortical oscillator with a resonant frequency of ∼40 Hz, as revealed by analysis of both rhythmic and nonrhythmic BF PV stimulation. Selective saporin lesions of BF cholinergic neurons did not alter the enhancement of cortical GBO power induced by BF PV stimulation. Importantly, bilateral optogenetic inhibition of BF PV neurons decreased the power of the 40-Hz auditory steady-state response, a read-out of the ability of the cortex to generate GBO used in clinical studies. Our results are surprising and novel in indicating that this presumptively inhibitory BF PV input controls cortical GBO, likely by synchronizing the activity of cortical PV interneurons. BF PV neurons may represent a previously unidentified therapeutic target to treat disorders involving abnormal GBO, such as schizophrenia. PMID:25733878

  18. Independent measurement of femoral cortical thickness and cortical bone density using clinical CT.

    PubMed

    Treece, G M; Gee, A H

    2015-02-01

    The local structure of the proximal femoral cortex is of interest since both fracture risk, and the effects of various interventions aimed at reducing that risk, are associated with cortical properties focused in particular regions rather than dispersed over the whole bone. Much of the femoral cortex is less than 3mm thick, appearing so blurred in clinical CT that its actual density is not apparent in the data, and neither thresholding nor full-width half-maximum techniques are capable of determining its width. Our previous work on cortical bone mapping showed how to produce more accurate estimates of cortical thickness by assuming a fixed value of the cortical density for each hip. However, although cortical density varies much less over the proximal femur than thickness, what little variation there is leads to errors in thickness measurement. In this paper, we develop the cortical bone mapping technique by exploiting local estimates of imaging blur to correct the global density estimate, thus providing a local density estimate as well as more accurate estimates of thickness. We also consider measurement of cortical mass surface density and the density of trabecular bone immediately adjacent to the cortex. Performance is assessed with ex vivo clinical QCT scans of proximal femurs, with true values derived from high resolution HRpQCT scans of the same bones. We demonstrate superior estimation of thickness than is possible with alternative techniques (accuracy 0.12 ± 0.39 mm for cortices in the range 1-3mm), and that local cortical density estimation is feasible for densities >800 mg/cm(3).

  19. Education for the Hearing Impaired (Auditorily Impaired).

    ERIC Educational Resources Information Center

    World Federation of the Deaf, Rome (Italy).

    Education for the hearing impaired is discussed in nine conference papers. J. N. Howarth describes "The Education of Deaf Children in Schools for Hearing Pupils in the United Kingdom" and A.I.Dyachkov of the U.S.S.R. outlines Didactical Principles of Educating the Deaf in the Light of their Rehabilitation Goal." Seven papers from Poland are also…

  20. Development or Impairment?

    ERIC Educational Resources Information Center

    Hakansson, Gisela

    2010-01-01

    Joanne Paradis' Keynote Article on bilingualism and specific language impairment (SLI) is an impressive overview of research in language acquisition and language impairment. Studying different populations is crucial both for theorizing about language acquisition mechanisms, and for practical purposes of diagnosing and supporting children with…

  1. Motor Cortex and Motor Cortical Interhemispheric Communication in Walking After Stroke: The Roles of Transcranial Magnetic Stimulation and Animal Models in Our Current and Future Understanding.

    PubMed

    Charalambous, Charalambos C; Bowden, Mark G; Adkins, DeAnna L

    2016-01-01

    Despite the plethora of human neurophysiological research, the bilateral involvement of the leg motor cortical areas and their interhemispheric interaction during both normal and impaired human walking is poorly understood. Using transcranial magnetic stimulation (TMS), we have expanded our understanding of the role upper-extremity motor cortical areas play in normal movements and how stroke alters this role, and probed the efficacy of interventions to improve post-stroke arm function. However, similar investigations of the legs have lagged behind, in part, due to the anatomical difficulty in using TMS to stimulate the leg motor cortical areas. Additionally, leg movements are predominately bilaterally controlled and require interlimb coordination that may involve both hemispheres. The sensitive, but invasive, tools used in animal models of locomotion hold great potential for increasing our understanding of the bihemispheric motor cortical control of walking. In this review, we discuss 3 themes associated with the bihemispheric motor cortical control of walking after stroke: (a) what is known about the role of the bihemispheric motor cortical control in healthy and poststroke leg movements, (b) how the neural remodeling of the contralesional hemisphere can affect walking recovery after a stroke, and (c) what is the effect of behavioral rehabilitation training of walking on the neural remodeling of the motor cortical areas bilaterally. For each theme, we discuss how rodent models can enhance the present knowledge on human walking by testing hypotheses that cannot be investigated in humans, and how these findings can then be back-translated into the neurorehabilitation of poststroke walking.

  2. Pharmacokinetics of cefuroxime in porcine cortical and cancellous bone determined by microdialysis.

    PubMed

    Tøttrup, Mikkel; Hardlei, Tore Forsingdal; Bendtsen, Michael; Bue, Mats; Brock, Birgitte; Fuursted, Kurt; Søballe, Kjeld; Birke-Sørensen, Hanne

    2014-06-01

    Traditionally, the pharmacokinetics of antimicrobials in bone have been investigated using bone biopsy specimens, but this approach suffers from considerable methodological limitations. Consequently, new methods are needed. The objectives of this study were to assess the feasibility of microdialysis (MD) for measuring cefuroxime in bone and to obtain pharmacokinetic profiles for the same drug in porcine cortical and cancellous bone. The measurements were conducted in bone wax sealed and unsealed drill holes in cortical bone and in drill holes in cancellous bone and in subcutaneous tissue. As a reference, the free and total plasma concentrations were also measured. The animals received a bolus of 1,500 mg cefuroxime over 30 min. No significant differences were found between the key pharmacokinetic parameters for sealed and unsealed drill holes in cortical bone. The mean ± standard error of the mean area under the concentration-time curve (AUC) values from 0 to 5 h were 6,013 ± 1,339, 3,222 ± 1086, 2,232 ± 635, and 952 ± 290 min · μg/ml for free plasma, subcutaneous tissue, cancellous bone, and cortical bone, respectively (P < 0.01, analysis of variance). The AUC for cortical bone was also significantly different from that for cancellous bone (P = 0.04). This heterogeneous tissue distribution was also reflected in other key pharmacokinetic parameters. This study validates MD as a suitable method for measuring cefuroxime in bone. Cefuroxime penetration was impaired for all tissues, and bone may not be considered one distinct compartment.

  3. N-Cadherin Sustains Motility and Polarity of Future Cortical Interneurons during Tangential Migration

    PubMed Central

    Luccardini, Camilla; Hennekinne, Laetitia; Viou, Lucie; Yanagida, Mitsutoshi; Murakami, Fujio; Kessaris, Nicoletta; Ma, Xufei; Adelstein, Robert S.; Mège, René-Marc

    2013-01-01

    In the developing brain, cortical GABAergic interneurons migrate long distances from the medial ganglionic eminence (MGE) in which they are generated, to the cortex in which they settle. MGE cells express the cell adhesion molecule N-cadherin, a homophilic cell–cell adhesion molecule that regulates numerous steps of brain development, from neuroepithelium morphogenesis to synapse formation. N-cadherin is also expressed in embryonic territories crossed by MGE cells during their migration. In this study, we demonstrate that N-cadherin is a key player in the long-distance migration of future cortical interneurons. Using N-cadherin-coated substrate, we show that N-cadherin-dependent adhesion promotes the migration of mouse MGE cells in vitro. Conversely, mouse MGE cells electroporated with a construct interfering with cadherin function show reduced cell motility, leading process instability, and impaired polarization associated with abnormal myosin IIB dynamics. In vivo, the capability of electroporated MGE cells to invade the developing cortical plate is altered. Using genetic ablation of N-cadherin in mouse embryos, we show that N-cadherin-depleted MGEs are severely disorganized. MGE cells hardly exit the disorganized proliferative area. N-cadherin ablation at the postmitotic stage, which does not affect MGE morphogenesis, alters MGE cell motility and directionality. The tangential migration to the cortex of N-cadherin ablated MGE cells is delayed, and their radial migration within the cortical plate is perturbed. Altogether, these results identify N-cadherin as a pivotal adhesion substrate that activates cell motility in future cortical interneurons and maintains cell polarity over their long-distance migration to the developing cortex. PMID:24227724

  4. Mapping gray matter volume and cortical thickness in Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Guo, Xiaojuan; Li, Ziyi; Chen, Kewei; Yao, Li; Wang, Zhiqun; Li, Kuncheng

    2010-03-01

    Gray matter volume and cortical thickness are two important indices widely used to detect neuropathological changes in brain structural magnetic resonance imaging. Using optimized voxel-based morphometry (VBM) protocol and surface-based cortical thickness measure, this study comprehensively investigated the regional changes in cortical gray matter volume and cortical thickness in Alzheimer's disease (AD). Thirteen patients with AD and fourteen age- and gender-matched healthy controls were included in this study. Results showed that voxel-based gray matter volume and cortical thickness reductions were highly correlated in the temporal lobe and its medial structure in AD. Moreover significant reduced cortical regions of gray matter volume were obviously more than that of cortical thickness. These findings suggest that gray matter volume and cortical thickness, as two important imaging markers, are effective indices for detecting the neuroanatomical alterations and help us understand the neuropathology from different views in AD.

  5. Malformations of cortical development and neocortical focus.

    PubMed

    Luhmann, Heiko J; Kilb, Werner; Clusmann, Hans

    2014-01-01

    Developmental neocortical malformations resulting from abnormal neurogenesis, disturbances in programmed cell death, or neuronal migration disorders may cause a long-term hyperexcitability. Early generated Cajal-Retzius and subplate neurons play important roles in transient cortical circuits, and structural/functional disorders in early cortical development may induce persistent network disturbances and epileptic disorders. In particular, depolarizing GABAergic responses are important for the regulation of neurodevelopmental events, like neurogenesis or migration, while pathophysiological alterations in chloride homeostasis may cause epileptic activity. Although modern imaging techniques may provide an estimate of the structural lesion, the site and extent of the cortical malformation may not correlate with the epileptogenic zone. The neocortical focus may be surrounded by widespread molecular, structural, and functional disturbances, which are difficult to recognize with imaging technologies. However, modern imaging and electrophysiological techniques enable focused hypotheses of the neocortical epileptogenic zone, thus allowing more specific epilepsy surgery. Focal cortical malformation can be successfully removed with minimal rim, close to or even within eloquent cortex with a promising risk-benefit ratio.

  6. Touch inhibits subcortical and cortical nociceptive responses

    PubMed Central

    Mancini, Flavia; Beaumont, Anne-Lise; Hu, Li; Haggard, Patrick; Iannetti, Gian Domenico D.

    2015-01-01

    Abstract The neural mechanisms of the powerful analgesia induced by touching a painful body part are controversial. A long tradition of neurophysiologic studies in anaesthetized spinal animals indicate that touch can gate nociceptive input at spinal level. In contrast, recent studies in awake humans have suggested that supraspinal mechanisms can be sufficient to drive touch-induced analgesia. To investigate this issue, we evaluated the modulation exerted by touch on established electrophysiologic markers of nociceptive function at both subcortical and cortical levels in humans. Aδ and C skin nociceptors were selectively activated by high-power laser pulses. As markers of subcortical and cortical function, we recorded the laser blink reflex, which is generated by brainstem circuits before the arrival of nociceptive signals at the cortex, and laser-evoked potentials, which reflect neural activity of a wide array of cortical areas. If subcortical nociceptive responses are inhibited by concomitant touch, supraspinal mechanisms alone are unlikely to be sufficient to drive touch-induced analgesia. Touch induced a clear analgesic effect, suppressed the laser blink reflex, and inhibited both Aδ-fibre and C-fibre laser-evoked potentials. Thus, we conclude that touch-induced analgesia is likely to be mediated by a subcortical gating of the ascending nociceptive input, which in turn results in a modulation of cortical responses. Hence, supraspinal mechanisms alone are not sufficient to mediate touch-induced analgesia. PMID:26058037

  7. Cortical Memory Mechanisms and Language Origins

    ERIC Educational Resources Information Center

    Aboitiz, Francisco; Garcia, Ricardo R.; Bosman, Conrado; Brunetti, Enzo

    2006-01-01

    We have previously proposed that cortical auditory-vocal networks of the monkey brain can be partly homologized with language networks that participate in the phonological loop. In this paper, we suggest that other linguistic phenomena like semantic and syntactic processing also rely on the activation of transient memory networks, which can be…

  8. Junk DNA Used in Cerebral Cortical Evolution.

    PubMed

    Pratt, Thomas; Price, David J

    2016-06-15

    In this issue of Neuron, Rani et al. (2016) address important questions about the mechanisms of cerebral cortical evolution. They describe how a primate-specific long non-coding RNA titrates the levels of a microRNA that regulates an ancient signaling pathway controlling neuronal numbers. PMID:27311076

  9. Cortical connectivity during word association search.

    PubMed

    Ivanitsky, A M; Nikolaev, A R; Ivanitsky, G A

    2001-08-01

    Cortical connectivity was studied in tasks of generating the use of words in comparison with reading aloud the same words. These tasks were used earlier in PET and high density ERP recordings studies (Posner and Raichle, 1997; Abdullaev and Posner, 1998), in which both the functional anatomy and the time course of cortical areas involved in word processing were described. The wavelet transforms of ERP records and the calculation of correlations between wavelet curves were used to reveal connections between cortical areas. Three stages of intracortical communications while task performance were found. These were: (1) the connections between right and left frontal and central areas which preceded stimulus delivery and persisted up to 180 ms after it; (2) the network connecting right and left frontal with left posterior temporal-parietal junction at 280-450 ms; and (3) communications between left and right temporal zones in 550-800 ms. The data are in good agreement with results of previous PET and ERP studies and supply the earlier findings with circuitry of cortical information transfer.

  10. Development of Cortical Circuitry and Cognitive Function.

    ERIC Educational Resources Information Center

    Goldman-Rakic, Patricia S.

    1987-01-01

    Recent studies on the biological development of the prefrontal cortex in rhesus monkeys are reviewed. These studies have elucidated the basic neural circuitry underlying the delayed-response function in adult nonhuman primates and suggest that a critical mass of cortical synapses is important for the emergence of this cognitive function. (BN)

  11. Central cortical cleanup and zonular deficiency

    PubMed Central

    Mansour, Ahmad M; Antonios, Rafic S; Ahmed, Iqbal Ike K

    2016-01-01

    Background Complete removal of the cortex has been advocated to prevent posterior capsular opacification but carries the risk of zonular dehiscence, hence there is a need for a safe maximal cortical cleanup technique in eyes with severe diffuse zonulopathy in subjects above age 90. Methods We used bimanual central cortical cleaning by elevating central fibers and aspirating them toward the periphery. Peripheral cortical fibers were removed passively only when they became loose due to copious irrigation. A one-piece foldable implant was inserted without a capsular tension ring. Postoperative corticosteroid drops were used. Results This technique was safely performed in a dozen eyes with severe pseudo-exfoliation or brunescent cataract with weak zonules. Posterior capsular rupture, iritis, vitreous loss, and lens subluxation were not observed. Moderate capsular phimosis occurred but with maintained central vision. Conclusion The dogma of “complete cortical cleanup” in severe zonulopathy needs to be revisited in favor of a clear visual axis with maximal preservation of the damaged zonules. This technique is ideal in patients above age 90 where posterior capsular opacification and late dislocation of intraocular lens–capsule bag complex are unlikely to occur until several years postoperatively. PMID:27784979

  12. Stroke rehabilitation using noninvasive cortical stimulation: aphasia.

    PubMed

    Mylius, Veit; Zouari, Hela G; Ayache, Samar S; Farhat, Wassim H; Lefaucheur, Jean-Pascal

    2012-08-01

    Poststroke aphasia results from the lesion of cortical areas involved in the motor production of speech (Broca's aphasia) or in the semantic aspects of language comprehension (Wernicke's aphasia). Such lesions produce an important reorganization of speech/language-specific brain networks due to an imbalance between cortical facilitation and inhibition. In fact, functional recovery is associated with changes in the excitability of the damaged neural structures and their connections. Two main mechanisms are involved in poststroke aphasia recovery: the recruitment of perilesional regions of the left hemisphere in case of small lesion and the acquisition of language processing ability in homotopic areas of the nondominant right hemisphere when left hemispheric language abilities are permanently lost. There is some evidence that noninvasive cortical stimulation, especially when combined with language therapy or other therapeutic approaches, can promote aphasia recovery. Cortical stimulation was mainly used to either increase perilesional excitability or reduce contralesional activity based on the concept of reciprocal inhibition and maladaptive plasticity. However, recent studies also showed some positive effects of the reinforcement of neural activities in the contralateral right hemisphere, based on the potential compensatory role of the nondominant hemisphere in stroke recovery. PMID:23002940

  13. The Diversity of Cortical Inhibitory Synapses

    PubMed Central

    Kubota, Yoshiyuki; Karube, Fuyuki; Nomura, Masaki; Kawaguchi, Yasuo

    2016-01-01

    The most typical and well known inhibitory action in the cortical microcircuit is a strong inhibition on the target neuron by axo-somatic synapses. However, it has become clear that synaptic inhibition in the cortex is much more diverse and complicated. Firstly, at least ten or more inhibitory non-pyramidal cell subtypes engage in diverse inhibitory functions to produce the elaborate activity characteristic of the different cortical states. Each distinct non-pyramidal cell subtype has its own independent inhibitory function. Secondly, the inhibitory synapses innervate different neuronal domains, such as axons, spines, dendrites and soma, and their inhibitory postsynaptic potential (IPSP) size is not uniform. Thus, cortical inhibition is highly complex, with a wide variety of anatomical and physiological modes. Moreover, the functional significance of the various inhibitory synapse innervation styles and their unique structural dynamic behaviors differ from those of excitatory synapses. In this review, we summarize our current understanding of the inhibitory mechanisms of the cortical microcircuit. PMID:27199670

  14. Individual subject classification for Alzheimer's disease based on incremental learning using a spatial frequency representation of cortical thickness data.

    PubMed

    Cho, Youngsang; Seong, Joon-Kyung; Jeong, Yong; Shin, Sung Yong

    2012-02-01

    Patterns of brain atrophy measured by magnetic resonance structural imaging have been utilized as significant biomarkers for diagnosis of Alzheimer's disease (AD). However, brain atrophy is variable across patients and is non-specific for AD in general. Thus, automatic methods for AD classification require a large number of structural data due to complex and variable patterns of brain atrophy. In this paper, we propose an incremental method for AD classification using cortical thickness data. We represent the cortical thickness data of a subject in terms of their spatial frequency components, employing the manifold harmonic transform. The basis functions for this transform are obtained from the eigenfunctions of the Laplace-Beltrami operator, which are dependent only on the geometry of a cortical surface but not on the cortical thickness defined on it. This facilitates individual subject classification based on incremental learning. In general, methods based on region-wise features poorly reflect the detailed spatial variation of cortical thickness, and those based on vertex-wise features are sensitive to noise. Adopting a vertex-wise cortical thickness representation, our method can still achieve robustness to noise by filtering out high frequency components of the cortical thickness data while reflecting their spatial variation. This compromise leads to high accuracy in AD classification. We utilized MR volumes provided by Alzheimer's Disease Neuroimaging Initiative (ADNI) to validate the performance of the method. Our method discriminated AD patients from Healthy Control (HC) subjects with 82% sensitivity and 93% specificity. It also discriminated Mild Cognitive Impairment (MCI) patients, who converted to AD within 18 months, from non-converted MCI subjects with 63% sensitivity and 76% specificity. Moreover, it showed that the entorhinal cortex was the most discriminative region for classification, which is consistent with previous pathological findings. In

  15. Aniline Is Rapidly Converted Into Paracetamol Impairing Male Reproductive Development.

    PubMed

    Holm, Jacob Bak; Chalmey, Clementine; Modick, Hendrik; Jensen, Lars Skovgaard; Dierkes, Georg; Weiss, Tobias; Jensen, Benjamin Anderschou Holbech; Nørregård, Mette Marie; Borkowski, Kamil; Styrishave, Bjarne; Martin Koch, Holger; Mazaud-Guittot, Severine; Jegou, Bernard; Kristiansen, Karsten; Kristensen, David Møbjerg

    2015-11-01

    Industrial use of aniline is increasing worldwide with production estimated to surpass 5.6 million metric tons in 2016. Exposure to aniline occurs via air, diet, and water augmenting the risk of exposing a large number of individuals. Early observations suggest that aniline is metabolized to paracetamol/acetaminophen, likely explaining the omnipresence of low concentrations of paracetamol in European populations. This is of concern as recent studies implicate paracetamol as a disrupter of reproduction. Here, we show through steroidogenic profiling that exposure to aniline led to increased levels of the Δ4 steroids, suggesting that the activity of CYP21 was decreased. By contrast, paracetamol decreased levels of androgens likely through inhibition of CYP17A1 activity. We confirm that aniline in vivo is rapidly converted to paracetamol by the liver. Intrauterine exposure to aniline and paracetamol in environmental and pharmaceutical relevant doses resulted in shortening of the anogenital distance in mice, a sensitive marker of fetal androgen levels that in humans is associated with reproductive malformations and later life reproductive disorders. In conclusion, our results provide evidence for a scenario where aniline, through its conversion into antiandrogenic paracetamol, impairs male reproductive development.

  16. Aniline Is Rapidly Converted Into Paracetamol Impairing Male Reproductive Development.

    PubMed

    Holm, Jacob Bak; Chalmey, Clementine; Modick, Hendrik; Jensen, Lars Skovgaard; Dierkes, Georg; Weiss, Tobias; Jensen, Benjamin Anderschou Holbech; Nørregård, Mette Marie; Borkowski, Kamil; Styrishave, Bjarne; Martin Koch, Holger; Mazaud-Guittot, Severine; Jegou, Bernard; Kristiansen, Karsten; Kristensen, David Møbjerg

    2015-11-01

    Industrial use of aniline is increasing worldwide with production estimated to surpass 5.6 million metric tons in 2016. Exposure to aniline occurs via air, diet, and water augmenting the risk of exposing a large number of individuals. Early observations suggest that aniline is metabolized to paracetamol/acetaminophen, likely explaining the omnipresence of low concentrations of paracetamol in European populations. This is of concern as recent studies implicate paracetamol as a disrupter of reproduction. Here, we show through steroidogenic profiling that exposure to aniline led to increased levels of the Δ4 steroids, suggesting that the activity of CYP21 was decreased. By contrast, paracetamol decreased levels of androgens likely through inhibition of CYP17A1 activity. We confirm that aniline in vivo is rapidly converted to paracetamol by the liver. Intrauterine exposure to aniline and paracetamol in environmental and pharmaceutical relevant doses resulted in shortening of the anogenital distance in mice, a sensitive marker of fetal androgen levels that in humans is associated with reproductive malformations and later life reproductive disorders. In conclusion, our results provide evidence for a scenario where aniline, through its conversion into antiandrogenic paracetamol, impairs male reproductive development. PMID:26259604

  17. Quantifying the deficit—imaging neurobehavioural impairment in childhood epilepsy

    PubMed Central

    2015-01-01

    Background Neurobehavioral impairments such as learning difficulty, autism, attention deficit hyperactivity disorder (ADHD) and mood or behavioural problems are known to be increased in children with epilepsy; however, they remain under-recognised and often cause considerable morbidity. Quantitative neuroimaging techniques offer a potential avenue to improving our understanding of the underlying pathological basis for these disorders, aiding with diagnosis and risk stratification. Methods A systematic review was undertaken for original research articles involving magnetic resonance imaging in children with epilepsy and one or more neurobehavioural impairments. Studies were reviewed with respect to patient population, methodology and magnetic resonance imaging (MRI) findings. Results A total of 25 studies were identified and included in this review. The majority of studies looked at single impairments, commonly cognitive impairment or ADHD, with few studies reporting on other impairments. Reductions in cortical grey matter and disruptions of functional and structural brain networks were associated with poorer cognitive performance and disruptions of grey and white matter within a fronto-striatal-cerebellar network associated with ADHD. Insufficient studies were available to report on other impairments. Conclusions Relatively few studies exist in this field and those that do are methodologically diverse. Further investigation is required to determine if the changes reported to date are epilepsy syndrome specific or have broader applicability. PMID:25853081

  18. Trajectories of cortical surface area and cortical volume maturation in normal brain development

    PubMed Central

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

    2015-01-01

    This is a report of developmental trajectories of cortical surface area and cortical volume in the NIH MRI Study of Normal Brain Development. The quality-controlled sample included 384 individual typically-developing subjects with repeated scanning (1–3 per subject, total scans n=753) from 4.9 to 22.3 years of age. The best-fit model (cubic, quadratic, or first-order linear) was identified at each vertex using mixed-effects models, with statistical correction for multiple comparisons using random field theory. Analyses were performed with and without controlling for total brain volume. These data are provided for reference and comparison with other databases. Further discussion and interpretation on cortical developmental trajectories can be found in the associated Ducharme et al.׳s article “Trajectories of cortical thickness maturation in normal brain development – the importance of quality control procedures” (Ducharme et al., 2015) [1]. PMID:26702424

  19. Posterior cortical atrophy--a prototypical case of dementia beginning with visual symptoms: case report.

    PubMed

    Caixeta, Leonardo Ferreira; Taleb, Alexandre Chater; Ghini, Bruno Galafassi; Soares, Vânia Lúcia Dias; Caixeta, Victor de Melo; Vargas, Ciro

    2013-10-01

    Dementia presenting with prominent higher order visual symptoms may be observed in a range of neurodegenerative conditions and is often challenging to diagnose. We describe a case of progressive dementia presenting with prominent visual cortical symptoms. A 55-year-old, right-handed, woman with early onset of visual impairment not associated with anterior visual pathology, presenting with dyslexia, visual agnosia, Balint's syndrome, and spatial disorientation. Ophthalmologists should consider this condition especially in presenile patients with slowly progressive higher-order visual symptoms. Although described in association with different conditions, it may also occur in Alzheimer disease.

  20. Different levels of implicit emotional recognition in posterior cortical atrophy (PCA).

    PubMed

    Gonzalez-Gadea, María Luz; Ibanez, Agustín; Damm, Juliane; Ramirez Romero, Diana Andrea; Abrevaya, Sofia; Manes, Facundo; Richly, Pablo; Roca, Maria

    2015-01-01

    Previous single-case reports in posterior cortical atrophy (PCA) have shown preserved nonconscious visual recognition despite the absence of explicit recognition. In this study, we investigated three levels of visual recognition in both a female patient with PCA and a control group during the presentation of neutral, positive, and negative affective stimuli. Our results confirmed the profile of impaired explicit recognition and intact psychophysiological responses in the patient. In addition, she was able to implicitly recognize the valence and intensity of arousal of these stimuli. We suggest that implicit emotional awareness may mediates explicit and psychophysiological recognition in PCA.

  1. Localization of metastatic adrenal cortical carcinoma with Ga-67

    SciTech Connect

    Ward, F.T.; Anderson, J.H.; Jelinek, J.; Anderson, D.W. )

    1991-02-01

    Data are limited on the localization of Ga-67 in primary or metastatic adrenal cortical carcinoma. We report the localization of Ga-67 to pathologically confirmed adrenal cortical carcinoma metastatic to the lung. A review of the literature revealed four patients have previously been reported to have metastatic adrenal cortical carcinoma detected on Ga-67 scan. Gallium imaging may be useful in the evaluation of patients with adrenal cortical carcinoma. SPECT imaging should further improve lesion resolution and localization.

  2. Abnormal functioning of the left temporal lobe in language-impaired children.

    PubMed

    Helenius, Päivi; Sivonen, Päivi; Parviainen, Tiina; Isoaho, Pia; Hannus, Sinikka; Kauppila, Timo; Salmelin, Riitta; Isotalo, Leena

    2014-03-01

    Specific language impairment is associated with enduring problems in language-related functions. We followed the spatiotemporal course of cortical activation in SLI using magnetoencephalography. In the experiment, children with normal and impaired language development heard spoken real words and pseudowords presented only once or two times in a row. In typically developing children, the activation in the bilateral superior temporal cortices was attenuated to the second presentation of the same word. In SLI children, this repetition effect was nearly nonexistent in the left hemisphere. Furthermore, the activation was equally strong to words and pseudowords in SLI children whereas in the typically developing children the left hemisphere activation persisted longer for pseudowords than words. Our results indicate that the short-term maintenance of linguistic activation that underlies spoken word recognition is defective in SLI particularly in the left language-dominant hemisphere. The unusually rapid decay of speech-evoked activation can contribute to impaired vocabulary growth.

  3. Abnormal functioning of the left temporal lobe in language-impaired children.

    PubMed

    Helenius, Päivi; Sivonen, Päivi; Parviainen, Tiina; Isoaho, Pia; Hannus, Sinikka; Kauppila, Timo; Salmelin, Riitta; Isotalo, Leena

    2014-03-01

    Specific language impairment is associated with enduring problems in language-related functions. We followed the spatiotemporal course of cortical activation in SLI using magnetoencephalography. In the experiment, children with normal and impaired language development heard spoken real words and pseudowords presented only once or two times in a row. In typically developing children, the activation in the bilateral superior temporal cortices was attenuated to the second presentation of the same word. In SLI children, this repetition effect was nearly nonexistent in the left hemisphere. Furthermore, the activation was equally strong to words and pseudowords in SLI children whereas in the typically developing children the left hemisphere activation persisted longer for pseudowords than words. Our results indicate that the short-term maintenance of linguistic activation that underlies spoken word recognition is defective in SLI particularly in the left language-dominant hemisphere. The unusually rapid decay of speech-evoked activation can contribute to impaired vocabulary growth. PMID:24568877

  4. Impairment in Non-Word Repetition: A Marker for Language Impairment or Reading Impairment?

    ERIC Educational Resources Information Center

    Baird, Gillian; Slonims, Vicky; Simonoff, Emily; Dworzynski, Katharina

    2011-01-01

    Aim: A deficit in non-word repetition (NWR), a measure of short-term phonological memory proposed as a marker for language impairment, is found not only in language impairment but also in reading impairment. We evaluated the strength of association between language impairment and reading impairment in children with current, past, and no language…

  5. Variability in Cortical Representations of Speech Sound Perception

    ERIC Educational Resources Information Center

    Boatman, Dana F.

    2007-01-01

    Recent brain mapping studies have provided new insights into the cortical systems that mediate human speech perception. Electrocortical stimulation mapping (ESM) is a brain mapping method that is used clinically to localize cortical functions in neurosurgical patients. Recent ESM studies have yielded new insights into the cortical systems that…

  6. Hearing or speech impairment - resources

    MedlinePlus

    Resources - hearing or speech impairment ... The following organizations are good resources for information on hearing impairment or speech impairment: Alexander Graham Bell Association for the Deaf and Hard of Hearing -- www.agbell. ...

  7. Predicting perception in noise using cortical auditory evoked potentials.

    PubMed

    Billings, Curtis J; McMillan, Garnett P; Penman, Tina M; Gille, Sun Mi

    2013-12-01

    Speech perception in background noise is a common challenge across individuals and health conditions (e.g., hearing impairment, aging, etc.). Both behavioral and physiological measures have been used to understand the important factors that contribute to perception-in-noise abilities. The addition of a physiological measure provides additional information about signal-in-noise encoding in the auditory system and may be useful in clarifying some of the variability in perception-in-noise abilities across individuals. Fifteen young normal-hearing individuals were tested using both electrophysiology and behavioral methods as a means to determine (1) the effects of signal-to-noise ratio (SNR) and signal level and (2) how well cortical auditory evoked potentials (CAEPs) can predict perception in noise. Three correlation/regression approaches were used to determine how well CAEPs predicted behavior. Main effects of SNR were found for both electrophysiology and speech perception measures, while signal level effects were found generally only for speech testing. These results demonstrate that when signals are presented in noise, sensitivity to SNR cues obscures any encoding of signal level cues. Electrophysiology and behavioral measures were strongly correlated. The best physiological predictors (e.g., latency, amplitude, and area of CAEP waves) of behavior (SNR at which 50 % of the sentence is understood) were N1 latency and N1 amplitude measures. In addition, behavior was best predicted by the 70-dB signal/5-dB SNR CAEP condition. It will be important in future studies to determine the relationship of electrophysiology and behavior in populations who experience difficulty understanding speech in noise such as those with hearing impairment or age-related deficits.

  8. The neural correlates of motor intentional disorders in patients with subcortical vascular cognitive impairment.

    PubMed

    Kim, Geon Ha; Seo, Sang Won; Jung, Kihyo; Kwon, Oh-Hun; Kwon, Hunki; Kim, Jong Hun; Roh, Jee Hoon; Kim, Min-Jeong; Lee, Byung Hwa; Yoon, Doo Sang; Hwang, Jung Won; Lee, Jong Min; Jeong, Jee Hyang; You, Heecheon; Heilman, Kenneth M; Na, Duk L

    2016-01-01

    Subcortical vascular cognitive impairment (SVCI) refers to cognitive impairment associated with small vessel disease. Motor intentional disorders (MID) have been reported in patients with SVCI. However, there are no studies exploring the neuroanatomical regions related to MID in SVCI patients. The aim of this study, therefore, was to investigate the neural correlates of MID in SVCI patients. Thirty-one patients with SVCI as well as 10 healthy match control participants were included. A "Pinch-Grip" apparatus was used to quantify the force control capabilities of the index finger in four different movement phases including initiation, development, maintenance, and termination. All participants underwent magnetic resonance imaging (MRI). Topographical cortical areas and white matter tracts correlated with the performances of the four different movement phases were assessed by the surface-based morphometry and tract-based spatial statistics analyses. Poorer performance in the maintenance task was related to cortical thinning in bilateral dorsolateral prefrontal, orbitofrontal and parietal cortices, while poorer performance in the termination task was associated with the disruption of fronto-parietal cortical areas as well as the white matter tracts including splenium and association fibers such as superior longitudinal fasciculus. Our study demonstrates that cortical areas and underlying white matter tracts associated with fronto-parietal attentional system play an important role in motor impersistence and perseveration in SVCI patients. PMID:26514838

  9. Transcranial magnetic stimulation (TMS)/repetitive TMS in mild cognitive impairment and Alzheimer's disease.

    PubMed

    Nardone, R; Tezzon, F; Höller, Y; Golaszewski, S; Trinka, E; Brigo, F

    2014-06-01

    Several Transcranial Magnetic Stimulation (TMS) techniques can be applied to noninvasively measure cortical excitability and brain plasticity in humans. TMS has been used to assess neuroplastic changes in Alzheimer's disease (AD), corroborating findings that cortical physiology is altered in AD due to the underlying neurodegenerative process. In fact, many TMS studies have provided physiological evidence of abnormalities in cortical excitability, connectivity, and plasticity in patients with AD. Moreover, the combination of TMS with other neurophysiological techniques, such as high-density electroencephalography (EEG), makes it possible to study local and network cortical plasticity directly. Interestingly, several TMS studies revealed abnormalities in patients with early AD and even with mild cognitive impairment (MCI), thus enabling early identification of subjects in whom the cholinergic degeneration has occurred. Furthermore, TMS can influence brain function if delivered repetitively; repetitive TMS (rTMS) is capable of modulating cortical excitability and inducing long-lasting neuroplastic changes. Preliminary findings have suggested that rTMS can enhance performances on several cognitive functions impaired in AD and MCI. However, further well-controlled studies with appropriate methodology in larger patient cohorts are needed to replicate and extend the initial findings. The purpose of this paper was to provide an updated and comprehensive systematic review of the studies that have employed TMS/rTMS in patients with MCI and AD.

  10. Impairments to Vision

    MedlinePlus

    ... an external Non-Government web site. Impairments to Vision Normal Vision Diabetic Retinopathy Age-related Macular Degeneration In this ... pictures, fixate on the nose to simulate the vision loss. In diabetic retinopathy, the blood vessels in ...

  11. Kids' Quest: Vision Impairment

    MedlinePlus

    ... important job. Â Return to Steps World-Wide Web Search Kids Health: What is Vision Impairment What ... for the Blind (AFB) created the Braille Bug web site to teach sighted children about braille, and ...

  12. Serotonin modulation of cortical neurons and networks

    PubMed Central

    Celada, Pau; Puig, M. Victoria; Artigas, Francesc

    2013-01-01

    The serotonergic pathways originating in the dorsal and median raphe nuclei (DR and MnR, respectively) are critically involved in cortical function. Serotonin (5-HT), acting on postsynaptic and presynaptic receptors, is involved in cognition, mood, impulse control and motor functions by (1) modulating the activity of different neuronal types, and (2) varying the release of other neurotransmitters, such as glutamate, GABA, acetylcholine and dopamine. Also, 5-HT seems to play an important role in cortical development. Of all cortical regions, the frontal lobe is the area most enriched in serotonergic axons and 5-HT receptors. 5-HT and selective receptor agonists modulate the excitability of cortical neurons and their discharge rate through the activation of several receptor subtypes, of which the 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT3 subtypes play a major role. Little is known, however, on the role of other excitatory receptors moderately expressed in cortical areas, such as 5-HT2C, 5-HT4, 5-HT6, and 5-HT7. In vitro and in vivo studies suggest that 5-HT1A and 5-HT2A receptors are key players and exert opposite effects on the activity of pyramidal neurons in the medial prefrontal cortex (mPFC). The activation of 5-HT1A receptors in mPFC hyperpolarizes pyramidal neurons whereas that of 5-HT2A receptors results in neuronal depolarization, reduction of the afterhyperpolarization and increase of excitatory postsynaptic currents (EPSCs) and of discharge rate. 5-HT can also stimulate excitatory (5-HT2A and 5-HT3) and inhibitory (5-HT1A) receptors in GABA interneurons to modulate synaptic GABA inputs onto pyramidal neurons. Likewise, the pharmacological manipulation of various 5-HT receptors alters oscillatory activity in PFC, suggesting that 5-HT is also involved in the control of cortical network activity. A better understanding of the actions of 5-HT in PFC may help to develop treatments for mood and cognitive disorders associated with an abnormal function of the frontal lobe

  13. Novel Cortical Thickness Pattern for Accurate Detection of Alzheimer's Disease.

    PubMed

    Zheng, Weihao; Yao, Zhijun; Hu, Bin; Gao, Xiang; Cai, Hanshu; Moore, Philip

    2015-01-01

    Brain network occupies an important position in representing abnormalities in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Currently, most studies only focused on morphological features of regions of interest without exploring the interregional alterations. In order to investigate the potential discriminative power of a morphological network in AD diagnosis and to provide supportive evidence on the feasibility of an individual structural network study, we propose a novel approach of extracting the correlative features from magnetic resonance imaging, which consists of a two-step approach for constructing an individual thickness network with low computational complexity. Firstly, multi-distance combination is utilized for accurate evaluation of between-region dissimilarity; and then the dissimilarity is transformed to connectivity via calculation of correlation function. An evaluation of the proposed approach has been conducted with 189 normal controls, 198 MCI subjects, and 163 AD patients using machine learning techniques. Results show that the observed correlative feature suggests significant promotion in classification performance compared with cortical thickness, with accuracy of 89.88% and area of 0.9588 under receiver operating characteristic curve. We further improved the performance by integrating both thickness and apolipoprotein E ɛ4 allele information with correlative features. New achieved accuracies are 92.11% and 79.37% in separating AD from normal controls and AD converters from non-converters, respectively. Differences between using diverse distance measurements and various correlation transformation functions are also discussed to explore an optimal way for network establishment. PMID:26444768

  14. Posterior cortical dementia with alexia: neurobehavioural, MRI, and PET findings.

    PubMed Central

    Freedman, L; Selchen, D H; Black, S E; Kaplan, R; Garnett, E S; Nahmias, C

    1991-01-01

    A progressive disorder of relatively focal but asymmetric biposterior dysfunction is described in a 54 year old right handed male. Initial clinical features included letter-by-letter alexia, visual anomia, acalculia, mild agraphia, constructional apraxia, and visuospatial compromise. Serial testing demonstrated relentless deterioration with additional development of transcortical sensory aphasia, Gerstmann's tetrad, and severe visuoperceptual impairment. Amnesia was not an early clinical feature. Judgment, personality, insight, and awareness remained preserved throughout most of the clinical course. Extinction in the right visual field to bilateral stimulation was the sole neurological abnormality. Early CT was normal and late MRI showed asymmetrical bioccipitoparietal atrophy with greater involvement of the left hemisphere. Results from positron emission tomography (PET) showed bilaterally asymmetric (left greater than right) occipitotemporoparietal hypometabolism. The metabolic decrement was strikingly asymmetric with a 50% reduction in glucose consumption confined to the left occipital cortex. The picture of occipitotemporoparietal compromise verified by MRI, PET, and neurobehavioural testing would be unusual for such degenerative dementias as Alzheimer's (AD) and Pick's disease, although atypical AD with predominant occipital lobe involvement cannot be excluded. This case supports the concepts of posterior cortical dementia (PCD) as a clinically distinct entity and for the first time documents its corresponding metabolic deficit using PET. Images PMID:1865209

  15. Literacy and visual impairment.

    PubMed

    Erickson, Karen A; Hatton, Deborah

    2007-02-01

    Research supporting specific instructional approaches for young children with visual impairments and blindness is limited. There is, however, a growing body of evidence to support the belief that the critical components of emergent and early conventional literacy for children with visual impairments do not differ markedly from those of their sighted peers. Specifically, infants and toddlers with visual impairments and blindness require interactions that support their oral language development, awareness of print or braille, and opportunities to explore writing. Although these very young children are often delayed in developing emergent literacy understandings, the path of their development is consistent with emergent literacy development of sighted children. The research regarding older children with visual impairments and blindness suggests that they too benefit from instruction that emphasizes the critical elements of early literacy instruction for all children. Research also suggests that specific strategies, such as repeated readings, direct instruction in phonics, and big word decoding that emphasizes morphemes, can benefit school-aged children with visual impairments and blindness. Further research is needed if we are to understand fully the most effective approaches to emergent and early literacy instruction for children with visual impairments and blindness, but there is a solid base from which we can begin. PMID:17340383

  16. Rab3A, a possible marker of cortical granules, participates in cortical granule exocytosis in mouse eggs.

    PubMed

    Bello, Oscar Daniel; Cappa, Andrea Isabel; de Paola, Matilde; Zanetti, María Natalia; Fukuda, Mitsunori; Fissore, Rafael A; Mayorga, Luis S; Michaut, Marcela A

    2016-09-10

    Fusion of cortical granules with the oocyte plasma membrane is the most significant event to prevent polyspermy. This particular exocytosis, also known as cortical reaction, is regulated by calcium and its molecular mechanism is still not known. Rab3A, a member of the small GTP-binding protein superfamily, has been implicated in calcium-dependent exocytosis and is not yet clear whether Rab3A participates in cortical granules exocytosis. Here, we examine the involvement of Rab3A in the physiology of cortical granules, particularly, in their distribution during oocyte maturation and activation, and their participation in membrane fusion during cortical granule exocytosis. Immunofluorescence and Western blot analysis showed that Rab3A and cortical granules have a similar migration pattern during oocyte maturation, and that Rab3A is no longer detected after cortical granule exocytosis. These results suggested that Rab3A might be a marker of cortical granules. Overexpression of EGFP-Rab3A colocalized with cortical granules with a Pearson correlation coefficient of +0.967, indicating that Rab3A and cortical granules have almost a perfect colocalization in the egg cortical region. Using a functional assay, we demonstrated that microinjection of recombinant, prenylated and active GST-Rab3A triggered cortical granule exocytosis, indicating that Rab3A has an active role in this secretory pathway. To confirm this active role, we inhibited the function of endogenous Rab3A by microinjecting a polyclonal antibody raised against Rab3A prior to parthenogenetic activation. Our results showed that Rab3A antibody microinjection abolished cortical granule exocytosis in parthenogenetically activated oocytes. Altogether, our findings confirm that Rab3A might function as a marker of cortical granules and participates in cortical granule exocytosis in mouse eggs. PMID:27423421

  17. Rab3A, a possible marker of cortical granules, participates in cortical granule exocytosis in mouse eggs.

    PubMed

    Bello, Oscar Daniel; Cappa, Andrea Isabel; de Paola, Matilde; Zanetti, María Natalia; Fukuda, Mitsunori; Fissore, Rafael A; Mayorga, Luis S; Michaut, Marcela A

    2016-09-10

    Fusion of cortical granules with the oocyte plasma membrane is the most significant event to prevent polyspermy. This particular exocytosis, also known as cortical reaction, is regulated by calcium and its molecular mechanism is still not known. Rab3A, a member of the small GTP-binding protein superfamily, has been implicated in calcium-dependent exocytosis and is not yet clear whether Rab3A participates in cortical granules exocytosis. Here, we examine the involvement of Rab3A in the physiology of cortical granules, particularly, in their distribution during oocyte maturation and activation, and their participation in membrane fusion during cortical granule exocytosis. Immunofluorescence and Western blot analysis showed that Rab3A and cortical granules have a similar migration pattern during oocyte maturation, and that Rab3A is no longer detected after cortical granule exocytosis. These results suggested that Rab3A might be a marker of cortical granules. Overexpression of EGFP-Rab3A colocalized with cortical granules with a Pearson correlation coefficient of +0.967, indicating that Rab3A and cortical granules have almost a perfect colocalization in the egg cortical region. Using a functional assay, we demonstrated that microinjection of recombinant, prenylated and active GST-Rab3A triggered cortical granule exocytosis, indicating that Rab3A has an active role in this secretory pathway. To confirm this active role, we inhibited the function of endogenous Rab3A by microinjecting a polyclonal antibody raised against Rab3A prior to parthenogenetic activation. Our results showed that Rab3A antibody microinjection abolished cortical granule exocytosis in parthenogenetically activated oocytes. Altogether, our findings confirm that Rab3A might function as a marker of cortical granules and participates in cortical granule exocytosis in mouse eggs.

  18. Malformations of Cortical Development: From Postnatal to Fetal Imaging.

    PubMed

    Lerman-Sagie, Tally; Leibovitz, Zvi

    2016-09-01

    Abnormal fetal corticogenesis results in malformations of cortical development (MCD). Abnormal cell proliferation leads to microcephaly or megalencephaly, incomplete neuronal migration results in heterotopia and lissencephaly, neuronal overmigration manifests as cobblestone malformations, and anomalous postmigrational cortical organization is responsible for polymicrogyria and focal cortical dysplasias. MCD comprises various congenital brain disorders, caused by different genetic, infectious, or vascular etiologies and is associated with significant neurological morbidity. Although MCD are rarely diagnosed prenatally, both dedicated multiplanar neurosonography and magnetic resonance imaging enable good demonstration of fetal cortical development. The imaging signs of fetal MCD are: delayed or absent cerebral sulcation; premature abnormal sulci; thin and irregular hemispheric parenchyma; wide abnormal overdeveloped gyri; wide opening of isolated sulci; nodular bulging into the lateral ventricles; cortical clefts; intraparenchymal echogenic nodules; and cortical thickening. The postnatal and prenatal imaging features of four main malformations of cortical development-lissencephaly, cobblestone malformations, periventricular nodular heterotopia, and polymicrogyria-are described. PMID:27670206

  19. Impaired neural discrimination of emotional speech prosody in children with autism spectrum disorder and language impairment.

    PubMed

    Lindström, R; Lepistö-Paisley, T; Vanhala, R; Alén, R; Kujala, T

    2016-08-15

    Autism spectrum disorders (ASD) are characterized by deficient social and communication skills, including difficulties in perceiving speech prosody. The present study addressed processing of emotional prosodic changes (sad, scornful and commanding) in natural word stimuli in typically developed school-aged children and in children with ASD and language impairment. We found that the responses to a repetitive word were diminished in amplitude in the children with ASD, reflecting impaired speech encoding. Furthermore, the amplitude of the MMN/LDN component, reflecting cortical discrimination of sound changes, was diminished in the children with ASD for the scornful deviant. In addition, the amplitude of the P3a, reflecting involuntary orienting to attention-catching changes, was diminished in the children with ASD for the scornful deviant and tended to be smaller for the sad deviant. These results suggest that prosody processing in ASD is impaired at various levels of neural processing, including deficient pre-attentive discrimination and involuntary orientation to speech prosody. PMID:27291458

  20. Neuropsychology of cognitive ageing, minimal cognitive impairment, Alzheimer's disease, and vascular cognitive impairment.

    PubMed

    Lindeboom, Jaap; Weinstein, Henry

    2004-04-19

    In this review, the neuropsychological symptoms of different diseases in the elderly are described. After a brief explanation of relevant principles in the neuropsychological assessment of older individuals, a summary of the complex relation between ageing and cognition is presented. It may be concluded that cognitive decline is not an inevitable outcome of ageing, and may well be the result of unrecognised pathology. The term mild cognitive impairment is reserved for patients whose impairment is objectively demonstrable but is not pronounced in more than one domain of cognition and does not seriously affect activities of daily living. The initial phase of Alzheimer's disease is marked by a progressive deterioration of episodic memory. When the process advances, the impairment spreads to other functions, such as semantic memory, language and visuo-spatial ability. Vascular dementia is the second most common type of dementia; however, it is increasingly being recognised that vascular dementia is actually a heterogeneous syndrome and that several vascular pathologies can lead to cognitive deterioration. In contrast to the striking deficits produced by cortical infarcts, lesions of the subcortical white matter are mainly associated with a non-specific slowing of behaviour. Cerebrovascular disease also plays an important role in forms of cognitive decline other than dementia, and as such, it appears to be no less prevalent in old age than Alzheimer's disease. Neuropsychology is an important asset to the study and treatment of cognitive decline, but must be embedded in a multi-disciplinary context.

  1. Shining a light on posterior cortical atrophy.

    PubMed

    Crutch, Sebastian J; Schott, Jonathan M; Rabinovici, Gil D; Boeve, Bradley F; Cappa, Stefano F; Dickerson, Bradford C; Dubois, Bruno; Graff-Radford, Neill R; Krolak-Salmon, Pierre; Lehmann, Manja; Mendez, Mario F; Pijnenburg, Yolande; Ryan, Natalie S; Scheltens, Philip; Shakespeare, Tim; Tang-Wai, David F; van der Flier, Wiesje M; Bain, Lisa; Carrillo, Maria C; Fox, Nick C

    2013-07-01

    Posterior cortical atrophy (PCA) is a clinicoradiologic syndrome characterized by progressive decline in visual processing skills, relatively intact memory and language in the early stages, and atrophy of posterior brain regions. Misdiagnosis of PCA is common, owing not only to its relative rarity and unusual and variable presentation, but also because patients frequently first seek the opinion of an ophthalmologist, who may note normal eye examinations by their usual tests but may not appreciate cortical brain dysfunction. Seeking to raise awareness of the disease, stimulate research, and promote collaboration, a multidisciplinary group of PCA research clinicians formed an international working party, which had its first face-to-face meeting on July 13, 2012 in Vancouver, Canada, prior to the Alzheimer's Association International Conference. PMID:23274153

  2. Cortical dysplasia, genetic abnormalities and neurocutaneous syndromes.

    PubMed

    Vinters, H V; Park, S H; Johnson, M W; Mischel, P S; Catania, M; Kerfoot, C

    1999-11-01

    Cortical dysplasia (CD) represents a common neuropathologic substrate of pediatric epilepsy, one frequently encountered in surgical resection specimens from infants and children with intractable seizure disorders, including infantile spasms. Severe CD shows similarities to structural features noted in tubers from individuals with tuberous sclerosis (TSC). The latter disorder, one with neurocutaneous and visceral manifestations, results from mutations in one of two recently cloned genes, TSC1 or TSC2, which encode (respectively) the proteins hamartin and tuberin. There is circumstantial evidence that both proteins may influence cell growth and differentiation, specifically that they may represent growth suppressors. Neither protein has a defined role in brain development. We discuss and illustrate neuropathologic features of both CD and TSC, and discuss the patterns and time course of hamartin/tuberin expression in normal brain, CD and TSC. Other recently cloned genes associated with cortical malformations encompassed by the term CD are briefly described. PMID:10575248

  3. Parcellating Cortical Functional Networks in Individuals

    PubMed Central

    Wang, Danhong; Buckner, Randy L.; Fox, Michael D.; Holt, Daphne J.; Holmes, Avram J.; Stoecklein, Sophia; Langs, Georg; Pan, Ruiqi; Qian, Tianyi; Li, Kuncheng; Baker, Justin T.; Stufflebeam, Steven M.; Wang, Kai; Wang, Xiaomin; Hong, Bo; Liu, Hesheng

    2015-01-01

    The capacity to identify the unique functional architecture of an individual’s brain is a critical step towards personalized medicine and understanding the neural basis of variations in human cognition and behavior. Here, we developed a novel cortical parcellation approach to accurately map functional organization at the individual level using resting-state fMRI. A population-based functional atlas and a map of inter-individual variability were employed to guide the iterative search for functional networks in individual subjects. Functional networks mapped by this approach were highly reproducible within subjects and effectively captured the variability across subjects, including individual differences in brain lateralization. The algorithm performed well across different subject populations and data types including task fMRI data. The approach was then validated by invasive cortical stimulation mapping in surgical patients, suggesting great potential for use in clinical applications. PMID:26551545

  4. Plasticity of Cortical Excitatory-Inhibitory Balance

    PubMed Central

    Froemke, Robert C.

    2015-01-01

    Synapses are highly plastic and are modified by changes in patterns of neural activity or sensory experience. Plasticity of cortical excitatory synapses is thought to be important for learning and memory, leading to alterations in sensory representations and cognitive maps. However, these changes must be coordinated across other synapses within local circuits to preserve neural coding schemes and the organization of excitatory and inhibitory inputs, i.e., excitatory-inhibitory balance. Recent studies indicate that inhibitory synapses are also plastic and are controlled directly by a large number of neuromodulators, particularly during episodes of learning. Many modulators transiently alter excitatory-inhibitory balance by decreasing inhibition, and thus disinhibition has emerged as a major mechanism by which neuromodulation might enable long-term synaptic modifications naturally. This review examines the relationships between neuromodulation and synaptic plasticity, focusing on the induction of long-term changes that collectively enhance cortical excitatory-inhibitory balance for improving perception and behavior. PMID:25897875

  5. Massive cortical reorganization in sighted Braille readers.

    PubMed

    Siuda-Krzywicka, Katarzyna; Bola, Łukasz; Paplińska, Małgorzata; Sumera, Ewa; Jednoróg, Katarzyna; Marchewka, Artur; Śliwińska, Magdalena W; Amedi, Amir; Szwed, Marcin

    2016-03-15

    The brain is capable of large-scale reorganization in blindness or after massive injury. Such reorganization crosses the division into separate sensory cortices (visual, somatosensory...). As its result, the visual cortex of the blind becomes active during tactile Braille reading. Although the possibility of such reorganization in the normal, adult brain has been raised, definitive evidence has been lacking. Here, we demonstrate such extensive reorganization in normal, sighted adults who learned Braille while their brain activity was investigated with fMRI and transcranial magnetic stimulation (TMS). Subjects showed enhanced activity for tactile reading in the visual cortex, including the visual word form area (VWFA) that was modulated by their Braille reading speed and strengthened resting-state connectivity between visual and somatosensory cortices. Moreover, TMS disruption of VWFA activity decreased their tactile reading accuracy. Our results indicate that large-scale reorganization is a viable mechanism recruited when learning complex skills.

  6. Inhibitory interneurons in visual cortical plasticity.

    PubMed

    van Versendaal, Daniëlle; Levelt, Christiaan N

    2016-10-01

    For proper maturation of the neocortex and acquisition of specific functions and skills, exposure to sensory stimuli is vital during critical periods of development when synaptic connectivity is highly malleable. To preserve reliable cortical processing, it is essential that these critical periods end after which learning becomes more conditional and active interaction with the environment becomes more important. How these age-dependent forms of plasticity are regulated has been studied extensively in the primary visual cortex. This has revealed that inhibitory innervation plays a crucial role and that a temporary decrease in inhibition is essential for plasticity to take place. Here, we discuss how different interneuron subsets regulate plasticity during different stages of cortical maturation. We propose a theory in which different interneuron subsets select the sources of neuronal input that undergo plasticity.

  7. Massive cortical reorganization in sighted Braille readers.

    PubMed

    Siuda-Krzywicka, Katarzyna; Bola, Łukasz; Paplińska, Małgorzata; Sumera, Ewa; Jednoróg, Katarzyna; Marchewka, Artur; Śliwińska, Magdalena W; Amedi, Amir; Szwed, Marcin

    2016-01-01

    The brain is capable of large-scale reorganization in blindness or after massive injury. Such reorganization crosses the division into separate sensory cortices (visual, somatosensory...). As its result, the visual cortex of the blind becomes active during tactile Braille reading. Although the possibility of such reorganization in the normal, adult brain has been raised, definitive evidence has been lacking. Here, we demonstrate such extensive reorganization in normal, sighted adults who learned Braille while their brain activity was investigated with fMRI and transcranial magnetic stimulation (TMS). Subjects showed enhanced activity for tactile reading in the visual cortex, including the visual word form area (VWFA) that was modulated by their Braille reading speed and strengthened resting-state connectivity between visual and somatosensory cortices. Moreover, TMS disruption of VWFA activity decreased their tactile reading accuracy. Our results indicate that large-scale reorganization is a viable mechanism recruited when learning complex skills. PMID:26976813

  8. Relearning to See in Cortical Blindness.

    PubMed

    Melnick, Michael D; Tadin, Duje; Huxlin, Krystel R

    2016-04-01

    The incidence of cortically induced blindness is increasing as our population ages. The major cause of cortically induced blindness is stroke affecting the primary visual cortex. While the impact of this form of vision loss is devastating to quality of life, the development of principled, effective rehabilitation strategies for this condition lags far behind those used to treat motor stroke victims. Here we summarize recent developments in the still emerging field of visual restitution therapy, and compare the relative effectiveness of different approaches. We also draw insights into the properties of recovered vision, its limitations and likely neural substrates. We hope that these insights will guide future research and bring us closer to the goal of providing much-needed rehabilitation solutions for this patient population. PMID:26659828

  9. Bioengineered functional brain-like cortical tissue

    PubMed Central

    Tang-Schomer, Min D.; White, James D.; Tien, Lee W.; Schmitt, L. Ian; Valentin, Thomas M.; Graziano, Daniel J.; Hopkins, Amy M.; Omenetto, Fiorenzo G.; Haydon, Philip G.; Kaplan, David L.

    2014-01-01

    The brain remains one of the most important but least understood tissues in our body, in part because of its complexity as well as the limitations associated with in vivo studies. Although simpler tissues have yielded to the emerging tools for in vitro 3D tissue cultures, functional brain-like tissues have not. We report the construction of complex functional 3D brain-like cortical tissue, maintained for months in vitro, formed from primary cortical neurons in modular 3D compartmentalized architectures with electrophysiological function. We show that, on injury, this brain-like tissue responds in vitro with biochemical and electrophysiological outcomes that mimic observations in vivo. This modular 3D brain-like tissue is capable of real-time nondestructive assessments, offering previously unidentified directions for studies of brain homeostasis and injury. PMID:25114234

  10. Permanent Cortical Blindness After Bronchial Artery Embolization

    SciTech Connect

    Doorn, Colette S. van De Boo, Diederick W.; Weersink, Els J. M.; Delden, Otto M. van Reekers, Jim A. Lienden, Krijn P. van

    2013-12-15

    A 35-year-old female with a known medical history of cystic fibrosis was admitted to our institution for massive hemoptysis. CTA depicted a hypertrophied bronchial artery to the right upper lobe and showed signs of recent bleeding at that location. Bronchial artery embolization (BAE) was performed with gelfoam slurry, because pronounced shunting to the pulmonary artery was present. Immediately after BAE, the patient developed bilateral cortical blindness. Control angiography showed an initially not opacified anastomosis between the embolized bronchial artery and the right subclavian artery, near to the origin of the right vertebral artery. Cessation of outflow in the bronchial circulation reversed the flow through the anastomosis and allowed for spill of embolization material into the posterior circulation. Unfortunately the cortical blindness presented was permanent.

  11. Do Cortical Circuits Need Protecting from Themselves?

    PubMed

    Trevelyan, Andrew J

    2016-08-01

    All hippocampal and neocortical networks can be driven to seize quite easily. This can be done using drugs, by altering the ionic constituency of the bathing medium [cerebrospinal fluid (CSF)], or by electrical stimulation (both experimentally and clinically, as in electroconvulsive therapy). It is worth asking why this is so, because this will both tell us more about potentially devastating neurological disorders and extend our understanding of cortical function and architecture. Here I review work examining the features of cortical networks that bias activity towards and away from hyperexcitability. I suggest that several cellular- and circuit-level features of rapidly responsive interneuron networks tip the balance away from seizure in the healthy brain. PMID:27378547

  12. APC/C-Cdh1 coordinates neurogenesis and cortical size during development

    NASA Astrophysics Data System (ADS)

    Delgado-Esteban, Maria; García-Higuera, Irene; Maestre, Carolina; Moreno, Sergio; Almeida, Angeles

    2013-12-01

    The morphology of the adult brain is the result of a delicate balance between neural progenitor proliferation and the initiation of neurogenesis in the embryonic period. Here we assessed whether the anaphase-promoting complex/cyclosome (APC/C) cofactor, Cdh1—which regulates mitosis exit and G1-phase length in dividing cells—regulates neurogenesis in vivo. We use an embryo-restricted Cdh1 knockout mouse model and show that functional APC/C-Cdh1 ubiquitin ligase activity is required for both terminal differentiation of cortical neurons in vitro and neurogenesis in vivo. Further, genetic ablation of Cdh1 impairs the ability of APC/C to promote neurogenesis by delaying the exit of the progenitor cells from the cell cycle. This causes replicative stress and p53-mediated apoptotic death resulting in decreased number of cortical neurons and cortex size. These results demonstrate that APC/C-Cdh1 coordinates cortical neurogenesis and size, thus posing Cdh1 in the molecular pathogenesis of congenital neurodevelopmental disorders, such as microcephaly.

  13. Albuminuria, Cerebrovascular Disease and Cortical Atrophy: among Cognitively Normal Elderly Individuals.

    PubMed

    Cho, Eun Bin; Shin, Hee-Young; Park, Sang Eon; Chun, Phillip; Jang, Hye Ryoun; Yang, Jin-ju; Kim, Hee Jin; Kim, Yeo Jin; Jung, Na-Yeon; Lee, Jin San; Lee, Juyoun; Jang, Young Kyoung; Jang, Eun Young; Kang, Mira; Lee, Jong-Min; Kim, Changsoo; Min, Ju-Hong; Ryu, Seungho; Na, Duk L; Seo, Sang Won

    2016-02-15

    We tested the hypothesis that decreased glomerular filtration rate and albuminuria have different roles in brain structure alterations. We enrolled 1,215 cognitively normal individuals, all of whom underwent high-resolution T1-weighted volumetric magnetic resonance imaging scans. The cerebral small vessel disease burdens were assessed with white matter hyperintensities (WMH), lacunes, and microbleeds. Subjects were considered to have an abnormally elevated urine albumin creatinine ratio if the value was ≥17 mg/g for men and ≥25 mg/g for women. Albuminuria, but not estimated glomerular filtration rate (eGFR), was associated with increased WMH burdens (p = 0.002). The data was analyzed after adjusting for age, sex, education, history of hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease, stroke, total cholesterol level, body mass index, status of smoking and alcohol drinking, and intracranial volume. Albuminuria was also associated with cortical thinning, predominantly in the frontal and occipital regions (both p < 0.01) in multiple linear regression analysis. However, eGFR was not associated with cortical thickness. Furthermore, path analysis for cortical thickness showed that albuminuria was associated with frontal thinning partially mediated by WMH burdens. The assessment of albuminuria is needed to improve our ability to identify individuals with high risk for cognitive impairments, and further institute appropriate preventive measures.

  14. A novel cortical thickness estimation method based on volumetric Laplace-Beltrami operator and heat kernel.

    PubMed

    Wang, Gang; Zhang, Xiaofeng; Su, Qingtang; Shi, Jie; Caselli, Richard J; Wang, Yalin

    2015-05-01

    Cortical thickness estimation in magnetic resonance imaging (MRI) is an important technique for research on brain development and neurodegenerative diseases. This paper presents a heat kernel based cortical thickness estimation algorithm, which is driven by the graph spectrum and the heat kernel theory, to capture the gray matter geometry information from the in vivo brain magnetic resonance (MR) images. First, we construct a tetrahedral mesh that matches the MR images and reflects the inherent geometric characteristics. Second, the harmonic field is computed by the volumetric Laplace-Beltrami operator and the direction of the steamline is obtained by tracing the maximum heat transfer probability based on the heat kernel diffusion. Thereby we can calculate the cortical thickness information between the point on the pial and white matter surfaces. The new method relies on intrinsic brain geometry structure and the computation is robust and accurate. To validate our algorithm, we apply it to study the thickness differences associated with Alzheimer's disease (AD) and mild cognitive impairment (MCI) on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Our preliminary experimental results on 151 subjects (51 AD, 45 MCI, 55 controls) show that the new algorithm may successfully detect statistically significant difference among patients of AD, MCI and healthy control subjects. Our computational framework is efficient and very general. It has the potential to be used for thickness estimation on any biological structures with clearly defined inner and outer surfaces.

  15. A Novel Cortical Thickness Estimation Method based on Volumetric Laplace-Beltrami Operator and Heat Kernel

    PubMed Central

    Wang, Gang; Zhang, Xiaofeng; Su, Qingtang; Shi, Jie; Caselli, Richard J.; Wang, Yalin

    2015-01-01

    Cortical thickness estimation in magnetic resonance imaging (MRI) is an important technique for research on brain development and neurodegenerative diseases. This paper presents a heat kernel based cortical thickness estimation algorithm, which is driven by the graph spectrum and the heat kernel theory, to capture the grey matter geometry information from the in vivo brain magnetic resonance (MR) images. First, we construct a tetrahedral mesh that matches the MR images and reflects the inherent geometric characteristics. Second, the harmonic field is computed by the volumetric Laplace-Beltrami operator and the direction of the steamline is obtained by tracing the maximum heat transfer probability based on the heat kernel diffusion. Thereby we can calculate the cortical thickness information between the point on the pial and white matter surfaces. The new method relies on intrinsic brain geometry structure and the computation is robust and accurate. To validate our algorithm, we apply it to study the thickness differences associated with Alzheimer’s disease (AD) and mild cognitive impairment (MCI) on the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. Our preliminary experimental results on 151 subjects (51 AD, 45 MCI, 55 controls) show that the new algorithm may successfully detect statistically significant difference among patients of AD, MCI and healthy control subjects. Our computational framework is efficient and very general. It has the potential to be used for thickness estimation on any biological structures with clearly defined inner and outer surfaces. PMID:25700360

  16. Reduced cerebral cortical thickness in Non-cirrhotic patients with hepatitis C.

    PubMed

    Hjerrild, Simon; Renvillard, Signe Groth; Leutscher, Peter; Sørensen, Leif Hougaard; Østergaard, Leif; Eskildsen, Simon Fristed; Videbech, Poul

    2016-04-01

    Hepatitis C virus (HCV) infection is associated with fatigue, depression, and cognitive impairment even in the absence of severe liver fibrosis or cirrhosis. HCV has been hypothesised to cause neurodegenerative changes through low-grade neuroinflammation. Our aim was to examine whether cortical thickness (CTh) differs between chronic HCV patients and healthy controls, suggestive of cortical atrophy. In this case-control study 43 HCV patients without severe liver fibrosis, substance abuse, or comorbid HIV or hepatitis B virus infection, and 43 age and sex matched controls underwent MRI. Cortical thickness was measured using a surface based approach. Participants underwent semi-structured psychiatric interview and fatigue was assessed using the fatigue severity scale. HCV was associated with higher fatigue scores, and 58 % of HCV patients suffered from significant fatigue (p < 0.0001). Depression was observed in 16 % of patients. Areas of significantly reduced CTh were found in both left and right occipital cortex and in the left frontal lobe after correction for multiple comparisons (p < 0.05). No association between fatigue, former substance abuse, or psychotropic medication and CTh was found. No overall difference in cerebral white and grey matter volume was found. The findings support the hypothesis that HCV is associated with neurodegenerative changes. PMID:26530221

  17. Albuminuria, Cerebrovascular Disease and Cortical Atrophy: among Cognitively Normal Elderly Individuals.

    PubMed

    Cho, Eun Bin; Shin, Hee-Young; Park, Sang Eon; Chun, Phillip; Jang, Hye Ryoun; Yang, Jin-ju; Kim, Hee Jin; Kim, Yeo Jin; Jung, Na-Yeon; Lee, Jin San; Lee, Juyoun; Jang, Young Kyoung; Jang, Eun Young; Kang, Mira; Lee, Jong-Min; Kim, Changsoo; Min, Ju-Hong; Ryu, Seungho; Na, Duk L; Seo, Sang Won

    2016-01-01

    We tested the hypothesis that decreased glomerular filtration rate and albuminuria have different roles in brain structure alterations. We enrolled 1,215 cognitively normal individuals, all of whom underwent high-resolution T1-weighted volumetric magnetic resonance imaging scans. The cerebral small vessel disease burdens were assessed with white matter hyperintensities (WMH), lacunes, and microbleeds. Subjects were considered to have an abnormally elevated urine albumin creatinine ratio if the value was ≥17 mg/g for men and ≥25 mg/g for women. Albuminuria, but not estimated glomerular filtration rate (eGFR), was associated with increased WMH burdens (p = 0.002). The data was analyzed after adjusting for age, sex, education, history of hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease, stroke, total cholesterol level, body mass index, status of smoking and alcohol drinking, and intracranial volume. Albuminuria was also associated with cortical thinning, predominantly in the frontal and occipital regions (both p < 0.01) in multiple linear regression analysis. However, eGFR was not associated with cortical thickness. Furthermore, path analysis for cortical thickness showed that albuminuria was associated with frontal thinning partially mediated by WMH burdens. The assessment of albuminuria is needed to improve our ability to identify individuals with high risk for cognitive impairments, and further institute appropriate preventive measures. PMID:26878913

  18. Decoupling of Sleep-Dependent Cortical and Hippocampal Interactions in a Neurodevelopmental Model of Schizophrenia

    PubMed Central

    Phillips, Keith G.; Bartsch, Ullrich; McCarthy, Andrew P.; Edgar, Dale M.; Tricklebank, Mark D.; Wafford, Keith A.; Jones, Matt W.

    2012-01-01

    Summary Rhythmic neural network activity patterns are defining features of sleep, but interdependencies between limbic and cortical oscillations at different frequencies and their functional roles have not been fully resolved. This is particularly important given evidence linking abnormal sleep architecture and memory consolidation in psychiatric diseases. Using EEG, local field potential (LFP), and unit recordings in rats, we show that anteroposterior propagation of neocortical slow-waves coordinates timing of hippocampal ripples and prefrontal cortical spindles during NREM sleep. This coordination is selectively disrupted in a rat neurodevelopmental model of schizophrenia: fragmented NREM sleep and impaired slow-wave propagation in the model culminate in deficient ripple-spindle coordination and disrupted spike timing, potentially as a consequence of interneuronal abnormalities reflected by reduced parvalbumin expression. These data further define the interrelationships among slow-wave, spindle, and ripple events, indicating that sleep disturbances may be associated with state-dependent decoupling of hippocampal and cortical circuits in psychiatric diseases. PMID:23141065

  19. Cortical response to psycho-physiological changes in auto-adaptive robot assisted gait training.

    PubMed

    Jelinek, Herbert F; August, Katherine G; Imam, Md Hasan; Khandoker, Ahsan H; Koenig, Alexander; Riener, Robert

    2011-01-01

    Robot-assisted treadmill training improves motor function and walking ability in neurologically impaired patients. However, despite attention having been shown to play a role in training success, psychological responsiveness to task difficulty and motivational levels at task onset have not been measured. Seven healthy subjects participated in a robot-assist treadmill training task. Subjects engaged in a virtual task with varying difficulty levels that was shown to induce a feeling of being bored, excited and over-stressed. The participants' mental engagement was measured using the ECG-based heart rate variability in real time, during gait training as a proxy for EEG and psychological test batteries. Heart rate variability (HRV), which has been shown to reflect cortical engagement for both cognitive and physical tasks, was measured using nonlinear measures obtained from the Poincaré plot. We show that the cortical response to the task measured with HRV varies in relation to the level of mental engagement in response to the difficulty level of the virtual task. From these results we propose that nonlinear measures quantify cortical response / motivational level to robot-assist motor learning tasks and that the adaptation to the task is dependent on the level of motivation.

  20. Reduced cortical neurotransmitter receptor complex levels in fetal Down syndrome brain.

    PubMed

    Falsafi, Soheil Keihan; Dierssen, Mara; Ghafari, Maryam; Pollak, Arnold; Lubec, Gert

    2016-01-01

    In this study, cortical receptor complex levels were determined in fetal Down syndrome (DS, trisomy 21) brain. Frontal cortices were obtained from individuals with DS (19th-22nd week of gestation) and controls. Membrane proteins were extracted, assayed on blue native gels and immunoblotted with brain receptor antibodies. Levels of a D1R-containing complex were markedly decreased in male and female cortices of DS individuals. Females with DS had significant reductions of nicotinic acetylcholine receptors α4 and α7, NMDA receptor GluN1 and AMPA receptor GluA1- and GluA3-containing receptor complexes. Levels of other brain receptor complexes (5-hydroxytryptamine 1A, GluA2 and GluR4 receptor-containing complexes) were comparable between the groups of females. Levels of GluA2- and GluA3-containing complexes were significantly increased in males. Decreased levels of D1R complexes in both sexes, along with the significant reduction of α4, α7-containing receptor complexes observed in females, may explain the brain deficits and impaired cognition observed in DS.