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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. Community environment, cognitive impairment and dementia in later life: results from the Cognitive Function and Ageing Study

    PubMed Central

    Wu, Yu-Tzu; Prina, A. Matthew; Jones, Andrew P.; Barnes, Linda E.; Matthews, Fiona E.; Brayne, Carol

    2015-01-01

    Background: few studies have investigated the impact of the community environment, as distinct from area deprivation, on cognition in later life. This study explores cross-sectional associations between cognitive impairment and dementia and environmental features at the community level in older people. Method: the postcodes of the 2,424 participants in the year-10 interview of the Cognitive Function and Ageing Study in England were mapped into small area level geographical units (Lower-layer Super Output Areas) and linked to environmental data in government statistics. Multilevel logistic regression was conducted to investigate associations between cognitive impairment (defined as MMSE ≤ 25), dementia (organicity level ≥3 in GMS-AGECAT) and community level measurements including area deprivation, natural environment, land use mix and crime. Sensitivity analyses tested the impact of people moving residence within the last two years. Results: higher levels of area deprivation and crime were not significantly associated with cognitive impairment and dementia after accounting for individual level factors. Living in areas with high land use mix was significantly associated with a nearly 60% reduced odds of dementia (OR: 0.4; 95% CI: 0.2, 0.8) after adjusting for individual level factors and area deprivation, but there was no linear trend for cognitive impairment. Increased odds of dementia (OR: 2.2, 95% CI: 1.2, 4.2) and cognitive impairment (OR: 1.4, 95% CI: 1.0, 2.0) were found in the highest quartile of natural environment availability. Findings were robust to exclusion of the recently relocated. Conclusion: features of land use have complex associations with cognitive impairment and dementia. Further investigations should focus on environmental influences on cognition to inform health and social policies. PMID:26464419

  4. Cortical Visual Impairment: New Directions

    PubMed Central

    Good, William V.

    2009-01-01

    Cortical visual impairment is the leading cause of bilateral low vision in children in the U.S., yet very little research is being done to find new diagnostic measures and treatments. Dr. Velma Dobson's pioneering work on visual assessments of developmentally delayed children stands out as highly significant in this field. Future research will assess new diagnostic measures, including advanced imaging techniques. In addition, research will evaluate methods to prevent, treat, and rehabilitate infants and children afflicted with this condition. PMID:19417710

  5. Photophobia and cortical visual impairment.

    PubMed

    Jan, J E; Groenveld, M; Anderson, D P

    1993-06-01

    Photophobia, or intolerance of light, is not completely understood as a symptom. It has been divided into ocular and central types. This study shows that persistent, usually mild, photophobia occurs in about one-third of children with cortical visual impairment (CVI). When the CVI is congenital the photophobia is present from birth, and when it is acquired the sensitivity to light appears immediately after the brain insult. The intensity of photophobia tends to diminish with time and occasionally it may even disappear. The pathophysiology is unclear, as in all other neurological disorders associated with photophobia. PMID:8504889

  6. Creativity in later life.

    PubMed

    Price, K A; Tinker, A M

    2014-08-01

    The ageing population presents significant challenges for the provision of social and health services. Strategies are needed to enable older people to cope within a society ill prepared for the impacts of these demographic changes. The ability to be creative may be one such strategy. This review outlines the relevant literature and examines current public health policy related to creativity in old age with the aim of highlighting some important issues. As well as looking at the benefits and negative aspects of creative activity in later life they are considered in the context of the theory of "successful ageing". Creative activity plays an important role in the lives of older people promoting social interaction, providing cognitive stimulation and giving a sense of self-worth. Furthermore, it is shown to be useful as a tool in the multi-disciplinary treatment of health problems common in later life such as depression and dementia. There are a number of initiatives to encourage older people to participate in creative activities such as arts-based projects which may range from visual arts to dance to music to intergenerational initiatives. However, participation shows geographical variation and often the responsibility of provision falls to voluntary organisations. Overall, the literature presented suggests that creative activity could be a useful tool for individuals and society. However, further research is needed to establish the key factors which contribute to patterns of improved health and well-being, as well as to explore ways to improve access to services. PMID:24974278

  7. 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

  8. 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

  9. Focal cortical damage parallels cognitive impairment in minimal hepatic encephalopathy.

    PubMed

    Montoliu, Carmina; Gonzalez-Escamilla, Gabriel; Atienza, Mercedes; Urios, Amparo; Gonzalez, Olga; Wassel, Abdallah; Aliaga, Roberto; Giner-Duran, Remedios; Serra, Miguel A; Rodrigo, Jose M; Belloch, Vicente; Felipo, Vicente; Cantero, Jose L

    2012-07-16

    Little attention has been paid to cortical integrity in patients with minimal hepatic encephalopathy (MHE), although cognitive functions affected in early stages of liver disease are mainly allocated in different neocortical structures. Here we used cortical surface-based analysis techniques to investigate if patterns of cortical thinning accompany the mildest form of HE. To aim this goal, cortical thickness obtained from high-resolution 3T magnetic resonance imaging (MRI) was measured in patients with no MHE (NMHE), MHE, and healthy controls. Further correlation analyses were performed to examine whether scores in the critical flicker frequency (CFF) test, and blood ammonia levels accounted for the loss of cortical integrity in different stages of liver disease. Finally, we assessed group differences in volume of different subcortical regions and their potential relationships with CFF scores/blood ammonia levels. Results showed a focal thinning of the superior temporal cortex and precuneus in MHE patients when compared with NMHE and controls. Relationships between blood ammonia levels and cortical thickness of the calcarine sulcus accounted for impaired visual judgment in patients with MHE when compared to NMHE. Regression analyses between cortical thickness and CFF predicted differences between controls and the two groups of HE patients, but failed to discriminate between patients with NMHE and MHE. Taking together, these findings provide the first report of cortical thinning in MHE patients, and they yield novel insights into the neurobiological basis of cognitive impairment associated with early stages of liver diseases. PMID:22465844

  10. 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

  11. Verbal memory impairments in schizophrenia associated with cortical thinning

    PubMed Central

    Guimond, S.; Chakravarty, M.M.; Bergeron-Gagnon, L.; Patel, R.; Lepage, M.

    2015-01-01

    Verbal memory (VM) represents one of the most affected cognitive domains in schizophrenia. Multiple studies have shown that schizophrenia is associated with cortical abnormalities, but it remains unclear whether these are related to VM impairments. Considering the vast literature demonstrating the role of the frontal cortex, the parahippocampal cortex, and the hippocampus in VM, we examined the cortical thickness/volume of these regions. We used a categorical approach whereby 27 schizophrenia patients with ‘moderate to severe’ VM impairments were compared to 23 patients with ‘low to mild’ VM impairments and 23 healthy controls. A series of between-group vertex-wise GLM on cortical thickness were performed for specific regions of interest defining the parahippocampal gyrus and the frontal cortex. When compared to healthy controls, patients with ‘moderate to severe’ VM impairments revealed significantly thinner cortex in the left frontal lobe, and the parahippocampal gyri. When compared to patients with ‘low to mild’ VM impairments, patients with ‘moderate to severe’ VM impairments showed a trend of thinner cortex in similar regions. Virtually no differences were observed in the frontal area of patients with ‘low to mild’ VM impairments relative to controls. No significant group differences were observed in the hippocampus. Our results indicate that patients with greater VM impairments demonstrate significant cortical thinning in regions known to be important in VM performance. Treating VM deficits in schizophrenia could have a positive effect on the brain; thus, subgroups of patients with more severe VM deficits should be a prioritized target in the development of new cognitive treatments. PMID:26909322

  12. Antisaccade task reflects cortical involvement in mild cognitive impairment

    PubMed Central

    Mirsky, Jacob B.; Kong, Erwin L.; Dickerson, Bradford C.; Miller, Bruce L.; Kramer, Joel H.; Boxer, Adam L.

    2013-01-01

    Objective: The aims of this study were to examine executive dysfunction using an antisaccade (AS) task in normal elderly (NE) and patients with mild cognitive impairment (MCI) and Alzheimer disease (AD) as well as to evaluate the relationship between AS performance and cortical thinning within AD-associated regions. Methods: We recorded eye movements in 182 subjects (NE: 118; MCI: 36; AD: 28) during an AS task. We also performed neuropsychological measures of executive function for comparison. Brain MRI scans were collected on most subjects, and cortical thickness was determined in 9 regions known to exhibit atrophy in AD dementia (“AD signature”). We investigated the relationships between AS and neuropsychological performance, as well as possible correlations between AS performance and cortical thickness. Results: AS performance in MCI resembled that in NE; subjects with AD were impaired relative to both MCI and NE. In all subjects, AS performance correlated with neuropsychological measures of executive function, even after controlling for disease severity. In the subjects with MCI but not in NE, cortical thickness in frontoparietal AD signature regions correlated with AS performance. Conclusions: The AS task is a useful measure of executive function across the AD spectrum. In MCI, AS performance may reflect disease burden within cortical brain regions involved in oculomotor control; however, AS impairments in NE may have etiologies other than incipient AD. PMID:23986300

  13. Immobilization impairs tactile perception and shrinks somatosensory cortical maps.

    PubMed

    Lissek, Silke; Wilimzig, Claudia; Stude, Philipp; Pleger, Burkhard; Kalisch, Tobias; Maier, Christoph; Peters, Sören A; Nicolas, Volkmar; Tegenthoff, Martin; Dinse, Hubert R

    2009-05-26

    Use is a major factor driving plasticity of cortical processing and cortical maps. As demonstrated of blind Braille readers and musicians, long-lasting and exceptional usage of the fingers results in the development of outstanding sensorimotor skills and in expansions of the cortical finger representations. However, how periods of disuse affect cortical representations and perception in humans remains elusive. Here, we report that a few weeks of hand and arm immobilization by cast wearing significantly reduced hand use and impaired tactile acuity, associated with reduced activation of the respective finger representations in the somatosensory cortex (SI), measured by functional magnetic resonance imaging. Hemodynamic responses in the SI correlated positively with hand-use frequency and negatively with discrimination thresholds, indicating that reduced activation was most prominent in subjects with severe perceptual impairment. We found, strikingly, compensatory effects on the contralateral, healthy hand consisting of improved perceptual performance compared to healthy controls. Two to three weeks after cast removal, perceptual and cortical changes recovered, whereas tactile acuity on the healthy side remained superior to that on the formerly immobilized side. These findings suggest that brief periods of reduced use of a limb have overt consequences and thus constitute a significant driving force of brain organization equivalent to enhanced use. PMID:19398335

  14. Impaired cortical mitochondrial function following TBI precedes behavioral changes

    PubMed Central

    Watson, William D.; Buonora, John E.; Yarnell, Angela M.; Lucky, Jessica J.; D’Acchille, Michaela I.; McMullen, David C.; Boston, Andrew G.; Kuczmarski, Andrew V.; Kean, William S.; Verma, Ajay; Grunberg, Neil E.; Cole, Jeffrey T.

    2014-01-01

    Traumatic brain injury (TBI) pathophysiology can be attributed to either the immediate, primary physical injury, or the delayed, secondary injury which begins minutes to hours after the initial injury and can persist for several months or longer. Because these secondary cascades are delayed and last for a significant time period post-TBI, they are primary research targets for new therapeutics. To investigate changes in mitochondrial function after a brain injury, both the cortical impact site and ipsilateral hippocampus of adult male rats 7 and 17 days after a controlled cortical impact (CCI) injury were examined. State 3, state 4, and uncoupler-stimulated rates of oxygen consumption, respiratory control ratios (RCRs) were measured and membrane potential quantified, and all were significantly decreased in 7 day post-TBI cortical mitochondria. By contrast, hippocampal mitochondria at 7 days showed only non-significant decreases in rates of oxygen consumption and membrane potential. NADH oxidase activities measured in disrupted mitochondria were normal in both injured cortex and hippocampus at 7 days post-CCI. Respiratory and phosphorylation capacities at 17 days post-CCI were comparable to naïve animals for both cortical and hippocampus mitochondria. However, unlike oxidative phosphorylation, membrane potential of mitochondria in the cortical lining of the impact site did not recover at 17 days, suggesting that while diminished cortical membrane potential at 17 days does not adversely affect mitochondrial capacity to synthesize ATP, it may negatively impact other membrane potential-sensitive mitochondrial functions. Memory status, as assessed by a passive avoidance paradigm, was not significantly impaired until 17 days after injury. These results indicate pronounced disturbances in cortical mitochondrial function 7 days after CCI which precede the behavioral impairment observed at 17 days. PMID:24550822

  15. Toward Optimizing Cognitive Competence In Later Life

    ERIC Educational Resources Information Center

    Labouvie-Vief, Gisela

    1976-01-01

    Reviews evidence showing the view of pervasive decrement in later life is being challenged. Evidence is accumulated that the intellectual performance of the older adult responds favorably to a variety of ecological, training, and motivational conditions, and that intellectual development in later life is characterized by plasticity not universal…

  16. Cortical thinning in individuals with subjective memory impairment.

    PubMed

    Meiberth, Dix; Scheef, Lukas; Wolfsgruber, Steffen; Boecker, Henning; Block, Wolfgang; Träber, Frank; Erk, Susanne; Heneka, Michael T; Jacobi, Heike; Spottke, Annika; Walter, Henrik; Wagner, Michael; Hu, Xiaochen; Jessen, Frank

    2015-01-01

    Elderly individuals with subjective memory impairment (SMI) report memory decline, but perform within the age-, gender-, and education- adjusted normal range on neuropsychological tests. Longitudinal studies indicate SMI as a risk factor or early sign of Alzheimer's disease (AD). There is increasing evidence from neuroimaging that at the group level, subjects with SMI display evidence of AD related pathology. This study aimed to determine differences in cortical thickness between individuals with SMI and healthy control subjects (CO) using the FreeSurfer environment. 110 participants (41 SMI/69 CO) underwent structural 3D-T1 MR imaging. Cortical thickness values were compared between groups in predefined AD-related brain regions of the medial temporal lobe, namely the bilateral entorhinal cortex and bilateral parahippocampal cortex. Cortical thickness reduction was observed in the SMI group compared to controls in the left entorhinal cortex (p = 0.003). We interpret our findings as evidence of early AD-related brain changes in persons with SMI. PMID:25471190

  17. Memory Impairment at Initial Clinical Presentation in Posterior Cortical Atrophy.

    PubMed

    Ahmed, Samrah; Baker, Ian; Husain, Masud; Thompson, Sian; Kipps, Christopher; Hornberger, Michael; Hodges, John R; Butler, Christopher R

    2016-04-23

    Posterior cortical atrophy (PCA) is characterized by core visuospatial and visuoperceptual deficits, and predominant atrophy in the parieto-occipital cortex. The most common underlying pathology is Alzheimer's disease (AD). Existing diagnostic criteria suggest that episodic memory is relatively preserved. The aim of this study was to examine memory performance at initial clinical presentation in PCA, compared to early-onset AD patients (EOAD). 15 PCA patients and 32 EOAD patients, and 34 healthy controls were entered into the study. Patients were tested on the Addenbrooke's Cognitive Examination (ACE-R), consisting of subscales in memory and visuospatial skills. PCA and EOAD patients were significantly impaired compared to controls on the ACE total score (p < 0.001), visuospatial skills (p < 0.001), and memory (p < 0.001). Consistent with the salient diagnostic deficits, PCA patients were significantly more impaired on visuospatial skills compared to EOAD patients (p < 0.001). However, there was no significant difference between patient groups in memory. Further analysis of learning, recall, and recognition components of the memory subscale showed that EOAD and PCA patients were significantly impaired compared to controls on all three components (p < 0.001), however, there was no significant difference between EOAD and PCA patients. The results of this study show that memory is impaired in the majority of PCA patients at clinical presentation. The findings suggest that memory impairment must be considered in assessment and management of PCA. Further study into memory in PCA is warranted, since the ACE-R is a brief screening tool and is likely to underestimate the presence of memory impairment. PMID:27128371

  18. Cognitive impairment in paediatric multiple sclerosis patients is not related to cortical lesions.

    PubMed

    Rocca, Maria A; De Meo, Ermelinda; Amato, Maria P; Copetti, Massimiliano; Moiola, Lucia; Ghezzi, Angelo; Veggiotti, Pierangelo; Capra, Ruggero; Fiorino, Agnese; Pippolo, Lorena; Pera, Maria C; Falini, Andrea; Comi, Giancarlo; Filippi, Massimo

    2015-06-01

    We investigated the contribution of cortical lesions to cognitive impairment in 41 paediatric MS patients. Thirteen (32%) paediatric MS patients were considered as cognitively impaired. T2-hyperintense and T1-hypointense white matter lesion volumes did not differ between cognitively impaired and cognitively preserved MS patients. Cortical lesions number, cortical lesions volume and grey matter volume did not differ between cognitively impaired and cognitively preserved patients, whereas white matter volume was significantly lower in cognitively impaired versus cognitively preserved MS patients (p=0.01). Contrary to adult MS, cortical lesions do not seem to contribute to cognitive impairment in paediatric MS patients, which is likely driven by white matter damage. PMID:25392332

  19. 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…

  20. 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…

  1. 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…

  2. The Never-Married in Later Life.

    ERIC Educational Resources Information Center

    Ward, Russell A.

    1979-01-01

    Consequences of singlehood are analyzed for never-married persons. Highly-educated older women are most likely to remain single. Family background is not a predictor. Although the never-married find life more exciting than other marital statuses among younger respondents, this reverses in later life. Never-marrieds are also less happy than the…

  3. 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.

  4. 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

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

    PubMed

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

    2015-02-01

    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 neuroanatomic regions compared with control participants who remained cognitively normal (n = 96). Based on 8 years of annual magnetic resonance imaging scans beginning an average of 11 years before 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 with controls. No significant regional cortical thickness differences were found at baseline between the 2 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

  6. 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...

  7. Apathy is associated with lower inferior temporal cortical thickness in mild cognitive impairment and normal elderly individuals.

    PubMed

    Guercio, Brendan J; Donovan, Nancy J; Ward, Andrew; Schultz, Aaron; Lorius, Natacha; Amariglio, Rebecca E; Rentz, Dorene M; Johnson, Keith A; Sperling, Reisa A; Marshall, Gad A

    2015-01-01

    Apathy is a common neuropsychiatric symptom in Alzheimer's disease dementia and amnestic mild cognitive impairment and is associated with cortical atrophy in Alzheimer's disease dementia. This study investigated possible correlations between apathy and cortical atrophy in 47 individuals with mild cognitive impairment and 19 clinically normal elderly. Backward elimination multivariate linear regression was used to evaluate the cross-sectional relationship between scores on the Apathy Evaluation Scale and thickness of several cortical regions and covariates. Lower inferior temporal cortical thickness was predictive of greater apathy. Greater anterior cingulate cortical thickness was also predictive of greater apathy, suggesting an underlying reactive process. PMID:25716491

  8. Cognitive Correlates of Basal Forebrain Atrophy and Associated Cortical Hypometabolism in Mild Cognitive Impairment.

    PubMed

    Grothe, Michel J; Heinsen, Helmut; Amaro, Edson; Grinberg, Lea T; Teipel, Stefan J

    2016-06-01

    Degeneration of basal forebrain (BF) cholinergic nuclei is associated with cognitive decline, and this effect is believed to be mediated by neuronal dysfunction in the denervated cortical areas. MRI-based measurements of BF atrophy are increasingly being used as in vivo surrogate markers for cholinergic degeneration, but the functional implications of reductions in BF volume are not well understood. We used high-resolution MRI, fluorodeoxyglucose-positron emission tomography (PET), and neuropsychological test data of 132 subjects with mild cognitive impairment (MCI) and 177 cognitively normal controls to determine associations between BF atrophy, cortical hypometabolism, and cognitive deficits. BF atrophy in MCI correlated with both impaired memory function and attentional control deficits, whereas hippocampus volume was more specifically associated with memory deficits. BF atrophy was also associated with widespread cortical hypometabolism, and path analytic models indicated that hypometabolism in domain-specific cortical networks mediated the association between BF volume and cognitive dysfunction. The presence of cortical amyloid pathology, as assessed using AV45-PET, did not significantly interact with the observed associations. These data underline the potential of multimodal imaging markers to study structure-function-cognition relationships in the living human brain and provide important in vivo evidence for an involvement of the human BF in cortical activity and cognitive function. PMID:25840425

  9. 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…

  10. 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)

  11. Increasing a Functional Skill for an Adolescent with Cortical Visual Impairment.

    ERIC Educational Resources Information Center

    Farrenkopf, C.; McGregor, D.; Nes, S. L.; Koenig, A. J.

    1997-01-01

    The effectiveness of two treatment strategies (verbal prompts and a physical prompt) on the independent drinking skills of a 17-year-old girl with cortical visual impairment was investigated. Results found that the physical prompt was highly effective in promoting the target behavior, whereas verbal prompts were less effective. (Author/CR)

  12. 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.

  13. 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…

  14. Cortical Visual Impairment in Children: Presentation Intervention, and Prognosis in Educational Settings

    ERIC Educational Resources Information Center

    Swift, Suzanne H.; Davidson, Roseanna C.; Weems, Linda J.

    2008-01-01

    Children with cortical visual impairment (CVI) exhibit distinct visual behaviors which are often misinterpreted. As the incidence of CVI is on the rise, this has subsequently caused an increased need for identification and intervention with these children from teaching and therapy service providers. Distinguishing children with CVI from children…

  15. 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

  16. 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

  17. 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. PMID:26162722

  18. Modelling suicide risk in later life.

    PubMed

    Lo, C F; Kwok, Cordelia M Y

    2006-08-01

    Affective disorder is generally regarded as the prominent risk factor for suicide in the old age population. Despite the large number of empirical studies available in the literature, there is no attempt in modelling the dynamics of an individual's level of suicide risk theoretically yet. In particular, a dynamic model which can simulate the time evolution of an individual's level of risk for suicide and provide quantitative estimates of the probability of suicide risk is still lacking. In the present study we apply the contingent claims analysis of credit risk modelling in the field of quantitative finance to derive a theoretical stochastic model for estimation of the probability of suicide risk in later life in terms of a signalling index of affective disorder. Our model is based upon the hypothesis that the current state of affective disorder of a patient can be represented by a signalling index and exhibits stochastic movement and that a threshold of affective disorder, which signifies the occurrence of suicide, exists. According to the numerical results, the implications of our model are consistent with the clinical findings. Hence, we believe that such a dynamic model will be essential to the design of effective suicide prevention strategies in the target population of older adults, especially in the primary care setting. PMID:16797044

  19. Acidosis and alkalosis impair brain functions through weakening spike encoding at cortical GABAergic neurons.

    PubMed

    Song, Rongrong; Zhang, Liming; Yang, Zichao; Tian, Xiaoyan

    2011-05-15

    Acidosis and alkalosis, associated with metabolic disorders, lead to the pathological changes of cognition and behaviors in clinical practices of neurology and psychology. Cellular mechanisms for these functional disorders in the central nervous system remain unclear. We have investigated the influences of acidosis and alkalosis on the functions of cortical GABAergic neurons. Both acidosis and alkalosis impair the ability of encoding sequential spikes at these GABAergic neurons. The impairments of their spiking are associated with the increases of refractory periods, threshold potential and afterhyperpolarization. Our studies reveal that acidosis and alkalosis impair cortical GABAergic neurons and in turn deteriorate brain functions, in which their final targets may be voltage-gated channels of sodium and potassium. PMID:21353681

  20. Coping with anxiety in later life.

    PubMed

    Frazier, Leslie D; Waid, Lisa D; Fincke, Candy

    2002-12-01

    The goal of this study was to determine how older adults cope with three forms of anxiety, and potential avenues for applied interventions. Although the findings shed light on some interesting findings with potential psychosocial applications, several limitations need to be noted. First, this study was based on two assumptions. The assumption, based on earlier work (Carver et al., 1989; Lazarus & Folkman, 1984; Zeidner & Saklofske, 1996), that certain coping strategies are more effective than others, and an assumption of the direction of influence in which anxiety is a precursor of coping strategies. Because this was an exploratory study, the research questions did not directly test these assumptions. Second, this study is correlational in nature. Therefore, conclusions cannot be drawn about the causality of these associations. Third, as with any self-report data and self-selected sample, one needs to interpret the findings with caution. Similarly, for the purposes of the study, a non-clinical sample of older adults was examined using three distinct conceptualizations of anxiety. Suggestions for future research include: Replication of this study using a multidimensional measure of anxiety appropriate for clinical samples. A longitudinal replication of this study identifying patterns of coping that facilitate adjustment over time. Finally, a more general purpose of this study was to focus attention on a neglected issue in gerontology--the experience of anxietY in later life (Frazier & Waid, 1999; Gatz, 1995; Rabins, 1992; Shamoian, 1991; Sheikh, 1992; Smyer, 1995; Stanley & Beck, 1998), and, most importantly, the role of gerontological nurses in early assessment and intervention for successful treatment of anxiety in older adults. PMID:12567825

  1. 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

  2. Impaired consciousness in temporal lobe seizures: role of cortical slow activity

    PubMed Central

    Englot, Dario J.; Yang, Li; Hamid, Hamada; Danielson, Nathan; Bai, Xiaoxiao; Marfeo, Anthony; Yu, Lissa; Gordon, Aliza; Purcaro, Michael J.; Motelow, Joshua E.; Agarwal, Ravi; Ellens, Damien J.; Golomb, Julie D.; Shamy, Michel C. F.; Zhang, Heping; Carlson, Chad; Doyle, Werner; Devinsky, Orrin; Vives, Kenneth; Spencer, Dennis D.; Spencer, Susan S.; Schevon, Catherine; Zaveri, Hitten P.

    2010-01-01

    Impaired consciousness requires altered cortical function. This can occur either directly from disorders that impair widespread bilateral regions of the cortex or indirectly through effects on subcortical arousal systems. It has therefore long been puzzling why focal temporal lobe seizures so often impair consciousness. Early work suggested that altered consciousness may occur with bilateral or dominant temporal lobe seizure involvement. However, other bilateral temporal lobe disorders do not impair consciousness. More recent work supports a ‘network inhibition hypothesis’ in which temporal lobe seizures disrupt brainstem–diencephalic arousal systems, leading indirectly to depressed cortical function and impaired consciousness. Indeed, prior studies show subcortical involvement in temporal lobe seizures and bilateral frontoparietal slow wave activity on intracranial electroencephalography. However, the relationships between frontoparietal slow waves and impaired consciousness and between cortical slowing and fast seizure activity have not been directly investigated. We analysed intracranial electroencephalography recordings during 63 partial seizures in 26 patients with surgically confirmed mesial temporal lobe epilepsy. Behavioural responsiveness was determined based on blinded review of video during seizures and classified as impaired (complex-partial seizures) or unimpaired (simple-partial seizures). We observed significantly increased delta-range 1–2 Hz slow wave activity in the bilateral frontal and parietal neocortices during complex-partial compared with simple-partial seizures. In addition, we confirmed prior work suggesting that propagation of unilateral mesial temporal fast seizure activity to the bilateral temporal lobes was significantly greater in complex-partial than in simple-partial seizures. Interestingly, we found that the signal power of frontoparietal slow wave activity was significantly correlated with the temporal lobe fast seizure

  3. Impaired consciousness in temporal lobe seizures: role of cortical slow activity.

    PubMed

    Englot, Dario J; Yang, Li; Hamid, Hamada; Danielson, Nathan; Bai, Xiaoxiao; Marfeo, Anthony; Yu, Lissa; Gordon, Aliza; Purcaro, Michael J; Motelow, Joshua E; Agarwal, Ravi; Ellens, Damien J; Golomb, Julie D; Shamy, Michel C F; Zhang, Heping; Carlson, Chad; Doyle, Werner; Devinsky, Orrin; Vives, Kenneth; Spencer, Dennis D; Spencer, Susan S; Schevon, Catherine; Zaveri, Hitten P; Blumenfeld, Hal

    2010-12-01

    Impaired consciousness requires altered cortical function. This can occur either directly from disorders that impair widespread bilateral regions of the cortex or indirectly through effects on subcortical arousal systems. It has therefore long been puzzling why focal temporal lobe seizures so often impair consciousness. Early work suggested that altered consciousness may occur with bilateral or dominant temporal lobe seizure involvement. However, other bilateral temporal lobe disorders do not impair consciousness. More recent work supports a 'network inhibition hypothesis' in which temporal lobe seizures disrupt brainstem-diencephalic arousal systems, leading indirectly to depressed cortical function and impaired consciousness. Indeed, prior studies show subcortical involvement in temporal lobe seizures and bilateral frontoparietal slow wave activity on intracranial electroencephalography. However, the relationships between frontoparietal slow waves and impaired consciousness and between cortical slowing and fast seizure activity have not been directly investigated. We analysed intracranial electroencephalography recordings during 63 partial seizures in 26 patients with surgically confirmed mesial temporal lobe epilepsy. Behavioural responsiveness was determined based on blinded review of video during seizures and classified as impaired (complex-partial seizures) or unimpaired (simple-partial seizures). We observed significantly increased delta-range 1-2 Hz slow wave activity in the bilateral frontal and parietal neocortices during complex-partial compared with simple-partial seizures. In addition, we confirmed prior work suggesting that propagation of unilateral mesial temporal fast seizure activity to the bilateral temporal lobes was significantly greater in complex-partial than in simple-partial seizures. Interestingly, we found that the signal power of frontoparietal slow wave activity was significantly correlated with the temporal lobe fast seizure activity in

  4. The Non-Benzodiazepine Hypnotic Zolpidem Impairs Sleep-Dependent Cortical Plasticity

    PubMed Central

    Seibt, Julie; Aton, Sara J.; Jha, Sushil K.; Coleman, Tammi; Dumoulin, Michelle C.; Frank, Marcos G.

    2008-01-01

    Study Objectives: The effects of hypnotics on sleep-dependent brain plasticity are unknown. We have shown that sleep enhances a canonical model of in vivo cortical plasticity, known as ocular dominance plasticity (ODP). We investigated the effects of 3 different classes of hypnotics on ODP. Design: Polysomnographic recordings were performed during the entire experiment (20 h). After a baseline sleep/wake recording (6 h), cats received 6 h of monocular deprivation (MD) followed by an i.p. injection of triazolam (1–10 mg/kg i.p.), zolpidem (10 mg/kg i.p.), ramelteon (0.1–1 mg/kg i.p.), or vehicle (DMSO i.p.). They were then allowed to sleep ad lib for 8 h, after which they were prepared for optical imaging of intrinsic cortical signals and single-unit electrophysiology. Setting: Basic neurophysiology laboratory Patients or Participants: Cats (male and female) in the critical period of visual development (postnatal days 28–41) Interventions: N/A Measurements and Results: Zolpidem reduced cortical plasticity by ∼50% as assessed with optical imaging of intrinsic cortical signals. This was not due to abnormal sleep architecture because triazolam, which perturbed sleep architecture and sleep EEGs more profoundly than zolpidem, had no effect on plasticity. Ramelteon minimally altered sleep and had no effect on ODP. Conclusions: Our findings demonstrate that alterations in sleep architecture do not necessarily lead to impairments in sleep function. Conversely, hypnotics that produce more “physiological” sleep based on polysomnography may impair critical brain processes, depending on their pharmacology. Citation: Seibt J; Aton SJ; Jha SK; Coleman T; Dumoulin MC; Frank MG. The non-benzodiazepine hypnotic zolpidem impairs sleep-dependent cortical plasticity. SLEEP 2008;31(10):1381–1391. PMID:18853935

  5. Pronounced impairment of everyday skills and self-care in posterior cortical atrophy.

    PubMed

    Shakespeare, Timothy J; Yong, Keir X X; Foxe, David; Hodges, John; Crutch, Sebastian J

    2015-01-01

    Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by progressive visual dysfunction and parietal, occipital, and occipitotemporal atrophy. The aim of this study was to compare the impact of PCA and typical Alzheimer's disease (tAD) on everyday functional abilities and neuropsychiatric status. The Cambridge Behavioural Inventory-Revised was given to carers of 32 PCA and 71 tAD patients. PCA patients showed significantly greater impairment in everyday skills and self-care while the tAD group showed greater impairment in aspects of memory and orientation, and motivation. We suggest that PCA poses specific challenges for those caring for people affected by the condition. PMID:25096622

  6. 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

  7. 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

  8. Decreased White Matter Integrity in Neuropsychologically-Defined Mild Cognitive Impairment is Independent of Cortical Thinning

    PubMed Central

    Stricker, Nikki H.; Salat, David H.; Foley, Jessica M.; Zink, Tyler A.; Kellison, Ida L.; McFarland, Craig P.; Grande, Laura J.; McGlinchey, Regina E.; Milberg, William P.; Leritz, Elizabeth C.

    2014-01-01

    Improved understanding of the pattern of white matter changes in early and prodromal Alzheimer's disease (AD) states such as Mild Cognitive Impairment (MCI) is necessary to support earlier preclinical detection of AD, and debate remains whether white matter changes in MCI are secondary to gray matter changes. We applied neuropsychologically-based MCI criteria to a sample of normally aging older adults; 32 participants met criteria for MCI and 81 participants were classified as normal control (NC) subjects. Whole-head high resolution T1 and DTI scans were completed. Tract-Based Spatial Statistics was applied and a priori selected ROIs were extracted. Hippocampal volume and cortical thickness averaged across regions with known vulnerability to AD were derived. Controlling for cortical thickness, the MCI group showed decreased average FA and decreased FA in parietal white matter and in white matter underlying the entorhinal and posterior cingulate cortices relative to the NC group. Statistically controlling for cortical thickness, medial temporal FA was related to memory and parietal FA was related to executive functioning. These results provide further support for the potential role of white matter integrity as an early biomarker for individuals at risk for AD and highlight that changes in white matter may be independent of gray matter changes. PMID:23809097

  9. 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

  10. 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

  11. Reduced Cortical Activity Impairs Development and Plasticity after Neonatal Hypoxia Ischemia

    PubMed Central

    Ranasinghe, Sumudu; Or, Grace; Wang, Eric Y.; Ievins, Aiva; McLean, Merritt A.; Niell, Cristopher M.; Chau, Vann; Wong, Peter K. H.; Glass, Hannah C.; Sullivan, Joseph

    2015-01-01

    Survivors of preterm birth are at high risk of pervasive cognitive and learning impairments, suggesting disrupted early brain development. The limits of viability for preterm birth encompass the third trimester of pregnancy, a “precritical period” of activity-dependent development characterized by the onset of spontaneous and evoked patterned electrical activity that drives neuronal maturation and formation of cortical circuits. Reduced background activity on electroencephalogram (EEG) is a sensitive marker of brain injury in human preterm infants that predicts poor neurodevelopmental outcome. We studied a rodent model of very early hypoxic–ischemic brain injury to investigate effects of injury on both general background and specific patterns of cortical activity measured with EEG. EEG background activity is depressed transiently after moderate hypoxia–ischemia with associated loss of spindle bursts. Depressed activity, in turn, is associated with delayed expression of glutamate receptor subunits and transporters. Cortical pyramidal neurons show reduced dendrite development and spine formation. Complementing previous observations in this model of impaired visual cortical plasticity, we find reduced somatosensory whisker barrel plasticity. Finally, EEG recordings from human premature newborns with brain injury demonstrate similar depressed background activity and loss of bursts in the spindle frequency band. Together, these findings suggest that abnormal development after early brain injury may result in part from disruption of specific forms of brain activity necessary for activity-dependent circuit development. SIGNIFICANCE STATEMENT Preterm birth and term birth asphyxia result in brain injury from inadequate oxygen delivery and constitute a major and growing worldwide health problem. Poor outcomes are noted in a majority of very premature (<25 weeks gestation) newborns, resulting in death or life-long morbidity with motor, sensory, learning, behavioral

  12. 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

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

    PubMed

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

    2016-06-01

    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

  14. Lesions to Primary Sensory and Posterior Parietal Cortices Impair Recovery from Hand Paresis after Stroke

    PubMed Central

    Abela, Eugenio; Missimer, John; Wiest, Roland; Federspiel, Andrea; Hess, Christian; Sturzenegger, Matthias; Weder, Bruno

    2012-01-01

    Background Neuroanatomical determinants of motor skill recovery after stroke are still poorly understood. Although lesion load onto the corticospinal tract is known to affect recovery, less is known about the effect of lesions to cortical sensorimotor areas. Here, we test the hypothesis that lesions of somatosensory cortices interfere with the capacity to recover motor skills after stroke. Methods Standardized tests of motor skill and somatosensory functions were acquired longitudinally over nine months in 29 patients with stroke to the pre- and postcentral gyrus, including adjacent areas of the frontal, parietal and insular cortices. We derived the recovery trajectories of each patient for five motor subtest using least-squares curve fitting and objective model selection procedures for linear and exponential models. Patients were classified into subgroups based on their motor recovery models. Lesions were mapped onto diffusion weighted imaging scans and normalized into stereotaxic space using cost-function masking. To identify critical neuranatomical regions, voxel-wise subtractions were calculated between subgroup lesion maps. A probabilistic cytoarchitectonic atlas was used to quantify of lesion extent and location. Results Twenty-three patients with moderate to severe initial deficits showed exponential recovery trajectories for motor subtests that relied on precise distal movements. Those that retained a chronic motor deficit had lesions that extended to the center of the somatosensory cortex (area 2) and the intraparietal sulcus (areas hIP1, hIP2). Impaired recovery outcome correlated with lesion extent on this areas and somatosensory performance. The rate of recovery, however, depended on the lesion load onto the primary motor cortex (areas 4a, 4p). Conclusions Our findings support a critical role of uni-and multimodal somatosensory cortices in motor skill recovery. Whereas lesions to these areas influence recovery outcome, lesions to the primary motor

  15. 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

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

    PubMed

    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

  17. 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…

  18. 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…

  19. 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…

  20. 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

  1. Decisional impairments in cocaine addiction, reward bias, and cortical oscillation "unbalance".

    PubMed

    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

  2. Impaired plasticity of cortical dendritic spines in P301S tau transgenic mice

    PubMed Central

    2013-01-01

    Background Illuminating the role of the microtubule-associated protein tau in neurodegenerative diseases is of increasing importance, supported by recent studies establishing novel functions of tau in synaptic signalling and cytoskeletal organization. In severe dementias like Alzheimer’s disease (AD), synaptic failure and cognitive decline correlate best with the grade of tau-pathology. To address synaptic alterations in tauopathies, we analyzed the effects of mutant tau expression on excitatory postsynapses in vivo. Results Here we followed the fate of single dendritic spines in the neocortex of a tauopathy mouse model, expressing human P301S mutated tau, for a period of two weeks. We observed a continuous decrease in spine density during disease progression, which we could ascribe to a diminished fraction of gained spines. Remaining spines were enlarged and elongated, thus providing evidence for morphological reorganization in compensation for synaptic dysfunction. Remarkably, loss of dendritic spines in cortical pyramidal neurons occurred in the absence of neurofibrillary tangles (NFTs). Therefore, we consider prefibrillar tau species as causative for the observed impairment in spine plasticity. Conclusions Dendritic spine plasticity and morphology are altered in layer V cortical neurons of P301S tau transgenic mice in vivo. This does not coincide with the detection of hyperphosphorylated tau in dendritic spines. PMID:24344647

  3. 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

  4. Reduced Cortical Complexity in Children with Prader-Willi Syndrome and Its Association with Cognitive Impairment and Developmental Delay

    PubMed Central

    Lukoshe, Akvile; Hokken-Koelega, Anita C.; van der Lugt, Aad; White, Tonya

    2014-01-01

    Background Prader-Willi Syndrome (PWS) is a complex neurogenetic disorder with symptoms involving not only hypothalamic, but also a global, central nervous system dysfunction. Previously, qualitative studies reported polymicrogyria in adults with PWS. However, there have been no quantitative neuroimaging studies of cortical morphology in PWS and no studies to date in children with PWS. Thus, our aim was to investigate and quantify cortical complexity in children with PWS compared to healthy controls. In addition, we investigated differences between genetic subtypes of PWS and the relationship between cortical complexity and intelligence within the PWS group. Methods High-resolution structural magnetic resonance images were acquired in 24 children with genetically confirmed PWS (12 carrying a deletion (DEL), 12 with maternal uniparental disomy (mUPD)) and 11 age- and sex-matched typically developing siblings as healthy controls. Local gyrification index (lGI) was obtained using the FreeSurfer software suite. Results Four large clusters, two in each hemisphere, comprising frontal, parietal and temporal lobes, had lower lGI in children with PWS, compared to healthy controls. Clusters with lower lGI also had significantly lower cortical surface area in children with PWS. No differences in cortical thickness of the clusters were found between the PWS and healthy controls. lGI correlated significantly with cortical surface area, but not with cortical thickness. Within the PWS group, lGI in both hemispheres correlated with Total IQ and Verbal IQ, but not with Performance IQ. Children with mUPD, compared to children with DEL, had two small clusters with lower lGI in the right hemisphere. lGI of these clusters correlated with cortical surface area, but not with cortical thickness or IQ. Conclusions These results suggest that lower cortical complexity in children with PWS partially underlies cognitive impairment and developmental delay, probably due to alterations in gene

  5. 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

  6. Impaired spare respiratory capacity in cortical synaptosomes from Sod2 null mice

    PubMed Central

    Flynn, James M.; Choi, Sung W.; Day, Nicholas U.; Gerencser, Akos A.; Hubbard, Alan; Melov, Simon

    2011-01-01

    Pre-synaptic nerve terminals require high levels of ATP for the maintenance of synaptic function. Failure of synaptic mitochondria to generate adequate ATP has been implicated as a causative event preceding loss of synaptic networks in neurodegenerative disease. Endogenous oxidative stress has often been postulated as an etiological basis for this pathology, but has been difficult to test in vivo. Inactivation of the superoxide dismutase gene (Sod2) encoding the chief defense enzyme against mitochondrial superoxide radicals results in neonatal lethality. However, intervention with an SOD mimetic extends the lifespan of this model, and uncovers a neurodegenerative phenotype providing a unique model for the examination of in vivo oxidative stress. We present here studies on synaptic termini isolated from the frontal cortex of Sod2 null mice demonstrating impaired bioenergetic function as a result of mitochondrial oxidative stress. Cortical synaptosomes from Sod2 null mice demonstrate a severe decline in mitochondrial spare respiratory capacity to physiological demand induced by mitochondrial respiratory chain uncoupling with FCCP or plasma membrane depolarization induced by 4-aminopyridine treatment. However, Sod2 null animals compensate for impaired oxidative metabolism in part by Pasteur effect allowing for normal neurotransmitter release at the synapse, setting up a potentially detrimental energetic paradigm. The results of this study demonstrate that high throughput respirometry is a facile method for analyzing specific regions of the brain in transgenic models, and can uncover bioenergetic deficits in subcellular regions due to endogenous oxidative stress. PMID:21215798

  7. Shaping the aging brain: role of auditory input patterns in the emergence of auditory cortical impairments

    PubMed Central

    Kamal, Brishna; Holman, Constance; de Villers-Sidani, Etienne

    2013-01-01

    Age-related impairments in the primary auditory cortex (A1) include poor tuning selectivity, neural desynchronization, and degraded responses to low-probability sounds. These changes have been largely attributed to reduced inhibition in the aged brain, and are thought to contribute to substantial hearing impairment in both humans and animals. Since many of these changes can be partially reversed with auditory training, it has been speculated that they might not be purely degenerative, but might rather represent negative plastic adjustments to noisy or distorted auditory signals reaching the brain. To test this hypothesis, we examined the impact of exposing young adult rats to 8 weeks of low-grade broadband noise on several aspects of A1 function and structure. We then characterized the same A1 elements in aging rats for comparison. We found that the impact of noise exposure on A1 tuning selectivity, temporal processing of auditory signal and responses to oddball tones was almost indistinguishable from the effect of natural aging. Moreover, noise exposure resulted in a reduction in the population of parvalbumin inhibitory interneurons and cortical myelin as previously documented in the aged group. Most of these changes reversed after returning the rats to a quiet environment. These results support the hypothesis that age-related changes in A1 have a strong activity-dependent component and indicate that the presence or absence of clear auditory input patterns might be a key factor in sustaining adult A1 function. PMID:24062649

  8. Spousal caregiving in later life: an objective and subjective career.

    PubMed

    Ross, M M

    1991-01-01

    During later life, as a consequence of the deteriorating health of husbands, numerous women experience a period of spousal caregiving that can be considered a new phase in their caregiving career. This phase, which often precedes widowhood, is one that has been relatively neglected by researchers. In this article, the concepts of objective and subjective career (Hughes, 1971) are used as orienting concepts to examine the phenomenon of spousal caregiving in later life. Objectively, the caregiving career is seen as an age-related, gender-specific, and role-contingent phenomenon. The subjective career is seen as the meaning and purposes attributed to complex and extensive responsibilities and activities of caregiving and their potentially serious consequences for health and well-being. PMID:1989956

  9. 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…

  10. Cortical source multivariate EEG synchronization analysis on amnestic mild cognitive impairment in type 2 diabetes.

    PubMed

    Cui, Dong; Liu, Jing; 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

  11. Sleep deficits in mild cognitive impairment are related to increased levels of plasma amyloid-β and cortical thinning.

    PubMed

    Sanchez-Espinosa, Mayely P; Atienza, Mercedes; Cantero, Jose L

    2014-09-01

    Evidence suggests that amyloid-beta (Aβ) depositions parallel sleep deficits in Alzheimer's disease (AD). However, it remains unknown whether impaired sleep and changes in plasma Aβ levels are related in amnestic mild cognitive impairment (aMCI) subjects, and whether both markers are further associated with cortical thinning in canonical AD regions. To jointly address this issue, we investigated relationships between changes in physiological sleep and plasma Aβ concentrations in 21 healthy old (HO) adults and 21 aMCI subjects, and further assessed whether these two factors were associated with cortical loss in each group. aMCI, but not HO subjects, showed significant relationships between disrupted slow-wave sleep (SWS) and increased plasma levels of Aβ42. We also found that shortened rapid-eye movement (REM) sleep in aMCI correlated with thinning of the posterior cingulate, precuneus, and postcentral gyrus; whereas higher levels of Aβ40 and Aβ42 accounted for grey matter (GM) loss of posterior cingulate and entorhinal cortex, respectively. These results support preliminary relationships between Aβ burden and altered sleep physiology observed in animal models of AD amyloidosis, and provide precise cortical correlates of these changes in older adults with aMCI. Taken together, these findings open new research avenues on the combined role of sleep, peripheral Aβ levels and cortical integrity in tracking the progression from normal aging to early neurodegeneration. PMID:24845621

  12. Differences in cortical thickness in healthy controls, subjects with mild cognitive impairment, and Alzheimer's disease patients: a longitudinal study.

    PubMed

    Julkunen, Valtteri; Niskanen, Eini; Koikkalainen, Juha; Herukka, Sanna-Kaisa; Pihlajamäki, Maija; Hallikainen, Merja; Kivipelto, Miia; Muehlboeck, Sebastian; Evans, Alan C; Vanninen, Ritva; Hilkka Soininen

    2010-01-01

    In this study, we analyzed differences in cortical thickness (CTH) between healthy controls (HC), subjects with stable mild cognitive impairment (S-MCI), progressive MCI (P-MCI), and Alzheimer's disease (AD), and assessed correlations between CHT and clinical disease severity, education, and apolipoprotein E4 (APOE) genotype. Automated CTH analysis was applied to baseline high-resolution structural MR images of 145 subjects with a maximum followup time of 7.4 years pooled from population-based study databases held in the University of Kuopio. Statistical differences in CTH between study groups and significant correlations between CTH and clinical and demographic factors were assessed and displayed on a cortical surface model. Compared to HC group (n = 26), the AD (n = 21) group displayed significantly reduced CTH in several areas of frontal and temporal cortices of the right hemisphere. Higher education and lower MMSE scores were correlated with reduced CTH in the AD group, whereas no significant correlation was found between CDR-SB scores or APOE genotype and CTH. The P-MCI group demonstrated significantly reduced CTH compared to S-MCI in frontal, temporal and parietal cortices even after statistically adjusting for all confounding variables. Ultimately, analysis of CTH can be used to detect cortical thinning in subjects with progressive MCI several years before conversion and clinical diagnosis of AD dementia, irrespective of their cognitive performance, education level, or APOE genotype. PMID:21504134

  13. 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

  14. 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

  15. 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

  16. Dyslexia and language impairment associated genetic markers influence cortical thickness and white matter in typically developing children.

    PubMed

    Eicher, John D; Montgomery, Angela M; Akshoomoff, Natacha; Amaral, David G; Bloss, Cinnamon S; Libiger, Ondrej; Schork, Nicholas J; Darst, Burcu F; Casey, B J; Chang, Linda; Ernst, Thomas; Frazier, Jean; Kaufmann, Walter E; Keating, Brian; Kenet, Tal; Kennedy, David; Mostofsky, Stewart; Murray, Sarah S; Sowell, Elizabeth R; Bartsch, Hauke; Kuperman, Joshua M; Brown, Timothy T; Hagler, Donald J; Dale, Anders M; Jernigan, Terry L; Gruen, Jeffrey R

    2016-03-01

    Dyslexia and language impairment (LI) are complex traits with substantial genetic components. We recently completed an association scan of the DYX2 locus, where we observed associations of markers in DCDC2, KIAA0319, ACOT13, and FAM65B with reading-, language-, and IQ-related traits. Additionally, the effects of reading-associated DYX3 markers were recently characterized using structural neuroimaging techniques. Here, we assessed the neuroimaging implications of associated DYX2 and DYX3 markers, using cortical volume, cortical thickness, and fractional anisotropy. To accomplish this, we examined eight DYX2 and three DYX3 markers in 332 subjects in the Pediatrics Imaging Neurocognition Genetics study. Imaging-genetic associations were examined by multiple linear regression, testing for influence of genotype on neuroimaging. Markers in DYX2 genes KIAA0319 and FAM65B were associated with cortical thickness in the left orbitofrontal region and global fractional anisotropy, respectively. KIAA0319 and ACOT13 were suggestively associated with overall fractional anisotropy and left pars opercularis cortical thickness, respectively. DYX3 markers showed suggestive associations with cortical thickness and volume measures in temporal regions. Notably, we did not replicate association of DYX3 markers with hippocampal measures. In summary, we performed a neuroimaging follow-up of reading-, language-, and IQ-associated DYX2 and DYX3 markers. DYX2 associations with cortical thickness may reflect variations in their role in neuronal migration. Furthermore, our findings complement gene expression and imaging studies implicating DYX3 markers in temporal regions. These studies offer insight into where and how DYX2 and DYX3 risk variants may influence neuroimaging traits. Future studies should further connect the pathways to risk variants associated with neuroimaging/neurocognitive outcomes. PMID:25953057

  17. 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

  18. 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

  19. Impaired development and competitive refinement of the cortical frequency map in tumor necrosis factor-α-deficient mice.

    PubMed

    Yang, Sungchil; Zhang, Li S; Gibboni, Robert; Weiner, Benjamin; Bao, Shaowen

    2014-07-01

    Early experience shapes sensory representations in a critical period of heightened plasticity. This adaptive process is thought to involve both Hebbian and homeostatic synaptic plasticity. Although Hebbian plasticity has been investigated as a mechanism for cortical map reorganization, less is known about the contribution of homeostatic plasticity. We investigated the role of homeostatic synaptic plasticity in the development and refinement of frequency representations in the primary auditory cortex using the tumor necrosis factor-α (TNF-α) knockout (KO), a mutant mouse with impaired homeostatic but normal Hebbian plasticity. Our results indicate that these mice develop weaker tonal responses and incomplete frequency representations. Rearing in a single-frequency revealed a normal expansion of cortical representations in KO mice. However, TNF-α KOs lacked homeostatic adjustments of cortical responses following exposure to multiple frequencies. Specifically, while this sensory over-stimulation resulted in competitive refinement of frequency tuning in wild-type controls, it broadened frequency tuning in TNF-α KOs. Our results suggest that homeostatic plasticity plays an important role in gain control and competitive interaction in sensory cortical development. PMID:23448874

  20. Cortical phase changes measured using 7-T MRI in subjects with subjective cognitive impairment, and their association with cognitive function.

    PubMed

    van Rooden, Sanneke; Buijs, Mathijs; van Vliet, Marjolein E; Versluis, Maarten J; Webb, Andrew G; Oleksik, Ania M; van de Wiel, Lotte; Middelkoop, Huub A M; Blauw, Gerard Jan; Weverling-Rynsburger, Annelies W E; Goos, Jeroen D C; van der Flier, Wiesje M; Koene, Ted; Scheltens, Philip; Barkhof, Frederik; van de Rest, Ondine; Slagboom, P Eline; van Buchem, Mark A; van der Grond, Jeroen

    2016-09-01

    Studies have suggested that, in subjects with subjective cognitive impairment (SCI), Alzheimer's disease (AD)-like changes may occur in the brain. Recently, an in vivo study has indicated the potential of ultra-high-field MRI to visualize amyloid-beta (Aβ)-associated changes in the cortex in patients with AD, manifested by a phase shift on T2 *-weighted MRI scans. The main aim of this study was to investigate whether cortical phase shifts on T2 *-weighted images at 7 T in subjects with SCI can be detected, possibly implicating the deposition of Aβ plaques and associated iron. Cognitive tests and T2 *-weighted scans using a 7-T MRI system were performed in 28 patients with AD, 18 subjects with SCI and 27 healthy controls (HCs). Cortical phase shifts were measured. Univariate general linear modeling and linear regression analysis were used to assess the association between diagnosis and cortical phase shift, and between cortical phase shift and the different neuropsychological tests, adjusted for age and gender. The phase shift (mean, 1.19; range, 1.00-1.35) of the entire cortex in AD was higher than in both SCI (mean, 0.85; range, 0.73-0.99; p < 0.001) and HC (mean, 0.94; range, 0.79-1.10; p < 0.001). No AD-like changes, e.g. increased cortical phase shifts, were found in subjects with SCI compared with HCs. In SCI, a significant association was found between memory function (Wechsler Memory Scale, WMS) and cortical phase shift (β = -0.544, p = 0.007). The major finding of this study is that, in subjects with SCI, an increased cortical phase shift measured at high field is associated with a poorer memory performance, although, as a group, subjects with SCI do not show an increased phase shift compared with HCs. This increased cortical phase shift related to memory performance may contribute to the understanding of SCI as it is still unclear whether SCI is a sign of pre-clinical AD. Copyright © 2014 John Wiley & Sons, Ltd. PMID:25522735

  1. Impairment of learning the voluntary control of posture in patients with cortical lesions of different locations: the cortical mechanisms of pose regulation.

    PubMed

    Ustinova, K I; Chernikova, L A; Ioffe, M E; Sliva, S S

    2001-01-01

    The process of learning to produce voluntary changes in the position of the center of pressures using biological feedback was studied by stabilography in patients with hemipareses due to cerebrovascular lesions in the zone supplied by the middle cerebral artery. There were significant impairments to learning in all groups of patients, who had lesions in different sites, demonstrating that cortical mechanisms are involved in learning to control posture voluntarily. These studies showed that patients with lesions in the right hemisphere had rather greater deficits in performing the task than those with lesions in the left hemisphere. There were significant differences in the initial deficit in performing the task on the first day of training depending on the side of the lesion. All groups of patients differed from healthy subjects in that significant learning occurred only at the initial stages of training (the first five days). Learning at the initial stage in patients with concomitant lesions of the parietal-temporal area and with combined lesions with motor, premotor, and parietal-temporal involvement was significantly worse and the level of task performance at the end of the initial stage was significantly worse than in patient with local lesions of the motor cortex. The level of learning was independent of the severity of the motor deficit (paresis, spasticity), but was associated with the severity of impairment of the proprioceptive sense and the severity of disruption to the upright posture (asymmetry in the distribution of support pressures, amplitude of variation in the position of the center of pressures). The learning process had positive effects on the severity of motor impairment and on the asymmetry of the distribution of support pressures in the standing posture. Reorganization of posture during bodily movements occurred mainly because of impairment to the developed "non-use" stereotype of the paralyzed lower limb. PMID:11430569

  2. 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

  3. Impaired adrenergic-mediated plasticity of prefrontal cortical glutamate synapses in rats with developmental disruption of the ventral hippocampus.

    PubMed

    Bhardwaj, Sanjeev K; Tse, Yiu Chung; Ryan, Richard; Wong, Tak Pan; Srivastava, Lalit K

    2014-12-01

    Neonatal ventral hippocampus (nVH) lesion in rats is a useful model to study developmental origins of adult cognitive deficits and certain features of schizophrenia. nVH lesion-induced reorganization of excitatory and inhibitory neurotransmissions within prefrontal cortical (PFC) circuits is widely believed to be responsible for many of the behavioral abnormalities in these animals. Here we provide evidence that development of an aberrant medial PFC (mPFC) α-1 adrenergic receptor (α-1AR) function following neonatal lesion markedly affects glutamatergic synaptic plasticity within PFC microcircuits and contributes to PFC-related behavior abnormalities. Using whole-cell patch-clamp recording, we report that norepinephrine-induced α-1AR-dependent long-term depression (LTD) in a subset of cortico-cortical glutamatergic inputs is strikingly diminished in mPFC slices from nVH-lesioned rats. The LTD impairment occurs in conjunction with completely blunted α-1AR signaling through extracellular signal-regulated kinase 1/2. These α-1AR abnormalities have functional significance in a mPFC-related function, that is, extinction of conditioned fear memory. Post-pubertal animals with nVH lesion show significant resistance to extinction of fear by repeated presentations of the conditioned tone stimulus. mPFC infusion of an α-1AR antagonist (benoxathian) or LTD blocking peptide (Tat-GluR23Y) impaired fear extinction in sham controls, but had no significant effect in the lesioned animals. The data suggest that impaired α-1 adrenergic regulation of cortical glutamatergic synaptic plasticity may be an important mechanism in cognitive dysfunctions reported in neurodevelopmental psychiatric disorders. PMID:24917197

  4. Childbearing history, later-life health, and mortality in Germany.

    PubMed

    Hank, Karsten

    2010-11-01

    Using data from the German Socio-Economic Panel, we investigated the role of childbearing history in later-life health and mortality, paying particular attention to possible differences by sex and region. Higher parity is associated with better self-rated health in West German mothers and fathers aged 50+, but its relationship with East German women's physical health and survival is negative. Early motherhood is paralleled by poorer physical health in West Germany, whereas late motherhood is associated with lower psychological well-being in Eastern Germany. Moreover, among West German women, having had a non-marital first birth is weakly correlated with poorer physical health. Our findings support the notion of biosocial pathways playing an important role in shaping the fertility-health nexus. Specifically, the West German 'male-breadwinner' model of specialization appears to have buffered the stresses associated with childrearing, whereas fertility off the 'normative' life-course track appears to have had adverse effects on women's health in West Germany. PMID:20845224

  5. Mismatch negativity indexes illness-specific impairments of cortical plasticity in schizophrenia: a comparison with bipolar disorder and Alzheimer's disease.

    PubMed

    Baldeweg, Torsten; Hirsch, Steven R

    2015-02-01

    Cognitive impairment is an important predictor of functional outcome in patients with schizophrenia, yet its neurobiology is still incompletely understood. Neuropathological evidence of impaired synaptic connectivity and NMDA receptor-dependent transmission in superior temporal cortex motivated us to explore the correlation of in vivo mismatch negativity (MMN) with cognitive status in patients with schizophrenia. MMN elicited in a roving stimulus paradigm displayed a response proportional to the number of stimulus repetitions (memory trace effect). Preliminary evidence in patients with chronic schizophrenia suggests that attenuation of this MMN memory trace effect was correlated with the degree of neuropsychological memory dysfunction. Here we present data from a larger confirmatory study in patients with schizophrenia, bipolar disorder, probable Alzheimer's disease and healthy controls. We observed that the diminution of the MMN memory trace effect and its correlation with memory impairment was only found in the schizophrenia group. Recent pharmacological studies using the roving paradigm suggest that attenuation of the MMN trace effect can be understood as abnormal modulation of NMDA receptor-dependent plasticity. We suggest that the convergence of the previously identified synaptic pathology in supragranular cortical layers with the intracortical locus of MMN generation accounts for the remarkable robustness of MMN impairments in schizophrenia. We further speculate that this layer-specific synaptic pathology identified in supragranular neurons plays a pivotal computational role, by weakening the encoding and propagation of prediction errors to higher cortical modules. According to predictive coding theory such breakdown will have grave implications not only for perception, but also for higher-order cognition and may thus account for the MMN-cognition correlations observed here. Finally, MMN is a sensitive and specific biomarker for detecting the early prodromal

  6. A Qualitative Study of Alcohol, Health and Identities among UK Adults in Later Life

    PubMed Central

    Wilson, Graeme B.; Kaner, Eileen F. S.; Crosland, Ann; Ling, Jonathan; McCabe, Karen; Haighton, Catherine A.

    2013-01-01

    Increasing alcohol consumption among older individuals is a public health concern. Lay understandings of health risks and stigma around alcohol problems may explain why public health messages have not reduced rates of heavy drinking in this sector. A qualitative study aimed to elucidate older people's reasoning about drinking in later life and how this interacted with health concerns, in order to inform future, targeted, prevention in this group. In 2010 a diverse sample of older adults in North East England (ages 50–95) participated in interviews (n = 24, 12 male, 12 female) and three focus groups (participants n = 27, 6 male, 21 female). Data were analysed using grounded theory and discursive psychology methods. When talking about alcohol use older people oriented strongly towards opposed identities of normal or problematic drinker, defined by propriety rather than health considerations. Each of these identities could be applied in older people's accounts of either moderate or heavy drinking. Older adults portrayed drinking less alcohol as an appropriate response if one experienced impaired health. However continued heavy drinking was also presented as normal behaviour for someone experiencing relative wellbeing in later life, or if ill health was construed as unrelated to alcohol consumption. Older people displayed scepticism about health advice on alcohol when avoiding stigmatised identity as a drinker. Drinking patterns did not appear to be strongly defined by gender, although some gendered expectations of drinking were described. Identities offer a useful theoretical concept to explain the rises in heavy drinking among older populations, and can inform preventive approaches to tackle this. Interventions should engage and foster positive identities to sustain healthier drinking and encourage at the community level the identification of heavy drinking as neither healthy nor synonymous with dependence. Future research should test and assess such

  7. Altered fetal skeletal muscle nutrient metabolism following an adverse in utero environment and the modulation of later life insulin sensitivity.

    PubMed

    Dunlop, Kristyn; Cedrone, Megan; Staples, James F; Regnault, Timothy R H

    2015-01-01

    The importance of the in utero environment as a contributor to later life metabolic disease has been demonstrated in both human and animal studies. In this review, we consider how disruption of normal fetal growth may impact skeletal muscle metabolic development, ultimately leading to insulin resistance and decreased insulin sensitivity, a key precursor to later life metabolic disease. In cases of intrauterine growth restriction (IUGR) associated with hypoxia, where the fetus fails to reach its full growth potential, low birth weight (LBW) is often the outcome, and early in postnatal life, LBW individuals display modifications in the insulin-signaling pathway, a critical precursor to insulin resistance. In this review, we will present literature detailing the classical development of insulin resistance in IUGR, but also discuss how this impaired development, when challenged with a postnatal Western diet, may potentially contribute to the development of later life insulin resistance. Considering the important role of the skeletal muscle in insulin resistance pathogenesis, understanding the in utero programmed origins of skeletal muscle deficiencies in insulin sensitivity and how they may interact with an adverse postnatal environment, is an important step in highlighting potential therapeutic options for LBW offspring born of pregnancies characterized by placental insufficiency. PMID:25685986

  8. Altered Fetal Skeletal Muscle Nutrient Metabolism Following an Adverse In Utero Environment and the Modulation of Later Life Insulin Sensitivity

    PubMed Central

    Dunlop, Kristyn; Cedrone, Megan; Staples, James F.; Regnault, Timothy R.H.

    2015-01-01

    The importance of the in utero environment as a contributor to later life metabolic disease has been demonstrated in both human and animal studies. In this review, we consider how disruption of normal fetal growth may impact skeletal muscle metabolic development, ultimately leading to insulin resistance and decreased insulin sensitivity, a key precursor to later life metabolic disease. In cases of intrauterine growth restriction (IUGR) associated with hypoxia, where the fetus fails to reach its full growth potential, low birth weight (LBW) is often the outcome, and early in postnatal life, LBW individuals display modifications in the insulin-signaling pathway, a critical precursor to insulin resistance. In this review, we will present literature detailing the classical development of insulin resistance in IUGR, but also discuss how this impaired development, when challenged with a postnatal Western diet, may potentially contribute to the development of later life insulin resistance. Considering the important role of the skeletal muscle in insulin resistance pathogenesis, understanding the in utero programmed origins of skeletal muscle deficiencies in insulin sensitivity and how they may interact with an adverse postnatal environment, is an important step in highlighting potential therapeutic options for LBW offspring born of pregnancies characterized by placental insufficiency. PMID:25685986

  9. Is loneliness in later life a self-fulfilling prophecy?

    PubMed Central

    Pikhartova, Jitka; Bowling, Ann; Victor, Christina

    2016-01-01

    Objectives: There are many stereotypes about ageing and later life. We looked at the association between expectations and stereotyping of loneliness in old age and actual self-reported loneliness status 8 years later in English Longitudinal Study of Ageing (ELSA). Method: Data from 4465 ELSA core members aged over 50 who responded to Waves 2 (2004) did not report loneliness in Wave 2, and responded to loneliness questions at least once between Waves 3 and 6 (2006–2012) were used in multivariable repeated measures logit regression analysis to estimate relationship between perceived stereotypes and expectation of loneliness in older age and actual loneliness reported within 8 years of follow-up. Results: Twenty-four per cent of respondents from the analytical sample agreed at Wave 2 that old age is time of loneliness and 33% expected to be lonely in old age. Loneliness was reported by 11.5% of respondents at Waves 3–6. Both stereotypes and expectation were significantly associated with later reported loneliness (OR 2.65 (95% CI 2.05–3.42) for stereotypes and 2.98 (95% CI 2.33–3.75) for expectations in age-sex adjusted analysis). Both variables significantly predicted future loneliness even when socio-demographic circumstances were taken into account and both variables were mutually adjusted although the effect was reduced (OR's 1.53 (95% CI 1.16–2.01) for stereotypes and 2.38 (95% CI 1.84–3.07) for expectations). Conclusions: Stereotypes and expectations related to loneliness in the old age were significantly associated with reported loneliness 8 years later. Interventions aimed at changing age-related stereotypes in population may have more impact on reducing loneliness than individually based services. PMID:25806794

  10. 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. PMID:26579598

  11. 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…

  12. Regional Cortical Thickness and Subcortical Volume Changes Are Associated with Cognitive Impairments in the Drug-Naive Patients with Late-Onset Depression

    PubMed Central

    Lim, Hyun Kook; Jung, Won Sang; Ahn, Kook Jin; Won, Wang Youn; Hahn, Changtae; Lee, Seung Yup; Kim, InSeong; Lee, Chang Uk

    2012-01-01

    Previous studies have shown an association between late-onset depression (LOD) and cognitive impairment in older adults. However, the neural correlates of this relationship are not yet clear. The aim of this study was to investigate the differences in both cortical thickness and subcortical volumes between drug-naive LOD patients and healthy controls and explore the relationship between LOD and cognitive impairments. A total of 48 elderly, drug-naive patients with LOD and 47 group-matched healthy control subjects underwent 3T MRI scanning, and the cortical thickness was compared between the groups in multiple locations, across the continuous cortical surface. The subcortical volumes were also compared on a structure-by-structure basis. Subjects with LOD exhibited significantly decreased cortical thickness in the rostral anterior cingulate cortex, the medial orbitofrontal cortex, dorsolateral prefrontal cortex, the superior and middle temporal cortex, and the posterior cingulate cortex when compared with healthy subjects (all p<0.05, false discovery rate corrected). Reduced volumes of the right hippocampus was also observed in LOD patients when compared with healthy controls (p<0.001). There were significant correlations between memory functions and cortical thickness of medial temporal, isthmus cingulate, and precuneus (p<0.001). This study was the first study to explore the relationships between the cortical thickness/subcortical volumes and cognitive impairments of drug-naive patients with LOD. These structural changes might explain the neurobiological mechanism of LOD as a risk factor of dementia. PMID:22048467

  13. 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

  14. Assessment of Cortical Visual Impairment in Infants with Periventricular Leukomalacia: a Pilot Event-Related fMRI Study

    PubMed Central

    Yu, Bing; Fan, Guoguang; Liu, Na

    2011-01-01

    Objective We wanted to investigate the usefulness of event-related (ER) functional MRI (fMRI) for the assessment of cortical visual impairment in infants with periventricular leukomalacia (PVL). Materials and Methods FMRI data were collected from 24 infants who suffered from PVL and from 12 age-matched normal controls. Slow ER fMRI was performed using a 3.0T MR scanner while visual stimuli were being presented. Data analysis was performed using Statistical Parametric Mapping software (SPM2), the SPM toolbox MarsBar was used to analyze the region of interest data, and the time to peak (TTP) of hemodynamic response functions (HRFs) was estimated for the surviving voxels. The number of activated voxels and the TTP values of HRFs were compared. Pearson correlation analysis was performed to compare visual impairment evaluated by using Teller Acuity Cards (TAC) with the number of activated voxels in the occipital lobes in all patients. Results In all 12 control infants, the blood oxygenation level-dependent (BOLD) signal was negative and the maximum response was located in the anterior and superior part of the calcarine fissure, and this might correspond to the anterior region of the primary visual cortex (PVC). In contrast, for the 24 cases of PVL, there were no activated pixels in the PVC in four subjects, small and weak activations in six subjects, deviated activations in seven subjects and both small and deviated activations in three subjects. The number of active voxels in the occipital lobe was significantly correlated with the TAC-evaluated visual impairment (p < 0.001). The mean TTP of the HRFs was significantly delayed in the cases of PVL as compared with that of the normal controls. Conclusion Determining the characteristics of both the BOLD response and the ER fMRI activation may play an important role in the cortical visual assessment of infants with PVL. PMID:21852907

  15. 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

  16. Chronic ethanol consumption impairs spatial remote memory in rats but does not affect cortical cholinergic parameters.

    PubMed

    Pereira, S R; Menezes, G A; Franco, G C; Costa, A E; Ribeiro, A M

    1998-06-01

    We have studied learning, memory and cortical cholinergic parameters after oral administration of 20% v/v ethanol solution to male Fisher rats for 6 months. A group of rats were trained to behave efficiently in an eight-arm radial maze and after that split into two subgroups submitted to ethanol or control treatment. Ethanol-treated rats had more difficulty in relearning the same task 1 year later, compared to ethanol-untreated rats (control). Differences in working memory performance were found, but only in the first 10 training sessions. Another group of rats, which had not been pretrained, was also split into two subgroups submitted to ethanol or control treatment. After that, these rats were trained in the radial maze task for the first time. No significant difference was found between the reference memory performance of the untreated subgroup and the treated one. These two subgroups did not significantly differ in their working memory performance either. Moreover, there were no significant differences between treated and control subjects in the following biochemical brain cortical parameters: in vitro acetylcholinesterase (AChE) activity, and stimulated acetylcholine (ACh) release. This work presents an experimental design that allows assessment of remote memory performance after ethanol chronic consumption and shows that the experimental subject is able to retain the behaviors learned 1 year before. It was concluded that chronic ethanol treatment may cause retrograde amnesia, which does not seem to be linked with a cortical cholinergic deficit. PMID:9632211

  17. 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

  18. Alcohol Problems and Depression in Later Life: Development of Two Knowledge Quizzes.

    ERIC Educational Resources Information Center

    Pratt, Clara C.; And Others

    1992-01-01

    Notes that effective measures of knowledge about mental health in later life are valuable in needs assessments and educational program evaluations. Describes development of two short, true/false quizzes, one on alcohol problems, other on depression and suicide in later life. Discusses usefulness of quizzes in planning and evaluating community…

  19. Silencing TRPM7 in Mouse Cortical Astrocytes Impairs Cell Proliferation and Migration via ERK and JNK Signaling Pathways

    PubMed Central

    Zeng, Zhao; Leng, Tiandong; Feng, Xuechao; Sun, Huawei; Inoue, Koichi; Zhu, Li; Xiong, Zhi-Gang

    2015-01-01

    Transient receptor potential melastatin 7 (TRPM7), a non-selective cation channel, is highly expressed expressed in the brain and plays a critical role in ischemic neuronal death. Astrocyte, the most abundant cell type in central nervous system (CNS), exerts many essential functions in the physiological and pathological conditions. Here we investigated the expression and functions of the TRPM7 channel in mouse cortical astrocytes. Using reverse transcription (RT)-PCR, immunostaining, western blot and patch clamp recording, we showed that functional TRPM7 channel is expressed in cultured mouse cortical astrocytes. Knocking down TRPM7 with specific siRNA impairs the proliferation and migration of astrocytes by 40.2% ± 3.9% and 40.1% ± 11.5%, respectively. Consistently, inhibition of TRPM7 with 2-aminoethoxydiphenyl borate (2-APB) also decreases astrocyte proliferation and migration by 46.1% ± 2.5% and 64.2% ± 2.4%. MAPKs and Akt signaling pathways have been shown to be implicated in TRPM7-mediated responses including cell proliferation and migration. Our data show that suppression of TRPM7 in astrocytes reduces the phosphorylation of extracellular signal-regulated kinases (ERK) and c-Jun N-terminal kinases (JNK), but not p38 mitogen-activated protein kinase and Akt. In addition, TRPM7, as a cation channel, has been involved in the Ca2+ and Mg2+ homeostasis in several types of cells. In our study, we found that silencing TRPM7 decreases the intracellular basal Mg2+ concentration without affecting Ca2+ concentration in astrocytes. However, an addition of Mg2+ to the growth medium could not rescue the impaired proliferation of astrocytes. Together, our data suggest that TRPM7 channel may play a critical role in the proliferation and migration of astrocytes via the ERK and JNK pathways. PMID:25799367

  20. 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. PMID:26708494

  1. Automated Volumetry and Regional Thickness Analysis of Hippocampal Subfields and Medial Temporal Cortical Structures in Mild Cognitive Impairment

    PubMed Central

    Yushkevich, Paul A.; Pluta, John B.; Wang, Hongzhi; Xie, Long; Ding, Song-Lin; Gertje, E. C.; Mancuso, Lauren; Kliot, Daria; Das, Sandhitsu R.; Wolk, David A.

    2014-01-01

    We evaluate a fully automatic technique for labeling hippocampal subfields and cortical subregions in the medial temporal lobe (MTL) in in vivo 3 Tesla MRI. The method performs segmentation on a T2-weighted MRI scan with 0.4 × 0.4 × 2.0 mm3 resolution, partial brain coverage, and oblique orientation. Hippocampal subfields, entorhinal cortex, and perirhinal cortex are labeled using a pipeline that combines multi-atlas label fusion and learning-based error correction. In contrast to earlier work on automatic subfield segmentation in T2-weighted MRI (Yushkevich et al., 2010), our approach requires no manual initialization, labels hippocampal subfields over a greater anterior-posterior extent, and labels the perirhinal cortex, which is further subdivided into Brodmann areas 35 and 36. The accuracy of the automatic segmentation relative to manual segmentation is measured using cross-validation in 29 subjects from a study of amnestic Mild Cognitive Impairment (aMCI), and is highest for the dentate gyrus (Dice coefficient is 0.823), CA1 (0.803), perirhinal cortex (0.797) and entorhinal cortex (0.786) labels. A larger cohort of 83 subjects is used to examine the effects of aMCI in the hippocampal region using both subfield volume and regional subfield thickness maps. Most significant differences between aMCI and healthy aging are observed bilaterally in the CA1 subfield and in the left Brodmann area 35. Thickness analysis results are consistent with volumetry, but provide additional regional specificity and suggest non-uniformity in the effects of aMCI on hippocampal subfields and MTL cortical subregions. PMID:25181316

  2. Automated volumetry and regional thickness analysis of hippocampal subfields and medial temporal cortical structures in mild cognitive impairment.

    PubMed

    Yushkevich, Paul A; Pluta, John B; Wang, Hongzhi; Xie, Long; Ding, Song-Lin; Gertje, Eske C; Mancuso, Lauren; Kliot, Daria; Das, Sandhitsu R; Wolk, David A

    2015-01-01

    We evaluate a fully automatic technique for labeling hippocampal subfields and cortical subregions in the medial temporal lobe in in vivo 3 Tesla MRI. The method performs segmentation on a T2-weighted MRI scan with 0.4 × 0.4 × 2.0 mm(3) resolution, partial brain coverage, and oblique orientation. Hippocampal subfields, entorhinal cortex, and perirhinal cortex are labeled using a pipeline that combines multi-atlas label fusion and learning-based error correction. In contrast to earlier work on automatic subfield segmentation in T2-weighted MRI [Yushkevich et al., 2010], our approach requires no manual initialization, labels hippocampal subfields over a greater anterior-posterior extent, and labels the perirhinal cortex, which is further subdivided into Brodmann areas 35 and 36. The accuracy of the automatic segmentation relative to manual segmentation is measured using cross-validation in 29 subjects from a study of amnestic mild cognitive impairment (aMCI) and is highest for the dentate gyrus (Dice coefficient is 0.823), CA1 (0.803), perirhinal cortex (0.797), and entorhinal cortex (0.786) labels. A larger cohort of 83 subjects is used to examine the effects of aMCI in the hippocampal region using both subfield volume and regional subfield thickness maps. Most significant differences between aMCI and healthy aging are observed bilaterally in the CA1 subfield and in the left Brodmann area 35. Thickness analysis results are consistent with volumetry, but provide additional regional specificity and suggest nonuniformity in the effects of aMCI on hippocampal subfields and MTL cortical subregions. PMID:25181316

  3. 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)

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

    PubMed Central

    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

  5. 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

  6. Learning impairment by minimal cortical injury in a mouse model of Alzheimer's disease.

    PubMed

    Zou, Jingyu; Wang, Min; Uchiumi, Osamu; Shui, Yuan; Ishigaki, Yasuhito; Liu, Xiaoyan; Tajima, Nobuyoshi; Akai, Takuya; Iizuka, Hideaki; Kato, Nobuo

    2016-04-15

    Brain injury accelerates amyloid-β (Aβ) deposits and exacerbates Alzheimer's disease (AD). Accumulation of intracellular soluble Aβ impairs cognition prior to emergence of Aβ plaques. However, it is not known whether brain injury affects learning impairment attributable to intracellular soluble Aβ. We made a small injury by injecting glutamate into the parietal cortex in 3xTg AD mice of 4-5 months old, at which age soluble Aβ is accumulated without Aβ deposits. The size of glutamate-induced lesion was significantly larger than that of saline-injected control lesion. We reduced the relative difficulty of Morris water maze (MWM) task by repeating it twice, so that saline-injected 3xTg mice could perform as well as wild-type control mice. Under this condition, glutamate-injected 3xTg mice exhibited learning deficits. DNA microarray analysis revealed that 3 genes are upregulated, with one gene downregulated, more than 2 folds in the hippocampus. These 4 genes do not appear to be involved directly in learning but may be a part of signal cascade triggered by glutamate-induced small injury. Hippocampal content of soluble Aβ1-42 was increased in the glutamate 3xTg group. Facilitation of large-conductance calcium-activated potassium (BK) channel accompanied learning recovery in the saline-control 3xTg group in agreement with our previous reports, in which learning deficits attributable to intracellular Aβ were alleviated by facilitating BK channels. However, BK channel remained suppressed in the glutamate 3xTg group. It is suggested that glutamate-induced injury worsens learning by enhancing the toxicity of soluble Aβ or increasing its content per se. PMID:26876740

  7. 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

  8. 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

  9. 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

  10. Lifelong Socio Economic Position and biomarkers of later life health: testing the contribution of competing hypotheses.

    PubMed

    Ploubidis, George B; Benova, Lenka; Grundy, Emily; Laydon, Daniel; DeStavola, Bianca

    2014-10-01

    The relative contribution of early or later life Socio Economic Position (SEP) to later life health is not fully understood and there are alternative hypotheses about the pathways through which they may influence health. We used data from the English Longitudinal Study of Ageing with a formal approach for the identification of mediating factors in order to investigate alternative hypotheses about life course influences on biomarkers of later life health. We found that early life SEP predicts physical health at least 65 years later. However, a more complicated pattern of associations than that implied by previous findings was also observed. Age group specific effects emerged, with current SEP dominating the effect on later life physical health and fibrinogen levels in participants under 65, while early life SEP had a more prominent role in explaining inequalities in physical health for men and women over 75. We extend previous findings on mid adulthood and early old age, to old age and the beginnings of late old age. The complexity of our findings highlights the need for further research on the mechanisms that underlie the association between SEP and later life health. PMID:24636422

  11. 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

  12. 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

  13. 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

  14. Cholinergic-associated loss of hnRNP-A/B in Alzheimer's disease impairs cortical splicing and cognitive function in mice

    PubMed Central

    Berson, Amit; Barbash, Shahar; Shaltiel, Galit; Goll, Yael; Hanin, Geula; Greenberg, David S; Ketzef, Maya; Becker, Albert J; Friedman, Alon; Soreq, Hermona

    2012-01-01

    Genetic studies link inherited errors in RNA metabolism to familial neurodegenerative disease. Here, we report such errors and the underlying mechanism in sporadic Alzheimer's disease (AD). AD entorhinal cortices presented globally impaired exon exclusions and selective loss of the hnRNP A/B splicing factors. Supporting functional relevance, hnRNP A/B knockdown induced alternative splicing impairments and dendrite loss in primary neurons, and memory and electrocorticographic impairments in mice. Transgenic mice with disease-associated mutations in APP or Tau displayed no alterations in hnRNP A/B suggesting that its loss in AD is independent of Aβ and Tau toxicity. However, cholinergic excitation increased hnRNP A/B levels while in vivo neurotoxin-mediated destruction of cholinergic neurons caused cortical AD-like decrease in hnRNP A/B and recapitulated the alternative splicing pattern of AD patients. Our findings present cholinergic-mediated hnRNP A/B loss and impaired RNA metabolism as important mechanisms involved in AD. PMID:22628224

  15. 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

  16. 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

  17. Cortical Visual Impairment

    MedlinePlus

    ... Conditions Most Common Searches Adult Strabismus Amblyopia Cataract Conjunctivitis Corneal Abrasions Dilating Eye Drops Lazy eye (defined) ... Loading... Most Common Searches Adult Strabismus Amblyopia Cataract Conjunctivitis Corneal Abrasions Dilating Eye Drops Lazy eye (defined) ...

  18. 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 ...

  19. 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…

  20. 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…

  1. 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…

  2. 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…

  3. Living Arrangements, Social Integration, and Loneliness in Later Life: The Case of Physical Disability

    ERIC Educational Resources Information Center

    Russell, David

    2009-01-01

    Despite the theoretical linkages between household composition and social integration, relatively limited research has considered how living arrangements affect risk for loneliness in later life. Prior work has also failed to consider whether physical disability moderates this potentially important relationship. Using data from a sample of older…

  4. 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…

  5. Fetal programming by maternal obesity increases offspring’s susceptibility to obesity in later-life

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To examine whether exposure of the developing fetus to an obese mother during pregnancy increases the risk of obesity in the children in later-life, we have developed an overfeeding-based model of maternal obesity in rats by tube feeding of liquid diets directly into the stomach using total enteral ...

  6. 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…

  7. 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

  8. 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)

  9. Relationship between herpes simplex virus-1-specific antibody titers and cortical brain damage in Alzheimer’s disease and amnestic mild cognitive impairment

    PubMed Central

    Baglio, Francesca; Agostini, Simone; Agostini, Monia Cabinio; Laganà, Maria M.; Hernis, Ambra; Margaritella, Nicolò; Guerini, Franca R.; Zanzottera, Milena; Nemni, Raffaello; Clerici, Mario

    2014-01-01

    Alzheimer’s disease (AD) is a multifactorial disease with a still barely understood etiology. Herpes simplex virus 1 (HSV-1) has long been suspected to play a role in the pathogenesis of AD because of its neurotropism, high rate of infection in the general population, and life-long persistence in neuronal cells, particularly in the same brain regions that are usually altered in AD. The goal of this study was to evaluate HSV-1-specific humoral immune responses in patients with a diagnosis of either AD or amnestic mild cognitive impairment (aMCI), and to verify the possible relation between HSV-1-specific antibody (Ab) titers and cortical damage; results were compared to those obtained in a group of healthy controls (HC). HSV-1 serum IgG titers were measured in 225 subjects (83 AD, 68 aMCI, and 74 HC). HSV-specific Ab avidity and cortical gray matter volumes analyzed by magnetic resonance imaging (MRI) were evaluated as well in a subgroup of these individuals (44 AD, 23 aMCI, and 26 HC). Results showed that, whereas HSV-1 seroprevalence and IgG avidity were comparable in the three groups, increased Ab titers (p < 0.001) were detected in AD and aMCI compared to HC. Positive significant correlations were detected in AD patients alone between HSV-1 IgG titers and cortical volumes in orbitofrontal (region of interest, ROI1 RSp0.56; p = 0.0001) and bilateral temporal cortices (ROI2 RSp0.57; p < 0.0001; ROI3 RSp0.48; p = 0.001); no correlations could be detected between IgG avidity and MRI parameters. Results herein suggest that a strong HSV-1-specific humoral response could be protective toward AD-associated cortical damage. PMID:25360113

  10. 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

  11. Alternate models of sibling status effects on health in later life.

    PubMed

    Falbo, Toni; Kim, Sunghun; Chen, Kuan-Yi

    2009-05-01

    Although siblings are thought to be influential in child development, little is known about the influence of sibling status on the health of older adults. Using structural equation modeling, the authors created and tested a series of models with data from a sample (N = 3,968) of 1957 high school graduates from the Wisconsin Longitudinal Study. The results indicated that socioeconomic status of origin, adolescent aptitude, and educational attainment did have significant total effects on health in later life, but sibling status did not. Adults who grew up in families of higher socioeconomic status and who had greater aptitude in high school attained more education, and this advantage, in turn, led to better health in later life. Although the final model was cross-validated, it was not equally plausible for men and women. PMID:19413424

  12. Women narrate later life remarriage: Negotiating the cultural to create the personal

    PubMed Central

    Watson, Wendy K.; Bell, Nancy J.; Stelle, Charlie

    2013-01-01

    Narrative provides a window to experience in a way that is different from traditional research methods. In this study, narrative affords both a holistic vantage point on later life relationships, and at the same time, a “view from the inside”—older women's own accounts of single life, relationship development, and remarriage. The narratives were obtained in interviews with eight recently remarried women between the ages of sixty-five and eighty. A two-stage analysis addresses, first, the narrative content—the phenomenology of remarriage for these older women. The second stage focuses on process, analyzing how cultural-level narratives are drawn upon in the creation of the women's personal stories. Based upon these analyses, we discuss the ways that a narrative approach can inform our understanding of later life relationships, and we comment on the potential of narratives such as these to rewrite a script for older women's relationships. PMID:25197160

  13. [Fetal programming: prevention of perinatal acquired predispositions of diseases in later life].

    PubMed

    Kainer, F

    2007-02-01

    Alterations of the metabolic and hormonal environment of the fetus may cause predispositions to the development of disorders and diseases in later life. The timing, duration, severity, and type of insult during development determines the specific physiological outcome. Intrauterine programming of physiological systems occurs at the gene, cell, tissue, organ, and system levels and causes permanent structural and functional changes. Elevated insulin concentrations during critical periods of perinatal life may induce a lasting 'malprogramming' of neuroendocrine systems regulating body weight, food intake, and metabolism. Similar characteristics may occur due to perinatal hyperleptinism, hypercortisolism. Diagnosis and therapy of gestational diabetes in time may prevent metabolic and cardiovascular diseases in later life. This concept has new important implications for chances and challenges of perinatal preventive medicine in the future. PMID:17327986

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. Deconstructing positive affect in later life: a differential functionalist analysis of joy and interest.

    PubMed

    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 present study measured trait joy and interest in a population-based sample of 1,118 adults aged 65-86 years. As predicted, trait joy was associated with greater religious participation, while trait interest was associated with greater education. Joy was associated with lower morbidity and stress while interest was not. Interest was, in fact, associated with greater stress. Both emotions were positively associated with social support. We use the pattern of predictors to develop a functionalist conceptualization of these two emotions in later life, concluding that it is worthwhile to treat interest and joy as partially-independent positive affects contributing differentially to human emotionality and later life adaptation. PMID:15248472

  20. Dependence on place: A source of autonomy in later life for older Māori.

    PubMed

    Butcher, Elizabeth; Breheny, Mary

    2016-04-01

    Attachment to place is an important component of ageing. Although the importance of place for older people's well-being is known, the ways in which different conceptions of place and expectations for what later life may hold depend upon cultural beliefs, values, and expectations is underexplored. This study examined the ways that place influences experiences of ageing for older Māori in New Zealand. Eight interviews with older Māori were analysed thematically alongside field notes from a research visit. Attachment to place provided the foundation for experiences of ageing for older Māori. Through their connection to place, the participants drew on a comforting and comfortable dependence on land and family to enable autonomy in later life. Rather than seeking to maintain independence in terms of avoiding reliance on others, older Māori conceptualised older age through autonomy and freedom to live in accordance with Māori values encapsulated by whakawhanaungatanga. A good old age depended on balancing competing demands of living in wider society with attachment to place and Māori identity in later life. PMID:27131278

  1. 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

  2. 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

  3. 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

  4. Impaired consciousness during temporal lobe seizures is related to increased long-distance cortical-subcortical synchronization.

    PubMed

    Arthuis, Marie; Valton, Luc; Régis, Jean; Chauvel, Patrick; Wendling, Fabrice; Naccache, Lionel; Bernard, Christophe; Bartolomei, Fabrice

    2009-08-01

    Loss of consciousness (LOC) is a dramatic clinical manifestation of temporal lobe seizures. Its underlying mechanism could involve altered coordinated neuronal activity between the brain regions that support conscious information processing. The consciousness access hypothesis assumes the existence of a global workspace in which information becomes available via synchronized activity within neuronal modules, often widely distributed throughout the brain. Re-entry loops and, in particular, thalamo-cortical communication would be crucial to functionally bind different modules together. In the present investigation, we used intracranial recordings of cortical and subcortical structures in 12 patients, with intractable temporal lobe epilepsy (TLE), as part of their presurgical evaluation to investigate the relationship between states of consciousness and neuronal activity within the brain. The synchronization of electroencephalography signals between distant regions was estimated as a function of time by using non-linear regression analysis. We report that LOC occurring during temporal lobe seizures is characterized by increased long-distance synchronization between structures that are critical in processing awareness, including thalamus (Th) and parietal cortices. The degree of LOC was found to correlate with the amount of synchronization in thalamo-cortical systems. We suggest that excessive synchronization overloads the structures involved in consciousness processing, preventing them from treating incoming information, thus resulting in LOC. PMID:19416952

  5. 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.

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

    PubMed Central

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

    2014-01-01

    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. PMID:24530028

  7. 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

  8. 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

  9. 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

  10. Evidence for the intra-uterine programming of adiposity in later life

    PubMed Central

    Fall, Caroline HD

    2012-01-01

    Research in animals has shown that altering fetal nutrition by under-nourishing or over-nourishing the mother or rendering her diabetic, or fetal exposure to glucocorticoids and toxins, can programme obesity in later life. The increased adiposity is mediated by permanent changes in appetite, food choices, physical activity and energy metabolism. In humans, increased adiposity has been shown in people who experienced fetal under-nutrition due to maternal famine, or over-nutrition due to maternal diabetes. Lower birth weight (a proxy for fetal under-nutrition) is associated with a reduced adult lean mass and increased intra-abdominal fat. Higher birthweight caused by maternal diabetes is associated with increased total fat mass and obesity in later life. There is growing evidence that maternal obesity, without diabetes, is also a risk factor for obesity in the child, due to fetal over-nutrition effects. Maternal smoking is associated with an increased risk of obesity in the children, though a causal link has not been proven. Other fetal exposures associated with increased adiposity in animals include glucocorticoids and endocrine disruptors. Reversing the current obesity epidemic will require greater attention to, and better understanding of, these inter-generational (mother-offspring) factors that programme body composition during early development. PMID:21682572

  11. 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…

  12. 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

  13. Permanent impairment of birth and survival of cortical and hippocampal proliferating cells following excessive drinking during alcohol dependence

    PubMed Central

    Richardson, Heather N.; Chan, Stephanie H.; Crawford, Elena F.; Lee, Youn Kyung; Funk, Cindy K.; Koob, George F.; Mandyam, Chitra D.

    2009-01-01

    Experimenter-delivered alcohol decreases adult hippocampal neurogenesis, and hippocampal-dependent learning and memory. The present study used clinically relevant rodent models of nondependent limited access alcohol self-administration and excessive drinking during alcohol dependence (alcohol self-administration followed by intermittent exposure to alcohol vapors over several weeks) to compare alcohol-induced effects on cortical gliogenesis and hippocampal neurogenesis. Alcohol dependence, but not nondependent drinking, reduced proliferation and survival in the medial prefrontal cortex (mPFC). Apoptosis was reduced in both alcohol groups within the mPFC, which may reflect an initiation of a reparative environment following alcohol exposure as decreased proliferation was abolished after prolonged dependence. Reduced proliferation, differentiation, and neurogenesis was observed in the hippocampus of both alcohol groups, and prolonged dependence worsened the effects. Increased hippocampal apoptosis and neuronal degeneration following alcohol exposure suggests a loss in neuronal turnover and indicates that the hippocampal neurogenic niche is highly vulnerable to alcohol. PMID:19501165

  14. Feelings of Hopelessness in Midlife and Cognitive Health in Later Life: A Prospective Population-Based Cohort Study

    PubMed Central

    Håkansson, Krister; Soininen, Hilkka; Winblad, Bengt; Kivipelto, Miia

    2015-01-01

    .37 (1.05–1.78) for Alzheimer’s disease. These associations remained significant also after the final adjustments for depressive feelings and for hopelessness at follow-up. The individual changes in hopelessness scores between midlife and follow-up were not systematically related to cognitive health at the follow-up. Conclusion Our results suggest that feelings of hopelessness already in midlife may have long-term implications for cognitive health and increase the risk of Alzheimer’s disease in later life. PMID:26460971

  15. Complex Households and the Distribution of Multiple Resources in Later Life: Findings from A National Survey

    PubMed Central

    Kim, Juyeon; Link, Arts; Waite, Linda

    2016-01-01

    The availability of social and financial resources has profound implications for health and well-being in later life. Older adults often share resources with others who live with them, sometimes in households including relatives or friends. We examine differences in social support, social connections, money, and the household environment across types of living arrangements, develop hypotheses from two theoretical perspectives, one focusing on obligations toward kin, and one focused on social exchange within households, and test them using data from the National Social Life, Health, and Aging Project. We find that availability of resources is not consistently associated with the presence of grandchildren and other young relatives, but often differs with presence of other adults. These findings suggest that a single type of resource tells us little about the distribution of the resources of older adults, and call on us to examine multiple resources simultaneously. PMID:25904682

  16. Does caregiving increase poverty among women in later life? Evidence from the Health and Retirement survey.

    PubMed

    Wakabayashi, Chizuko; Donato, Katharine M

    2006-09-01

    Given the rapid aging of the U.S. population and reductions in federal funding, elder care has become a major issue for many families. This paper focuses on a long-term consequence of elder care by asking how caring for elderly parents affects women's subsequent risks of living in poverty. Using longitudinal data from the Health and Retirement Study, we examine whether and how caregiving for parents in 1991 increases women's risks of living in households with incomes less than the poverty threshold, receiving public assistance, and receiving Medicaid in 1999. Our findings illustrate that caregiving in earlier life raises women's poverty risks in later life by intensifying the negative effects of stopping work and declining health on women's economic well-being. PMID:17066776

  17. 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. PMID:25221351

  18. Complex Households and the Distribution of Multiple Resources in Later Life: Findings From a National Survey.

    PubMed

    Kim, Juyeon; Waite, Linda J

    2016-02-01

    The availability of social and financial resources has profound implications for health and well-being in later life. Older adults often share resources with others who live with them, sometimes in households including relatives or friends. We examine differences in social support, social connections, money, and the household environment across types of living arrangements, develop hypotheses from two theoretical perspectives, one focusing on obligations toward kin, and one focused on social exchange within households, and test them using data from the National Social Life, Health, and Aging Project. We find that availability of resources is not consistently associated with the presence of grandchildren and other young relatives, but often differs with presence of other adults. These findings suggest that a single type of resource tells us little about the distribution of the resources of older adults, and call on us to examine multiple resources simultaneously. PMID:25904682

  19. The reproduction of gender norms through downsizing in later life residential relocation.

    PubMed

    Addington, Aislinn; Ekerdt, David J

    2014-01-01

    Using data collected from qualitative interviews in 36 households, this article examines people's use of social relations based on gender to perform tasks associated with residential relocation in later life. Without prompting, our respondents addressed the social relations of gender in the meanings of things, in the persons of gift recipients, and in the persons of actors accomplishing the tasks. They matched gender-typed objects to same-sex recipients, reproducing circumstances of possession and passing on expectations for gender identity. The accounts of our respondents also depicted a gendered division of household labor between husbands and wives and a gendered division of care work by daughters and sons. These strategies economized a big task by shaping decisions about who should get what and who will do what. In turn, these practices affirmed the gendered nature of possession and care work into another generation. PMID:25651598

  20. Does food insufficiency in childhood contribute to dementia in later life?

    PubMed Central

    Momtaz, Yadollah Abolfathi; Haron, Sharifah Azizah; Hamid, Tengku Aizan; Ibrahim, Rahimah; Masud, Jariah

    2015-01-01

    Background Despite several studies attempting to identify the risk factors for dementia, little is known about the impact of childhood living conditions on cognitive function in later life. The present study aims to examine the unique contribution of food insufficiency in childhood to dementia in old age. Methods Data for this study of 2,745 older Malaysians aged 60 years and older was obtained from a national survey entitled “Mental Health and Quality of Life of Older Malaysians” conducted from 2003 through 2005 using a cross-sectional design. The Geriatric Mental State-Automated Geriatric Examination for Computer Assisted Taxonomy was used to measure dementia. A multiple binary logistic regression using Statistical Package for Social Sciences version 21 was conducted to assess the unique effect of food insufficiency in childhood on developing dementia in old age. Results A notably higher prevalence of dementia was found in respondents who indicated they had experienced food insufficiency in childhood than in their food-sufficient counterparts (23.5% versus 14.3%). The findings from multiple logistic regression analysis revealed that food insufficiency in childhood would independently increase the risk of developing dementia in old age by 81%, after adjusting for sociodemographic factors (odds ratio =1.81, 95% confidence interval 1.13–2.92, P<0.01). Conclusion Findings from the present study showing that food insufficiency in early life significantly contributes to dementia in later life highlight the importance of childhood living conditions in maintaining cognitive function in old age. It is, therefore, suggested that older adults with childhood food insufficiency might be targeted for programs designed to prevent dementia. PMID:25565786

  1. 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

  2. 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

  3. 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

  4. 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

  5. Inhibition of Tnf-α R1 signaling can rescue functional cortical plasticity impaired in early post-stroke period.

    PubMed

    Liguz-Lecznar, Monika; Zakrzewska, Renata; Kossut, Malgorzata

    2015-10-01

    Tumor necrosis factor-α (TNF-α) is one of the key players in stroke progression and can interfere with brain functioning. We previously documented an impairment of experience-dependent plasticity in the cortex neighboring the stroke-induced lesion, which was accompanied with an upregulation of Tnf-α level in the brain of ischemic mice 1 week after the stroke. Because TNF receptor 1 (TnfR1) signaling is believed to be a major mediator of the cytotoxicity of Tnf-α through activation of caspases, we used an anti-inflammatory intervention aimed at Tnf-α R1 pathway, in order to try to attenuate the detrimental effect of post-stroke inflammation, and investigated if this will be effective in protecting plasticity in the infarct proximity. Aged mice (12-14 months) were subjected to the photothrombotic stroke localized near somatosensory cortex, and immediately after ischemia sensory deprivation was introduced to induce plasticity. Soluble TNF-α R1 (sTNF-α R1), which competed for TNF-α with receptors localized in the brain, was delivered chronically directly into the brain tissue for the whole period of deprivation using ALZET Micro-Osmotic pumps. We have shown that such approach undertaken simultaneously with the stroke reduced the level of TNF-α in the peri-ischemic tissue and was successful in preserving the post-stroke deprivation-induced brain plasticity. PMID:26189092

  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. PMID:24984912

  7. The interaction of family background and personal education on depressive symptoms in later life.

    PubMed

    Schaan, Barbara

    2014-02-01

    This study assesses the interaction between personal education and family background during childhood on depressive symptoms in later life by applying Ross & Mirowsky's resource substitution and structural amplification theory of health and education. OLS regression models are estimated using data from the "Survey of Health, Ageing and Retirement in Europe" (SHARE), which covers information on current social and health status as well as retrospective life histories from 20,716 respondents aged 50 or older from thirteen European countries. Higher education helps to overcome the negative consequences of a poor family background. Since people from poor families are less likely to attain higher educational levels, they lack exactly the resource they need in order to overcome the negative consequences their non-prosperous background has on depressive symptoms. Thus, low family background and low personal education amplify each other. Examining the processes described by theory of resource substitution and structural amplification over different age groups from midlife to old-age suggests that the moderating effect of education remains constant over age among people coming from a poor family background. However, there is some evidence for a decrease with age in the buffering effect of a well-off family background on depressive symptoms among the low educated group. Furthermore, the educational gap in depression diverges with age among individuals originating from a well-off family background. Taken together the results cautiously allude to the conclusion that three processes - cumulative (dis-)advantage, age-as-leveler, and persistent inequalities - might take place. PMID:24565146

  8. 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

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

    PubMed Central

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

    2014-01-01

    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. PMID:25221351

  10. Early-Life Socioeconomic Status and the Prevalence of Breast Cancer in Later Life

    PubMed Central

    Pudrovska, Tetyana; Anishkin, Andriy; Shen, Yifang

    2012-01-01

    Knowledge of mechanisms linking early-life social environment and breast cancer remains limited. We explore direct and indirect effects of early-life socioeconomic status (SES) on breast cancer prevalence in later life. Using 50-year data from the Wisconsin Longitudinal Study (N = 4,275) and structural equation modeling, we found a negative direct effect of early-life SES, indicating that women from higher-SES family background had lower breast cancer prevalence than women from lower-SES families. Additionally, early-life SES has a positive indirect effect on breast cancer via women's adult SES and age at first birth. Were it not for their higher SES in adulthood and delayed childbearing, women from higher-SES families of origin would have had lower breast cancer prevalence than women from lower-SES families. Yet, early-life SES is associated positively with adult SES and age at first birth, and women's higher adult SES and delayed childbearing are related to higher breast cancer prevalence. PMID:22936839

  11. 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

  12. 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.

  13. 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

  14. Propositional Density and Cognitive Function in Later Life: Findings From the Precursors Study

    PubMed Central

    Agree, Emily M.; Meoni, Lucy A.; Klag, Michael J.

    2010-01-01

    Objectives. We used longitudinal data from the Johns Hopkins Precursors Study to test the hypothesis that written propositional density measured early in life is lower for people who develop dementia categorized as Alzheimer's disease (AD). This association was reported in 1996 for the Nun Study, and the Precursors Study offered an unprecedented chance to reexamine it among respondents with different gender, education, and occupation profiles. Methods. Eighteen individuals classified as AD patients (average age at diagnosis: 74) were assigned 2 sex-and-age matched controls, and propositional density in medical school admission essays (average age at writing: 22) was assessed via Computerized Propositional Idea Density Rater 3 linguistic analysis software. Adjusted odds ratios (ORs) for the matched case-control study were calculated using conditional (fixed-effects) logistic regression. Results. Mean propositional density is lower for cases than for controls (4.70 vs. 4.99 propositions per 10 words, 1-sided p = .01). Higher propositional density substantially lowers the odds of AD (OR = 0.16, 95% confidence interval = 0.03-0.90, 1-sided p = .02). Discussion. Propositional density scores in writing samples from early adulthood appear to predict AD in later life for men as well as women. Studies of cognition across the life course might beneficially incorporate propositional density as a potential marker of cognitive reserve. PMID:20837676

  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. Refashioning One’s Place in Time: Stories of Household Downsizing in Later Life

    PubMed Central

    Luborsky, Mark R.; Lysack, Catherine L.; Van Nuil, Jennifer

    2011-01-01

    Older adults face a daunting task: while continuing engagements in multiple relationships, investment in their own and others’ futures, and developing life interests and capacities, they also reexamine and sometimes reconfigure the place where their social lives and objects are housed. Some relocate, downsize, to a new smaller place and reducing possessions to ensure an environment supportive of their capacities and desired daily activities. This article examines how key contours of the experiences of place during residential downsizing are infused with unexpectedly heightened awareness and cultivation of one’s sense of place in multiple timeframes. In a discovery mode, the downsizing stories of 40 older adults in southeast Michigan are examined. Findings indicate conflicting temporalities and the natures of cognitions related to decision-making and thinking about being leave-taking and being in place. Findings also highlight in particular how making sense of one’s place is predicated on notions of its time, of being on time and downsizing on time. Further, these characterizations of the lived worlds of older adults’ modes of conceptualizing the nature of downsizing show how an understanding of the meaningfulness of place in later life relocations requires a layered sense of home as places-in multiple timelines. PMID:21765597

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

    PubMed Central

    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. PMID:27335648

  18. Patterns of intimate partner homicide suicide in later life: strategies for prevention.

    PubMed

    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

  19. "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…

  20. Substance use disorders and psychiatric comorbidity in mid and later life: a review

    PubMed Central

    Wu, Li-Tzy; Blazer, Dan G

    2014-01-01

    Background Globally, adults aged 65 years or older will increase from 516 million in 2009 to an estimated 1.53 billion in 2050. Due to substance use at earlier ages that may continue into later life, and ageing-related changes in medical conditions, older substance users are at risk for substance-related consequences. Methods MEDLINE and PsychInfo databases were searched using keywords: alcohol use disorder, drug use disorder, drug misuse, substance use disorder, prescription drug abuse, and substance abuse. Using the related-articles link, additional articles were screened for inclusion. This review focused on original studies published between 2005 and 2013 to reflect recent trends in substance use disorders. Studies on psychiatric comorbidity were also reviewed to inform treatment needs for older adults with a substance use disorder. Results Among community non-institutionalized adults aged 50+ years, about 60% used alcohol, 3% used illicit drugs and 1–2% used nonmedical prescription drugs in the past year. Among adults aged 50+, about 5% of men and 1.4% of women had a past-year alcohol use disorder. Among alcohol users, about one in 14 users aged 50–64 had a past-year alcohol use disorder vs one in 30 elder users aged 65+. Among drug users aged 50+, approximately 10–12% had a drug use disorder. Similar to depressive and anxiety disorders, substance use disorders were among the common psychiatric disorders among older adults. Older drug users in methadone maintenance treatment exhibited multiple psychiatric or medical conditions. There have been increases in treatment admissions for illicit and prescription drug problems in the United States. Conclusions Substance use in late life requires surveillance and research, including tracking substance use in the racial/ethnic populations and developing effective care models to address comorbid medical and mental health problems. PMID:24163278

  1. 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

  2. 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

  3. 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

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

    PubMed

    Ding, Saidan; Huang, Weilong; Ye, Yiru; Yang, Jianjing; Hu, Jiangnan; Wang, Xiaobin; Liu, Leping; Lu, Qin; Lin, Yuanshao

    2014-09-01

    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

  5. 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

  6. 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

  7. Peripheral Hearing and Cognition: Evidence from the Staying Keen in Later Life (SKILL) Study

    PubMed Central

    Bush, Aryn L. Harrison; Lister, Jennifer J.; Lin, Frank R.; Betz, Joshua; Edwards, Jerri D.

    2015-01-01

    Research has increasingly suggested a consistent relationship between peripheral hearing and selected measures of cognition in older adults. However, other studies yield conflicting findings. Objectives The primary purpose of the present study was to further elucidate the relationship between peripheral hearing and three domains of cognition and one measure of global cognitive status. It was hypothesized that peripheral hearing loss would be significantly associated with poorer performance across measures of cognition, even after adjusting for documented risk factors. No study to date has examined the relationship between peripheral hearing and such an extensive array of cognitive measures. Design 894 older adult participants from the Staying Keen in Later Life study cohort were eligible, agreed to participate, and completed the baseline evaluation. Inclusion criteria were minimal to include a sample of older adults with a wide range of sensory and cognitive abilities. Multiple linear regression analyses were conducted to evaluate the extent to which peripheral hearing predicted performance on a global measure of cognitive status, as well as multiple cognitive measures in the domains of speed of processing (Digit Symbol Substitution and Copy, Trail-Making Test Part A, Letter and Pattern Comparison, and Useful Field of View), executive function (Trail-Making Test Part B and Stroop Color-Word Interference Task), and memory (Digit Span, Spatial Span, and Hopkins Verbal Learning Test). Results Peripheral hearing, measured as the three-frequency PTA in the better ear, accounted for a significant, but minimal, amount of the variance in measures of speed of processing, executive function, and memory, as well as global cognitive status. Alternative measures of hearing (i.e., three-frequency PTAs in the right and left ears and a bilateral, six-frequency PTA [three frequencies per ear]) yielded similar findings across measures of cognition and did not alter the study

  8. Caregiving Networks in Later Life: Does Cognitive Status Make a Difference?

    ERIC Educational Resources Information Center

    Strain, Laurel A.; Blandford, Audrey A.

    2003-01-01

    This study examines the caregiving networks of older adults, with particular emphasis on differences according to cognitive status (n = 303). Individuals with cognitive impairment were significantly more likely than those who were cognitively intact to receive assistance with personal care, linking with the outside world, and mobility. The types…

  9. 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

  10. The Family Life Course and Health: Partnership, Fertility Histories, and Later-Life Physical Health Trajectories in Australia.

    PubMed

    O'Flaherty, Martin; Baxter, Janeen; Haynes, Michele; Turrell, Gavin

    2016-06-01

    Life course perspectives suggest that later-life health reflects long-term social patterns over an individual's life: in particular, the occurrence and timing of key roles and transitions. Such social patterns have been demonstrated empirically for multiple aspects of fertility and partnership histories, including timing of births and marriage, parity, and the presence and timing of a marital disruption. Most previous studies have, however, addressed particular aspects of fertility or partnership histories singly. We build on this research by examining how a holistic classification of family life course trajectories from ages 18 to 50, incorporating both fertility and partnership histories, is linked to later-life physical health for a sample of Australian residents. Our results indicate that long-term family life course trajectories are strongly linked to later-life health for men but only minimally for women. For men, family trajectories characterized by early family formation, no family formation, an early marital disruption, or high fertility are associated with poorer physical health. Among women, only those who experienced both a disrupted marital history and a high level of fertility were found to be in poorer health. PMID:27189018

  11. 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. PMID:24513634

  12. 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

  13. 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

  14. 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

  15. [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. PMID:25139446

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

    PubMed Central

    Youssim, Iaroslav; Hank, Karsten; Litwin, Howard

    2014-01-01

    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. PMID:25651548

  17. 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. PMID:25651548

  18. 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

  19. Empowerment for Later Life.

    ERIC Educational Resources Information Center

    Myers, Jane E.

    This monograph purports that American society limits the behavior of older individuals based on the arbitrary criterion of chronological age and proposes the concept of empowerment--gaining a sense of personal power or control over over's life--as the antidote for older persons who face devalued status as they age and the for the accompanying drop…

  20. Sexuality in Later Life

    MedlinePlus

    ... find that affection—hugging, kissing, touching, and spending time together—can make a good beginning. For More Information Here are some helpful resources: American Cancer Society 1-800-227-2345 (toll-free/24 hours) ...

  1. Long-term effects of childhood sexual abuse: objective and subjective characteristics of the abuse and psychopathology in later life.

    PubMed

    Lange, A; de Beurs, E; Dolan, C; Lachnit, T; Sjollema, S; Hanewald, G

    1999-03-01

    This study investigates the association between objective and subjective characteristics of childhood sexual abuse and psychopathology in later life. The sample consists of 404 Dutch female adults who had been sexually abused in their childhood or adolescence. The participants were recruited by means of articles about childhood sexual abuse in major Dutch newspapers. The characteristics and severity of the sexual abuse were assessed with the Questionnaire Unwanted Sexual Experiences in the Past (QUSEP). General psychopathology was measured with the Symptom Checklist (SCL-90), the degree of dissociation was measured with the Dissociation Questionnaire (DIS-Q). Stepwise multiple regression analyses showed a moderate association between psychopathology and objective characteristics of the abuse, such as number of different types of abusive events and the duration of the abuse. However, more strongly associated with later psychopathology were variables reflecting coping style, such as the degree of self-blame, and circumstantial factors, such as the emotional atmosphere in the family of origin and the reactions after disclosure. Whether or not the abuse was incestuous did not explain additional variance in later psychopathology. PMID:10086471

  2. Early-Life Socioeconomic Status and Mortality in Later Life: An Integration of Four Life-Course Mechanisms

    PubMed Central

    2014-01-01

    Objectives. Using data from the Wisconsin Longitudinal Study, we examine (a) how socioeconomic status (SES) at age 18 affects all-cause mortality at ages 54–72, and (b) whether the effect of early-life SES is consistent with the critical period, accumulation of risks, social mobility, and pathway models. We also explore gender differences in the effect of early-life SES and life-course mechanisms. Method. Participants (N = 6,547) were surveyed in 1957, 1975, and 1993, with vital status established until 2011. We combine discrete-time survival analysis with structural equation modeling. SES and health behaviors are modeled as latent factors. Results. Early-life SES affects mortality indirectly via status attainment and health behaviors in adulthood and midlife. This finding is contrary to the critical period and consistent with the pathway model. Persistent disadvantage at three life stages is a strong risk factor for mortality, thus, supporting the accumulation of risks. Moreover, the mortality risk of individuals who experienced downward socioeconomic mobility is comparable to their peers with persistent disadvantage. Discussion. This study highlights the complexity of interrelated life-course processes underlying the effect of early-life SES on mortality in later life. PMID:24496607

  3. Quality of care after early childhood trauma and well-being in later life: child Holocaust survivors reaching old age.

    PubMed

    van der Hal-Van Raalte, Elisheva; Van Ijzendoorn, Marinus H; Bakermans-Kranenburg, Marian J

    2007-10-01

    The link between deprivation and trauma during earliest childhood and psychosocial functioning and health in later life was investigated in a group of child Holocaust survivors. In a nonconvenience sample 203 survivors, born between 1935 and 1944, completed questionnaires on Holocaust survival experience and several inventories on current health, depression, posttraumatic stress, loneliness, and attachment style. Quality of postwar care arrangements and current physical health independently predicted lack of well-being in old age. Loss of parents during the persecution, year of birth of the survivors (being born before or during the war), and memories of the Holocaust did not significantly affect present well-being. Lack of adequate care after the end of World War II is associated with lower well-being of the youngest Holocaust child survivors, even after an intervening period of 60 years. Our study validates Keilson's (1992) concept of "sequential traumatization," and points to the importance of aftertrauma care in decreasing the impact of early childhood trauma. PMID:18194031

  4. 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

  5. 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. PMID:26325301

  6. 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

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

    PubMed Central

    Singh, Shilpee; Zhuo, Ming; Gorgun, Murat; Englander, Ella W.

    2013-01-01

    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. PMID:23587847

  8. 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. PMID:23587847

  9. Holding On and Letting Go: The Perspectives of Pre-Seniors and Seniors on Driving Self-Regulation in Later Life

    ERIC Educational Resources Information Center

    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…

  10. 8-Oxoguanine accumulation in mitochondrial DNA causes mitochondrial dysfunction and impairs neuritogenesis in cultured adult mouse cortical neurons under oxidative conditions

    PubMed Central

    Leon, Julio; Sakumi, Kunihiko; Castillo, Erika; Sheng, Zijing; Oka, Sugako; Nakabeppu, Yusaku

    2016-01-01

    Oxidative stress and mitochondrial dysfunction are implicated in aging-related neurodegenerative disorders. 8-Oxoguanine (8-oxoG), a common oxidised base lesion, is often highly accumulated in brains from patients with neurodegenerative disorders. MTH1 hydrolyses 8-oxo-2′-deoxyguanosine triphosphate (8-oxo-dGTP) to 8-oxo-dGMP and pyrophosphate in nucleotide pools, while OGG1 excises 8-oxoG paired with cytosine in DNA, thereby minimising the accumulation of 8-oxoG in DNA. Mth1/Ogg1-double knockout (TO-DKO) mice are highly susceptible to neurodegeneration under oxidative conditions and show increased accumulation of 8-oxoG in mitochondrial DNA (mtDNA) in neurons, suggesting that 8-oxoG accumulation in mtDNA causes mitochondrial dysfunction. Here, we evaluated the contribution of MTH1 and OGG1 to the prevention of mitochondrial dysfunction during neuritogenesis in vitro. We isolated cortical neurons from adult wild-type and TO-DKO mice and maintained them with or without antioxidants for 2 to 5 days and then examined neuritogenesis. In the presence of antioxidants, both TO-DKO and wild-type neurons exhibited efficient neurite extension and arborisation. However, in the absence of antioxidants, the accumulation of 8-oxoG in mtDNA of TO-DKO neurons was increased resulting in mitochondrial dysfunction. Cells also exhibited poor neurite outgrowth with decreased complexity of neuritic arborisation, indicating that MTH1 and OGG1 are essential for neuritogenesis under oxidative conditions. PMID:26912170

  11. Early Life Dietary Spray Dried Plasma Influences Immunological and Intestinal Injury Responses to Later Life Salmonella Typhimurium Challenge

    PubMed Central

    Boyer, P.E.; D’Costa, S.; Edwards, L.L.; Milloway, M.; Susick, E.; Borst, L.B.; Thakur, S.; Campbell, J.M.; Crenshaw, J.D.; Polo, J.; Moeser, A.J.

    2015-01-01

    Increasing evidence supports that early life environmental influences, including nutrition and stress, impact long-term health outcomes and disease susceptibility. The objective of the current study was to determine whether dietary spray-dried plasma (SDP) fed during the first 2 weeks post-weaning (PW) influences subsequent immunological and intestinal injury responses to S. Typhimurium challenge. Thirty two piglets (16–17 d of age) were weaned onto nursery diets containing 0% SDP, 2.5% SDP (fed for 7 d PW), or 5% SDP (for 14 d PW) and were then fed control diets (without SDP), for the remainder of the experiment. At 34 d PW (50 d of age), pigs were challenged with 3×109 cfu S. Typhimurium. A control group (non-challenged) that was fed 0% SDP in the nursery was included. At 2 d post-challenge, distal ileum was harvested for measurement of inflammatory, histological, and intestinal physiological parameters. S. Typhimurium challenge induced elevated ileal histological scores, myeloperoxidase (MPO), IL-8, and TNF, and increased intestinal permeability (indicated by reduced transepithelial voltage (PD) and elevated FD4 flux rates). Compared with S. Typhimurium-challenged controls (0% SDP), pigs fed 5% SDP-14 d exhibited reduced ileal histological scores, MPO, IL-8, and FD4 flux rates. Pigs fed 5% SDP-14 d in the nursery exhibited increased levels of plasma and ileal TNFα in response to challenge, compared with other treatments. These results indicate that inclusion of SDP into PW diets can have influence subsequent immunological responses and intestinal injury induced by later life S. Typhimurium challenge. PMID:25671331

  12. Is regular drinking in later life an indicator of good health? Evidence from the English Longitudinal Study of Ageing

    PubMed Central

    Holdsworth, Clare; Mendonça, Marina; Pikhart, Hynek; Frisher, Martin; de Oliveira, Cesar; Shelton, Nicola

    2016-01-01

    Background Older people who drink have been shown to have better health than those who do not. This might suggest that moderate drinking is beneficial for health, or, as considered here, that older people modify their drinking as their health deteriorates. The relationship between how often older adults drink and their health is considered for two heath states: self-rated health (SRH) and depressive symptoms. Methods Data were analysed from the English Longitudinal Study of Ageing (ELSA), a prospective cohort study of older adults, using multilevel ordered logit analysis. The analysis involved 4741 participants present at wave 0, (1998/1999 and 2001), wave 4 (2008/2009) and wave 5 (2010/2011). The outcome measure was frequency of drinking in last year recorded at all three time points. Results Older adults with fair/poor SRH at the onset of the study drank less frequently compared with adults with good SRH (p<0.05). Drinking frequency declined over time for all health statuses, though respondents with both continual fair/poor SRH and declining SRH experienced a sharper reduction in the frequency of their drinking over time compared with older adults who remained in good SRH or whose health improved. The findings were similar for depression, though the association between depressive symptoms and drinking frequency at the baseline was not significant after adjusting for confounding variables. Conclusions The frequency of older adults’ drinking responds to changes in health status and drinking frequency in later life may be an indicator, rather than a cause, of health status. PMID:26797821

  13. 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. PMID:23872286

  14. Dopamine D1 receptor activation rescues extinction impairments in low-estrogen female rats and induces cortical layer-specific activation changes in prefrontal-amygdala circuits.

    PubMed

    Rey, Colin D; Lipps, Jennifer; Shansky, Rebecca M

    2014-04-01

    Post-traumatic stress disorder (PTSD) is twice as common in women as in men; it is a major public health problem whose neurobiological basis is unknown. In preclinical studies using fear conditioning and extinction paradigms, women and female animals with low estrogen levels exhibit impaired extinction retrieval, but the mechanisms that underlie these hormone-based discrepancies have not been identified. There is much evidence that estrogen can modulate dopaminergic transmission, and here we tested the hypothesis that dopamine-estrogen interactions drive extinction processes in females. Intact male and female rats were trained on cued fear conditioning, and received an intraperitoneal injection of a D1 agonist or vehicle before extinction learning. As reported previously, females that underwent extinction during low estrogen estrous phases (estrus/metaestrus/diestrus (EMD)) froze more during extinction retrieval than those that had been in the high-estrogen phase (proestrus; PRO). However, D1 stimulation reversed this relationship, impairing extinction retrieval in PRO and enhancing it in EMD. We also combined retrograde tracing and fluorescent immunohistochemistry to measure c-fos expression in infralimbic (IL) projections to the basolateral area of the amygdala (BLA), a neural pathway known to be critical to extinction retrieval. Again we observed diverging, estrous-dependent effects; SKF treatment induced a positive correlation between freezing and IL-BLA circuit activation in EMD animals, and a negative correlation in PRO animals. These results show for the first time that hormone-dependent extinction deficits can be overcome with non-hormone-based interventions, and suggest a circuit-specific mechanism by which these behavioral effects occur. PMID:24343528

  15. Combined alpha2 and D2/3 receptor blockade enhances cortical glutamatergic transmission and reverses cognitive impairment in the rat.

    PubMed

    Marcus, Monica M; Jardemark, Kent E; Wadenberg, Marie-Louise; Langlois, Xavier; Hertel, Peter; Svensson, Torgny H

    2005-09-01

    The alpha(2) adrenoceptor antagonist idazoxan enhances antipsychotic efficacy of classical dopamine D(2) antagonists in treatment-resistant schizophrenia. The mechanisms are not fully understood, but we have previously shown that the combination of idazoxan with the D(2/3) receptor antagonist raclopride, similarly to clozapine but not classical antipsychotic drugs, augments dopamine efflux in the prefrontal cortex, and also generates an enhanced suppression of the conditioned avoidance response. We have now investigated the effects of clozapine, raclopride, idazoxan and the combination of raclopride and idazoxan on (i) electrically evoked excitatory post-synaptic potentials and currents in pyramidal cells of the rat medial prefrontal cortex, using intracellular electrophysiological recording in vitro, (ii) the impaired cognitive function induced by the selective N-methyl-D-aspartate (NMDA) receptor antagonist MK-801, using the 8-arm radial maze test, (iii) the in-vivo D2, alpha(2A) and alpha(2C) receptor occupancies of these pharmacological treatments, using ex-vivo autoradiography. Whereas neither idazoxan nor raclopride alone had any effect, the combination exerted the same facilitation of glutamatergic transmission in rat prefrontal pyramidal neurons as clozapine, and this effect was found to be mediated by dopamine acting at D(1) receptors. Similarly to clozapine, the combination of idazoxan and raclopride also completely reversed the working-memory impairment in rats induced by MK-801. Moreover, these effects of the two treatment regimes were obtained at similar occupancies at D(2), alpha(2A) and alpha(2C) receptors respectively. Our results provide novel neurobiological and behavioural support for a pro-cognitive effect of adjunctive use of idazoxan with antipsychotic drugs that lack appreciable alpha(2) adrenoceptor-blocking properties, and define presynaptic alpha(2) adrenoceptors as major targets in antipsychotic drug development. PMID:15857571

  16. 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

  17. Antibodies directed to Neisseria gonorrhoeae impair nerve growth factor-dependent neurite outgrowth in Rat PC12 cells.

    PubMed

    Reuss, B

    2014-03-01

    In children born from mothers with prenatal infections with the Gram-negative bacterium Neisseria gonorrhoeae, schizophrenia risk is increased in later life. Since cortical neuropil formation is frequently impaired during this disease, actions of a rabbit polyclonal antiserum directed to N. gonorrhoeae on neurite outgrowth in nerve growth factor-stimulated PC12 cells were investigated here. It turned out that 10 μg/ml of the antiserum leads indeed to a significant reduction in neurite outgrowth, whereas an antiserum directed to Neisseria meningitidis had no such effect. Furthermore, reduction in neurite outgrowth could be reversed by the neuroleptic drugs haloperidol, clozapine, risperidone, and olanzapine. On the molecular level, the observed effects seem to include the known neuritogenic transcription factors FoxO3a and Stat3, since reduced neurite outgrowth caused by the antiserum was accompanied by a reduced phosphorylation of both factors. In contrast, restitution of neurite outgrowth by neuroleptic drugs revealed no correlation to the phosphorylation state of these factors. The present report gives a first hint that bacterial infections could indeed lead to impaired neuropil formation in vitro; however, the in vivo relevance of this finding for schizophrenia pathogenesis remains to be clarified in the future. PMID:24203572

  18. Movement-related cortical activation in familial Parkinson disease.

    PubMed

    Delval, A; Defebvre, L; Labyt, E; Douay, X; Bourriez, J-L; Waucquiez, N; Derambure, P; Destée, A

    2006-09-26

    We sought to determine whether or not first-degree relatives of patients with familial Parkinson disease (FDRs) present impaired movement-related cortical activity. We studied 10 familial Parkinson disease subjects, 10 FDRs, and 10 controls and analyzed event-related mu desynchronization (ERD) and beta synchronization. Forty percent FDRs presented reduced premovement mu ERD latency, suggesting that premovement cortical activation is impaired in FDRs. PMID:17000986

  19. 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

  20. ‘You learn to live with all the things that are wrong with you’: gender and the experience of multiple chronic conditions in later life

    PubMed Central

    CLARKE, LAURA HURD; BENNETT, ERICA

    2014-01-01

    This article examines how older adults experience the physical and social realities of having multiple chronic conditions in later life. Drawing on data from in-depth interviews with 16 men and 19 women aged 73+ who had between three and 14 chronic conditions, we address the following research questions: (a) What is it like to have multiple chronic conditions in later life? (b) How do older men and women ‘learn to live’ with the physical and social realities of multiple morbidities? (c) How are older adults’ experiences of illness influenced by age and gender norms? Our participants experienced their physical symptoms and the concomitant limitations to their activities to be a source of personal disruption. However, they normalised their illnesses and made social comparisons in order to achieve a sense of biographical flow in distinctly gendered ways. Forthright in their frustration over their loss of autonomy and physicality but resigned and stoic, the men’s stories reflected masculine norms of control, invulnerability, physical prowess, self-reliance and toughness. The women were dismayed by their bodies’ altered appearances and concerned about how their illnesses might affect their significant others, thereby responding to feminine norms of selflessness, sensitivity to others and nurturance. We discuss the findings in relation to the competing concepts of biographical disruption and biographical flow, as well as successful ageing discourses. PMID:24976658

  1. Cortical Thickness Abnormalities in Late Adolescence with Online Gaming Addiction

    PubMed Central

    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. PMID:23326379

  2. 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. PMID:23326379

  3. 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

  4. 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

  5. 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

  6. Developmental Programming of Nonalcoholic Fatty Liver Disease: The Effect of Early Life Nutrition on Susceptibility and Disease Severity in Later Life

    PubMed Central

    Li, Minglan; Reynolds, Clare M.; Segovia, Stephanie A.; Vickers, Mark H.

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is fast becoming the most common liver disease globally and parallels rising obesity rates. The developmental origins of health and disease hypothesis have linked alterations in the early life environment to an increased risk of metabolic disorders in later life. Altered early life nutrition, in addition to increasing risk for the development of obesity, type 2 diabetes, and cardiovascular disease in offspring, is now associated with an increased risk for the development of NAFLD. This review summarizes emerging research on the developmental programming of NAFLD by both maternal obesity and undernutrition with a particular focus on the possible mechanisms underlying the development of hepatic dysfunction and potential strategies for intervention. PMID:26090409

  7. 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

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

    PubMed

    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(ICN-TG)). Following exposure of adult Notch(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 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 Notch(ICN-TG) offspring have a peripheral T cell pool heavily biased toward the CD4 lineage, while TCDD-exposed Notch(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. PMID:25585350

  9. 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

  10. Cortical thinning in former professional soccer players.

    PubMed

    Koerte, Inga K; Mayinger, Michael; Muehlmann, Marc; Kaufmann, David; Lin, Alexander P; Steffinger, Denise; Fisch, Barbara; Rauchmann, Boris-Stephan; Immler, Stefanie; Karch, Susanne; Heinen, Florian R; Ertl-Wagner, Birgit; Reiser, Maximilian; Stern, Robert A; Zafonte, Ross; Shenton, Martha E

    2016-09-01

    Soccer is the most popular sport in the world. Soccer players are at high risk for repetitive subconcussive head impact when heading the ball. Whether this leads to long-term alterations of the brain's structure associated with cognitive decline remains unknown. The aim of this study was to evaluate cortical thickness in former professional soccer players using high-resolution structural MR imaging. Fifteen former male professional soccer players (mean age 49.3 [SD 5.1] years) underwent high-resolution structural 3 T MR imaging, as well as cognitive testing. Fifteen male, age-matched former professional non-contact sport athletes (mean age 49.6 [SD 6.4] years) served as controls. Group analyses of cortical thickness were performed using voxel-based statistics. Soccer players demonstrated greater cortical thinning with increasing age compared to controls in the right inferolateral-parietal, temporal, and occipital cortex. Cortical thinning was associated with lower cognitive performance as well as with estimated exposure to repetitive subconcussive head impact. Neurocognitive evaluation revealed decreased memory performance in the soccer players compared to controls. The association of cortical thinning and decreased cognitive performance, as well as exposure to repetitive subconcussive head impact, further supports the hypothesis that repetitive subconcussive head impact may play a role in early cognitive decline in soccer players. Future studies are needed to elucidate the time course of changes in cortical thickness as well as their association with impaired cognitive function and possible underlying neurodegenerative process. PMID:26286826

  11. Substance abuse in later life.

    PubMed Central

    D'Archangelo, E.

    1993-01-01

    Substance abuse affects an appreciable portion of the elderly population. Elderly people have characteristics that could hinder identification, diagnosis, intervention, and treatment of substance abuse. If physicians use strategies specific to the elderly, management is often successful. PMID:8219846

  12. 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

  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 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

  14. 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

  15. 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

  16. 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

  17. Oral antigen exposure in extreme early life in lambs influences the magnitude of the immune response which can be generated in later life

    PubMed Central

    2013-01-01

    Background Previous investigations in newborn lambs determined that adenovirus-mediated expression of antigen to a localized region of the gut induced antigen-specific mucosal and systemic immunity. These experiments were limited in that the localized region of the gut to which antigen was introduced was sterile and the influence of colostrum on the antigen was not assessed but they do suggest that mucosal vaccines may be an effective vaccination strategy to protect neonatal lambs. We propose that persistent oral antigen exposure introduced in extreme early life can induce immunity in lambs, despite the presence of commensal bacteria and colostrum. Results To test this hypothesis, conventionally raised newborn lambs (n = 4 per group) were gavaged with ovalbumin (OVA) starting the day after birth for either a single day (2.27 g), every day for 3 days (0.23 g/day), or every day for 3 days then every second day until nine days of age (0.023 g/day). Lambs gavaged with OVA for 3 to 9 days developed significant serum anti-OVA IgG titres (p < 0.05), but not IgA titres, relative to control lambs (n = 4) after 3 and 4 weeks. At 4 weeks of age, lambs were immunized with OVA in Incomplete Freund’s Adjuvant via intraperitoneal (i.p.) injection then lambs were euthanized at 7 weeks. Serum anti-OVA IgG titres were further augmented after i.p. immunization indicating immunity persisted and tolerance was not induced. Serum IgA titres remained low regardless of treatment. It is known that i.p. priming of sheep with antigen in Freund’s complete adjuvant leads to an enhanced number of IgA and IgG antibody containing cells in the respiratory mucosa (Immunology 53(2):375–384, 1984). Lambs gavaged with a single bolus of 2.27 g OVA prior to i.p. immunization showed very low titres of anti-OVA IgA in the lung lavage. These data suggest that a single, high dose exposure to OVA can promote tolerance which impacts response to systemic vaccination in later life

  18. Programme and policy issues related to promoting positive early nutritional influences to prevent obesity, diabetes and cardiovascular disease in later life: a developing countries view.

    PubMed

    Solomons, Noel W

    2005-07-01

    Public health policy differs from programme insofar as the former is the expression of goals at a higher decision-making level (international, regional, national or provincial) and the latter involves the execution of intervention measures at the community or individual level. It has recently become fashionable to speak of "evidence-based" policy. There is now ample evidence to suggest that early nutritional influences on chronic disease risk in later life are contributing to the acceleration of the overall worldwide epidemic of obesity and non-transmissible diseases. In developing countries, in which 80% of the world's population resides, the opportunities for preventive policy must be balanced against needs, cost and effectiveness considerations and the intrinsic limitations of policy execution. Not everyone in the population is at risk of suffering from any given negative condition of interest, nor will everyone at risk benefit from any given intervention. Hence, decisions must be made between universal or targeted policies, seeking maximal cost-efficiency, but without sowing the seeds of either discrimination or stigmatization with a non-universal application of benefits. Moreover, although large segments of the covered population may benefit from a public health measure, it may produce adverse and harmful effects on another segment. It is ethically incumbent on policy makers to minimize unintended consequences of public health measures. With respect to the particular case of mothers, fetuses and infants and long-term health, only a limited number of processes are amenable to intervention measures that could be codified in policy and executed as programmes. PMID:16881901

  19. 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

  20. 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

  1. Prenatal Cerebral Ischemia Disrupts MRI-Defined Cortical Microstructure Through Disturbances in Neuronal Arborization

    PubMed Central

    Hansen, Kelly; Azimi-Zonooz, Aryan; Chen, Kevin; Riddle, Art; Gong, Xi; Sharifnia, Elica; Hagen, Matthew; Ahmad, Tahir; Leigland, Lindsey A.; Back, Stephen A.

    2013-01-01

    Children who survive preterm birth exhibit persistent unexplained disturbances in cerebral cortical growth with associated cognitive and learning disabilities. The mechanisms underlying these deficits remain elusive. We used ex vivo diffusion magnetic resonance imaging to demonstrate in a preterm large-animal model that cerebral ischemia impairs cortical growth and the normal maturational decline in cortical fractional anisotropy (FA). Analysis of pyramidal neurons revealed that cortical deficits were associated with impaired expansion of the dendritic arbor and reduced synaptic density. Together, these findings suggest a link between abnormal cortical FA and disturbances of neuronal morphological development. To experimentally investigate this possibility, we measured the orientation distribution of dendritic branches and observed that it corresponds with the theoretically predicted pattern of increased anisotropy within cases that exhibited elevated cortical FA after ischemia. We conclude that cortical growth impairments are associated with diffuse disturbances in the dendritic arbor and synapse formation of cortical neurons, which may underlie the cognitive and learning disabilities in survivors of preterm birth. Further, measurement of cortical FA may be useful for noninvasively detecting neurological disorders affecting cortical development. PMID:23325800

  2. 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

  3. Pharmacology of cortical inhibition

    PubMed Central

    Krnjević, K.; Randić, Mirjana; Straughan, D. W.

    1966-01-01

    1. We have studied the effects of various pharmacological agents on the cortical inhibitory process described in the previous two papers (Krnjević, Randić & Straughan, 1966a, b); the drugs were mostly administered directly by iontophoresis from micropipettes and by systemic injection (I.V.). 2. Strychnine given by iontophoresis or by the application of a strong solution to the cortical surface potentiated excitatory effects, but very large iontophoretic doses also depressed neuronal firing. Subconvulsive and even convulsive systemic doses had little or no effect at the cortical level. There was no evidence, with any method of application, that strychnine directly interferes with the inhibitory process. 3. Tetanus toxin, obtained from two different sources and injected into the cortex 12-48 hr previously, also failed to block cortical inhibition selectively. As with strychnine, there was some evidence of increased responses to excitatory inputs. 4. Other convulsant drugs which failed to block cortical inhibition included picrotoxin, pentamethylene tetrazole, thiosemicarbazide, longchain ω-amino acids and morphine. 5. The inhibition was not obviously affected by cholinomimetic agents or by antagonists of ACh. 6. α- and β-antagonists of adrenergic transmission were also ineffective. 7. Cortical inhibition was fully developed in the presence of several general anaesthetics, including ether, Dial, pentobarbitone, Mg and chloralose. A temporary reduction in inhibition which is sometimes observed after systemic doses of pentobarbitone, is probably secondary to a fall in blood pressure. 8. Several central excitants such as amphetamine, caffeine and lobeline also failed to show any specific antagonistic action on cortical inhibition. 9. In view of the possibility that GABA is the chemical agent mediating cortical inhibition, an attempt was made to find a selective antagonist of its depressant action on cortical neurones. None of the agents listed above, nor any other

  4. Abnormalities of fixation, saccade and pursuit in posterior cortical atrophy.

    PubMed

    Shakespeare, Timothy J; Kaski, Diego; Yong, Keir X X; Paterson, Ross W; Slattery, Catherine F; Ryan, Natalie S; Schott, Jonathan M; Crutch, Sebastian J

    2015-07-01

    whose frequency correlated significantly with generalized reductions in cortical thickness. Patients with both posterior cortical atrophy and typical Alzheimer's disease showed lower gain in smooth pursuit compared to controls. The current study establishes that eye movement abnormalities are near-ubiquitous in posterior cortical atrophy, and highlights multiple aspects of saccadic performance which distinguish posterior cortical atrophy from typical Alzheimer's disease. We suggest the posterior cortical atrophy oculomotor profile (e.g. exacerbation of the saccadic gap/overlap effect, preserved saccadic velocity) reflects weak input from degraded occipito-parietal spatial representations of stimulus location into a superior collicular spatial map for eye movement regulation. This may indicate greater impairment of identification of oculomotor targets rather than generation of oculomotor movements. The results highlight the critical role of spatial attention and object identification but also precise stimulus localization in explaining the complex real world perception deficits observed in posterior cortical atrophy and many other patients with dementia-related visual impairment. PMID:25895507

  5. Abnormalities of fixation, saccade and pursuit in posterior cortical atrophy

    PubMed Central

    Kaski, Diego; Yong, Keir X. X.; Paterson, Ross W.; Slattery, Catherine F.; Ryan, Natalie S.; Schott, Jonathan M.; Crutch, Sebastian J.

    2015-01-01

    saccadic intrusions whose frequency correlated significantly with generalized reductions in cortical thickness. Patients with both posterior cortical atrophy and typical Alzheimer’s disease showed lower gain in smooth pursuit compared to controls. The current study establishes that eye movement abnormalities are near-ubiquitous in posterior cortical atrophy, and highlights multiple aspects of saccadic performance which distinguish posterior cortical atrophy from typical Alzheimer’s disease. We suggest the posterior cortical atrophy oculomotor profile (e.g. exacerbation of the saccadic gap/overlap effect, preserved saccadic velocity) reflects weak input from degraded occipito-parietal spatial representations of stimulus location into a superior collicular spatial map for eye movement regulation. This may indicate greater impairment of identification of oculomotor targets rather than generation of oculomotor movements. The results highlight the critical role of spatial attention and object identification but also precise stimulus localization in explaining the complex real world perception deficits observed in posterior cortical atrophy and many other patients with dementia-related visual impairment. PMID:25895507

  6. 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

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

    PubMed

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

    2016-03-01

    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

  8. Cholinergic systems are essential for late-stage maturation and refinement of motor cortical circuits

    PubMed Central

    Ramanathan, Dhakshin S.; Conner, James M.; Anilkumar, Arjun A.

    2014-01-01

    Previous studies reported that early postnatal cholinergic lesions severely perturb early cortical development, impairing neuronal cortical migration and the formation of cortical dendrites and synapses. These severe effects of early postnatal cholinergic lesions preclude our ability to understand the contribution of cholinergic systems to the later-stage maturation of topographic cortical representations. To study cholinergic mechanisms contributing to the later maturation of motor cortical circuits, we first characterized the temporal course of cortical motor map development and maturation in rats. In this study, we focused our attention on the maturation of cortical motor representations after postnatal day 25 (PND 25), a time after neuronal migration has been accomplished and cortical volume has reached adult size. We found significant maturation of cortical motor representations after this time, including both an expansion of forelimb representations in motor cortex and a shift from proximal to distal forelimb representations to an extent unexplainable by simple volume enlargement of the neocortex. Specific cholinergic lesions placed at PND 24 impaired enlargement of distal forelimb representations in particular and markedly reduced the ability to learn skilled motor tasks as adults. These results identify a novel and essential role for cholinergic systems in the late refinement and maturation of cortical circuits. Dysfunctions in this system may constitute a mechanism of late-onset neurodevelopmental disorders such as Rett syndrome and schizophrenia. PMID:25505106

  9. Cholinergic systems are essential for late-stage maturation and refinement of motor cortical circuits.

    PubMed

    Ramanathan, Dhakshin S; Conner, James M; Anilkumar, Arjun A; Tuszynski, Mark H

    2015-03-01

    Previous studies reported that early postnatal cholinergic lesions severely perturb early cortical development, impairing neuronal cortical migration and the formation of cortical dendrites and synapses. These severe effects of early postnatal cholinergic lesions preclude our ability to understand the contribution of cholinergic systems to the later-stage maturation of topographic cortical representations. To study cholinergic mechanisms contributing to the later maturation of motor cortical circuits, we first characterized the temporal course of cortical motor map development and maturation in rats. In this study, we focused our attention on the maturation of cortical motor representations after postnatal day 25 (PND 25), a time after neuronal migration has been accomplished and cortical volume has reached adult size. We found significant maturation of cortical motor representations after this time, including both an expansion of forelimb representations in motor cortex and a shift from proximal to distal forelimb representations to an extent unexplainable by simple volume enlargement of the neocortex. Specific cholinergic lesions placed at PND 24 impaired enlargement of distal forelimb representations in particular and markedly reduced the ability to learn skilled motor tasks as adults. These results identify a novel and essential role for cholinergic systems in the late refinement and maturation of cortical circuits. Dysfunctions in this system may constitute a mechanism of late-onset neurodevelopmental disorders such as Rett syndrome and schizophrenia. PMID:25505106

  10. 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

  11. 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

  12. Cortical motion deafness.

    PubMed

    Ducommun, Christine Y; Michel, Christoph M; Clarke, Stephanie; Adriani, Michela; Seeck, Margitta; Landis, Theodor; Blanke, Olaf

    2004-09-16

    The extent to which the auditory system, like the visual system, processes spatial stimulus characteristics such as location and motion in separate specialized neuronal modules or in one homogeneously distributed network is unresolved. Here we present a patient with a selective deficit for the perception and discrimination of auditory motion following resection of the right anterior temporal lobe and the right posterior superior temporal gyrus (STG). Analysis of stimulus identity and location within the auditory scene remained intact. In addition, intracranial auditory evoked potentials, recorded preoperatively, revealed motion-specific responses selectively over the resected right posterior STG, and electrical cortical stimulation of this region was experienced by the patient as incoming moving sounds. Collectively, these data present a patient with cortical motion deafness, providing evidence that cortical processing of auditory motion is performed in a specialized module within the posterior STG. PMID:15363389

  13. Cortical development and neuroplasticity in Auditory Neuropathy Spectrum Disorder.

    PubMed

    Sharma, Anu; Cardon, Garrett

    2015-12-01

    Cortical development is dependent to a large extent on stimulus-driven input. Auditory Neuropathy Spectrum Disorder (ANSD) is a recently described form of hearing impairment where neural dys-synchrony is the predominant characteristic. Children with ANSD provide a unique platform to examine the effects of asynchronous and degraded afferent stimulation on cortical auditory neuroplasticity and behavioral processing of sound. In this review, we describe patterns of auditory cortical maturation in children with ANSD. The disruption of cortical maturation that leads to these various patterns includes high levels of intra-individual cortical variability and deficits in cortical phase synchronization of oscillatory neural responses. These neurodevelopmental changes, which are constrained by sensitive periods for central auditory maturation, are correlated with behavioral outcomes for children with ANSD. Overall, we hypothesize that patterns of cortical development in children with ANSD appear to be markers of the severity of the underlying neural dys-synchrony, providing prognostic indicators of success of clinical intervention with amplification and/or electrical stimulation. This article is part of a Special Issue entitled . PMID:26070426

  14. 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. PMID:24139950

  15. Cognitive Impairment After Stroke

    PubMed Central

    Gauba, Charu; Chaudhari, Dinesh

    2015-01-01

    Background: Vascular dementia is extremely common and contributes to stroke-associated morbidity and mortality. The study of vascular dementia may help to plan preventive interventions. Aims: To study the frequency of cognitive impairment after stroke in a series of consecutive patients with acute stroke, along with factors which influence it. Methods: Fifty adults with acute infarct or hemorrhage (as seen on computed tomography of the brain) were included in the study. The National Institute of Health Stroke Scale (NIHSS) and Barthel’s Index scores were done. Cognitive testing was done by PGI Battery of Brain Dysfunction (PGI-BBD) and Short Form of the Informant Questionnaire on Cognitive Decline in the Elderly (SIQCODE). Statistical analysis was by Student’s t-test, Chi-square test, Fisher’s exact test, and Mann-Whitney U test. Results: Mean age of patients was 61.82 years; males and ischemic strokes predominated. Dementia was seen in 30%, cognitive impairment no dementia (CIND) in 42%, and normal cognition in 28% patients. Factors associated with vascular cognitive impairment included old age, male sex, low education, hemorrhages, recurrent or severe stroke, silent infarcts, severe cortical atrophy, and left hemispheric or subcortical involvement. Conclusions: Up to 72% of patients have some form of cognitive impairment after a stroke. Secondary stroke prevention could reduce the incidence of vascular dementia. PMID:26543693

  16. 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

  17. Grammatical Impairments in PPA

    PubMed Central

    Thompson, Cynthia K.; Mack, Jennifer E.

    2015-01-01

    Background Grammatical impairments are commonly observed in the agrammatic subtype of primary progressive aphasia (PPA-G), whereas grammatical processing is relatively preserved in logopenic (PPA-L) and semantic (PPA-S) subtypes. Aims We review research on grammatical deficits in PPA and associated neural mechanisms, with discussion focused on production and comprehension of four aspects of morphosyntactic structure: grammatical morphology, functional categories, verbs and verb argument structure, and complex syntactic structures. We also address assessment of grammatical deficits in PPA, with emphasis on behavioral tests of grammatical processing. Finally, we address research examining the effects of treatment for progressive grammatical impairments. Main Contribution PPA-G is associated with grammatical deficits that are evident across linguistic domains in both production and comprehension. PPA-G is associated with damage to regions including the left inferior frontal gyrus (IFG) and dorsal white matter tracts, which have been linked to impaired comprehension and production of complex sentences. Detailing grammatical deficits in PPA is important for estimating the trajectory of language decline and associated neuropathology. We, therefore, highlight several new assessment tools for examining different aspects of morphosyntactic processing in PPA. Conclusions Individuals with PPA-G present with agrammatic deficit patterns distinct from those associated with PPA-L and PPA-S, but similar to those seen in agrammatism resulting from stroke, and patterns of cortical atrophy and white matter changes associated with PPA-G have been identified. Methods for clinical evaluation of agrammatism, focusing on comprehension and production of grammatical morphology, functional categories, verbs and verb argument structure, and complex syntactic structures are recommended and tools for this are emerging in the literature. Further research is needed to investigate the real

  18. Amyloid Beta-Weighted Cortical Thickness: A New Imaging Biomarker in Alzheimer's Disease.

    PubMed

    Kim, Chan Mi; Hwang, Jihye; Lee, Jong-Min; Roh, Jee Hoon; Lee, Jae-Hong; Koh, Jae-Young

    2015-01-01

    Alzheimer's disease (AD) is the most common neurodegenerative disorder pathologically characterized by amyloid-beta (Aβ) plaques and neurofibrillary tangles. The aggregation of Aβ precedes tau pathologies in AD; however, the causal relation between the two pathologies and the mechanisms by which aggregated forms of Aβ contribute to cortical thinning are not fully understood. We proposed quantitative Aβ-weighted cortical thickness analysis to investigate the regional relationship between cortical thinning and amyloid plaque deposition using magnetic resonance (MR) and Pittsburg Compound B (PiB) positron emission tomography (PET) images in patients with AD, mild cognitive impairment (MCI), and subjects with normal cognition. We hypothesized that there are cortical areas that have prominent changes associated with Aβ deposition and there are areas that are relatively independent from Aβ deposition where pathologies other than Aβ (such as tau) are predominant. The study was performed using MRI and PiB PET data from the Alzheimer's Disease Neuroimaging Initiative. We measured accuracy of classification models in three different pairs of groups comparing AD, MCI, and normal cognition. Classification models that used Aβ-weighted cortical thickness were not inferior to classification models that used only cortical thickness or amyloid deposition. In addition, based on timing of changes in cortical thinning and Aβ deposition such as Aβ deposition after cortical thinning; cortical thinning after Aβ deposition, or concurrent Aβ deposition and cortical thinning, we identified three types of relationships between cortical thinning and Aβ deposition: (1) Aβ-associated cortical thinning; (2) Aβ-independent cortical thinning; and (3) Aβ deposition only without cortical thinning. Taken together, these findings suggest that Aβ-weighted cortical thickness values can be used as an objective biomarker of structural changes caused by amyloid pathology in the brain. PMID

  19. It is not just muscle mass: a review of muscle quality, composition and metabolism during ageing as determinants of muscle function and mobility in later life.

    PubMed

    McGregor, Robin A; Cameron-Smith, David; Poppitt, Sally D

    2014-01-01

    Worldwide estimates predict 2 billion people will be aged over 65 years by 2050. A major current challenge is maintaining mobility and quality of life into old age. Impaired mobility is often a precursor of functional decline, disability and loss of independence. Sarcopenia which represents the age-related decline in muscle mass is a well-established factor associated with mobility limitations in older adults. However, there is now evidence that not only changes in muscle mass but other factors underpinning muscle quality including composition, metabolism, aerobic capacity, insulin resistance, fat infiltration, fibrosis and neural activation may also play a role in the decline in muscle function and impaired mobility associated with ageing. Importantly, changes in muscle quality may precede loss of muscle mass and therefore provide new opportunities for the assessment of muscle quality particularly in middle-aged adults who could benefit from interventions to improve muscle function. This review will discuss the accumulating evidence that in addition to muscle mass, factors underpinning muscle quality influence muscle function and mobility with age. Further development of tools to assess muscle quality in community settings is needed. Preventative diet, exercise or treatment interventions particularly in middle-aged adults at the low end of the spectrum of muscle function may help preserve mobility in later years and improve healthspan. PMID:25520782

  20. 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

  1. Nutrition as a part of healthy aging and reducing cardiovascular risk: improving functionality in later life using quality protein, with optimized timing and distribution.

    PubMed

    Dawson, Beryl M; Axford, Samantha

    2014-09-01

    Aging is associated with many physiological changes, which may in time lead to numerous pathophysiological outcomes, including adverse vascular events. For example, senescence of the immune system and cellular senescence both contribute to rising inflammation with age, potentially induced by the overall burden of comorbid illness, adipose tissue mass, diet, socioeconomic status, and physical activity. In turn, this chronic inflammation decreases physical and cognitive performance, and promotes sarcopenia and the syndrome of frailty. These events and others decrease the functionality of life as we age and include an increased risk of thrombosis and adverse cardiovascular outcomes. In this review, we aim to overview the aging process primarily as related to functional impairment, and provide evidence for the role of protein, and specifically differential quality protein, in particular whey protein, and timing and distribution of intake, to help reduce some of the morbid effects of aging, including reducing obesity, improving glycemic control, and improving vascular function. PMID:25151523

  2. 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

  3. 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

  4. 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

  5. The Crucial Role of Atg5 in Cortical Neurogenesis During Early Brain Development

    PubMed Central

    Lv, Xiaohui; Jiang, Huihui; Li, Baoguo; Liang, Qingli; Wang, Shukun; Zhao, Qianwei; Jiao, Jianwei

    2014-01-01

    Autophagy plays an important role in the central nervous system. However, it is unknown how autophagy regulates cortical neurogenesis during early brain development. Here, we report that autophagy-related gene 5 (Atg5) expression increased with cortical development and differentiation. The suppression of Atg5 expression by knockdown led to inhibited differentiation and increased proliferation of cortical neural progenitor cells (NPCs). Additionally, Atg5 suppression impaired cortical neuronal cell morphology. We lastly observed that Atg5 was involved in the regulation of the β-Catenin signaling pathway. The β-Catenin phosphorylation level decreased when Atg5 was blocked. Atg5 cooperated with β-Catenin to modulate cortical NPCs differentiation and proliferation. Our results revealed that Atg5 has a crucial role in cortical neurogenesis during early embryonic brain development, which may contribute to the understanding of neurodevelopmental disorders caused by autophagy dysregulation. PMID:25109817

  6. 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

  7. Malformations of cortical development

    PubMed Central

    Pang, Trudy; Atefy, Ramin; Sheen, Volney

    2012-01-01

    Background Malformations of cortical development (MCD) are increasingly recognized as an important cause of epilepsy and developmental delay. MCD encompass a wide spectrum of disorders with various underlying genetic etiologies and clinical manifestations. High resolution imaging has dramatically improved our recognition of MCD. Review Summary This review will provide a brief overview of the stages of normal cortical development, including neuronal proliferation, neuroblast migration, and neuronal organization. Disruptions at various stages lead to characteristic MCD. Disorders of neurogenesis give rise to microcephaly (small brain) or macrocephaly (large brain). Disorders of early neuroblast migration give rise to periventricular heterotopia (neurons located along the ventricles), whereas abnormalities later in migration lead to lissencephaly (smooth brain) or subcortical band heterotopia (smooth brain with a band of heterotopic neurons under the cortex). Abnormal neuronal migration arrest give rise to over-migration of neurons in cobblestone lissencephaly. Lastly, disorders of neuronal organization cause polymicrogyria (abnormally small gyri and sulci). This review will also discuss the known genetic mutations and potential mechanisms that contribute to these syndromes. Conclusion Identification of various gene mutations has not only given us greater insight into some of the pathophysiologic basis of MCD, but also an understanding of the processes involved in normal cortical development. PMID:18469675

  8. 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.

  9. Malformations of cortical development and aberrant cortical networks: epileptogenesis and functional organization.

    PubMed

    Guerrini, Renzo; Barba, Carmen

    2010-12-01

    Malformations of cortical development are a major cause of drug-resistant epilepsy. Focal cortical dysplasia, heterotopia, and polymicrogyria are often manifested as discrete areas of abnormal neuronal migration and improper development of the cerebral cortex. Some of the patients harboring these malformations have obvious neurologic impairment, but others show unexpected deficits that are detectable only by screening. The role of surgical treatment of epilepsy due to localized malformations of cortical development is now established. However, its technical application can be challenging in that localization of function based on anatomic landmarks may not be reliable. Intracranial recordings have shown a high propensity for complex epileptogenic networks that may include remote cortical and subcortical regions. The MRI visible area of cortical abnormality should therefore be regarded as just an indicator of the epileptogenic zone rather than its tangible substrate. Completeness of resection, after delineation of the ictal onset zone, a key factor for successful epilepsy surgery, may be particularly difficult, and invasive EEG monitoring is necessary in most patients. Neural plasticity issues are of primary importance to surgical planning as the possibility of removing eloquent cortex permits more complete procedures with potentially higher rates of success. However, the functional consequences of malformative lesions are still poorly understood; conservation of function in the dysplastic cortex, its atypical representation, and relocation outside the malformed area are all possible. Surgical planning for associated epilepsy should therefore be based on individual assessments of structural imaging and of the major functions relevant to the area in question in the individual patient. PMID:21076336

  10. 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

  11. Cortical basal ganglionic degeneration.

    PubMed

    Scarmeas, N; Chin, S S; Marder, K

    2001-10-01

    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

  12. Cortical trajectories during adolescence in preterm born teenagers with very low birthweight.

    PubMed

    Rimol, Lars M; Bjuland, Knut J; Løhaugen, Gro C C; Martinussen, Marit; Evensen, Kari Anne I; Indredavik, Marit S; Brubakk, Ann-Mari; Eikenes, Live; Håberg, Asta K; Skranes, Jon

    2016-02-01

    While cross-sectional neuroimaging studies on cortical development predict reductions in cortical volume (surface area and thickness) during adolescence, this is the first study to undertake a longitudinal assessment of cortical surface area changes across the continuous cortical surface during this period. We studied the developmental dynamics of cortical surface area and thickness in adolescents and young adults (aged 15-20) born with very low birth weight (VLBW; <1500 g) as well as in term-born controls. Previous studies have demonstrated brain structural abnormalities in cortical morphology, as well as long-term motor, cognitive and behavioral impairments, in adolescents and young adults with VLBW, but the developmental dynamics throughout adolescence have not been fully explored. T1-weighted MRI scans from 51 VLBW (27 scanned twice) and 79 term-born adolescents (37 scanned twice) were used to reconstruct the cortical surface and produce longitudinal estimates of cortical surface area and cortical thickness. Linear mixed model analyses were performed, and the main effects of time and group, as well as time × group interaction effects, were investigated. In both groups, cortical surface area decreased up to 5% in some regions, and cortical thickness up to 8%, over the five-year period. The most affected regions were located on the lateral aspect of the hemispheres, in posterior temporal, parietal and to some extent frontal regions. There was no significant interaction between time and group for either morphometry variable. In conclusion, cortical thickness decreases from 15 to 20 years of age, in a similar fashion in the clinical and control groups. Moreover, we show for the first time that developmental trajectories of cortical surface area in preterm and term-born adolescents do not diverge during adolescence. PMID:26773236

  13. 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

  14. 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

  15. 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

  16. More sensitivity of cortical GABAergic neurons than glutamatergic neurons in response to acidosis.

    PubMed

    Liu, Hua; Li, Fang; Wang, Chunyan; Su, Zhiqiang

    2016-05-25

    Acidosis impairs brain functions. Neuron-specific mechanisms underlying acidosis-induced brain dysfunction remain elusive. We studied the sensitivity of cortical GABAergic neurons and glutamatergic neurons to acidosis by whole-cell recording in brain slices. The acidification to the neurons was induced by perfusing artificial cerebral spinal fluid with lower pH. This acidification impairs excitability and synaptic transmission in the glutamatergic and GABAergic neurons. Acidosis impairs spiking capacity in the GABAergic neurons more than in the glutamatergic neurons. Acidosis also strengthens glutamatergic synaptic transmission and attenuates GABAergic synaptic transmission on the GABAergic neurons more than the glutamatergic neurons, which results in the functional impairment of these GABAergic neurons. This acidosis-induced dysfunction predominantly in the cortical GABAergic neurons drives the homeostasis of neuronal networks toward overexcitation and exacerbates neuronal impairment. PMID:27116702

  17. 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

  18. Decoding of Covert Vowel Articulation Using Electroencephalography Cortical Currents.

    PubMed

    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

  19. 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

  20. Muscle synergy patterns as physiological markers of motor cortical damage

    PubMed Central

    Cheung, Vincent C. K.; Turolla, Andrea; Agostini, Michela; Silvoni, Stefano; Bennis, Caoimhe; Kasi, Patrick; Paganoni, Sabrina; Bonato, Paolo; Bizzi, Emilio

    2012-01-01

    The experimental findings herein reported are aimed at gaining a perspective on the complex neural events that follow lesions of the motor cortical areas. Cortical damage, whether by trauma or stroke, interferes with the flow of descending signals to the modular interneuronal structures of the spinal cord. These spinal modules subserve normal motor behaviors by activating groups of muscles as individual units (muscle synergies). Damage to the motor cortical areas disrupts the orchestration of the modules, resulting in abnormal movements. To gain insights into this complex process, we recorded myoelectric signals from multiple upper-limb muscles in subjects with cortical lesions. We used a factorization algorithm to identify the muscle synergies. Our factorization analysis revealed, in a quantitative way, three distinct patterns of muscle coordination—including preservation, merging, and fractionation of muscle synergies—that reflect the multiple neural responses that occur after cortical damage. These patterns varied as a function of both the severity of functional impairment and the temporal distance from stroke onset. We think these muscle-synergy patterns can be used as physiological markers of the status of any patient with stroke or trauma, thereby guiding the development of different rehabilitation approaches, as well as future physiological experiments for a further understanding of postinjury mechanisms of motor control and recovery. PMID:22908288

  1. 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.

  2. Abnormal Cortical Development after Premature Birth Shown by Altered Allometric Scaling of Brain Growth

    PubMed Central

    Kapellou, Olga; Counsell, Serena J; Kennea, Nigel; Dyet, Leigh; Saeed, Nadeem; Stark, Jaroslav; Maalouf, Elia; Duggan, Philip; Ajayi-Obe, Morenike; Hajnal, Jo; Allsop, Joanna M; Boardman, James; Rutherford, Mary A; Cowan, Frances; Edwards, A. David

    2006-01-01

    Background We postulated that during ontogenesis cortical surface area and cerebral volume are related by a scaling law whose exponent gives a quantitative measure of cortical development. We used this approach to investigate the hypothesis that premature termination of the intrauterine environment by preterm birth reduces cortical development in a dose-dependent manner, providing a neural substrate for functional impairment. Methods and Findings We analyzed 274 magnetic resonance images that recorded brain growth from 23 to 48 wk of gestation in 113 extremely preterm infants born at 22 to 29 wk of gestation, 63 of whom underwent neurodevelopmental assessment at a median age of 2 y. Cortical surface area was related to cerebral volume by a scaling law with an exponent of 1.29 (95% confidence interval, 1.25–1.33), which was proportional to later neurodevelopmental impairment. Increasing prematurity and male gender were associated with a lower scaling exponent (p < 0.0001) independent of intrauterine or postnatal somatic growth. Conclusions Human brain growth obeys an allometric scaling relation that is disrupted by preterm birth in a dose-dependent, sexually dimorphic fashion that directly parallels the incidence of neurodevelopmental impairments in preterm infants. This result focuses attention on brain growth and cortical development during the weeks following preterm delivery as a neural substrate for neurodevelopmental impairment after premature delivery. PMID:16866579

  3. 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

  4. Hearing Impairments

    NASA Astrophysics Data System (ADS)

    Cavender, Anna; Ladner, Richard E.

    For many people with hearing impairments, the degree of hearing loss is only a small aspect of their disability and does not necessarily determine the types of accessibility solutions or accommodations that may be required. For some people, the ability to adjust the audio volume may be sufficient. For others, translation to a signed language may be more appropriate. For still others, access to text alternatives may be the best solution. Because of these differences, it is important for researchers in Web accessibility to understand that people with hearing impairments may have very different cultural-linguistic traditions and personal backgrounds.

  5. Functional neural substrates of posterior cortical atrophy patients.

    PubMed

    Shames, H; Raz, N; Levin, Netta

    2015-07-01

    Posterior cortical atrophy (PCA) is a neurodegenerative syndrome in which the most pronounced pathologic involvement is in the occipito-parietal visual regions. Herein, we aimed to better define the cortical reflection of this unique syndrome using a thorough battery of behavioral and functional MRI (fMRI) tests. Eight PCA patients underwent extensive testing to map their visual deficits. Assessments included visual functions associated with lower and higher components of the cortical hierarchy, as well as dorsal- and ventral-related cortical functions. fMRI was performed on five patients to examine the neuronal substrate of their visual functions. The PCA patient cohort exhibited stereopsis, saccadic eye movements and higher dorsal stream-related functional impairments, including simultant perception, image orientation, figure-from-ground segregation, closure and spatial orientation. In accordance with the behavioral findings, fMRI revealed intact activation in the ventral visual regions of face and object perception while more dorsal aspects of perception, including motion and gestalt perception, revealed impaired patterns of activity. In most of the patients, there was a lack of activity in the word form area, which is known to be linked to reading disorders. Finally, there was evidence of reduced cortical representation of the peripheral visual field, corresponding to the behaviorally assessed peripheral visual deficit. The findings are discussed in the context of networks extending from parietal regions, which mediate navigationally related processing, visually guided actions, eye movement control and working memory, suggesting that damage to these networks might explain the wide range of deficits in PCA patients. PMID:25976028

  6. Risk Factors and Consequences of Cortical Thickness in an Asian Population.

    PubMed

    Hilal, Saima; Xin, Xu; Ang, Seow Li; Tan, Chuen Seng; Venketasubramanian, Narayanaswamy; Niessen, Wiro J; Vrooman, Henri; Wong, Tien Yin; Chen, Christopher; Ikram, Mohammad Kamran

    2015-06-01

    Cortical thickness has been suggested to be one of the most important markers of cortical atrophy. In this study, we examined potential risk factors of cortical thickness and its association with cognition in an elderly Asian population from Singapore. This is a cross-sectional study among 572 Chinese and Malay patients from the ongoing Epidemiology of Dementia in Singapore (EDIS) Study, who underwent comprehensive examinations including neuropsychological testing and brain magnetic resonance imaging (MRI). Cortical thickness (in micrometers) was measured using a model-based automated procedure. Cognitive function was expressed as composite and domain-specific Z-scores. Cognitive impairment was categorized into cognitive impairment no dementia (CIND)-mild, CIND-moderate, and dementia in accordance with accepted criteria. Linear regression models were used to examine the association between various risk factors and cortical thickness. With respect to cognition as outcome, both linear (for Z-scores) and logistic (for CIND/dementia) regression models were constructed. Initial adjustments were made for age, sex, and education, and subsequently for other cardiovascular risk factors and MRI markers. Out of 572 included patients, 171 (29.9%) were diagnosed with CIND-mild, 197 (34.4%) with CIND-moderate, and 28 (4.9%) with dementia. Risk factors related to a smaller cortical thickness were increased age, male sex, Malay ethnicity, higher blood glucose, and body mass index levels and presence of lacunar infarcts on MRI. Smaller cortical thickness was associated with CIND moderate/dementia [odds ratio (OR) per standard deviation (SD) decrease: 1.70; 95% confidence interval (CI): 1.19-2.44, P = 0.004] and with composite Z-score reflecting global cognitive functioning [mean difference per SD decrease: -0.094; 95% CI: -0.159; -0.030, P = 0.004]. In particular, smaller cortical thicknesses in the occipital and temporal lobes were related to cognitive impairment. Finally

  7. Cortical thickness mediates the effect of β-amyloid on episodic memory

    PubMed Central

    Reed, Bruce R.; Wirth, Miranka; Haase, Claudia M.; Madison, Cindee M.; Ayakta, Nagehan; Mack, Wendy; Mungas, Dan; Chui, Helena C.; DeCarli, Charles; Weiner, Michael W.; Jagust, William J.

    2014-01-01

    Objective: To investigate the associations among β-amyloid (Aβ), cortical thickness, and episodic memory in a cohort of cognitively normal to mildly impaired individuals at increased risk of vascular disease. Methods: In 67 subjects specifically recruited to span a continuum of cognitive function and vascular risk, we measured brain Aβ deposition using [11C] Pittsburgh compound B–PET imaging and cortical thickness using MRI. Episodic memory was tested using a standardized composite score of verbal memory, and vascular risk was quantified using the Framingham Coronary Risk Profile index. Results: Increased Aβ was associated with cortical thinning, notably in frontoparietal regions. This relationship was strongest in persons with high Aβ deposition. Increased Aβ was also associated with lower episodic memory performance. Cortical thickness was found to mediate the relationship between Aβ and memory performance. While age had a marginal effect on these associations, the relationship between Aβ and cortical thickness was eliminated after controlling for vascular risk except when examined in only Pittsburgh compound B–positive subjects, in whom Aβ remained associated with thinner cortex in precuneus and occipital lobe. In addition, only the precuneus was found to mediate the relationship between Aβ and memory after controlling for vascular risk. Conclusion: These results suggest strong links among Aβ, cortical thickness, and memory. They highlight that, in individuals without dementia, vascular risk also contributes to cortical thickness and influences the relationships among Aβ, cortical thickness, and memory. PMID:24489134

  8. Stress and Diabetes Mellitus in Later Life.

    ERIC Educational Resources Information Center

    Krause, Neal

    1995-01-01

    Examines the relationship between stress and diabetes with data provided by a recent nationwide survey of older adults. Two main findings emerged. First, stressors arising in social roles that are highly important to older adults are more strongly related to diabetes than events associated with less important roles. Second, social support buffers…

  9. 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)

  10. 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

  11. 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

  12. Motivation in Later Life: Theory and Assessment.

    ERIC Educational Resources Information Center

    Vallerand, Robert J.; And Others

    1995-01-01

    Study utilizing self-determination theory (which poses four types of motivation: intrinsic, self-determined extrinsic, nonself-determined extrinsic, and amotivation) postulates varying consequences for adaptation and well-being. Finds the four types of motivation could be reliably measured and that intercorrelations between them were consistent…

  13. 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. PMID:25546500

  14. 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

  15. Marriage and Morale in Later Life

    ERIC Educational Resources Information Center

    Lee, Gary R.

    1978-01-01

    Investigates net effect of marital satisfaction on morale for a sample of married residents aged 60 and over. Results indicate existence of a positive effect and this effect appears notably stronger for females. (Author)

  16. Managing Complications of Diabetes in Later Life

    MedlinePlus

    ... 3orMore Aging & Health A to Z Find a Geriatrics Healthcare Professional Medications & Older Adults Making Your Wishes ... all of your healthcare providers. Note: The American Geriatrics Society’s 2012 Beers Criteria includes a list of ...

  17. 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. PMID:25850077

  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. 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

  20. [Cortical control of saccades].

    PubMed

    Pierrot-Deseilligny, C

    1989-01-01

    Among saccades triggered by the cerebral cortex, visually guided saccades are the best known and their cortical control is reviewed here. Only two immediately supra-reticular structures are able to trigger saccades (whatever their type): the frontal eye fields (FEF) and the superior colliculus (SC). These structures control two parallel excitatory pathways, which can replace each other in the event of lesion. Experimental findings have suggested that the colliculo-reticular pathway would, in the normal state, play the main role in the triggering of reflexive visually guided saccades. Furthermore experimental and clinical data suggest that the SC would receive an excitatory afference from the posterior part of the intraparietal sulcus, which could be involved in the triggering of these saccades. The parietal lobe could influence the SC by increasing the pre-excitation due to the onset of the visual target. There are also inhibitory pathways which prevent saccades, in particular during fixation. Two groups of tonic neurons inhibit the excitatory pathways. These are the omnipause neurons and the neurons of the substantia nigra (pars reticulata), which project upon the premotor reticular formations and the SC respectively. The pathways projecting upon these 2 types of neurons are multiple and still little known. Nevertheless, some arguments suggest that the frontal lobe partly controls inhibition. These arguments are based on a somewhat disinhibited triggering of reflexive visually guided saccades in focal or degenerative (progressive supranuclear palsy) frontal lesions. The prefrontal cortex could be involved in inhibition control, and it could act functionally above the FEF. PMID:2682934

  1. 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

  2. Maturation of cortical circuits requires Semaphorin 7A.

    PubMed

    Carcea, Ioana; Patil, Shekhar B; Robison, Alfred J; Mesias, Roxana; Huntsman, Molly M; Froemke, Robert C; Buxbaum, Joseph D; Huntley, George W; Benson, Deanna L

    2014-09-23

    Abnormal cortical circuits underlie some cognitive and psychiatric disorders, yet the molecular signals that generate normal cortical networks remain poorly understood. Semaphorin 7A (Sema7A) is an atypical member of the semaphorin family that is GPI-linked, expressed principally postnatally, and enriched in sensory cortex. Significantly, SEMA7A is deleted in individuals with 15q24 microdeletion syndrome, characterized by developmental delay, autism, and sensory perceptual deficits. We studied the role that Sema7A plays in establishing functional cortical circuitry in mouse somatosensory barrel cortex. We found that Sema7A is expressed in spiny stellate cells and GABAergic interneurons and that its absence disrupts barrel cytoarchitecture, reduces asymmetrical orientation of spiny stellate cell dendrites, and functionally impairs thalamocortically evoked synaptic responses, with reduced feed-forward GABAergic inhibition. These data identify Sema7A as a regulator of thalamocortical and local circuit development in layer 4 and provide a molecular handle that can be used to explore the coordinated generation of excitatory and inhibitory cortical circuits. PMID:25201975

  3. Mapping ventricular expansion onto cortical gray matter in older adults.

    PubMed

    Madsen, Sarah K; Gutman, Boris A; Joshi, Shantanu H; Toga, Arthur W; Jack, Clifford R; Weiner, Michael W; Thompson, Paul M

    2015-01-01

    Dynamic changes in the brain's lateral ventricles on magnetic resonance imaging are powerful biomarkers of disease progression in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Ventricular measures can represent accumulation of diffuse brain atrophy with very high effect sizes. Despite having no direct role in cognition, ventricular expansion co-occurs with volumetric loss in gray and white matter structures. To better understand relationships between ventricular and cortical changes over time, we related ventricular expansion to atrophy in cognitively relevant cortical gray matter surfaces, which are more challenging to segment. In ADNI participants, percent change in ventricular volumes at 1-year (N = 677) and 2-year (N = 536) intervals was significantly associated with baseline cortical thickness and volume in the full sample controlling for age, sex, and diagnosis, and in MCI separately. Ventricular expansion in MCI was associated with thinner gray matter in frontal, temporal, and parietal regions affected by AD. Ventricular expansion reflects cortical atrophy in early AD, offering a useful biomarker for clinical trials of interventions to slow AD progression. PMID:25311280

  4. 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

  5. A SPECT Imaging Study Of Driving Impairment In Patients With Alzheimer's Disease

    PubMed Central

    Ott, Brian R.; Heindel, William C.; Whelihan, William M.; Caron, Mark D.; Piatt, Andrea L.; Noto, Richard B.

    2012-01-01

    Single photon emission computed tomography (SPECT) was used in this study to examine the neurophysiologic basis of driving impairment in 79 subjects with dementia. Driving impairment, as measured by caregiver ratings, was significantly related to regional reduction of right hemisphere cortical perfusion on SPECT, particularly in the temporo-occipital area. With increased severity of driving impairment, frontal cortical perfusion was also reduced. Clock drawing was more significantly related to driving impairment than the Mini-Mental State Examination. Driving impairment in Alzheimer's disease is related to changes in cortical function which vary according to severity of disease. Cognitive tests of visuoperceptual and executive functions may be more useful screening tools for identifying those at greatest risk for driving problems than examinations like the Mini-Mental State Examination, that are weighted toward left hemisphere based verbal tasks. PMID:10765046

  6. [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

  7. Vascular Contributions to Cognitive Impairment and Dementia

    PubMed Central

    Gorelick, Philip B.; Scuteri, Angelo; Black, Sandra E.; DeCarli, Charles; Greenberg, Steven M.; Iadecola, Costantino; Launer, Lenore J.; Laurent, Stephane; Lopez, Oscar L.; Nyenhuis, David; Petersen, Ronald C.; Schneider, Julie A.; Tzourio, Christophe; Arnett, Donna K.; Bennett, David A.; Chui, Helena C.; Higashida, Randall T.; Lindquist, Ruth; Nilsson, Peter M.; Roman, Gustavo C.; Sellke, Frank W.; Seshadri, Sudha

    2013-01-01

    Background and Purpose This scientific statement provides an overview of the evidence on vascular contributions to cognitive impairment and dementia. Vascular contributions to cognitive impairment and dementia of later life are common. Definitions of vascular cognitive impairment (VCI), neuropathology, basic science and pathophysiological aspects, role of neuroimaging and vascular and other associated risk factors, and potential opportunities for prevention and treatment are reviewed. This statement serves as an overall guide for practitioners to gain a better understanding of VCI and dementia, prevention, and treatment. Methods Writing group members were nominated by the writing group co-chairs on the basis of their previous work in relevant topic areas and were approved by the American Heart Association Stroke Council Scientific Statement Oversight Committee, the Council on Epidemiology and Prevention, and the Manuscript Oversight Committee. The writing group used systematic literature reviews (primarily covering publications from 1990 to May 1, 2010), previously published guidelines, personal files, and expert opinion to summarize existing evidence, indicate gaps in current knowledge, and, when appropriate, formulate recommendations using standard American Heart Association criteria. All members of the writing group had the opportunity to comment on the recommendations and approved the final version of this document. After peer review by the American Heart Association, as well as review by the Stroke Council leadership, Council on Epidemiology and Prevention Council, and Scientific Statements Oversight Committee, the statement was approved by the American Heart Association Science Advisory and Coordinating Committee. Results The construct of VCI has been introduced to capture the entire spectrum of cognitive disorders associated with all forms of cerebral vascular brain injury—not solely stroke—ranging from mild cognitive impairment through fully developed

  8. All Vision Impairment

    MedlinePlus

    ... Jobs Home > Statistics and Data > All Vision Impairment All Vision Impairment Vision Impairment Defined Vision impairment is ... being blind by the U.S. definition.) The category “All Vision Impairment” includes both low vision and blindness. ...

  9. 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

  10. 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

  11. Emerging roles of Axin in cerebral cortical development

    PubMed Central

    Ye, Tao; Fu, Amy K. Y.; Ip, Nancy Y.

    2015-01-01

    Proper functioning of the cerebral cortex depends on the appropriate production and positioning of neurons, establishment of axon–dendrite polarity, and formation of proper neuronal connectivity. Deficits in any of these processes greatly impair neural functions and are associated with various human neurodevelopmental disorders including microcephaly, cortical heterotopias, and autism. The application of in vivo manipulation techniques such as in utero electroporation has resulted in significant advances in our understanding of the cellular and molecular mechanisms that underlie neural development in vivo. Axin is a scaffold protein that regulates neuronal differentiation and morphogenesis in vitro. Recent studies provide novel insights into the emerging roles of Axin in gene expression and cytoskeletal regulation during neurogenesis, neuronal polarization, and axon formation. This review summarizes current knowledge on Axin as a key molecular controller of cerebral cortical development. PMID:26106297

  12. 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

  13. Effects of Age and Symptomatology on Cortical Thickness in Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Doyle-Thomas, Krissy A. R.; Duerden, Emma G.; Taylor, Margot J.; Lerch, Jason P.; Soorya, Latha V.; Wang, A. Ting; Fan, Jin; Hollander, Eric; Anagnostou, Evdokia

    2013-01-01

    Several brain regions show structural and functional abnormalities in individuals with autism spectrum disorders (ASD), but the developmental trajectory of abnormalities in these structures and how they may relate to social and communicative impairments are still unclear. We assessed the effects of age on cortical thickness in individuals with…

  14. Nicotine exposure during adolescence alters the rules for prefrontal cortical synaptic plasticity during adulthood

    PubMed Central

    Goriounova, Natalia A.; Mansvelder, Huibert D.

    2012-01-01

    The majority of adolescents report to have smoked a cigarette at least once. Adolescence is a critical period of brain development during which maturation of areas involved in cognitive functioning, such as the medial prefrontal cortex (mPFC), is still ongoing. Tobacco smoking during this age may compromise the normal course of prefrontal development and lead to cognitive impairments in later life. In addition, adolescent smokers suffer from attention deficits, which progress with the years of smoking. Recent studies in rodents reveal the molecular changes induced by adolescent nicotine exposure that alter the functioning of synapses in the PFC and underlie the lasting effects on cognitive function. In particular, the expression and function of metabotropic glutamate receptors (mGluRs) are changed and this has an impact on short- and long-term plasticity of glutamatergic synapses in the PFC and ultimately on the attention performance. Here, we review and discuss these recent findings. PMID:22876231

  15. LAYER I NEOCORTICAL ECTOPIA: CELLULAR ORGANIZATION AND LOCAL CORTICAL CIRCUITRY

    PubMed Central

    Gabel, Lisa Ann

    2011-01-01

    Focal cortical dysplasia (FCD) are associated with neurological disorders and cognitive impairments in humans. Molecular layer ectopia, clusters of misplaced cells in layer I of the neocortex, have been identified in patients with developmental dyslexia and psychomotor retardation. Mouse models of this developmental disorder display behavioral impairments and increased seizure susceptibility. Although there is a correlation between cortical malformations and neurological dysfunction, little is known about the morphological and physiological properties of cells within cortical malformations. In the present study we used electrophysiological and immunocytochemical analyses to examine the distribution of neuronal and non-neuronal cell types within and surrounding layer I neocortical ectopia in NXSMD/EiJ mice. We show that cells within ectopia have membrane properties of both pyramidal and a variety of nonpyramidal cell types, including fast-spiking cells. Immunocytochemical analysis for different interneuronal subtypes demonstrates that ectopia contain nonpyramidal cells immunoreactive for calbindin-D28K (CALB), parvalbumin (PARV), and calretinin (CR). Ectopia also contain astrocytes, positive for glial fibrillary acidic protein (GFAP) and oligodendrocyte precursor cells positive for NG2 proteoglycan (NG2). Lastly, we provide electrophysiological and morphological evidence to demonstrate that cells within ectopia receive input from cells within layers I, upper and deeper II/III, and V and provide outputs to cells within deep layer II/III and layer V, but not layers I and upper II/III. These results indicate that ectopia contain cells of different lineages with diverse morphological and physiological properties, and appear to cause disruptions in local cortical circuitry. PMID:21256119

  16. 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

  17. 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

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

    PubMed

    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

  19. 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

  20. 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%).

  1. Communication Structure of Cortical Networks

    PubMed Central

    da Fontoura Costa, Luciano; Batista, João Luiz B.; Ascoli, Giorgio A.

    2011-01-01

    Large-scale cortical networks exhibit characteristic topological properties that shape communication between brain regions and global cortical dynamics. Analysis of complex networks allows the description of connectedness, distance, clustering, and centrality that reveal different aspects of how the network's nodes communicate. Here, we focus on a novel analysis of complex walks in a series of mammalian cortical networks that model potential dynamics of information flow between individual brain regions. We introduce two new measures called absorption and driftness. Absorption is the average length of random walks between any two nodes, and takes into account all paths that may diffuse activity throughout the network. Driftness is the ratio between absorption and the corresponding shortest path length. For a given node of the network, we also define four related measurements, namely in- and out-absorption as well as in- and out-driftness, as the averages of the corresponding measures from all nodes to that node, and from that node to all nodes, respectively. We find that the cat thalamo-cortical system incorporates features of two classic network topologies, Erdös–Rényi graphs with respect to in-absorption and in-driftness, and configuration models with respect to out-absorption and out-driftness. Moreover, taken together these four measures separate the network nodes based on broad functional roles (visual, auditory, somatomotor, and frontolimbic). PMID:21427794

  2. 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

  3. Alcohol consumption and cognitive impairment in older men

    PubMed Central

    Hankey, Graeme J.; Yeap, Bu B.; Golledge, Jonathan; Flicker, Leon

    2014-01-01

    Objective: To determine whether alcohol consumption is causally associated with cognitive impairment in older men as predicted by mendelian randomization. Methods: Retrospective analysis of a cohort study of 3,542 community-dwelling men aged 65 to 83 years followed for 6 years. Cognitive impairment was established by a Mini-Mental State Examination score of 23 or less. Participants provided detailed information about their use of alcohol during the preceding year and were classified as abstainers, occasional drinkers, and regular drinkers: mild (<15 drinks/wk), moderate (15–27 drinks/wk), heavy (28–34 drinks/wk), and abusers (≥35 drinks/wk). We genotyped the rs1229984 G→A variant of the alcohol dehydrogenase 1B (ADH1B) gene, which is associated with lower prevalence of alcohol abuse and dependence. Other measures included age, education, marital status, smoking and physical activity, body mass index, diabetes, hypertension, and cardiovascular diseases. Results: At study entry, rs1229984 G→A polymorphism was associated with lower prevalence of regular use of alcohol and decreased consumption among regular users. Six years later, 502 men (14.2%) showed evidence of cognitive impairment. Abstainers and irregular drinkers had higher odds of cognitive impairment than regular drinkers (odds ratio [OR] = 1.23, 95% confidence interval [CI] = 1.00–1.51, after adjustment for other measured factors). The rs1229984 G→A polymorphism did not decrease the odds of cognitive impairment (AA/GG OR = 1.35, 95% CI = 0.29–6.27; GA/GG OR = 1.05, 95% CI = 0.71–1.55). Conclusions: Alcohol consumption, including heavy regular drinking and abuse, is not a direct cause of cognitive impairment in later life. Our results are consistent with the possibility, but do not prove, that regular moderate drinking decreases the risk of cognitive impairment in older men. PMID:24553426

  4. 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. PMID:25815252

  5. 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

  6. The language profile of Posterior Cortical Atrophy

    PubMed Central

    Crutch, Sebastian J.; Lehmann, Manja; Warren, Jason D.; Rohrer, Jonathan D.

    2015-01-01

    Background Posterior Cortical Atrophy (PCA) is typically considered to be a visual syndrome, primarily characterised by progressive impairment of visuoperceptual and visuospatial skills. However patients commonly describe early difficulties with word retrieval. This paper details the first systematic analysis of linguistic function in PCA. Characterising and quantifying the aphasia associated with PCA is important for clarifying diagnostic and selection criteria for clinical and research studies. Methods Fifteen patients with PCA, 7 patients with logopenic/phonological aphasia (LPA) and 18 age-matched healthy participants completed a detailed battery of linguistic tests evaluating auditory input processing, repetition and working memory, lexical and grammatical comprehension, single word retrieval and fluency, and spontaneous speech. Results Relative to healthy controls, PCA patients exhibited language impairments across all the domains examined, but with anomia, reduced phonemic fluency and slowed speech rate the most prominent deficits. PCA performance most closely resembled that of LPA patients on tests of auditory input processing, repetition and digit span, but was relatively stronger on tasks of comprehension and spontaneous speech. Conclusions The study demonstrates that in addition to the well-reported degradation of vision, literacy and numeracy, PCA is characterised by a progressive oral language dysfunction with prominent word retrieval difficulties. Overlap in the linguistic profiles of PCA and LPA, which are both most commonly caused by Alzheimer’s disease, further emphasises the notion of a phenotypic continuum between typical and atypical manifestations of the disease. Clarifying the boundaries between AD phenotypes has important implications for diagnosis, clinical trial recruitment and investigations into biological factors driving phenotypic heterogeneity in AD. Rehabilitation strategies to ameliorate the phonological deficit in PCA are required

  7. Double cortical stimulation in amyotrophic lateral sclerosis.

    PubMed Central

    Yokota, T; Yoshino, A; Inaba, A; Saito, Y

    1996-01-01

    OBJECTIVE: Transcranial double magnetic stimulation on the motor cortex was used to investigate central motor tract function in 16 patients with amyotrophic lateral sclerosis, five with spinal muscular atrophy, and 16 age matched normal controls. METHODS: Surface EMG responses were recorded from the relaxed abductor pollicis brevis (APB) muscle. RESULTS: Responses to test stimuli were markedly attenuated by a subthreshold conditioning stimulus given at a condition-test (C-T) interval of 1-4 ms in normal controls and patients with spinal muscular atrophy, but attenuation was mild in patients with amyotrophic lateral sclerosis. In the normal controls this suppression was caused by activation of the intracortical inhibitory mechanism because responses to electrical test stimuli and the H wave were not suppressed by the same magnetic subthreshold conditioning stimulus. In amyotrophic lateral sclerosis the effect of the conditioning cortical stimulus on the H wave was also in the normal range. CONCLUSION: The intracortical inhibitory mechanism may be impaired in patients with amyotrophic lateral sclerosis. PMID:8971106

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. Motor features in posterior cortical atrophy and their imaging correlates.

    PubMed

    Ryan, Natalie S; Shakespeare, Timothy J; Lehmann, Manja; Keihaninejad, Shiva; Nicholas, Jennifer M; Leung, Kelvin K; Fox, Nick C; Crutch, Sebastian J

    2014-12-01

    Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by impaired higher visual processing skills; however, motor features more commonly associated with corticobasal syndrome may also occur. We investigated the frequency and clinical characteristics of motor features in 44 PCA patients and, with 30 controls, conducted voxel-based morphometry, cortical thickness, and subcortical volumetric analyses of their magnetic resonance imaging. Prominent limb rigidity was used to define a PCA-motor subgroup. A total of 30% (13) had PCA-motor; all demonstrating asymmetrical left upper limb rigidity. Limb apraxia was more frequent and asymmetrical in PCA-motor, as was myoclonus. Tremor and alien limb phenomena only occurred in this subgroup. The subgroups did not differ in neuropsychological test performance or apolipoprotein E4 allele frequency. Greater asymmetry of atrophy occurred in PCA-motor, particularly involving right frontoparietal and peri-rolandic cortices, putamen, and thalamus. The 9 patients (including 4 PCA-motor) with pathology or cerebrospinal fluid all showed evidence of Alzheimer's disease. Our data suggest that PCA patients with motor features have greater atrophy of contralateral sensorimotor areas but are still likely to have underlying Alzheimer's disease. PMID:25086839

  15. Cortical thickness in relation to clinical symptom onset in preclinical AD.

    PubMed

    Pettigrew, Corinne; Soldan, Anja; Zhu, Yuxin; Wang, Mei-Cheng; Moghekar, Abhay; Brown, Timothy; Miller, Michael; Albert, Marilyn

    2016-01-01

    Mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia are preceded by a phase of disease, referred to as 'preclinical AD', during which cognitively normal individuals have evidence of AD pathology in the absence of clinical impairment. This study examined whether a magnetic resonance imaging (MRI) measure of cortical thickness in brain regions, collectively known as 'AD vulnerable' regions, predicted the time to onset of clinical symptoms associated with MCI and whether cortical thickness was similarly predictive of clinical symptom onset within 7 years post baseline versus progression at a later point in time. These analyses included 240 participants from the BIOCARD study, a cohort of longitudinally followed individuals who were cognitively normal at the time of their MRI (mean age = 56 years). Participants have been followed for up to 18 years (M follow-up = 11.8 years) and 50 participants with MRIs at baseline have developed MCI or dementia over time (mean time to clinical symptom onset = 7 years). Cortical thickness in AD vulnerable regions was based on the mean thickness of eight cortical regions. Using Cox regression models, we found that lower mean cortical thickness was associated with an increased risk of progression from normal cognition to clinical symptom onset within 7 years of baseline (p = 0.03), but not with progression > 7 years from baseline (p = 0.30). Lower cortical thickness was also associated with higher levels of phosphorylated tau, measured in cerebrospinal fluid at baseline. These results suggest that cortical thinning in AD vulnerable regions is detectable in cognitively normal individuals several years prior to the onset of clinical symptoms that are a harbinger of a diagnosis of MCI, and that the changes are more likely to be evident in the years proximal to clinical symptom onset, consistent with hypothetical AD biomarker models. PMID:27408796

  16. 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

  17. LRP12 silencing during brain development results in cortical dyslamination and seizure sensitization.

    PubMed

    Grote, Alexander; Robens, Barbara K; Blümcke, Ingmar; Becker, Albert J; Schoch, Susanne; Gembé, Eva

    2016-02-01

    Correct positioning and differentiation of neurons during brain development is a key precondition for proper function. Focal cortical dysplasias (FCDs) are increasingly recognized as causes of therapy refractory epilepsies. Neuropathological analyses of respective surgical specimens from neurosurgery for seizure control often reveal aberrant cortical architecture and/or aberrantly shaped neurons in FCDs. However, the molecular pathogenesis particularly of FCDs with aberrant lamination (so-called FCD type I) is largely unresolved. Lipoproteins and particularly low-density lipoprotein receptor-related protein 12 (LRP12) are involved in brain development. Here, we have examined a potential role of LRP12 in the pathogenesis of FCDs. In vitro knockdown of LRP12 in primary neurons results in impaired neuronal arborization. In vivo ablation of LRP12 by intraventricularly in utero electroporated shRNAs elicits cortical maldevelopment, i.e. aberrant lamination by malpositioning of upper cortical layer neurons. Subsequent epilepsy phenotyping revealed pentylenetetrazol (PTZ)-induced seizures to be aggravated in cortical LRP12-silenced mice. Our data demonstrates IUE mediated cortical gene silencing as an excellent approach to study the role of distinct molecules for epilepsy associated focal brain lesions and suggests LRP12 and lipoprotein homeostasis as potential molecular target structures for the emergence of epilepsy-associated FCDs. PMID:26639854

  18. 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

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

    PubMed

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

    2016-06-01

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

  20. 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

  1. Multisensory dysfunction accompanies crossmodal plasticity following adult hearing impairment

    PubMed Central

    Meredith, M. Alex; Keniston, Leslie P.; Allman, Brian L.

    2012-01-01

    Until now, cortical crossmodal plasticity has largely been regarded as the effect of early and complete sensory loss. Recently, massive crossmodal cortical reorganization was demonstrated to result from profound hearing loss in adult ferrets (Allman et al., 2009a). Moderate adult hearing loss, on the other hand, induced not just crossmodal reorganization, but also merged new crossmodal inputs with residual auditory function to generate multisensory neurons. Because multisensory convergence can lead to dramatic levels of response integration when stimuli from more than one modality are present (and thereby potentially interfere with residual auditory processing), the present investigation sought to evaluate the multisensory properties of auditory cortical neurons in partially deafened adult ferrets. When compared with hearing controls, partially-deaf animals revealed elevated spontaneous levels and a dramatic increase (~2 times) in the proportion of multisensory cortical neurons, but few of which showed multisensory integration. Moreover, a large proportion (68%) of neurons with somatosensory and/or visual inputs was vigorously active in core auditory cortex in the absence of auditory stimulation. Collectively, these results not only demonstrate multisensory dysfunction in core auditory cortical neurons from hearing impaired adults but also reveal a potential cortical substrate for maladaptive perceptual effects such as tinnitus. PMID:22516008

  2. 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

  3. 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

  4. 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

    2016-01-01

    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

  5. 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

  6. 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

  7. Inhibitory Circuits in Cortical Layer 5.

    PubMed

    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

  8. 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

  9. 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

  10. 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

  11. Atypical coordination of cortical oscillations in response to speech in autism

    PubMed Central

    Jochaut, Delphine; Lehongre, Katia; Saitovitch, Ana; Devauchelle, Anne-Dominique; Olasagasti, Itsaso; Chabane, Nadia; Zilbovicius, Monica; Giraud, Anne-Lise

    2015-01-01

    Subjects with autism often show language difficulties, but it is unclear how they relate to neurophysiological anomalies of cortical speech processing. We used combined EEG and fMRI in 13 subjects with autism and 13 control participants and show that in autism, gamma and theta cortical activity do not engage synergistically in response to speech. Theta activity in left auditory cortex fails to track speech modulations, and to down-regulate gamma oscillations in the group with autism. This deficit predicts the severity of both verbal impairment and autism symptoms in the affected sample. Finally, we found that oscillation-based connectivity between auditory and other language cortices is altered in autism. These results suggest that the verbal disorder in autism could be associated with an altered balance of slow and fast auditory oscillations, and that this anomaly could compromise the mapping between sensory input and higher-level cognitive representations. PMID:25870556

  12. 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

  13. Family History of Alzheimer's Disease and Cortical Thickness in Patients With Dementia.

    PubMed

    Ganske, Steffi; Haussmann, Robert; Gruschwitz, Antonia; Werner, Annett; Osterrath, Antje; Baumgaertel, Johanna; Lange, Jan; Donix, Katharina L; Linn, Jennifer; Donix, Markus

    2016-08-01

    A first-degree family history of Alzheimer's disease reflects genetic risks for the neurodegenerative disorder. Recent imaging data suggest localized effects of genetic risks on brain structure in healthy people. It is unknown whether this association can also be found in patients who already have dementia. Our aim was to investigate whether family history risk modulates regional medial temporal lobe cortical thickness in patients with Alzheimer's disease. We performed high-resolution magnetic resonance imaging and cortical unfolding data analysis on 54 patients and 53 nondemented individuals. A first-degree family history of Alzheimer's disease was associated with left hemispheric cortical thinning in the subiculum among patients and controls. The contribution of Alzheimer's disease family history to regional brain anatomy changes independent of cognitive impairment may reflect genetic risks that modulate onset and clinical course of the disease. PMID:27303063

  14. 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

  15. 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

  16. Cytoarchitectural, behavioural and neurophysiological dysfunctions in the BCNU-treated rat model of cortical dysplasia.

    PubMed

    Inverardi, Francesca; Chikhladze, Maia; Donzelli, Andrea; Moroni, Ramona Frida; Regondi, Maria Cristina; Pennacchio, Paolo; Zucca, Ileana; Corradini, Irene; Braida, Daniela; Sala, Mariaelvina; Franceschetti, Silvana; Frassoni, Carolina

    2013-01-01

    Cortical dysplasias (CDs) include a spectrum of cerebral lesions resulting from cortical development abnormalities during embryogenesis that lead to cognitive disabilities and epilepsy. The experimental model of CD obtained by means of in utero administration of BCNU (1-3-bis-chloroethyl-nitrosurea) to pregnant rats on embryonic day 15 mimics the histopathological abnormalities observed in many patients. The aim of this study was to investigate the behavioural, electrophysiological and anatomical profile of BCNU-treated rats in order to determine whether cortical and hippocampal lesions can directly lead to cognitive dysfunction. The BCNU-treated rats showed impaired short-term working memory but intact long-term aversive memory, whereas their spontaneous motor activity and anxiety-like response were normal. The histopathological and immunohistochemical analyses, made after behavioural tests, revealed the disrupted integrity of neuronal populations and connecting fibres in hippocampus and prefrontal and entorhinal cortices, which are involved in memory processes. An electrophysiological evaluation of the CA1 region of in vitro hippocampal slices indicated a decrease in the efficiency of excitatory synaptic transmission and impaired paired pulse facilitation, but enhanced long-term potentiation (LTP) associated with hyperexcitability in BCNU-treated rats compared with controls. The enhanced LTP, associated with hyperexcitability, may indicate a pathological distortion of long-term plasticity. These findings suggest that prenatal developmental insults at the time of peak cortical neurogenesis can induce anatomical abnormalities associated with severe impairment of spatial working memory in adult BCNU-treated rats and may help to clarify the pathophysiological mechanisms of cognitive dysfunction that is often associated with epilepsy in patients with CD. PMID:23095101

  17. Dysfunctional cortical inhibition in adult ADHD: neural correlates in auditory event-related potentials.

    PubMed

    Schubert, J K; Gonzalez-Trejo, E; Retz, W; Rösler, M; Corona-Strauss, F I; Steidl, G; Teuber, T; Strauss, D J

    2014-09-30

    In recent times, the relevance of an accurate diagnosis of attention-deficit/hyperactivity disorder (ADHD) in adults has been the focus of several studies. No longer considered a pathology exclusive to children and adolescents, and taking into account its social implications, developing enhanced support tools for the current diagnostic procedure becomes a priority. Here we present a method for the objective assessment of ADHD in adults using chirp-evoked, paired auditory late responses (ALRs) combined with a two-dimensional ALR denoising scheme to extract correlates of intracortical inhibition. Our method allows for an effective single-sweep denoising, thus requiring less trials to obtain recognizable physiological features, useful as pointers of cortical impairment. Results allow an optimized diagnosis, reduction of data loss and acquisition time; moreover, they do not account exclusively for critical elements within clinical evaluations, but also allow studying the pathophysiology of the condition by providing objective information regarding impaired cortical functions. PMID:25033725

  18. 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

  19. 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

  20. Cortical inhibition and habituation to evoked potentials: relevance for pathophysiology of migraine.

    PubMed

    Brighina, Filippo; Palermo, Antonio; Fierro, Brigida

    2009-04-01

    Dysfunction of neuronal cortical excitability has been supposed to play an important role in etiopathogenesis of migraine. Neurophysiological techniques like evoked potentials (EP) and in the last years non-invasive brain stimulation techniques like transcranial magnetic stimulation (TMS) and transcranial direct current stimulation gave important contribution to understanding of such issue highlighting possible mechanisms of cortical dysfunctions in migraine. EP studies showed impaired habituation to repeated sensorial stimulation and this abnormality was confirmed across all sensorial modalities, making defective habituation a neurophysiological hallmark of the disease. TMS was employed to test more directly cortical excitability in visual cortex and then also in motor cortex. Contradictory results have been reported pointing towards hyperexcitability or on the contrary to reduced preactivation of sensory cortex in migraine. Other experimental evidence speaks in favour of impairment of inhibitory circuits and analogies have been proposed between migraine and conditions of sensory deafferentation in which down-regulation of GABA circuits is considered the more relevant pathophysiological mechanism. Whatever the mechanism involved, it has been found that repeated sessions of high-frequency rTMS trains that have been shown to up-regulate inhibitory circuits could persistently normalize habituation in migraine. This could give interesting insight into pathophysiology establishing a link between cortical inhibition and habituation and opening also new treatment strategies in migraine. PMID:19209386

  1. Early deficits in cortical control of swallowing in Alzheimer’s disease

    PubMed Central

    Humbert, Ianessa A.; McLaren, Donald G.; Kosmatka, Kris; Fitzgerald, Michelle; Johnson, Sterling; Porcaro, Eva; Kays, Stephanie; Umoh, Eno-Obong; Robbins, JoAnne

    2010-01-01

    The goal of this study was to determine whether functional changes in cortical control of swallowing are evident in early Alzheimer’s disease (AD), before dysphagia (swallowing impairment) is evident. Cortical function was compared between an early AD group and a group of age-matched controls during swallowing. Swallowing oropharyngeal biomechanics examined from videofluoroscopic recordings were also obtained to more comprehensively characterize changes in swallowing associated with early AD. Our neuroimaging results show that the AD group had significantly lower BOLD response in many cortical areas that are traditionally involved in normal swallowing (i.e. pre and postcentral gyri, Rolandic and frontal opercula). There were no regions where the AD group recruited more brain activity than the healthy controls during swallowing and only 13% of all active voxels were unique to the AD group, even at this early stage. This suggests that the AD group is not recruiting new regions, nor are they compensating within regions that are active during swallowing. In videofluoroscopic measures, the AD group had significantly reduced hyo-laryngeal elevation than the controls. Although, swallowing impairment is usually noted in the late stages of AD, changes in cortical control of swallowing may begin long before dysphagia becomes apparent. PMID:20308785

  2. GABAergic activity in autism spectrum disorders: an investigation of cortical inhibition via transcranial magnetic stimulation.

    PubMed

    Enticott, Peter G; Kennedy, Hayley A; Rinehart, Nicole J; Tonge, Bruce J; Bradshaw, John L; Fitzgerald, Paul B

    2013-05-01

    Mounting evidence suggests a possible role for γ-aminobutyric acid (GABA) in the neuropathophysiology of autism spectrum disorders (ASD), but the extent of this impairment is unclear. A non-invasive, in vivo measure of GABA involves transcranial magnetic stimulation (TMS) of the primary motor cortex to probe cortical inhibition. Individuals diagnosed with ASD (high-functioning autism or Asperger's disorder) (n = 36 [28 male]; mean age: 26.00 years) and a group of healthy individuals (n = 34 [23 male]; mean age: 26.21 years) (matched for age, gender, and cognitive function) were administered motor cortical TMS paradigms putatively measuring activity at GABAA and GABAB receptors (i.e., short and long interval paired pulse TMS, cortical silent period). All cortical inhibition paradigms yielded no difference between ASD and control groups. There was, however, evidence for short interval cortical inhibition (SICI) deficits among those ASD participants who had experienced early language delay, suggesting that GABA may be implicated in an ASD subtype. The current findings do not support a broad role for GABA in the neuropathophysiology of ASD, but provide further indication that GABAA could be involved in ASD where there is a delay in language acquisition. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'. PMID:22727823

  3. Caloric restriction stimulates autophagy in rat cortical neurons through neuropeptide Y and ghrelin receptors activation.

    PubMed

    Ferreira-Marques, Marisa; Aveleira, Célia A; Carmo-Silva, Sara; Botelho, Mariana; Pereira de Almeida, Luís; Cavadas, Cláudia

    2016-07-01

    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

  4. Loss of MeCP2 From Forebrain Excitatory Neurons Leads to Cortical Hyperexcitation and Seizures

    PubMed Central

    Zhang, Wen; Peterson, Matthew; Beyer, Barbara; Frankel, Wayne N.

    2014-01-01

    Mutations of MECP2 cause Rett syndrome (RTT), a neurodevelopmental disorder leading to loss of motor and cognitive functions, impaired social interactions, and seizure at young ages. Defects of neuronal circuit development and function are thought to be responsible for the symptoms of RTT. The majority of RTT patients show recurrent seizures, indicating that neuronal hyperexcitation is a common feature of RTT. However, mechanisms underlying hyperexcitation in RTT are poorly understood. Here we show that deletion of Mecp2 from cortical excitatory neurons but not forebrain inhibitory neurons in the mouse leads to spontaneous seizures. Selective deletion of Mecp2 from excitatory but not inhibitory neurons in the forebrain reduces GABAergic transmission in layer 5 pyramidal neurons in the prefrontal and somatosensory cortices. Loss of MeCP2 from cortical excitatory neurons reduces the number of GABAergic synapses in the cortex, and enhances the excitability of layer 5 pyramidal neurons. Using single-cell deletion of Mecp2 in layer 2/3 pyramidal neurons, we show that GABAergic transmission is reduced in neurons without MeCP2, but is normal in neighboring neurons with MeCP2. Together, these results suggest that MeCP2 in cortical excitatory neurons plays a critical role in the regulation of GABAergic transmission and cortical excitability. PMID:24523563

  5. Altered Resting-State Cortical EEG Oscillations in Patients With Severe Asymptomatic Carotid Stenosis.

    PubMed

    Hsiao, Fu-Jung; Hsieh, Fang-Yuh; Chen, Wei-Ta; Chu, Da-Chen; Lin, Yung-Yang

    2016-04-01

    Asymptomatic carotid stenosis is characterized by altered cerebral hemodynamics and cognitive impairment, but the underlying neurophysiological mechanism remains unclear. To elucidate the alterations of cortical activities, resting-state electrophysiological activities were recorded from patients with mild (<30%; n=10; age 57-85 years), moderate (30% to 50%; n=11; age 66-88 years), and severe (>50%; n=8; age 67-91 years) carotid stenosis. The current density and oscillatory power of the cortical sources were analyzed using the minimum norm estimates method combined with fast Fourier transform analysis. Our results indicate that the cortical current density among regions of the brain was similar, irrespective of the degree of carotid stenosis. With regard to the cortical oscillations, augmented theta activities in the bilateral parietal, left temporal, and left occipital regions and attenuated alpha activities in the bilateral frontal and right central regions were obtained in patients with severe asymptomatic carotid stenosis. We suggest that the source-based cortical oscillations at theta and alpha bands might reflect the alterations of the brain activities and characterize the altered neurophysiological mechanism of the brain with at least 50% occlusion of the carotid artery. Further longitudinal studies with larger populations are warranted to verify the present findings. PMID:25465434

  6. 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

  7. Dimensionality reduced cortical features and their use in predicting longitudinal changes in Alzheimer's disease.

    PubMed

    Park, Hyunjin; Yang, Jin-ju; Seo, Jongbum; Lee, Jong-min

    2013-08-29

    Neuroimaging features derived from the cortical surface provide important information in detecting changes related to the progression of Alzheimer's disease (AD). Recent widespread adoption of neuroimaging has allowed researchers to study longitudinal data in AD. We adopted cortical thickness and sulcal depth, parameterized by three-dimensional meshes, from magnetic resonance imaging as the surface features. The cortical feature is high-dimensional, and it is difficult to use directly with a classifier because of the "small sample size" problem. We applied manifold learning to reduce the dimensionality of the feature and then tested the usage of the dimensionality reduced feature with a support vector machine classifier. Principal component analysis (PCA) was chosen as the method of manifold learning. PCA was applied to a region of interest within the cortical surface. We used 30 normal, 30 mild cognitive impairment (MCI) and 12 conversion cases taken from the ADNI database. The classifier was trained using the cortical features extracted from normal and MCI patients. The classifier was tested for the 12 conversion patients only using the imaging data before the actual conversion. The conversion was predicted early with an accuracy of 83%. PMID:23827219

  8. Effects of age and symptomatology on cortical thickness in autism spectrum disorders

    PubMed Central

    Doyle-Thomas, Krissy A.R.; Duerden, Emma G.; Taylor, Margot J.; Lerch, Jason P.; Soorya, Latha V.; Wang, A. Ting; Fan, Jin; Hollander, Eric; Anagnostou, Evdokia

    2013-01-01

    Several brain regions show structural and functional abnormalities in individuals with autism spectrum disorders (ASD), but the developmental trajectory of abnormalities in these structures and how they may relate to social and communicative impairments are still unclear. We assessed the effects of age on cortical thickness in individuals with ASD, between the ages of 7 and 39 years in comparison to typically developing controls. Additionally, we examined differences in cortical thickness in relation to symptomatology in the ASD group, and their association with age. Analyses were conducted using a general linear model, controlling for sex. Social and communication scores from the Autism Diagnostic Interview-Revised (ADI-R) were correlated with the thickness of regions implicated in those functions. Controls showed widespread cortical thinning relative to the ASD group. Within regions-of-interest, increased thickness in the rostral anterior cingulate cortex was associated with poorer social scores. Additionally, a significant interaction between age and social impairment was found in the orbitofrontal cortex, with more impaired younger children having decreased thickness in this region. These results suggest that differential neurodevelopmental trajectories are present in individuals with ASD and some differences are associated with diagnostic behaviours. PMID:23678367

  9. 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

  10. Reduced modulation of scanpaths in response to task demands in posterior cortical atrophy.

    PubMed

    Shakespeare, Timothy J; Pertzov, Yoni; Yong, Keir X X; Nicholas, Jennifer; Crutch, Sebastian J

    2015-02-01

    A difficulty in perceiving visual scenes is one of the most striking impairments experienced by patients with the clinico-radiological syndrome posterior cortical atrophy (PCA). However whilst a number of studies have investigated perception of relatively simple experimental stimuli in these individuals, little is known about multiple object and complex scene perception and the role of eye movements in posterior cortical atrophy. We embrace the distinction between high-level (top-down) and low-level (bottom-up) influences upon scanning eye movements when looking at scenes. This distinction was inspired by Yarbus (1967), who demonstrated how the location of our fixations is affected by task instructions and not only the stimulus' low level properties. We therefore examined how scanning patterns are influenced by task instructions and low-level visual properties in 7 patients with posterior cortical atrophy, 8 patients with typical Alzheimer's disease, and 19 healthy age-matched controls. Each participant viewed 10 scenes under four task conditions (encoding, recognition, search and description) whilst eye movements were recorded. The results reveal significant differences between groups in the impact of test instructions upon scanpaths. Across tasks without a search component, posterior cortical atrophy patients were significantly less consistent than typical Alzheimer's disease patients and controls in where they were looking. By contrast, when comparing search and non-search tasks, it was controls who exhibited lowest between-task similarity ratings, suggesting they were better able than posterior cortical atrophy or typical Alzheimer's disease patients to respond appropriately to high-level needs by looking at task-relevant regions of a scene. Posterior cortical atrophy patients had a significant tendency to fixate upon more low-level salient parts of the scenes than controls irrespective of the viewing task. The study provides a detailed characterisation of

  11. 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

  12. 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. 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 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

  15. 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

  16. Speech impairment (adult)

    MedlinePlus

    Language impairment; Impairment of speech; Inability to speak; Aphasia; Dysarthria; Slurred speech; Dysphonia voice disorders ... disorders develop gradually, but anyone can develop a speech and ... suddenly, usually in a trauma. APHASIA Alzheimer disease ...

  17. Mild Cognitive Impairment

    MedlinePlus

    ... Research Portfolio (IADRP) AMP-AD Detecting Cognitive Impairment Database ... Mild cognitive impairment (MCI) is a condition in which people have more memory or other thinking problems than normal for their ...

  18. Speech impairment (adult)

    MedlinePlus

    Language impairment; Impairment of speech; Inability to speak; Aphasia; Dysarthria; Slurred speech; Dysphonia voice disorders ... Common speech and language disorders include: APHASIA Aphasia is ... understand or express spoken or written language. It commonly ...

  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. 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.

  1. 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.

  2. 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. PMID:27056553

  3. 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.

  4. Cortical thickness, surface area, and folding alterations in male youths with conduct disorder and varying levels of callous–unemotional traits

    PubMed Central

    Fairchild, Graeme; Toschi, Nicola; Hagan, Cindy C.; Goodyer, Ian M.; Calder, Andrew J.; Passamonti, Luca

    2015-01-01

    Purpose Previous studies have reported changes in gray matter volume in youths with conduct disorder (CD), although these differences are difficult to interpret as they may have been driven by alterations in cortical thickness, surface area (SA), or folding. The objective of this study was to use surface-based morphometry (SBM) methods to compare male youths with CD and age and sex-matched healthy controls (HCs) in cortical thickness, SA, and folding. We also tested for structural differences between the childhood-onset and adolescence-onset subtypes of CD and performed regression analyses to assess for relationships between CD symptoms and callous–unemotional (CU) traits and SBM-derived measures. Methods We acquired structural neuroimaging data from 20 HCs and 36 CD participants (18 with childhood-onset CD and 18 with adolescence-onset CD) and analyzed the data using FreeSurfer. Results Relative to HCs, youths with CD showed reduced cortical thickness in the superior temporal gyrus, reduced SA in the orbitofrontal cortex (OFC), and increased cortical folding in the insula. There were no significant differences between the childhood-onset and adolescence-onset CD subgroups in cortical thickness or SA, but several frontal and temporal regions showed increased cortical folding in childhood-onset relative to adolescence-onset CD participants. Both CD subgroups also showed increased cortical folding relative to HCs. CD symptoms were negatively correlated with OFC SA whereas CU traits were positively correlated with insula folding. Conclusions Cortical thinning in the superior temporal gyrus may contribute to the social cognitive impairments displayed by youths with CD, whereas reduced OFC SA may lead to impairments in emotion regulation and reward processing in youths with CD. The increased cortical folding observed in the insula may reflect a maturational delay in this region and could mediate the link between CU traits and empathy deficits. Altered cortical folding

  5. Hearing loss severity: impaired processing of formant transition duration.

    PubMed

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

    2010-08-01

    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 same duration, 84 mild to severe hearing impaired listeners and 5 normal hearing listeners were asked to detect 10 synthesized stimuli with long (200 ms) or short (40 ms) FT among 30 stimuli of the same duration without FT. Hearing impaired listeners were tested with and without hearing aids. The effect of the difficulty of the task (short/long FT) was analysed as a function of the hearing loss with and without hearing aids. Normal hearing listeners were able to detect every FT (short and long). For hearing impaired listeners, the detection of long FT was better than that of short ones irrespective of their degree of hearing loss. The use of hearing aids improved detection of both kinds of FT; however, the detection of long FT remained much better than the detection of the short ones. The length of FT modified the ability of hearing impaired patients to detect FT. Short FT had access to less cortical processing than long FT and cochlea damages enhanced this specific deficit in short FT brain processing. These findings help to understand the limit of deafness rehabilitation in the time domain and should be taken into account in future devices development. PMID:20600193

  6. The Impaired Social Worker.

    ERIC Educational Resources Information Center

    Reamer, Frederic G.

    1992-01-01

    Discusses concept of the impaired professional; reviews research on various types of impairment (personality disorders, depression and other emotional problems, marital problems, and physical illness), prevalence and causes of impairment, and responses to it; and outlines model assessment and action plan for social workers who encounter an…

  7. ABE. The Hearing Impaired.

    ERIC Educational Resources Information Center

    Carver, L. Sue

    This handbook was written to help teachers of adult basic education (ABE) adapt their teaching methods for hearing impaired persons. Written in a narrative format, the guide covers the following topics: ABE for the hearing impaired, hints for working with the hearing impaired without an interpreter, peer pairing, interpreters in the classroom…

  8. Adapting for Impaired Patrons.

    ERIC Educational Resources Information Center

    Schuyler, Michael

    1999-01-01

    Describes how a library, with an MCI Corporation grant, approached the process of setting up computers for the visually impaired. Discusses preparations, which included hiring a visually-impaired user as a consultant and contacting the VIP (Visually Impaired Persons) group; equipment; problems with the graphical user interface; and training.…

  9. Degraded attentional modulation of cortical neural populations in strabismic amblyopia.

    PubMed

    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

  10. Regional cortical volume and cognitive functioning following traumatic brain injury.

    PubMed

    Spitz, Gershon; Bigler, Erin D; Abildskov, Tracy; Maller, Jerome J; O'Sullivan, Richard; Ponsford, Jennie L

    2013-10-01

    There has been limited examination of the effect of brain pathology on subsequent function. The current study examined the relationships between regional variation in grey matter volume, age and cognitive impairment using a semi-automated image analysis tool. This study included 69 individuals with mild-to-severe TBI, 41 of whom also completed neuropsychological tests of attention, working memory, processing speed, memory and executive functions. A widespread reduction in grey matter volume was associated with increasing age. Regional volumes that were affected also related to the severity of injury, whereby the most severe TBI participants displayed the most significant pathology. Poorer retention of newly learned material was associated with reduced cortical volume in frontal, parietal, and occipital brain regions. In addition, poorer working memory and executive control performance was found for individuals with lower cortical volume in temporal, parietal, and occipital regions. These findings are largely in line with previous literature, which suggests that frontal, temporal, and parietal regions are integral for the encoding of memories into long-term storage, memory retrieval, and working memory. The present study suggests that automated image analysis methods may be used to explore the relationships between regional variation in grey matter volume and cognitive function following TBI. PMID:23872098

  11. 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

  12. Mitochondrial dysfunction precedes depression of AMPK/AKT signaling in insulin resistance induced by high glucose in primary cortical neurons.

    PubMed

    Peng, Yunhua; Liu, Jing; Shi, Le; Tang, Ying; Gao, Dan; Long, Jiangang; Liu, Jiankang

    2016-06-01

    Recent studies have demonstrated brain insulin signaling impairment and mitochondrial dysfunction in diabetes. Hyperinsulinemia and hyperlipidemia arising from diabetes have been linked to neuronal insulin resistance, and hyperglycemia induces peripheral sensory neuronal impairment and mitochondrial dysfunction. However, how brain glucose at diabetic conditions elicits cortical neuronal insulin signaling impairment and mitochondrial dysfunction remains unknown. In the present study, we cultured primary cortical neurons with high glucose levels and investigated the neuronal mitochondrial function and insulin response. We found that mitochondrial function was declined in presence of 10 mmol/L glucose, prior to the depression of AKT signaling in primary cortical neurons. We further demonstrated that the cerebral cortex of db/db mice exhibited both insulin resistance and loss of mitochondrial complex components. Moreover, we found that adenosine monophosphate-activated protein kinase (AMPK) inactivation is involved in high glucose-induced mitochondrial dysfunction and insulin resistance in primary cortical neurons and neuroblastoma cells, as well as in cerebral cortex of db/db mice, and all these impairments can be rescued by mitochondrial activator, resveratrol. Taken together, our results extend the finding that high glucose (≥10 mmol/L) comparable to diabetic brain extracellular glucose level leads to neuronal mitochondrial dysfunction and resultant insulin resistance, and targeting mitochondria-AMPK signaling might be a promising strategy to protect against diabetes-related neuronal impairment in central nerves system. We found that high glucose (≥10 mmol/L), comparable to diabetic brain extracellular glucose level, leads to neuronal mitochondrial dysfunction and resultant insulin resistance in an AMPK-dependent manner, and targeting mitochondria-AMPK signaling might be a promising strategy to protect against diabetes-related neuronal impairment in central

  13. Cortical feedback control of olfactory bulb circuits.

    PubMed

    Boyd, Alison M; Sturgill, James F; Poo, Cindy; Isaacson, Jeffry S

    2012-12-20

    Olfactory cortex pyramidal cells integrate sensory input from olfactory bulb mitral and tufted (M/T) cells and project axons back to the bulb. However, the impact of cortical feedback projections on olfactory bulb circuits is unclear. Here, we selectively express channelrhodopsin-2 in olfactory cortex pyramidal cells and show that cortical feedback projections excite diverse populations of bulb interneurons. Activation of cortical fibers directly excites GABAergic granule cells, which in turn inhibit M/T cells. However, we show that cortical inputs preferentially target short axon cells that drive feedforward inhibition of granule cells. In vivo, activation of olfactory cortex that only weakly affects spontaneous M/T cell firing strongly gates odor-evoked M/T cell responses: cortical activity suppresses odor-evoked excitation and enhances odor-evoked inhibition. Together, these results indicate that although cortical projections have diverse actions on olfactory bulb microcircuits, the net effect of cortical feedback on M/T cells is an amplification of odor-evoked inhibition. PMID:23259951

  14. Influence of contralateral homologous cortices on motor cortical reorganization after brachial plexus injuries in rats.

    PubMed

    Zhang, Jie; Chen, Liang; Gu, Yu-dong

    2015-10-01

    Brachial plexus injuries induce corresponding cortical representations to be occupied by adjacent cortices. The purpose of this study was to clarify if contralateral homologous motor regions of adjacent cortices influence occupation of deafferented motor cortex. 36 rats were divided into 3 groups of 12 each. In group 1, total brachial plexus root avulsion (tBPRA) was made on the left side. In group 2, rats underwent left tBPRA combined with corpus callosum transection (CCX). In group 3, only CCX was performed. 6 rats in each group were used for intracortical microstimulation (ICMS) to map representations of motor cortex in the right hemisphere at 7 days and the other 6 rats, at 3 months. 18 more rats without any operation underwent ICMS, with 6 each taken to serve as normal control for motor cortical representations' changes caused by different surgery. Results showed that in groups 1 and 2, sites for motor cortical representations of vibrissae, of neck and of the hindlimb was statistically more than that of control, respectively, and statistically more sites were found at 3 months than at 7 days, respectively. At the two time points, sites for vibrissa cortices and that for the hindlimb were statistically more in group 2 than in group 1, respectively. CCX alone did not induce change of site number for motor cortical representations. We conclude that after tBPRA, contralateral homologous motor cortices may, to some extent, prevent neighboring cortices from encroachment on motor cortical representations of the brachial plexus. PMID:26314511

  15. Cerebral perfusion and cortical thickness indicate cortical involvement in mild Parkinson's disease.

    PubMed

    Madhyastha, Tara M; Askren, Mary K; Boord, Peter; Zhang, Jing; Leverenz, James B; Grabowski, Thomas J

    2015-12-01

    Cortical dysfunction in Parkinson's disease (PD) may be caused by disruption to ascending systems or by intrinsic cortical neuropathology. We introduce and conduct a joint analysis of metabolism and atrophy capable of identifying whether metabolic disruption occurs in mild PD without cortical atrophy, to determine the extent and spatial pattern of cortical involvement in mild PD. The design was observational, studying 23 cognitively normal participants with mild PD (mean Hoehn & Yahr stage 2) and 21 healthy controls. Cortical thickness (obtained from analysis of structural magnetic resonance imaging [MRI] with FreeSurfer) and cerebral perfusion measures (obtained from arterial spin labeling [ASL]) analyzed independently and then together in a joint multiple factorial analysis to identify spatial patterns of perfusion and cortical thickness. We identify a pattern of changes in perfusion and cortical thickness characterized by symmetric parietal cortical thinning and reduced precuneus perfusion, with relative preservation of thickness and perfusion in the anterior cingulate cortex (ACC), right prefrontal gyrus, and medial frontal gyrus. The expression of this pattern is correlated with motor system symptoms and speed of processing. A spatial pattern of joint parietal cortical thinning and disproportionate reduction in perfusion occurs in our nondemented PD sample. We found no PD-related components of reduced perfusion without cortical thinning. This suggests that PD affects the cortex itself, even when symptoms are relatively mild. PMID:25759166

  16. 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.

  17. 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

  18. Encoding Cortical Dynamics in Sparse Features

    PubMed Central

    Khan, Sheraz; Lefèvre, Julien; Baillet, Sylvain; Michmizos, Konstantinos P.; Ganesan, Santosh; Kitzbichler, Manfred G.; Zetino, Manuel; Hämäläinen, Matti S.; Papadelis, Christos; Kenet, Tal

    2014-01-01

    Distributed cortical solutions of magnetoencephalography (MEG) and electroencephalography (EEG) exhibit complex spatial and temporal dynamics. The extraction of patterns of interest and dynamic features from these cortical signals has so far relied on the expertise of investigators. There is a definite need in both clinical and neuroscience research for a method that will extract critical features from high-dimensional neuroimaging data in an automatic fashion. We have previously demonstrated the use of optical flow techniques for evaluating the kinematic properties of motion field projected on non-flat manifolds like in a cortical surface. We have further extended this framework to automatically detect features in the optical flow vector field by using the modified and extended 2-Riemannian Helmholtz–Hodge decomposition (HHD). Here, we applied these mathematical models on simulation and MEG data recorded from a healthy individual during a somatosensory experiment and an epilepsy pediatric patient during sleep. We tested whether our technique can automatically extract salient dynamical features of cortical activity. Simulation results indicated that we can precisely reproduce the simulated cortical dynamics with HHD; encode them in sparse features and represent the propagation of brain activity between distinct cortical areas. Using HHD, we decoded the somatosensory N20 component into two HHD features and represented the dynamics of brain activity as a traveling source between two primary somatosensory regions. In the epilepsy patient, we displayed the propagation of the epileptic activity around the margins of a brain lesion. Our findings indicate that HHD measures computed from cortical dynamics can: (i) quantitatively access the cortical dynamics in both healthy and disease brain in terms of sparse features and dynamic brain activity propagation between distinct cortical areas, and (ii) facilitate a reproducible, automated analysis of experimental and clinical

  19. Encoding cortical dynamics in sparse features.

    PubMed

    Khan, Sheraz; Lefèvre, Julien; Baillet, Sylvain; Michmizos, Konstantinos P; Ganesan, Santosh; Kitzbichler, Manfred G; Zetino, Manuel; Hämäläinen, Matti S; Papadelis, Christos; Kenet, Tal

    2014-01-01

    Distributed cortical solutions of magnetoencephalography (MEG) and electroencephalography (EEG) exhibit complex spatial and temporal dynamics. The extraction of patterns of interest and dynamic features from these cortical signals has so far relied on the expertise of investigators. There is a definite need in both clinical and neuroscience research for a method that will extract critical features from high-dimensional neuroimaging data in an automatic fashion. We have previously demonstrated the use of optical flow techniques for evaluating the kinematic properties of motion field projected on non-flat manifolds like in a cortical surface. We have further extended this framework to automatically detect features in the optical flow vector field by using the modified and extended 2-Riemannian Helmholtz-Hodge decomposition (HHD). Here, we applied these mathematical models on simulation and MEG data recorded from a healthy individual during a somatosensory experiment and an epilepsy pediatric patient during sleep. We tested whether our technique can automatically extract salient dynamical features of cortical activity. Simulation results indicated that we can precisely reproduce the simulated cortical dynamics with HHD; encode them in sparse features and represent the propagation of brain activity between distinct cortical areas. Using HHD, we decoded the somatosensory N20 component into two HHD features and represented the dynamics of brain activity as a traveling source between two primary somatosensory regions. In the epilepsy patient, we displayed the propagation of the epileptic activity around the margins of a brain lesion. Our findings indicate that HHD measures computed from cortical dynamics can: (i) quantitatively access the cortical dynamics in both healthy and disease brain in terms of sparse features and dynamic brain activity propagation between distinct cortical areas, and (ii) facilitate a reproducible, automated analysis of experimental and clinical

  20. 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

  1. 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

  2. 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

  3. 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,…

  4. 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. PMID:24906703

  5. Prefrontal cognitive deficits in mice with altered cerebral cortical GABAergic interneurons.

    PubMed

    Bissonette, Gregory B; Bae, Mihyun H; Suresh, Tejas; Jaffe, David E; Powell, Elizabeth M

    2014-02-01

    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

  6. 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

  7. 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. PMID:21251921

  8. 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

  9. Cultured Human Renal Cortical Cells

    NASA Technical Reports Server (NTRS)

    1998-01-01

    During the STS-90 shuttle flight in April 1998, cultured renal cortical cells revealed new information about genes. Timothy Hammond, an investigator in NASA's microgravity biotechnology program was interested in culturing kidney tissue to study the expression of proteins useful in the treatment of kidney diseases. Protein expression is linked to the level of differentiation of the kidney cells, and Hammond had difficulty maintaining differentiated cells in vitro. Intrigued by the improvement in cell differentiation that he observed in rat renal cells cultured in NASA's rotating wall vessel (a bioreactor that simulates some aspects of microgravity) and during an experiment performed on the Russian Space Station Mir, Hammond decided to sleuth out which genes were responsible for controlling differentiation of kidney cells. To do this, he compared the gene activity of human renal cells in a variety of gravitational environments, including the microgravity of the space shuttle and the high-gravity environment of a centrifuge. Hammond found that 1,632 genes out of 10,000 analyzed changed their activity level in microgravity, more than in any of the other environments. These results have important implications for kidney research as well as for understanding the basic mechanism for controlling cell differentiation.

  10. Cortical mechanisms of pretense observation.

    PubMed

    Smith, Eric D; Englander, Zoë A; Lillard, Angeline S; Morris, James P

    2013-01-01

    Pretend play emerges in children the world over around 18 months and continues into adolescence and even adulthood. Observing and engaging in pretense are thought to rely on similar neural mechanisms, but little is known about them. Here we examined neural activation patterns associated with observing pretense acts, including high-likelihood, low-likelihood, and imaginary substitute objects, as compared with activation patterns when observing parallel real acts. The association between fantasy predisposition and cortical representations of pretense was also explored. Supporting prior research that used more limited types of pretense, observed pretense acts, when contrasted with real acts, elicited activity in regions associated with mentalizing. A novel contribution here is that substitute object pretense (high- and low-likelihood) elicited significantly more activity than imaginary (pantomime) acts not only in theory of mind regions but also in the superior parietal lobule, a region thought to aid in the prediction and error-monitoring of motor actions. Finally, when high-likelihood pretense acts were contrasted with real acts, participants with elevated fantasy predispositions evidenced significantly different activation patterns than their more reality-prone peers. Future research will explore the intersection of fantasy predisposition and experience with the neural representation of pretense. PMID:23802124

  11. Cortical high-density counterstream architectures.

    PubMed

    Markov, Nikola T; Ercsey-Ravasz, Mária; Van Essen, David C; Knoblauch, Kenneth; Toroczkai, Zoltán; Kennedy, Henry

    2013-11-01

    Small-world networks provide an appealing description of cortical architecture owing to their capacity for integration and segregation combined with an economy of connectivity. Previous reports of low-density interareal graphs and apparent small-world properties are challenged by data that reveal high-density cortical graphs in which economy of connections is achieved by weight heterogeneity and distance-weight correlations. These properties define a model that predicts many binary and weighted features of the cortical network including a core-periphery, a typical feature of self-organizing information processing systems. Feedback and feedforward pathways between areas exhibit a dual counterstream organization, and their integration into local circuits constrains cortical computation. Here, we propose a bow-tie representation of interareal architecture derived from the hierarchical laminar weights of pathways between the high-efficiency dense core and periphery. PMID:24179228

  12. 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

  13. 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. PMID:25833839

  14. Environmental stimulation rescues maternal high fructose intake-impaired learning and memory in female offspring: Its correlation with redistribution of histone deacetylase 4.

    PubMed

    Wu, Kay L H; Wu, Chih-Wei; Tain, You-Lin; Huang, Li-Tung; Chao, Yung-Mei; Hung, Chun-Ying; Wu, Jin-Cheng; Chen, Siang-Ru; Tsai, Pei-Chia; Chan, Julie Y H

    2016-04-01

    Impairment of learning and memory has been documented in the later life of offspring to maternal consumption with high energy diet. Environmental stimulation enhances the ability of learning and memory. However, potential effects of environmental stimulation on the programming-associated deficit of learning and memory have not been addressed. Here, we examined the effects of enriched-housing on hippocampal learning and memory in adult female offspring rats from mother fed with 60% high fructose diet (HFD) during pregnancy and lactation. Impairment of spatial learning and memory performance in HFD group was observed in offspring at 3-month-old. Hippocampal brain-derived neurotrophic factor (BDNF) was decreased in the offspring. Moreover, the HFD group showed an up-regulation of histone deacetylase 4 (HDAC4) in the nuclear fractions of hippocampal neurons. Stimulation to the offspring for 4weeks after winning with an enriched-housing environment effectively rescued the decrease in cognitive function and hippocampal BDNF level; alongside a reversal of the increased distribution of nuclear HDAC4. Together these results suggest that later life environmental stimulation effectively rescues the impairment of hippocampal learning and memory in female offspring to maternal HFD intake through redistributing nuclear HDAC4 to increase BDNF expression. PMID:26872592

  15. Cortical swallowing processing in early subacute stroke

    PubMed Central

    2011-01-01

    Background Dysphagia is a major complication in hemispheric as well as brainstem stroke patients causing aspiration pneumonia and increased mortality. Little is known about the recovery from dysphagia after stroke. The aim of the present study was to determine the different patterns of cortical swallowing processing in patients with hemispheric and brainstem stroke with and without dysphagia in the early subacute phase. Methods We measured brain activity by mean of whole-head MEG in 37 patients with different stroke localisation 8.2 +/- 4.8 days after stroke to study changes in cortical activation during self-paced swallowing. An age matched group of healthy subjects served as controls. Data were analyzed by means of synthetic aperture magnetometry and group analyses were performed using a permutation test. Results Our results demonstrate strong bilateral reduction of cortical swallowing activation in dysphagic patients with hemispheric stroke. In hemispheric stroke without dysphagia, bilateral activation was found. In the small group of patients with brainstem stroke we observed a reduction of cortical activation and a right hemispheric lateralization. Conclusion Bulbar central pattern generators coordinate the pharyngeal swallowing phase. The observed right hemispheric lateralization in brainstem stroke can therefore be interpreted as acute cortical compensation of subcortically caused dysphagia. The reduction of activation in brainstem stroke patients and dysphagic patients with cortical stroke could be explained in terms of diaschisis. PMID:21392404

  16. 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

  17. 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

  18. Diffuse malformations of cortical development.

    PubMed

    Bahi-Buisson, Nadia; Guerrini, Renzo

    2013-01-01

    Malformations of cortical development (MCD) represent a major cause of developmental disabilities and severe epilepsy. Advances in imaging and genetics have improved the diagnosis and classification of these conditions. Up to now, eight genes have been involved in different types of MCD. Lissencephaly-pachygyria and subcortical band heterotopia (SBH) represent a malformative spectrum resulting from mutations of either LIS1 or DCX genes. LIS1 mutations cause a more severe malformation in the posterior brain regions. DCX mutations usually cause anteriorly predominant lissencephaly in males and SBH in female patients. Additional forms are X-linked lissencephaly with corpus callosum agenesis and ambiguous genitalia associated with mutations of the ARX gene. Lissencephaly with cerebellar hypoplasia (LCH) encompass heterogeneous disorders named LCH types a to d. LCHa is related to mutation in LIS1 or DCX, LCHb with mutation of the RELN gene, and LCHd could be related to the TUBA1A gene. Polymicrogyria encompasses a wide range of clinical, etiological, and histological findings. Among several syndromes, recessive bilateral fronto-parietal polymicrogyria has been associated with mutations of the GPR56 gene. Bilateral perisylvian polymicrogyria has been associated with mutations in the SRPX2 gene in a few individuals and with linkage to chromosome Xq28 in a some other families. X-linked bilateral periventricular nodular heterotopia (PNH) consists of PNH with focal epilepsy in females and prenatal lethality in males. Filamin A (FLNA) mutations have been reported in some families and in sporadic patients. It is possible to infer the most likely causative gene by brain imaging studies and other clinical findings. PMID:23622213

  19. Cortical mechanisms of cocaine sensitization.

    PubMed

    Steketee, Jeffery D

    2005-01-01

    Behavioral sensitization is the augmented motor-stimulant response that occurs with repeated, intermittent exposure to most drugs of abuse, including cocaine. Sensitization, which is a long-lasting phenomenon, is thought to underlie drug craving and relapse to drug use. Much research has been conducted to determine the neural mechanisms of sensitization. The bulk of this effort has focused on the nucleus accumbens and ventral tegmental area (VTA) that comprise a portion of the mesolimbic dopamine system. Recently, studies have begun to also explore the role of the medial prefrontal cortex (mPFC) in sensitization, in part because this region provides glutamatergic innervation to the VTA and nucleus accumbens. The present review will coalesce these studies into a working hypothesis that states that cocaine sensitization results from a decrease in inhibitory modulation of excitatory transmission from the mPFC to the VTA and nucleus accumbens. The discussion will revolve around how repeated cocaine exposure alters dopamine, gamma-aminobutyric acid (GABA), and glutamate regulation of pyramidal cell activity. It will be proposed that cocaine-induced alterations in cortical transmission occur in two phases. During early withdrawal from repeated cocaine exposure, changes in neurotransmitter release are thought to underlie the decreased inhibitory modulation of pyramidal projection neurons. Following more prolonged withdrawal, the attenuation in inhibitory transmission appears to occur at the receptor level. A model will be presented that may serve to direct future studies on the involvement of the mPFC in the development of cocaine sensitization, which ultimately could lead to development of pharmacotherapies for cocaine addiction. PMID:16808728

  20. Patterns of cortical thinning in idiopathic rapid eye movement sleep behavior disorder.

    PubMed

    Rahayel, Shady; Montplaisir, Jacques; Monchi, Oury; Bedetti, Christophe; Postuma, Ronald B; Brambati, Simona; Carrier, Julie; Joubert, Sven; Latreille, Véronique; Jubault, Thomas; Gagnon, Jean-François

    2015-04-15

    Idiopathic rapid eye movement sleep behavior disorder is a parasomnia that is a risk factor for dementia with Lewy bodies and Parkinson's disease. Brain function impairments have been identified in this disorder, mainly in the frontal and posterior cortical regions. However, the anatomical support for these dysfunctions remains poorly understood. We investigated gray matter thickness, gray matter volume, and white matter integrity in patients with idiopathic rapid eye movement sleep behavior disorder. Twenty-four patients with polysomnography-confirmed idiopathic rapid eye movement sleep behavior disorder and 42 healthy individuals underwent a 3-tesla structural and diffusion magnetic resonance imaging examination using corticometry, voxel-based morphometry, and diffusion tensor imaging. In the patients with idiopathic rapid eye movement sleep behavior disorder, decreased cortical thickness was observed in the frontal cortex, the lingual gyrus, and the fusiform gyrus. Gray matter volume was reduced in the superior frontal sulcus only. Patients showed no increased gray matter thickness or volume. Diffusion tensor imaging analyses revealed no significant white matter differences between groups. Using corticometry in patients with idiopathic rapid eye movement sleep behavior disorder, several new cortical regions with gray matter alterations were identified, similar to those reported in dementia with Lewy bodies and Parkinson's disease. These findings provide some anatomical support for previously identified brain function impairments in this disorder. PMID:24676967

  1. 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

  2. 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

  3. State-Dependent Partial Occlusion of Cortical LTP-Like Plasticity in Major Depression.

    PubMed

    Kuhn, Marion; Mainberger, Florian; Feige, Bernd; Maier, Jonathan G; Mall, Volker; Jung, Nicolai H; Reis, Janine; Klöppel, Stefan; Normann, Claus; Nissen, Christoph

    2016-05-01

    The synaptic plasticity hypothesis of major depressive disorder (MDD) posits that alterations in synaptic plasticity represent a final common pathway underlying the clinical symptoms of the disorder. This study tested the hypotheses that patients with MDD show an attenuation of cortical synaptic long-term potentiation (LTP)-like plasticity in comparison with healthy controls, and that this attenuation recovers after remission. Cortical synaptic LTP-like plasticity was measured using a transcranial magnetic stimulation protocol, ie, paired associative stimulation (PAS), in 27 in-patients with MDD according to ICD-10 criteria and 27 sex- and age-matched healthy controls. The amplitude of motor-evoked potentials was measured before and after PAS. Patients were assessed during the acute episode and at follow-up to determine the state- or trait-character of LTP-like changes. LTP-like plasticity, the PAS-induced increase in motor-evoked potential amplitudes, was significantly attenuated in patients with an acute episode of MDD compared with healthy controls. Patients with remission showed a restoration of synaptic plasticity, whereas the deficits persisted in patients without remission, indicative for a state-character of impaired LTP-like plasticity. The results provide first evidence for a state-dependent partial occlusion of cortical LTP-like plasticity in MDD. This further identifies impaired LTP-like plasticity as a potential pathomechanism and treatment target of the disorder. PMID:26442602

  4. Longitudinal Evaluation of Residual Cortical and Subcortical Motor Evoked Potentials in Spinal Cord Injured Rats.

    PubMed

    Redondo-Castro, Elena; Navarro, Xavier; García-Alías, Guillermo

    2016-05-15

    We have applied transcranial electrical stimulation to rats with spinal cord injury and selectively tested the motor evoked potentials (MEPs) conveyed by descending motor pathways with cortical and subcortical origin. MEPs were elicited by electrical stimulation to the brain and recorded on the tibialis anterior muscles. Stimulation parameters were characterized and changes in MEP responses tested in uninjured rats, in rats with mild or moderate contusion, and in animals with complete transection of the spinal cord. All injuries were located at the T8 vertebral level. Two peaks, termed N1 and N2, were obtained when changing from single pulse stimulation to trains of 9 pulses at 9 Hz. Selective injuries to the brain or spinal cord funiculi evidenced the subcortical origin of N1 and the cortical origin of N2. Animals with mild contusion showed small behavioral deficits and abolished N1 but maintained small amplitude N2 MEPs. Substantial motor deficits developed in rats with moderate contusion, and these rats had completely eliminated N1 and N2 MEPs. Animals with complete cord transection had abolished N1 and N2 and showed severe impairment of locomotion. The results indicate the reliability of MEP testing to longitudinally evaluate over time the degree of impairment of cortical and subcortical spinal pathways after spinal cord injuries of different severity. PMID:26560177

  5. 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

  6. 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…

  7. Epidural cortical stimulation and aphasia therapy

    PubMed Central

    Cherney, Leora R.; Harvey, Richard L.; Babbitt, Edna M.; Hurwitz, Rosalind; Kaye, Rosalind C.; Lee, Jaime B.; Small, Steven. L.

    2013-01-01

    Background There are several methods of delivering cortical brain stimulation to modulate cortical excitability and interest in their application as an adjuvant strategy in aphasia rehabilitation after stroke is growing. Epidural cortical stimulation, although more invasive than other methods, permits high frequency stimulation of high spatial specificity to targeted neuronal populations. Aims First, we review evidence supporting the use of epidural cortical stimulation for upper limb recovery after focal cortical injury in both animal models and human stroke survivors. These data provide the empirical and theoretical platform underlying the use of epidural cortical stimulation in aphasia. Second, we summarize evidence for the application of epidural cortical stimulation in aphasia. We describe the procedures and primary outcomes of a safety and feasibility study (Cherney, Erickson & Small, 2010), and provide previously unpublished data regarding secondary behavioral outcomes from that study. Main Contribution In a controlled study comparing epidural cortical stimulation plus language treatment (CS/LT) to language treatment alone (LT), eight stroke survivors with nonfluent aphasia received intensive language therapy for 6 weeks. Four of these participants also underwent surgical implantation of an epidural stimulation device which was activated only during therapy sessions. Behavioral data were collected before treatment, immediately after treatment, and at 6 and 12 weeks following the end of treatment. The effect size for the primary outcome measure, the Western Aphasia Battery Aphasia Quotient, was benchmarked as moderate from baseline to immediately post-treatment, and large from baseline to the 12-week follow-up. Similarly, effect sizes obtained at the 12-week follow-up for the Boston Naming Test, the Communicative Effectiveness Index, and for correct information units on a picture description task were greater than those obtained immediately post treatment

  8. Mapping early changes of cortical motor output after subcortical stroke: a transcranial magnetic stimulation study.

    PubMed

    Chieffo, Raffaella; Inuggi, Alberto; Straffi, Laura; Coppi, Elisabetta; Gonzalez-Rosa, Javier; Spagnolo, Francesca; Poggi, Antonella; Comi, Giancarlo; Comola, Mauro; Leocani, Letizia

    2013-05-01

    After acute stroke several changes in cortical excitability occur involving affected (AH) and unaffected hemisphere (UH) but whether they contribute to motor recovery is still controversial. We performed transcranial magnetic stimulation mapping of several upper limb muscles over the two hemispheres in thirteen patients at 4-12 days from subcortical stroke and after 1 month. The occurrence of mirror movements (MMs) on the healthy side during contraction of paretic muscles was measured. At baseline, cortical excitability parameters over the AH decreased in comparison with controls, while excitability over the UH increased correlating with severity of motor deficits of the affected arm at baseline as well as with poor recovery. At follow-up, map parameters of the UH became closer to those of controls independently from recovery, while for the AH the number of responsive sites increased significantly. Ipsilateral motor evoked responses (iMEPs) in the affected arm were never elicited. We observed an early impairment in dexterity of the ipsilesional hand that recovered over-time but persistently differed in comparison with controls. MMs occurrence increased at baseline correlating with reduced cortical excitability of the AH as well as with increased map density over the UH. The acute increased excitability of the UH after stroke has a negative prognostic value on recovery and negatively affects motor performance of the ipsilesional hand. Moreover, the absence of iMEPs and the normalization of motor cortical excitability at follow-up indicate that the UH primary motor area does not contribute to recovery. PMID:22776700

  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. Role of IGF-1 in cortical plasticity and functional deficit induced by sensorimotor restriction.

    PubMed

    Mysoet, Julien; Dupont, Erwan; Bastide, Bruno; Canu, Marie-Hélène

    2015-09-01

    In the adult rat, sensorimotor restriction by hindlimb unloading (HU) is known to induce impairments in motor behavior as well as a disorganization of somatosensory cortex (shrinkage of the cortical representation of the hindpaw, enlargement of the cutaneous receptive fields, decreased cutaneous sensibility threshold). Recently, our team has demonstrated that IGF-1 level was decreased in the somatosensory cortex of rats submitted to a 14-day period of HU. To determine whether IGF-1 is involved in these plastic mechanisms, a chronic cortical infusion of this substance was performed by means of osmotic minipump. When administered in control rats, IGF-1 affects the size of receptive fields and the cutaneous threshold, but has no effect on the somatotopic map. In addition, when injected during the whole HU period, IGF-1 is interestingly implied in cortical changes due to hypoactivity: the shrinkage of somatotopic representation of hindlimb is prevented, whereas the enlargement of receptive fields is reduced. IGF-1 has no effect on the increase in neuronal response to peripheral stimulation. We also explored the functional consequences of IGF-1 level restoration on tactile sensory discrimination. In HU rats, the percentage of paw withdrawal after a light tactile stimulation was decreased, whereas it was similar to control level in HU-IGF-1 rats. Taken together, the data clearly indicate that IGF-1 plays a key-role in cortical plastic mechanisms and in behavioral alterations induced by a decrease in sensorimotor activity. PMID:25958232

  11. Subjective memory complaints in Italian elderly with mild cognitive impairment: implication of psychological status.

    PubMed

    Giuli, Cinzia; Fabbietti, Paolo; Paoloni, Cristina; Pensieri, Mirko; Lattanzio, Fabrizia; Postacchini, Demetrio

    2016-07-01

    Subjective cognitive and memory complaints (SMC) are common in later life and are considered an indicator for progression to cognitive decline. The aim of the present study was to identify the relationship among SMC, neuropsychiatric symptoms and psychological aspects in elderly subjects with mild cognitive impairment (MCI) as well as to analyse the effect on SMC of a comprehensive cognitive training. Data from a sample of 94 patients enrolled in 'My Mind Project' (Grant No. 154/GR-2009-1584108) were collected. The study evidenced that depression was a significant predictor of SMC and that after the training, the number of subjects with SMC was significantly reduced in the experimental group in comparison to the control one. These results suggest that the participation in cognitive stimulation protocols may improve the perception of SMC in subjects with MCI. PMID:27025607

  12. EEG upper/low alpha frequency power ratio relates to temporo-parietal brain atrophy and memory performances in mild cognitive impairment

    PubMed Central

    Moretti, Davide V.; Paternicò, Donata; Binetti, Giuliano; Zanetti, Orazio; Frisoni, Giovanni B.

    2013-01-01

    Objective: Temporo-parietal cortex thinning is associated to mild cognitive impairment (MCI) due to Alzheimer disease (AD). The increase of EEG upper/low alpha power ratio has been associated with AD-converter MCI subjects. We investigated the association of alpha3/alpha2 ratio with patterns of cortical thickness in MCI. Materials and Methods: Seventy-four adult subjects with MCI underwent clinical and neuropsychological evaluation, electroencephalogram (EEG) recording and high resolution 3D magnetic resonance imaging. Alpha3/alpha2 power ratio as well as cortical thickness was computed for each subject. Three MCI groups were detected according to increasing tertile values of upper/low alpha power ratio. Difference of cortical thickness among the groups was estimated. Pearson’s r was used to assess the topography of the correlation between cortical thinning and memory impairment. Results: High upper/low alpha power ratio group had total cortical gray matter volume reduction of 471 mm2 than low upper/low alpha power ratio group (p < 0.001). Upper/low alpha group showed a similar but less marked pattern (160 mm2) of cortical thinning when compared to middle upper/low alpha power ratio group (p < 0.001). Moreover, high upper/low alpha group had wider cortical thinning than other groups, mapped to the Supramarginal and Precuneus bilaterally. Finally, in high upper/low alpha group temporo-parietal cortical thickness was correlated to memory performance. No significant cortical thickness differences was found between middle and low alpha3/alpha2 power ratio groups. Conclusion: High EEG upper/low alpha power ratio was associated with temporo-parietal cortical thinning and memory impairment in MCI subjects. The combination of EEG upper/low alpha ratio and cortical thickness measure could be useful for identifying individuals at risk for progression to AD dementia and may be of value in clinical context. PMID:24187540

  13. Concurrent impairments in sleep and memory in amnestic mild cognitive impairment.

    PubMed

    Westerberg, Carmen E; Mander, Bryce A; Florczak, Susan M; Weintraub, Sandra; Mesulam, M-Marsel; Zee, Phyllis C; Paller, Ken A

    2012-05-01

    Whereas patients with Alzheimer's disease (AD) experience difficulties forming and retrieving memories, their memory impairments may also partially reflect an unrecognized dysfunction in sleep-dependent consolidation that normally stabilizes declarative memory storage across cortical areas. Patients with amnestic mild cognitive impairment (aMCI) exhibit circumscribed declarative memory deficits, and many eventually progress to an AD diagnosis. Whether sleep is disrupted in aMCI and whether sleep disruptions contribute to memory impairment is unknown. We measured sleep physiology and memory for two nights and found that aMCI patients had fewer stage-2 spindles than age-matched healthy adults. Furthermore, aMCI patients spent less time in slow-wave sleep and showed lower delta and theta power during sleep compared to controls. Slow-wave and theta activity during sleep appear to reflect important aspects of memory processing, as evening-to-morning change in declarative memory correlated with delta and theta power during intervening sleep in both groups. These results suggest that sleep changes in aMCI patients contribute to memory impairments by interfering with sleep-dependent memory consolidation. PMID:22300710

  14. Increased Intrinsic Activity of Medial-Temporal Lobe Subregions is Associated with Decreased Cortical Thickness of Medial-Parietal Areas in Patients with Alzheimer's Disease Dementia.

    PubMed

    Pasquini, Lorenzo; Scherr, Martin; Tahmasian, Masoud; Myers, Nicholas E; Ortner, Marion; Kurz, Alexander; Förstl, Hans; Zimmer, Claus; Grimmer, Timo; Akhrif, Atae; Wohlschläger, Afra M; Riedl, Valentin; Sorg, Christian

    2016-01-21

    In Alzheimer's disease (AD), disrupted connectivity between medial-parietal cortices and medial-temporal lobes (MTL) is linked with increased MTL local functional connectivity, and parietal atrophy is associated with increased MTL memory activation. We hypothesized that intrinsic activity in MTL subregions is increased and associated with medial-parietal degeneration and impaired memory in AD. To test this hypothesis, resting-state-functional and structural-MRI was assessed in 22 healthy controls, 22 mild cognitive impairment patients, and 21 AD-dementia patients. Intrinsic activity was measured by power-spectrum density of blood-oxygenation-level-dependent signal, medial-parietal degeneration by cortical thinning. In AD-dementia patients, intrinsic activity was increased for several right MTL subregions. Raised intrinsic activity in dentate gyrus and cornu ammonis 1 was associated with cortical thinning in posterior cingulate cortices, and at-trend with impaired delayed recall. Critically, increased intrinsic activity in the right entorhinal cortex was associated with ipsilateral posterior cingulate degeneration. Our results provide evidence that in AD, intrinsic activity in MTL subregions is increased and associated with medial-parietal atrophy. Results fit a model in which medial-parietal degeneration contributes to MTL dysconnectivity from medial-parietal cortices, potentially underpinning disinhibition-like changes in MTL activity. PMID:26836175

  15. 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

  16. 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

  17. Intellectual impairment in Parkinson's disease: clinical, pathologic, and biochemical correlates.

    PubMed

    Cummings, J L

    1988-01-01

    The prevalence of overt dementia in 27 studies representing 4,336 Parkinson's disease (PD) patients was 39.9%. The studies reporting the highest incidence of intellectual impairment (69.9%) used psychologic assessment techniques, whereas studies identifying the lowest prevalence of dementia (30.2%) depended on nonstandardized clinical examinations. Neuropsychologic investigations reveal that PD patients manifest impairment in memory, visuospatial skills, and set aptitude. Language function is largely spared. Intellectual deterioration in PD correlates with age, akinesia, duration, and treatment status. Neuropathologic and neurochemical observations demonstrate that PD is a heterogeneous disorder: the classic subcortical pathology with dopamine deficiency may be complicated by atrophy of nucleus basalis and superimposed cortical cholinergic deficits, and a few patients have the histopathologic hallmarks of Alzheimer's disease. Mild intellectual loss occurs with the classic pathology, and the more severe dementia syndromes have cholinergic alterations or Alzheimer's disease. Thus, PD includes several syndromes of intellectual impairment with variable pathologic and neurochemical correlates. PMID:2908099

  18. 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…

  19. 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…

  20. Symmetry breaking in reconstituted actin cortices.

    PubMed

    Abu Shah, Enas; Keren, Kinneret

    2014-01-01

    The actin cortex plays a pivotal role in cell division, in generating and maintaining cell polarity and in motility. In all these contexts, the cortical network has to break symmetry to generate polar cytoskeletal dynamics. Despite extensive research, the mechanisms responsible for regulating cortical dynamics in vivo and inducing symmetry breaking are still unclear. Here we introduce a reconstituted system that self-organizes into dynamic actin cortices at the inner interface of water-in-oil emulsions. This artificial system undergoes spontaneous symmetry breaking, driven by myosin-induced cortical actin flows, which appears remarkably similar to the initial polarization of the embryo in many species. Our in vitro model system recapitulates the rich dynamics of actin cortices in vivo, revealing the basic biophysical and biochemical requirements for cortex formation and symmetry breaking. Moreover, this synthetic system paves the way for further exploration of artificial cells towards the realization of minimal model systems that can move and divide.DOI: http://dx.doi.org/10.7554/eLife.01433.001. PMID:24843007

  1. 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.

  2. 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

  3. Accelerated longitudinal cortical thinning in adolescence.

    PubMed

    Zhou, Dongming; Lebel, Catherine; Treit, Sarah; Evans, Alan; Beaulieu, Christian

    2015-01-01

    It remains unclear if changes of the cerebral cortex occur gradually from childhood to adulthood, or if adolescence marks a differential period of cortical development. In the current study of 90 healthy volunteers aged 5-32years (48 females, 85 right handed) with 180 scans (2 scans for each participant with ~4year gaps), thinning of overall mean thickness and across the four major cortical lobes bilaterally was observed across this full age span. However, the thinning rate, calculated as Δcortical thickness/Δage (mm/year) between scans of each participant, revealed an accelerated cortical thinning during adolescence, which was preceded by less thinning in childhood and followed by decelerated thinning in young adulthood. Males and females showed similarly faster thinning rates during adolescence relative to young adults. The underlying basis and role of accelerated cortical thinning during adolescence for cognition, behaviour and disorders that appear at such a stage of development remains to be determined in future work. PMID:25312772

  4. Symmetry breaking in reconstituted actin cortices

    PubMed Central

    Abu Shah, Enas; Keren, Kinneret

    2014-01-01

    The actin cortex plays a pivotal role in cell division, in generating and maintaining cell polarity and in motility. In all these contexts, the cortical network has to break symmetry to generate polar cytoskeletal dynamics. Despite extensive research, the mechanisms responsible for regulating cortical dynamics in vivo and inducing symmetry breaking are still unclear. Here we introduce a reconstituted system that self-organizes into dynamic actin cortices at the inner interface of water-in-oil emulsions. This artificial system undergoes spontaneous symmetry breaking, driven by myosin-induced cortical actin flows, which appears remarkably similar to the initial polarization of the embryo in many species. Our in vitro model system recapitulates the rich dynamics of actin cortices in vivo, revealing the basic biophysical and biochemical requirements for cortex formation and symmetry breaking. Moreover, this synthetic system paves the way for further exploration of artificial cells towards the realization of minimal model systems that can move and divide. DOI: http://dx.doi.org/10.7554/eLife.01433.001 PMID:24843007

  5. 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

  6. Oxytocin Enhances Social Recognition by Modulating Cortical Control of Early Olfactory Processing.

    PubMed

    Oettl, Lars-Lennart; Ravi, Namasivayam; Schneider, Miriam; Scheller, Max F; Schneider, Peggy; Mitre, Mariela; da Silva Gouveia, Miriam; Froemke, Robert C; Chao, Moses V; Young, W Scott; Meyer-Lindenberg, Andreas; Grinevich, Valery; Shusterman, Roman; Kelsch, Wolfgang

    2016-05-01

    Oxytocin promotes social interactions and recognition of conspecifics that rely on olfaction in most species. The circuit mechanisms through which oxytocin modifies olfactory processing are incompletely understood. Here, we observed that optogenetically induced oxytocin release enhanced olfactory exploration and same-sex recognition of adult rats. Consistent with oxytocin's function in the anterior olfactory cortex, particularly in social cue processing, region-selective receptor deletion impaired social recognition but left odor discrimination and recognition intact outside a social context. Oxytocin transiently increased the drive of the anterior olfactory cortex projecting to olfactory bulb interneurons. Cortical top-down recruitment of interneurons dynamically enhanced the inhibitory input to olfactory bulb projection neurons and increased the signal-to-noise of their output. In summary, oxytocin generates states for optimized information extraction in an early cortical top-down network that is required for social interactions with potential implications for sensory processing deficits in autism spectrum disorders. PMID:27112498

  7. The SH2 domain is crucial for function of Fyn in neuronal migration and cortical lamination

    PubMed Central

    Lu, Xi; Hu, Xinde; Song, Lingzhen; An, Lei; Duan, Minghui; Chen, Shulin; Zhao, Shanting

    2015-01-01

    Neurons in the developing brain form the cortical plate (CP) in an inside-out manner, in which the late-born neurons are located more superficially than the early-born neurons. Fyn, a member of the Src family kinases, plays an important role in neuronal migration by binding to many substrates. However, the role of the Src-homology 2 (SH2) domain in function of Fyn in neuronal migration remains poorly understood. Here, we demonstrate that the SH2 domain is essential for the action of Fyn in neuronal migration and cortical lamination. A point mutation in the Fyn SH2 domain (FynR176A) impaired neuronal migration and their final location in the cerebral cortex, by inducing neuronal aggregation and branching. Thus, we provide the first evidence of the Fyn SH2 domain contributing to neuronal migration and neuronal morphogenesis. [BMB Reports 2015; 48(2): 97-102] PMID:24912779

  8. 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

  9. 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

  10. Amyloid beta-peptide disrupts carbachol-induced muscarinic cholinergic signal transduction in cortical neurons.

    PubMed Central

    Kelly, J F; Furukawa, K; Barger, S W; Rengen, M R; Mark, R J; Blanc, E M; Roth, G S; Mattson, M P

    1996-01-01

    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

  11. 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

  12. 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

  13. 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

  14. Behavioral Dependence of Auditory Cortical Responses

    PubMed Central

    Osmanski, Michael S.; Wang, Xiaoqin

    2015-01-01

    Neural responses in the auditory cortex have historically been measured from either anesthetized or awake but non-behaving animals. A growing body of work has begun to focus instead on recording from auditory cortex of animals actively engaged in behavior tasks. These studies have shown that auditory cortical responses are dependent upon the behavioral state of the animal. The longer ascending subcortical pathway of the auditory system and unique characteristics of auditory processing suggest that such dependencies may have a more profound influence on cortical processing in auditory system compared to other sensory systems. It is important to understand the nature of these dependencies and their functional implications. In this article, we review the literature on this topic pertaining to cortical processing of sounds. PMID:25690831

  15. History of Alcohol Use Disorders and Risk of Severe Cognitive Impairment: A 19-Year Prospective Cohort Study

    PubMed Central

    Kuźma, Elżbieta; Llewellyn, David J.; Langa, Kenneth M.; Wallace, Robert B.; Lang, Iain A.

    2014-01-01

    Objective To assess the effects of a history of alcohol use disorders (AUDs) on risk of severe cognitive and memory impairment in later life. Methods We studied the association between history of AUDs and the onset of severe cognitive and memory impairment in 6,542 middle-aged adults born 1931 through 1941 who participated in the Health and Retirement Study, a prospective nationally representative U.S. cohort. Participants were assessed at 1992 baseline and follow-up cognitive assessments were conducted biannually from 1996 through 2010. History of AUDs was identified using the three-item modified CAGE questionnaire. Cognitive outcomes were assessed using the 35-item modified Telephone Interview for Cognitive Status at last follow-up with incident severe cognitive impairment defined as a score ≤8, and incident severe memory impairment defined as a score ≤1 on a 20-item memory subscale. Results During up to 19 years of follow-up (mean: 16.7 years, standard deviation: 3.0, range: 3.5–19.1 years), 90 participants experienced severe cognitive impairment and 74 participants experienced severe memory impairment. History of AUDs more than doubled the odds of severe memory impairment (odds ratio [OR] = 2.21, 95% confidence interval [CI] = 1.27–3.85, t = 2.88, df = 52, p = 0.01). The association with severe cognitive impairment was statistically non-significant but in the same direction (OR = 1.80, 95% CI = 0.97–3.33, t = 1.92, df = 52, p = 0.06). Conclusion Middle-aged adults with a history of AUDs have increased odds of developing severe memory impairment later in life. These results reinforce the need to consider the relationship between alcohol consumption and cognition from a multifactorial lifespan perspective. PMID:25091517

  16. Focal cortical dysplasias in autism spectrum disorders

    PubMed Central

    2013-01-01

    Background Previous reports indicate the presence of histological abnormalities in the brains of individuals with autism spectrum disorders (ASD) suggestive of a dysplastic process. In this study we identified areas of abnormal cortical thinning within the cerebral cortex of ASD individuals and examined the same for neuronal morphometric abnormalities by using computerized image analysis. Results The study analyzed celloidin-embedded and Nissl-stained serial full coronal brain sections of 7 autistic (ADI-R diagnosed) and 7 age/sex-matched neurotypicals. Sections were scanned and manually segmented before implementing an algorithm using Laplace’s equation to measure cortical width. Identified areas were then subjected to analysis for neuronal morphometry. Results of our study indicate the presence within our ASD population of circumscribed foci of diminished cortical width that varied among affected individuals both in terms of location and overall size with the frontal lobes being particularly involved. Spatial statistic indicated a reduction in size of neurons within affected areas. Granulometry confirmed the presence of smaller pyramidal cells and suggested a concomitant reduction in the total number of interneurons. Conclusions The neuropathology is consistent with a diagnosis of focal cortical dysplasia (FCD). Results from the medical literature (e.g., heterotopias) and our own study suggest that the genesis of this cortical malformation seemingly resides in the heterochronic divisions of periventricular germinal cells. The end result is that during corticogenesis radially migrating neuroblasts (future pyramidal cells) are desynchronized in their development from those that follow a tangential route (interneurons). The possible presence of a pathological mechanism in common among different conditions expressing an autism-like phenotype argue in favor of considering ASD a “sequence” rather than a syndrome. Focal cortical dysplasias in ASD may serve to

  17. 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…

  18. 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. ...

  19. Evidence for cortical inhibitory and excitatory dysfunction in obsessive compulsive disorder.

    PubMed

    Richter, Margaret A; de Jesus, Danilo R; Hoppenbrouwers, Sylco; Daigle, Melissa; Deluce, Jasna; Ravindran, Lakshmi N; Fitzgerald, Paul B; Daskalakis, Zafiris J

    2012-04-01

    Several lines of evidence suggest that obsessive-compulsive disorder (OCD) is associated with an inability to inhibit unwanted intrusive thoughts. The neurophysiological mechanisms mediating such inhibitory deficits include abnormalities in cortical γ-aminobutyric acid (GABA) inhibitory as well as N-methyl-D-aspartate (NMDA) receptor-mediated mechanisms. Molecular evidence suggests that both these neurotransmitter systems are involved in OCD. Transcranial magnetic stimulation (TMS) represents a noninvasive technique to ascertain neurophysiological indices of inhibitory GABA and facilitatory NMDA receptor-mediated mechanisms. In this study, both mechanisms were indexed in 34 patients with OCD (23 unmedicated and 11 medicated) and compared with 34 healthy subjects. Cortical inhibitory and facilitatory neurotransmission was measured using TMS paradigms known as short-interval cortical inhibition (SICI), cortical silent period (CSP), and intracortical facilitation (ICF). Patients with OCD demonstrated significantly shortened CSP (p<0.001, Cohen's d=0.91) and increased ICF (p<0.009, Cohen's d=0.71) compared with healthy subjects. By contrast, there were no significant deficits in SICI. After excluding patients with OCD and comorbid major depressive disorder (MDD) from the analysis, these differences remained significant. Our findings suggest that OCD is associated with dysregulation in cortical inhibitory and facilitatory neurotransmission. Specifically, these findings suggest impairments in GABA(B) receptor-mediated and NMDA receptor-mediated neurotransmission. These findings are consistent with previously published genetic studies implicating GABA(B), and NMDA transporter and receptor genes in OCD. It is posited that dysregulation of such mechanisms may lead to the generation and persistence of intrusive thoughts that form the basis for this disorder. PMID:22169948

  20. Valproic acid potentiates both typical and atypical antipsychotic-induced prefrontal cortical dopamine release.

    PubMed

    Ichikawa, Junji; Chung, Young-Chul; Dai, Jin; Meltzer, Herbert Y

    2005-08-01

    Antipsychotic drugs (APD)s and anticonvulsant mood-stabilizers are now frequently used in combination with one another in treating both schizophrenia and bipolar disorder. We have recently reported that the atypical APDs, e.g. clozapine and risperidone, as well as the anticonvulsant mood-stabilizers, valproic acid (VPA), zonisamide, and carbamazepine, but not the typical APD haloperidol, increase dopamine (DA) release in rat medial prefrontal cortex (mPFC). The increased DA release was partially (atypical APDs) or completely (mood-stabilizers) blocked by the serotonin (5-HT)1A receptor antagonist WAY100635. Diminished prefrontal cortical DA activity may contribute to cognitive impairment in virtually all the patients with schizophrenia and, perhaps, bipolar disorder. Thus, the enhanced release of cortical DA by these agents may be beneficial in this regard. It is, therefore, of considerable interest to determine whether combined administration of these agents augments prefrontal cortical DA release, and if so, whether the increase is dependent upon 5-HT1A receptor activation. VPA (50 mg/kg), which was insufficient by itself to increase prefrontal cortical DA release, potentiated the ability of clozapine (20 mg/kg) and risperidone (1 mg/kg) to increase DA release in the mPFC, but not in the nucleus accumbens (NAC). VPA (50 mg/kg) also potentiated haloperidol (0.5 mg/kg)-induced DA release in the mPFC; this increase was completely abolished by WAY100635 (0.2 mg/kg). These results suggest that, in combination with VPA, both typical and atypical APDs produce greater increases in prefrontal cortical DA release than either type of drug alone via a mechanism dependent upon 5-HT(1A) receptor activation. Furthermore, they provide a strong rationale for testing for possible clinical synergism of an APD and anticonvulsant mood-stabilizer in improving the cognitive deficits present in patients with schizophrenia and bipolar disorder. PMID:16061211

  1. Pharmacokinetics of Cefuroxime in Porcine Cortical and Cancellous Bone Determined by Microdialysis

    PubMed Central

    Hardlei, Tore Forsingdal; Bendtsen, Michael; Bue, Mats; Brock, Birgitte; Fuursted, Kurt; Søballe, Kjeld; Birke-Sørensen, Hanne

    2014-01-01

    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. PMID:24663019

  2. Motor Cortical Functional Geometry in Cerebral Palsy and its Relationship to Disability

    PubMed Central

    Kesar, T.M.; Sawaki, L.; Burdette, J. H.; Cabrera, N.; Kolaski, K.; Smith, B.P.; O’Shea, T. M.; Koman, L. A.; Wittenberg, G. F.

    2011-01-01

    Objective To investigate motor cortical map patterns in children with diplegic and hemiplegic cerebral palsy (CP), and the relationships between motor cortical geometry and motor function in CP. Methods Transcranial magnetic stimulation (TMS) was used to map motor cortical representations of the first dorsal interosseus (FDI) and tibialis anterior (TA) muscles in 13 children with CP (age 9–16 years, 6 males.) The Gross Motor Function Measure (GMFM) and Melbourne upper extremity function were used to quantify motor ability. Results In the hemiplegic participants (N=7), the affected (right) FDI cortical representation was mapped on the ipsilateral (N=4), contralateral (N=2), or bilateral (N=1) cortex. Participants with diplegia (N=6) showed either bilateral (N=2) or contralateral (N=4) cortical hand maps. The FDI and TA motor map center-of-gravity mediolateral location ranged from 2–8 cm and 3–6 cm from the midline, respectively. Among diplegics, more lateral FDI representation locations were associated with lower Melbourne scores, i.e. worse hand motor function (Spearman’s Rho = −0.841, p=0.036) Conclusions Abnormalities in TMS-derived motor maps cut across the clinical classifications of hemiplegic and diplegic CP. The lateralization of the upper and lower extremity motor representation demonstrates reorganization after insults to the affected hemispheres of both diplegic and hemiplegic children. Significance The current study is a step towards defining the relationship between changes in motor maps and functional impairments in CP. These results suggest the need for further work to develop improved classification schemes that integrate clinical, radiologic, and neurophysiologic measures in CP. PMID:22153667

  3. Common variants in ABCA7 and MS4A6A are associated with cortical and hippocampal atrophy.

    PubMed

    Ramirez, Leslie M; Goukasian, Naira; Porat, Shai; Hwang, Kristy S; Eastman, Jennifer A; Hurtz, Sona; Wang, Benjamin; Vang, Nouchee; Sears, Renee; Klein, Eric; Coppola, Giovanni; Apostolova, Liana G

    2016-03-01

    The precise physiologic function of many of the recently discovered Alzheimer's disease risk variants remains unknown. The downstream effects of genetic variants remain largely unexplored. We studied the relationship between the top 10 non-APOE genes with cortical and hippocampal atrophy as markers of neurodegeneration using 1.5T magnetic resonance imaging, 1-million single nucleotide polymorphism Illumina Human Omni-Quad array and Illumina Human BeadChip peripheral blood expression array data on 50 cognitively normal and 98 mild cognitive impairment subjects. After explicit matching of cortical and hippocampal morphology, we computed in 3D, the cortical thickness and hippocampal radial distance measures for each participant. Associations between the top 10 non-APOE genome-wide hits and neurodegeneration were explored using linear regression. Map-wise statistical significance was determined with permutations using threshold of p < 0.01. MS4A6A rs610932 and ABCA7 rs3764650 demonstrated significant associations with cortical and hippocampal atrophy. Exploratory MS4A6A and ABCA7 peripheral blood expression analyses revealed a similar pattern of associations with cortical neurodegeneration. To our knowledge, this is the first report of the effect of ABCA7 and MS4A6A on neurodegeneration. PMID:26923404

  4. 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

  5. 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

  6. 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 ...

  7. 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 ...

  8. Mild Cognitive Impairment

    MedlinePlus

    ... other people their age. This condition is called mild cognitive impairment, or MCI. People with MCI can take care of themselves and do their normal activities. MCI memory problems may include Losing things often Forgetting ...

  9. 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.

  10. Cortical Hemisphere Registration Via Large Deformation Diffeomorphic Metric Curve Mapping

    PubMed Central

    Qiu, Anqi; Miller, Michael I.

    2010-01-01

    We present large deformation diffeomorphic metric curve mapping (LDDMM-Curve) for registering cortical hemispheres. We showed global cortical hemisphere matching and evaluated the mapping accuracy in five subregions of the cortex in fourteen MRI scans. PMID:18051058

  11. Hippocampal formation lesions produce memory impairment in the rhesus monkey.

    PubMed

    Beason-Held, L L; Rosene, D L; Killiany, R J; Moss, M B

    1999-01-01

    There is much debate over the role of temporal lobe structures in the ability to learn and retain new information. To further assess the contributions of the hippocampal formation (HF), five rhesus monkeys received stereotactically placed ibotenic acid lesions of this region without involvement of surrounding ventromedial temporal cortices. After surgery, the animals were trained on two recognition memory tasks: the Delayed Non-Match to Sample (DNMS) task, which tests the ability to remember specific trial unique stimuli, and the Delayed Recognition Span Task (DRST), which tests the ability to remember an increasing array of stimuli. Relative to normal control monkeys, those with HF lesions demonstrated significant impairments in both learning and memory stages of the DNMS task. Additionally, the HF group was significantly impaired on spatial, color, and object versions of the DRST. Contrary to suggestions that damage to the entorhinal and parahippocampal cortices is required to produce significant behavioral deficits in the monkey, these results demonstrate that selective damage to the HF is sufficient to produce impairments on tasks involving delayed recognition and memory load. This finding illustrates the importance of the HF in the acquisition and retention of new information. PMID:10560927

  12. Impaired prefrontal sleep spindle regulation of hippocampal-dependent learning in older adults.

    PubMed

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

    2014-12-01

    A hallmark feature of cognitive aging is a decline in the ability to form new memories. Parallel to these cognitive impairments are marked disruptions in sleep physiology. Despite recent evidence in young adults establishing a role for sleep spindles in restoring hippocampal-dependent memory formation, the possibility that disrupted sleep physiology contributes to age-related decline in hippocampal-dependent learning remains unknown. Here, we demonstrate that reduced prefrontal sleep spindles by over 40% in older adults statistically mediates the effects of old age on next day episodic learning, such that the degree of impaired episodic learning is explained by the extent of impoverished prefrontal sleep spindles. In addition, prefrontal spindles significantly predicted the magnitude of impaired next day hippocampal activation, thereby determining the influence of spindles on post-sleep learning capacity. These data support the hypothesis that disrupted sleep physiology contributes to age-related cognitive decline in later life, the consequence of which has significant treatment intervention potential. PMID:23901074

  13. 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

  14. Comparative aspects of cerebral cortical development

    PubMed Central

    Molnár, Zoltán; Métin, Christine; Stoykova, Anastassia; Tarabykin, Victor; Price, David J.; Francis, Fiona; Meyer, Gundela; Dehay, Colette; Kennedy, Henry

    2006-01-01

    This review intends to provide examples how comparative and genetic analyses both contribute to our understanding of the rules for cortical development and evolution. Genetic studies helped to understand evolutionary rules of telencephalic organization in vertebrates. The control of the establishment of conserved telencephalic subdivisions and the formation of boundaries between these subdivisions has been examined and revealed the very specific alterations at the striatocortical junction. Comparative studies and genetic analyses both demonstrated the differential origin and migratory pattern of the two basic neuron types of the cerebral cortex. GABAergic interneurons are mostly generated in the subpallium and a common mechanisms govern their migration to the dorsal cortex in both mammals and sauropsids. The pyramidal neurons are generated within the cortical germinal zone and migrate radially. The earliest generated cell layers comprising preplate cells. Reelin positive Cajal-Retzius cells are a general feature of all vertebrates studied so far, however, there is a considerable amplification of the reelin signaling, which might have contributed to the establishment of the basic mammalian pattern of cortical development. Based on numerous recent observations we shall present an argument that specialization of the mitotic compartments might constitute a major drive behind the evolution of the mammalian cortex. Comparative developmental studies revealed distinct features in the early compartments of the developing macaque brain drawing our attention to the limitations of some of the current model systems for understanding human developmental abnormalities of the cortex. Comparative and genetic aspects of cortical development both reveal the workings of evolution. PMID:16519657

  15. 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…

  16. 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

  17. 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

  18. Cortical correlates of acquired deafness to dissonance.

    PubMed

    Brattico, Elvira; Tervaniemi, Mari; Valimaki, Vesa; Van Zuijen, Titia; Peretz, Isabelle

    2003-11-01

    Patient I.R., who had bilateral lesions in the auditory cortex but intact hearing, did not distinguish dissonant from consonant musical excerpts in behavioral testing. We additionally found that the electrical brain responses did not differentiate musical intervals in terms of their dissonance/consonance, consistent with the idea that this phenomenon depends on the integrity of cortical functions. PMID:14681131

  19. 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

  20. 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)

  1. Touch inhibits subcortical and cortical nociceptive responses.

    PubMed

    Mancini, Flavia; Beaumont, Anne-Lise; Hu, Li; Haggard, Patrick; Iannetti, Giandomenico D; Iannetti, Gian Domenico D

    2015-10-01

    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

  2. 21 CFR 882.1310 - Cortical electrode.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL...) 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...

  3. 21 CFR 882.1310 - Cortical electrode.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL...) 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, 2014 CFR

    2014-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL...) 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

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL...) 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, 2013 CFR

    2013-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL...) 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. 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.

  8. 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

  9. Instrumental Activities of Daily Living Impairment Is Associated with Increased Amyloid Burden

    PubMed Central

    Marshall, Gad A.; Olson, Lauren E.; Frey, Meghan T.; Maye, Jacqueline; Becker, J. Alex; Rentz, Dorene M.; Sperling, Reisa A.; Johnson, Keith A.

    2011-01-01

    Background/Aims Instrumental activities of daily living (IADL) impairment in Alzheimer's disease has been associated with global amyloid deposition in postmortem studies. We sought to determine whether IADL impairment is associated with increased cortical Pittsburgh Compound B (PiB) retention. Methods Fifty-five subjects (19 normal older controls, NC, and 36 with mild cognitive impairment, MCI) underwent clinical assessments and dynamic PiB positron emission tomography imaging. Results A linear multiple regression model showed that greater IADL impairment was associated with greater global PiB retention in all subjects (R2 = 0.40; unstandardized partial regression coefficient, β = 5.8; p = 0.0002) and in MCI subjects only (R2 = 0.28; β = 6.1; p = 0.003), but not in NC subjects only. Conclusion These results suggest that daily functional impairment is related to greater amyloid burden in MCI. PMID:21778725

  10. Revisiting enigmatic cortical calretinin-expressing interneurons

    PubMed Central

    Cauli, Bruno; Zhou, Xiaojuan; Tricoire, Ludovic; Toussay, Xavier; Staiger, Jochen F.

    2014-01-01

    Cortical calretinin (CR)-expressing interneurons represent a heterogeneous subpopulation of about 10–30% of GABAergic interneurons, which altogether total ca. 12–20% of all cortical neurons. In the rodent neocortex, CR cells display different somatodendritic morphologies ranging from bipolar to multipolar but the bipolar cells and their variations dominate. They are also diverse at the molecular level as they were shown to express numerous neuropeptides in different combinations including vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK), neurokinin B (NKB) corticotrophin releasing factor (CRF), enkephalin (Enk) but also neuropeptide Y (NPY) and somatostatin (SOM) to a lesser extent. CR-expressing interneurons exhibit different firing behaviors such as adapting, bursting or irregular. They mainly originate from the caudal ganglionic eminence (CGE) but a subpopulation also derives from the dorsal part of the medial ganglionic eminence (MGE). Cortical GABAergic CR-expressing interneurons can be divided in two main populations: VIP-bipolar interneurons deriving from the CGE and SOM-Martinotti-like interneurons originating in the dorsal MGE. Although bipolar cells account for the majority of CR-expressing interneurons, the roles they play in cortical neuronal circuits and in the more general metabolic physiology of the brain remained elusive and enigmatic. The aim of this review is, firstly, to provide a comprehensive view of the morphological, molecular and electrophysiological features defining this cell type. We will, secondly, also summarize what is known about their place in the cortical circuit, their modulation by subcortical afferents and the functional roles they might play in neuronal processing and energy metabolism. PMID:25009470

  11. CORTICAL INVOLVEMENT IN THE STARTREACT EFFECT

    PubMed Central

    Stevenson, Andrew J. T.; Chiu, Chenhao; Maslovat, Dana; Chua, Romeo; Gick, Bryan; Bl