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Sample records for predicts impaired episodic

  1. A calendar savant with episodic memory impairments.

    PubMed

    Olson, Ingrid R; Berryhill, Marian E; Drowos, David B; Brown, Lawrence; Chatterjee, Anjan

    2010-06-01

    Patients with memory disorders have severely restricted learning and memory. For instance, patients with anterograde amnesia can learn motor procedures and retain some restricted ability to learn new words and factual information. However, such learning is inflexible and frequently inaccessible to conscious awareness. Here we present a case of patient AC596, a 25-year-old male with severe episodic memory impairments, presumably due to anoxia during a preterm birth. In contrast to his poor episodic memory, he exhibits savant-like memory for calendar information that can be flexibly accessed by day, month, and year cues. He also has the ability to recollect the exact date of a wide range of personal experiences over the past 20 years. The patient appears to supplement his generally poor episodic memory by using memorized calendar information as a retrieval cue for autobiographical events. These findings indicate that islands of preserved memory functioning, such as a highly developed semantic memory system, can exist in individuals with severely impaired episodic memory systems. In this particular case, our patient's memory for dates far outstripped that of normal individuals and served as a keen retrieval cue, allowing him to access information that was otherwise unavailable.

  2. A Calendar Savant with Episodic Memory Impairments

    PubMed Central

    Olson, Ingrid R.; Berryhill, Marian E.; Drowos, David B.; Brown, Lawrence; Chatterjee, Anjan

    2010-01-01

    Patients with memory disorders have severely restricted learning and memory. For instance, patients with anterograde amnesia can learn motor procedures as well as retaining some restricted ability to learn new words and factual information. However, such learning is inflexible and frequently inaccessible to conscious awareness. Here we present a case of patient AC596, a 25-year old male with severe episodic memory impairments, presumably due to anoxia during a preterm birth. In contrast to his poor episodic memory, he exhibits savant-like memory for calendar information that can be flexibly accessed by day, month, and year cues. He also has the ability to recollect the exact date of a wide range of personal experiences over the past 20 years. The patient appears to supplement his generally poor episodic memory by using memorized calendar information as a retrieval cue for autobiographical events. These findings indicate that islands of preserved memory functioning, such as a highly developed semantic memory system, can exist in individuals with severely impaired episodic memory systems. In this particular case, our patient’s memory for dates far outstripped that of normal individuals and served as a keen retrieval cue, allowing him to access information that was otherwise unavailable. PMID:20104390

  3. Usefulness of an Integrated Analysis of Different Memory Tasks to Predict the Progression from Mild Cognitive Impairment to Alzheimer's Disease: The Episodic Memory Score (EMS).

    PubMed

    Marra, Camillo; Gainotti, Guido; Fadda, Lucia; Perri, Roberta; Lacidogna, Giordano; Scaricamazza, Eugenia; Piccininni, Chiara; Quaranta, Davide

    2016-01-01

    Taking into the account both the severity and the consistency of performances obtained on memory tests by patients with amnestic mild cognitive impairment (aMCI) could improve the power to predict their progression to Alzheimer's disease. For this purpose, we constructed the Episodic Memory Score (EMS), which is obtained by subdividing in tertiles performances obtained at baseline in verbal (RAVLT) and visual episodic memory (Rey-Osterrieth Figure-delayed recall) and giving a score ranging from 1 (worst result) to 3 (best result) to results falling within each tertile. The EMS was computed for each patient by summing the tertile score obtained on each memory task, so that the total score ranged from 4 (worst performance) to 12 (best performance). The aMCI sample consisted of 198 subjects who completed the two-year follow-up, at the end of which 55 subjects had converted to dementia. The mean EMS score obtained by aMCI converters was significantly lower than that of aMCI-stable patients. In detecting conversion to dementia, the comparison between EMS and individual memory scores obtained at baseline was made by computing ROC curves, and estimating the respective area under the curve (AUC). The EMS had a larger AUC than the individual memory scores. At baseline aMCI converters performed worse than non-converters not only on memory tasks, but also on executive functions tasks. However, in a multiple variables logistic regression analysis in which all scores showing statistically significant differences between aMCI-converters and aMCI-stable were entered, the EMS was the only reliable predictor of progression from aMCI to dementia.

  4. CA1 inactivation impairs episodic-like memory in rats.

    PubMed

    Drieskens, Davi Carvalho; Neves, Lívia Rodrigues; Pugliane, Karen Cristina; de Souza, Ingrid Brasilino Montenegro Bento; Lima, Álvaro da Costa; Salvadori, Mirian Graciela da Silva Stiebbe; Ribeiro, Alessandra Mussi; Silva, Regina Helena; Barbosa, Flávio Freitas

    2017-08-24

    Episodic memory was initially believed to be unique to humans. However, studies demonstrate that nonhuman species discriminate items based on the triad what, where and when. Here we addressed the role of the dorsal hippocampal subfield CA1 in an integrative what-where-when task in Wistar rats. We performed bilateral inactivation of dorsal CA1 with the GABAA agonist muscimol previously to the task. As expected, sham-operated animals recollected an integrative memory for objects (what), their places (where) and temporal order (when). However, the inactivation of CA1 impaired the performance of the three components of episodic-like memory. In addition, total time of objects exploration and distance traveled were not different between groups, indicating that rats had similar levels of motivation, thus, alterations in exploration does not account for impaired locomotor performance. Altogether, our data provides evidence that CA1 plays an important role in episodic-like memory. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Spatial Navigation Impairments Among Intellectually High-Functioning Adults With Autism Spectrum Disorder: Exploring Relations With Theory of Mind, Episodic Memory, and Episodic Future Thinking

    PubMed Central

    2013-01-01

    Research suggests that spatial navigation relies on the same neural network as episodic memory, episodic future thinking, and theory of mind (ToM). Such findings have stimulated theories (e.g., the scene construction and self-projection hypotheses) concerning possible common underlying cognitive capacities. Consistent with such theories, autism spectrum disorder (ASD) is characterized by concurrent impairments in episodic memory, episodic future thinking, and ToM. However, it is currently unclear whether spatial navigation is also impaired. Hence, ASD provides a test case for the scene construction and self-projection theories. The study of spatial navigation in ASD also provides a test of the extreme male brain theory of ASD, which predicts intact or superior navigation (purportedly a systemizing skill) performance among individuals with ASD. Thus, the aim of the current study was to establish whether spatial navigation in ASD is impaired, intact, or superior. Twenty-seven intellectually high-functioning adults with ASD and 28 sex-, age-, and IQ-matched neurotypical comparison adults completed the memory island virtual navigation task. Tests of episodic memory, episodic future thinking, and ToM were also completed. Participants with ASD showed significantly diminished performance on the memory island task, and performance was positively related to ToM and episodic memory, but not episodic future thinking. These results suggest that (contra the extreme male brain theory) individuals with ASD have impaired survey-based navigation skills—that is, difficulties generating cognitive maps of the environment—and adds weight to the idea that scene construction/self-projection are impaired in ASD. The theoretical and clinical implications of these results are discussed. PMID:24364620

  6. Spatial navigation impairments among intellectually high-functioning adults with autism spectrum disorder: exploring relations with theory of mind, episodic memory, and episodic future thinking.

    PubMed

    Lind, Sophie E; Williams, David M; Raber, Jacob; Peel, Anna; Bowler, Dermot M

    2013-11-01

    Research suggests that spatial navigation relies on the same neural network as episodic memory, episodic future thinking, and theory of mind (ToM). Such findings have stimulated theories (e.g., the scene construction and self-projection hypotheses) concerning possible common underlying cognitive capacities. Consistent with such theories, autism spectrum disorder (ASD) is characterized by concurrent impairments in episodic memory, episodic future thinking, and ToM. However, it is currently unclear whether spatial navigation is also impaired. Hence, ASD provides a test case for the scene construction and self-projection theories. The study of spatial navigation in ASD also provides a test of the extreme male brain theory of ASD, which predicts intact or superior navigation (purportedly a systemizing skill) performance among individuals with ASD. Thus, the aim of the current study was to establish whether spatial navigation in ASD is impaired, intact, or superior. Twenty-seven intellectually high-functioning adults with ASD and 28 sex-, age-, and IQ-matched neurotypical comparison adults completed the memory island virtual navigation task. Tests of episodic memory, episodic future thinking, and ToM were also completed. Participants with ASD showed significantly diminished performance on the memory island task, and performance was positively related to ToM and episodic memory, but not episodic future thinking. These results suggest that (contra the extreme male brain theory) individuals with ASD have impaired survey-based navigation skills--that is, difficulties generating cognitive maps of the environment--and adds weight to the idea that scene construction/self-projection are impaired in ASD. The theoretical and clinical implications of these results are discussed.

  7. Executive attention impairment in first-episode schizophrenia

    PubMed Central

    2012-01-01

    Background We compared the attention abilities of a group of first-episode schizophrenia (FES) patients and a group of healthy participants using the Attention Network Test (ANT), a standard procedure that estimates the functional state of three neural networks controlling the efficiency of three different attentional behaviors, i.e., alerting (achieving and maintaining a state of high sensitivity to incoming stimuli), orienting (ability to select information from sensory input), and executive attention (mechanisms for resolving conflict among thoughts, feelings, and actions). Methods We evaluated 22 FES patients from 17 to 29 years of age with a recent history of a single psychotic episode treated only with atypical neuroleptics, and 20 healthy persons matched with FES patients by sex, age, and educational level as the control group. Attention was estimated using the ANT in which participants indicate whether a central horizontal arrow is pointing to the left or the right. The central arrow may be preceded by spatial or temporal cues denoting where and when the arrow will appear, and may be flanked by other arrows (hereafter, flankers) pointing in the same or the opposite direction. Results The efficiency of the alerting, orienting, and executive networks was estimated by measuring how reaction time was influenced by congruency between temporal, spatial, and flanker cues. We found that the control group only demonstrated significantly greater attention efficiency than FES patients in the executive attention network. Conclusions FES patients are impaired in executive attention but not in alerting or orienting attention, suggesting that executive attention deficit may be a primary impairment during the progression of the disease. PMID:22998680

  8. Predictors of neurocognitive impairment at 2years after a first-episode major depressive disorder.

    PubMed

    Gu, Chuan-Zheng; He, Hui-Li; Duan, Hui-Feng; Su, Zhong-Hua; Chen, Hong; Gan, Jing-Li

    2016-07-01

    Neurocognitive impairment is a contributor to major depressive disorder (MDD). However, MDD patients show great variability in the level and course of deficits. The present longitudinal study was to identify predictors of neurocognitive impairment in first-episode MDD patients. Neurocognitive performance was analyzed in a cohort of 100 patients at 2years after a first-episode MDD. Subgroups, deficit type vs. non-deficit type, were compared on baseline clinical, neuropsychological, premorbid and sociodemographic characteristics. The analysis was performed using the multivariate logistic regression to obtain a model for neurocognitive impairment determination. The predicted probabilities of multivariate logistic regression were analyzed using receiver operating characteristic (ROC) curve. Fifty-two percent of MDD participants presented general neurocognitive impairment. The regression analyses demonstrated that clinical and sociodemographic characteristics were not predictive variables. A model composed of processing speed, executive function, and attention, dexterity correctly classified 85.8% of the MDD patients with deficit type. ROC curve indicated that the changes of these three cognitions could identify MDD with deficit type from MDD with non-deficit type. In addition, ROC curve also indicated that processing speed and executive function could identify MDD from CN subjects. Finally, processing speed performance was negatively correlated with Hamilton Depression Scale scores in both MDD with deficit and non-deficit type. The present study provides novel insights on frequency and neurocognitive profile of subtypes of patients showing impairment. Our results suggest that processing speed impairment is a trait dimension of the disorder related to specific cognitive dysfunctions and the severity of depression. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Predicting episodic memory formation for movie events

    PubMed Central

    Tang, Hanlin; Singer, Jed; Ison, Matias J.; Pivazyan, Gnel; Romaine, Melissa; Frias, Rosa; Meller, Elizabeth; Boulin, Adrianna; Carroll, James; Perron, Victoria; Dowcett, Sarah; Arellano, Marlise; Kreiman, Gabriel

    2016-01-01

    Episodic memories are long lasting and full of detail, yet imperfect and malleable. We quantitatively evaluated recollection of short audiovisual segments from movies as a proxy to real-life memory formation in 161 subjects at 15 minutes up to a year after encoding. Memories were reproducible within and across individuals, showed the typical decay with time elapsed between encoding and testing, were fallible yet accurate, and were insensitive to low-level stimulus manipulations but sensitive to high-level stimulus properties. Remarkably, memorability was also high for single movie frames, even one year post-encoding. To evaluate what determines the efficacy of long-term memory formation, we developed an extensive set of content annotations that included actions, emotional valence, visual cues and auditory cues. These annotations enabled us to document the content properties that showed a stronger correlation with recognition memory and to build a machine-learning computational model that accounted for episodic memory formation in single events for group averages and individual subjects with an accuracy of up to 80%. These results provide initial steps towards the development of a quantitative computational theory capable of explaining the subjective filtering steps that lead to how humans learn and consolidate memories. PMID:27686330

  10. Predicting episodic memory formation for movie events.

    PubMed

    Tang, Hanlin; Singer, Jed; Ison, Matias J; Pivazyan, Gnel; Romaine, Melissa; Frias, Rosa; Meller, Elizabeth; Boulin, Adrianna; Carroll, James; Perron, Victoria; Dowcett, Sarah; Arellano, Marlise; Kreiman, Gabriel

    2016-09-30

    Episodic memories are long lasting and full of detail, yet imperfect and malleable. We quantitatively evaluated recollection of short audiovisual segments from movies as a proxy to real-life memory formation in 161 subjects at 15 minutes up to a year after encoding. Memories were reproducible within and across individuals, showed the typical decay with time elapsed between encoding and testing, were fallible yet accurate, and were insensitive to low-level stimulus manipulations but sensitive to high-level stimulus properties. Remarkably, memorability was also high for single movie frames, even one year post-encoding. To evaluate what determines the efficacy of long-term memory formation, we developed an extensive set of content annotations that included actions, emotional valence, visual cues and auditory cues. These annotations enabled us to document the content properties that showed a stronger correlation with recognition memory and to build a machine-learning computational model that accounted for episodic memory formation in single events for group averages and individual subjects with an accuracy of up to 80%. These results provide initial steps towards the development of a quantitative computational theory capable of explaining the subjective filtering steps that lead to how humans learn and consolidate memories.

  11. Do the Cambridge Neuropsychological Test Automated Battery episodic memory measures discriminate amnestic mild cognitive impairment?

    PubMed

    Juncos-Rabadán, Onésimo; Pereiro, Arturo X; Facal, David; Reboredo, Alba; Lojo-Seoane, Cristina

    2014-06-01

    Although visual recognition memory and visuospatial paired associates learning has been shown to be impaired in amnestic mild cognitive impairment (aMCI), the sensitivity and specificity of the visual memory tests used to identify aMCI are not well defined. The current study attempted to analyze the sensitivity and specificity of three visual episodic memory tests (Pattern Recognition Memory [PRM], Delayed Matching to Sample [DMS], and Paired Associated Learning [PAL]) from the CANTAB, in differentiating aMCI patients from control healthy participants. Seventy seven aMCI patients and 85 cognitive normal controls aged over 50 years performed the PRM, DMS, and PAL tests. Univariate and multivariate logistic regression and receiver operating characteristic curve analyses were used to study the relationships between aMCI and visual memory measures. The three Cambridge Neuropsychological Test Automated Battery measures significantly predicted aMCI. The optimal predictive model combined the total percent correct responses for PRM and DMS with the PAL total errors (six shapes adjusted), with a sensitivity of 72%, specificity of 83%, and achieved predictive accuracy of 80%. Visual episodic memory tasks such as those involved in the PRM, DMS, and PAL tests (included in the Cambridge Neuropsychological Test Automated Battery) may sensitively discriminate aMCI patients from normal controls. These tests may be useful for correct diagnosis of aMCI. Copyright © 2013 John Wiley & Sons, Ltd.

  12. Emotional maltreatment and depression: prospective prediction of depressive episodes.

    PubMed

    Liu, Richard T; Alloy, Lauren B; Abramson, Lyn Y; Iacoviello, Brian M; Whitehouse, Wayne G

    2009-01-01

    Most research to date on the role of maltreatment experiences in depression has focused on physical and sexual maltreatment. However, several researchers have theorized that emotional maltreatment may be more strongly linked to depression. Furthermore, prospective studies in this area are lacking. This study addressed these issues by examining whether experiences of current emotional maltreatment predicted the development of new prospective episodes of major (MD) or minor depression (MiD), and the subtype of hopelessness depression (HD) in young adults. It also assessed whether current emotional maltreatment from peers and from authority figures separately predicted the occurrence of depressive episodes. One hundred and sixty-five participants from the Cognitive Vulnerability to Depression Project were followed prospectively for 2.5 years. Current emotional maltreatment and new depressive episodes were assessed with life event and diagnostic interviews administered every 6 weeks. Greater overall emotional maltreatment predicted shorter time to onset of new MD, MiD, and HD episodes. Peer- and authority-perpetrated emotional maltreatment separately predicted shorter time to development of new HD episodes. Greater emotional maltreatment in young adults prospectively predicts onset of depression, particularly HD. These findings highlight the importance of adult emotional maltreatment experiences in determining targets for prevention and treatment. (c) 2009 Wiley-Liss, Inc.

  13. Emotional Maltreatment and Depression: Prospective Prediction of Depressive Episodes

    PubMed Central

    Liu, Richard T.; Alloy, Lauren B.; Abramson, Lyn Y.; Iacoviello, Brian M.; Whitehouse, Wayne G.

    2010-01-01

    Background Most research to date on the role of maltreatment experiences in depression has focused on physical and sexual maltreatment. However, several researchers have theorized that emotional maltreatment may be more strongly linked to depression. Furthermore, prospective studies in this area are lacking. The present study addressed these issues by examining whether experiences of current emotional maltreatment predicted the development of new prospective episodes of major (MD) or minor depression (MiD), and the subtype of hopelessness depression (HD) in young adults. It also assessed whether current emotional maltreatment from peers and from authority figures separately predicted the occurrence of depressive episodes. Method One hundred and sixty-five participants from the Cognitive Vulnerability to Depression Project were followed prospectively for 2.5 years. Current emotional maltreatment and new depressive episodes were assessed with life event and diagnostic interviews administered every six weeks. Results Greater overall emotional maltreatment predicted shorter time to onset of new MD, MiD, and HD episodes. Peer- and authority-perpetrated emotional maltreatment separately predicted shorter time to development of new HD episodes. Conclusions Greater emotional maltreatment in young adults prospectively predicts onset of depression, particularly HD. These findings highlight the importance of adult emotional maltreatment experiences in determining targets for prevention and treatment. PMID:19152341

  14. Inter-episode affective intensity and instability: predictors of depression and functional impairment in bipolar disorder.

    PubMed

    Gershon, Anda; Eidelman, Polina

    2015-03-01

    Dysregulated affect is a hallmark feature of acute episodes of bipolar disorder (BD) and persists during inter-episode periods. Its contribution to course of illness is not yet known. The present report examines the prospective influence of inter-episode affect dysregulation on symptoms and functional impairment in BD. Twenty-seven participants diagnosed with inter-episode bipolar I disorder completed daily measures of negative and positive affect for 49 days (±8 days) while they remained inter-episode. One month following this daily assessment period, symptom severity interviews and a measure of functional impairment were administered by telephone. More intense negative affect and positive affect during the inter-episode period were associated with higher depressive, but not manic, symptoms at the one-month follow-up assessment. More intense and unstable negative affect, and more unstable positive affect, during the inter-episode period were associated with greater impairment in home and work functioning at the follow-up assessment. All associations remained significant after controlling for concurrent symptom levels. The findings need to be confirmed in larger samples with longer follow-up periods. A more comprehensive assessment of functional impairment is also warranted. The findings suggest that a persistent affective dysregulation between episodes of BD may be an important predictor of depression and functional impairment. Monitoring daily affect during inter-episode periods could allow for a more timely application of interventions that aim to prevent or reduce depressive symptoms and improve functioning for individuals with BD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Recognition of Famous Names Predicts Episodic Memory Decline in Cognitively Intact Elders

    PubMed Central

    Seidenberg, Michael; Kay, Christina; Woodard, John L.; Nielson, Kristy A.; Smith, J. Carson; Kandah, Cassandra; Guidotti Breting, Leslie M.; Novitski, Julia; Lancaster, Melissa; Matthews, Monica; Hantke, Nathan; Butts, Alissa; Rao, Stephen M.

    2013-01-01

    Objective: Semantic memory impairment is common in both Mild Cognitive Impairment (MCI) and early Alzheimer’s disease (AD), and the ability to recognize familiar people is particularly vulnerable. A time-limited temporal gradient (TG) in which well known people from decades earlier are better recalled than those learned recently is also reported in both AD and MCI. In this study, we hypothesized that the TG pattern on a famous name recognition task (FNRT) administered to cognitively intact elders would predict future episodic memory decline, and would also show a significant correlation with hippocampal volume. Methods: 78 healthy elders (ages 65-90) with normal cognition and episodic memory at baseline were administered a FNRT. Follow-up episodic memory testing 18 months later produced two groups: Declining (≥ 1 SD reduction in episodic memory) and Stable (< 1 SD). Results: The Declining group (N=27) recognized fewer recent famous names than the Stable group (N=51), while recognition for remote names was comparable. Baseline MRI volumes for both the left and right hippocampus was significantly smaller in the Declining group than the Stable group. Smaller baseline hippocampal volume was also significantly correlated with poorer performance for recent, but not remote famous names. Logistic regression analyses indicated that baseline TG performance was a significant predictor of group status (Declining versus Stable) independent of chronological age and APOE ε4 inheritance. Conclusions: Famous name recognition may serve as an early pre-clinical cognitive marker of episodic memory decline in older individuals. PMID:23688215

  16. Predicting regional episodic acidification of surface waters using empirical models

    NASA Astrophysics Data System (ADS)

    Eshleman, Keith N.

    1988-07-01

    Studies of individual lakes and streams have documented the occurrence of transient, short-term acidification of surface waters during hydrologic events, but a regional assessment of episodic chemical effects has not been made. Application of a two-box mixing model, together with regional chemistry and deposition data, indicates that acidic episodes (acid neutralizing capacity <0) are likely an important regional phenomenon. Population estimates of the total proportion of acidic stream reaches increased by 40-640% in six subrogions of the eastern United States when episodes were taken into account. Data from a small sample of lakes in the Adirondacks (which appear to be representative of the lake population) show that fall "index" acid neutralizing capacity is an excellent predictor of the minimum episodic ANC measured at the outlets of these lakes during spring snowmelt. While 11% of the Adirondack lakes were acidic at fall overturn, a linear regression model predicts that more than 35% were acidic at their outlets during the spring of 1986.

  17. Impaired theory of mind in first-episode schizophrenia: comparison with community, university and depressed controls.

    PubMed

    Kettle, Jonathan W L; O'Brien-Simpson, Laurie; Allen, Nicholas B

    2008-02-01

    First order theory of mind, as measured by the 'Reading the Mind in the Eyes Test' Revised, is impaired in schizophrenia. However, no study has investigated whether this occurs in first-episode schizophrenia. Also, it is unclear whether such a deficit is specific to schizophrenia, and whether convenience control samples, particularly undergraduate university students, represent valid comparison groups. This study investigated theory of mind ability, measured by the 'Reading the Mind in the Eyes Test' Revised, in a group of first-episode schizophrenia outpatients (n=13) and three control groups: outpatients with non-psychotic major depression (n=14), individuals from the general community (n=16) and from an undergraduate university course (n=27). The schizophrenia group exhibited significant theory of mind impairments compared to both non-psychiatric control groups but not the depression group. Unexpectedly, the depression group was not significantly impaired compared to the community control group, and the university control group exhibited superior theory of mind ability relative to all three groups. The findings indicate theory of mind deficits in first episode schizophrenia and support the implementation of theory of mind interventions in first-episode schizophrenia treatment programs. Results also indicate that community rather than university control groups represent more valid comparison groups in first-episode schizophrenia research.

  18. Neuropsychological Impairment in Prodromal, First-Episode, and Chronic Psychosis: Assessing RBANS Performance

    PubMed Central

    Stone, William S.; Woodberry, Kristen A.; Seidman, Larry J.; Tang, YingYing; Guo, Qian; Zhuo, KaiMing; Qian, ZhenYing; Cui, HuiRu; Zhu, YiKang; Jiang, LiJuan; Chow, Annabelle; Tang, YunXiang; Li, ChunBo; Jiang, KaiDa; Yi, ZhengHui; Xiao, ZePing; Wang, JiJun

    2015-01-01

    Background Cognitive deficits are observed throughout all developmental phases of psychosis. However, prior studies have usually focused on a limited illness period and used a wide variety of cognitive instruments. Therefore, it has been difficult to characterize or highlight cognitive functioning in different stages of psychosis. Method We administered the RBANS (Repeatable Battery for the Assessment of Neuropsychological Status) tests to 4 participant subgroups, including healthy volunteers (controls, HC, n = 28), subjects at high risk for clinical psychosis (prodrome, CHR, n = 27), first-episode schizophrenia patients (FE-Sz, n = 26), and mid-term and long-term chronic schizophrenia patients (Ch-Sz, n =147). Comparison, correlation, and regression analyses of RBANS index scores were assessed among groups. We examined clinical outcomes over 2 years between the CHR and HC subjects, and RBANS domains were used as possible predictors for conversion to psychosis. Results Performance on all RBANS domains was significantly impaired during a post-onset stage of psychosis (FE-Sz and Ch-Sz), and RBANS scores declined along with disease progression. Regression analyses showed that for CHR and HC subjects, baseline impairment in delayed memory (DM) significantly predicted conversion to psychosis. Additionally, partial correlations showed that for FE-Sz and Ch-Sz subjects, DM was the only correlate with a later stage of psychosis. Conclusions Cognitive deficits broadly emerged, and diminished functioning followed along with disease progression. Impairment in DM is perhaps one domain that helps us understand the development of psychosis. A critical need is to monitor and treat memory functioning for psychotic patients throughout all phases of the disease. PMID:25973925

  19. Premorbid proneness to distress and episodic memory impairment in Alzheimer's disease

    PubMed Central

    Wilson, R; Fleischman, D; Myers, R; Bennett, D; Bienias, J; Gilley, D; Evans, D

    2004-01-01

    Background: Chronic stress has been associated with impaired episodic memory, but the association of premorbidly experienced distress with memory function in Alzheimer's disease is unknown. Objective: To investigate the link between proneness to distress and Alzheimer's disease. Methods: Participants were 363 persons with clinically diagnosed Alzheimer's disease. At baseline, a knowledgeable informant rated each person's premorbid personality (that is, before dementia onset) along five dimensions, one of which was the tendency to experience psychological distress. Participants underwent structured clinical evaluations at baseline and then annually for up to four years. Each evaluation included 17 cognitive tests from which previously established measures of episodic memory, visuoconstruction, repetition, and naming were derived. Results: In a series of random effects models adjusted for age, sex, and education, premorbid distress proneness was associated with baseline impairment in episodic memory but not with impairment in other cognitive domains, or with change in any cognitive domain. No other trait was related to baseline function or rate of decline in any cognitive domain. Conclusions: The results suggest that premorbid proneness to experience psychological distress is related to level of impairment in episodic memory in persons with Alzheimer's disease, but neither distress proneness nor other personality traits are related to disease progression. PMID:14742585

  20. Music-related reward responses predict episodic memory performance.

    PubMed

    Ferreri, Laura; Rodriguez-Fornells, Antoni

    2017-09-22

    Music represents a special type of reward involving the recruitment of the mesolimbic dopaminergic system. According to recent theories on episodic memory formation, as dopamine strengthens the synaptic potentiation produced by learning, stimuli triggering dopamine release could result in long-term memory improvements. Here, we behaviourally test whether music-related reward responses could modulate episodic memory performance. Thirty participants rated (in terms of arousal, familiarity, emotional valence, and reward) and encoded unfamiliar classical music excerpts. Twenty-four hours later, their episodic memory was tested (old/new recognition and remember/know paradigm). Results revealed an influence of music-related reward responses on memory: excerpts rated as more rewarding were significantly better recognized and remembered. Furthermore, inter-individual differences in the ability to experience musical reward, measured through the Barcelona Music Reward Questionnaire, positively predicted memory performance. Taken together, these findings shed new light on the relationship between music, reward and memory, showing for the first time that music-driven reward responses are directly implicated in higher cognitive functions and can account for individual differences in memory performance.

  1. The ROKS Nomogram for Predicting a Second Symptomatic Stone Episode

    PubMed Central

    Lieske, John C.; Li, Xujian; Melton, L. Joseph; Krambeck, Amy E.; Bergstralh, Eric J.

    2014-01-01

    Most patients with first-time kidney stones undergo limited evaluations, and few receive preventive therapy. A prediction tool for the risk of a second kidney stone episode is needed to optimize treatment strategies. We identified adult first-time symptomatic stone formers residing in Olmsted County, Minnesota, from 1984 to 2003 and manually reviewed their linked comprehensive medical records through the Rochester Epidemiology Project. Clinical characteristics in the medical record before or up to 90 days after the first stone episode were evaluated as predictors for symptomatic recurrence. A nomogram was developed from a multivariable model based on these characteristics. There were 2239 first-time adult kidney stone formers with evidence of a passed, obstructing, or infected stone causing pain or gross hematuria. Symptomatic recurrence occurred in 707 of these stone formers through 2012 (recurrence rates at 2, 5, 10, and 15 years were 11%, 20%, 31%, and 39%, respectively). A parsimonious model had the following risk factors for recurrence: younger age, male sex, white race, family history of stones, prior asymptomatic stone on imaging, prior suspected stone episode, gross hematuria, nonobstructing (asymptomatic) stone on imaging, symptomatic renal pelvic or lower-pole stone on imaging, no ureterovesicular junction stone on imaging, and uric acid stone composition. Ten-year recurrence rates varied from 12% to 56% between the first and fifth quintiles of nomogram score. The Recurrence of Kidney Stone nomogram identifies kidney stone formers at greatest risk for a second symptomatic episode. Such individuals may benefit from medical intervention and be good candidates for prevention trials. PMID:25104803

  2. The ROKS nomogram for predicting a second symptomatic stone episode.

    PubMed

    Rule, Andrew D; Lieske, John C; Li, Xujian; Melton, L Joseph; Krambeck, Amy E; Bergstralh, Eric J

    2014-12-01

    Most patients with first-time kidney stones undergo limited evaluations, and few receive preventive therapy. A prediction tool for the risk of a second kidney stone episode is needed to optimize treatment strategies. We identified adult first-time symptomatic stone formers residing in Olmsted County, Minnesota, from 1984 to 2003 and manually reviewed their linked comprehensive medical records through the Rochester Epidemiology Project. Clinical characteristics in the medical record before or up to 90 days after the first stone episode were evaluated as predictors for symptomatic recurrence. A nomogram was developed from a multivariable model based on these characteristics. There were 2239 first-time adult kidney stone formers with evidence of a passed, obstructing, or infected stone causing pain or gross hematuria. Symptomatic recurrence occurred in 707 of these stone formers through 2012 (recurrence rates at 2, 5, 10, and 15 years were 11%, 20%, 31%, and 39%, respectively). A parsimonious model had the following risk factors for recurrence: younger age, male sex, white race, family history of stones, prior asymptomatic stone on imaging, prior suspected stone episode, gross hematuria, nonobstructing (asymptomatic) stone on imaging, symptomatic renal pelvic or lower-pole stone on imaging, no ureterovesicular junction stone on imaging, and uric acid stone composition. Ten-year recurrence rates varied from 12% to 56% between the first and fifth quintiles of nomogram score. The Recurrence of Kidney Stone nomogram identifies kidney stone formers at greatest risk for a second symptomatic episode. Such individuals may benefit from medical intervention and be good candidates for prevention trials. Copyright © 2014 by the American Society of Nephrology.

  3. Youth Meeting Symptom and Impairment Criteria for Mania-Like Episodes Lasting Less than Four Days: An Epidemiological Enquiry

    ERIC Educational Resources Information Center

    Stringaris, Argyris; Santosh, Paramala; Leibenluft, Ellen; Goodman, Robert

    2010-01-01

    Background: Little is known about short-duration episodes of mania-like symptoms in youth. Here we determine the prevalence, morbid associations, and contribution to social impairment of a phenotype characterised by episodes during which symptom and impairment criteria for mania are met, but DSM-IV duration criteria are not (bipolar not otherwise…

  4. Episodic simulation of future events is impaired in mild Alzheimer's disease

    PubMed Central

    Addis, Donna Rose; Sacchetti, Daniel C.; Ally, Brandon A.; Budson, Andrew E.; Schacter, Daniel L.

    2009-01-01

    Recent neuroimaging studies have demonstrated that both remembering the past and simulating the future activate a core neural network including the medial temporal lobes. Regions of this network, in particular the medial temporal lobes, are prime sites for amyloid deposition and are structurally and functionally compromised in Alzheimer's disease (AD). While we know some functions of this core network, specifically episodic autobiographical memory, are impaired in AD, no study has examined whether future episodic simulation is similarly impaired. We tested the ability of sixteen AD patients and sixteen age-matched controls to generate past and future autobiographical events using an adapted version of the Autobiographical Interview. Participants also generated five remote autobiographical memories from across the lifespan. Event transcriptions were segmented into distinct details, classified as either internal (episodic) or external (non-episodic). AD patients exhibited deficits in both remembering past events and simulating future events, generating fewer internal and external episodic details than healthy older controls. The internal and external detail scores were strongly correlated across past and future events, providing further evidence of the close linkages between the mental representations of past and future. PMID:19497331

  5. Homotaurine Effects on Hippocampal Volume Loss and Episodic Memory in Amnestic Mild Cognitive Impairment.

    PubMed

    Spalletta, Gianfranco; Cravello, Luca; Gianni, Walter; Piras, Federica; Iorio, Mariangela; Cacciari, Claudia; Casini, Anna Rosa; Chiapponi, Chiara; Sancesario, Giuseppe; Fratangeli, Claudia; Orfei, Maria Donata; Caltagirone, Carlo; Piras, Fabrizio

    2016-01-01

    Homotaurine supplementation may have a positive effect on early Alzheimer's disease. Here, we investigated its potential neuroprotective effect on the hippocampus structure and episodic memory performances in amnestic mild cognitive impairment (aMCI). Neuropsychological, clinical, and neuroimaging assessment in 11 treated and 22 untreated patients were performed at baseline and after 1 year. Magnetic resonance data were analyzed using voxel-based morphometry to explore significant differences (Family Wise Error corrected) between the two groups over time. Patients treated with homotaurine showed decreased volume loss in the left and right hippocampal tail, left and right fusiform gyrus, and right inferior temporal cortex which was associated with improved short-term episodic memory performance as measured by the recency effect of the Rey 15-word list learning test immediate recall. Thus, homotaurine supplementation in individuals with aMCI has a positive effect on hippocampus atrophy and episodic memory loss. Future studies should further clarify the mechanisms of its effects on brain morphometry.

  6. Contour integration impairment in schizophrenia and first episode psychosis: state or trait?

    PubMed

    Feigenson, Keith A; Keane, Brian P; Roché, Matthew W; Silverstein, Steven M

    2014-11-01

    Contour integration is a fundamental visual process that recovers object structure by representing spatially separated edge elements as a continuous contour or shape boundary. Clinically stable persons with schizophrenia have repeatedly been shown to be impaired at contour integration but it is unclear whether this process varies with clinical state or whether it arises as early as the first episode of psychosis. To consider these issues, we administered a contour integration test to persons with chronic schizophrenia and to those with a first episode of psychosis. The test was administered twice-once at admission to short term psychiatric hospitalization and once again at discharge. A well-matched healthy control group was also tested across the same time points. We found that contour integration performance improved to the same degree in all groups over time, indicating that there were no recovery effects over and above normal practice effects. Moreover, the schizophrenia group demonstrated poorer contour integration than the control group and the first episode group exhibited intermediate performance that could not be distinguished from the other groups. These results suggest that contour integration ability does not vary as a function of short-term changes in clinical state, and that it may become further impaired with an increased number of psychotic episodes.

  7. Episodic memory and episodic future thinking impairments in high-functioning autism spectrum disorder: an underlying difficulty with scene construction or self-projection?

    PubMed

    Lind, Sophie E; Williams, David M; Bowler, Dermot M; Peel, Anna

    2014-01-01

    There appears to be a common network of brain regions that underlie the ability to recall past personal experiences (episodic memory) and the ability to imagine possible future personal experiences (episodic future thinking). At the cognitive level, these abilities are thought to rely on "scene construction" (the ability to bind together multimodal elements of a scene in mind--dependent on hippocampal functioning) and temporal "self-projection" (the ability to mentally project oneself through time--dependent on prefrontal cortex functioning). Although autism spectrum disorder (ASD) is characterized by diminished episodic memory, it is unclear whether episodic future thinking is correspondingly impaired. Moreover, the underlying basis of such impairments (difficulties with scene construction, self-projection, or both) is yet to be established. The current study therefore aimed to elucidate these issues. Twenty-seven intellectually high-functioning adults with ASD and 29 age- and IQ-matched neurotypical comparison adults were asked to describe (a) imagined atemporal, non-self-relevant fictitious scenes (assessing scene construction), (b) imagined plausible self-relevant future episodes (assessing episodic future thinking), and (c) recalled personally experienced past episodes (assessing episodic memory). Tests of narrative ability and theory of mind were also completed. Performances of participants with ASD were significantly and equally diminished in each condition and, crucially, this diminution was independent of general narrative ability. Given that participants with ASD were impaired in the fictitious scene condition, which does not involve self-projection, we suggest the underlying difficulty with episodic memory/future thinking is one of scene construction.

  8. Episodic Memory and Episodic Future Thinking Impairments in High-Functioning Autism Spectrum Disorder: An Underlying Difficulty With Scene Construction or Self-Projection?

    PubMed Central

    2013-01-01

    Objective: There appears to be a common network of brain regions that underlie the ability to recall past personal experiences (episodic memory) and the ability to imagine possible future personal experiences (episodic future thinking). At the cognitive level, these abilities are thought to rely on “scene construction” (the ability to bind together multimodal elements of a scene in mind—dependent on hippocampal functioning) and temporal “self-projection” (the ability to mentally project oneself through time—dependent on prefrontal cortex functioning). Although autism spectrum disorder (ASD) is characterized by diminished episodic memory, it is unclear whether episodic future thinking is correspondingly impaired. Moreover, the underlying basis of such impairments (difficulties with scene construction, self-projection, or both) is yet to be established. The current study therefore aimed to elucidate these issues. Method: Twenty-seven intellectually high-functioning adults with ASD and 29 age- and IQ-matched neurotypical comparison adults were asked to describe (a) imagined atemporal, non-self-relevant fictitious scenes (assessing scene construction), (b) imagined plausible self-relevant future episodes (assessing episodic future thinking), and (c) recalled personally experienced past episodes (assessing episodic memory). Tests of narrative ability and theory of mind were also completed. Results: Performances of participants with ASD were significantly and equally diminished in each condition and, crucially, this diminution was independent of general narrative ability. Conclusions: Given that participants with ASD were impaired in the fictitious scene condition, which does not involve self-projection, we suggest the underlying difficulty with episodic memory/future thinking is one of scene construction. PMID:24015827

  9. Neuron-specific Sumo1-3 knockdown in mice impairs episodic and fear memories.

    PubMed

    Wang, Liangli; Rodriguiz, Ramona M; Wetsel, William C; Sheng, Huaxin; Zhao, Shengli; Liu, Xiaozhi; Paschen, Wulf; Yang, Wei

    2014-07-01

    Growing evidence suggests that small ubiquitin-like modifier (SUMO) conjugation plays a key role in brain plasticity by modulating activity-dependent synaptic transmission. However, these observations are based largely on cell culture experiments. We hypothesized that episodic and fear memories would be affected by silencing SUMO1-3 expression. To investigate the role of SUMO conjugation in neuronal functioning in vivo, we generated a novel Sumo transgenic mouse model in which a Thy1 promoter drives expression of 3 distinct microRNAs to silence Sumo1-3 expression, specifically in neurons. Wild-type and Sumo1-3 knockdown mice were subjected to a battery of behavioural tests to elucidate whether Sumoylation is involved in episodic and emotional memory. Expression of Sumo1-3 microRNAs and the corresponding silencing of Sumo expression were particularly pronounced in hippocampal, amygdala and layer V cerebral cortex neurons. The Sumo knockdown mice displayed anxiety-like responses and were impaired in episodic memory processes, contextual and cued fear conditioning and fear-potentiated startle. Since expression of Sumo1-3 was silenced in this mouse model, we need to verify in future studies which of the SUMO paralogues play the pivotal role in episodic and emotional memory. Our results indicate that a functional SUMO conjugation pathway is essential for emotionality and cognition. This novel Sumo knockdown mouse model and the technology used in generating this mutant may help to reveal novel mechanisms that underlie a variety of neuropsychiatric conditions associated with anxiety and impairment of episodic and emotional memory.

  10. Episodic future thinking is impaired in the behavioural variant of frontotemporal dementia.

    PubMed

    Irish, Muireann; Hodges, John R; Piguet, Olivier

    2013-10-01

    Remembering the past and imagining the future are complex endeavours proposed to rely on a core neurobiological brain system. In the behavioural variant of frontotemporal dementia (bvFTD), regional patterns of brain atrophy affect medial prefrontal and temporal cortices of this core network. While autobiographical memory impairments have been documented in bvFTD, it remains unknown whether the ability to imagine future events is also compromised. Here, we investigated episodic future thinking in 10 bvFTD patients and contrasted their performance with Alzheimer's disease (AD, n = 10) and healthy matched Control (n = 10) participants. Participants were asked to remember 3 events from the previous year and to envisage 3 possible events that could occur in the next year. Both patient groups showed equivalent episodic detail performance for the retrieval of past events and the simulation of possible future episodes. Patients with bvFTD, however, showed additional impairments for the generation of external (non-episodic) details irrespective of condition. Voxel-based morphometry analyses revealed divergent neural correlates of episodic past and future thinking performance specific to each patient group. Atrophy in the posterior cingulate cortex was implicated in the disruption of past and future thinking in AD. In contrast, in bvFTD, disruption of past retrieval correlated with atrophy in medial prefrontal regions, whereas future thinking deficits were associated with atrophy of frontopolar, medial temporal regions including the right hippocampus, and lateral temporal and occipital cortices. Our results point to the involvement of multiple brain regions in facilitating retrieval of past, and simulation of future, events. Damage to any of these key regions thus adversely affects the ability to engage in personally relevant mental time travel. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Serum biomarkers predictive of depressive episodes in panic disorder.

    PubMed

    Gottschalk, M G; Cooper, J D; Chan, M K; Bot, M; Penninx, B W J H; Bahn, S

    2016-02-01

    Panic disorder with or without comorbid agoraphobia (PD/PDA) has been linked to an increased risk to develop subsequent depressive episodes, yet the underlying pathophysiology of these disorders remains poorly understood. We aimed to identify a biomarker panel predictive for the development of a depressive disorder (major depressive disorder and/or dysthymia) within a 2-year-follow-up period. Blood serum concentrations of 165 analytes were evaluated in 120 PD/PDA patients without depressive disorder baseline diagnosis (6-month-recency) in the Netherlands Study of Depression and Anxiety (NESDA). We assessed the predictive performance of serum biomarkers, clinical, and self-report variables using receiver operating characteristics curves (ROC) and the area under the ROC curve (AUC). False-discovery-rate corrected logistic regression model selection of serum analytes and covariates identified an optimal predictive panel comprised of tetranectin and creatine kinase MB along with patient gender and scores from the Inventory of Depressive Symptomatology (IDS) rating scale. Combined, an AUC of 0.87 was reached for identifying the PD/PDA patients who developed a depressive disorder within 2 years (n = 44). The addition of biomarkers represented a significant (p = 0.010) improvement over using gender and IDS alone as predictors (AUC = 0.78). For the first time, we report on a combination of biological serum markers, clinical variables and self-report inventories that can detect PD/PDA patients at increased risk of developing subsequent depressive disorders with good predictive performance in a naturalistic cohort design. After an independent validation our proposed biomarkers could prove useful in the detection of at-risk PD/PDA patients, allowing for early therapeutic interventions and improving clinical outcome.

  12. Theory of mind impairments in patients with first-episode schizophrenia and their unaffected siblings.

    PubMed

    Ho, Karen K Y; Lui, Simon S Y; Hung, Karen S Y; Wang, Yi; Li, Zhi; Cheung, Eric F C; Chan, Raymond C K

    2015-08-01

    Theory of mind (ToM) impairment has been consistently demonstrated in patients with schizophrenia, but whether ToM impairments exist in unaffected siblings of patients with schizophrenia remains unclear. Few studies have examined the affective and cognitive components of ToM in schizophrenia. This study aimed to examine whether ToM impairments exist in patients with first-episode schizophrenia and their unaffected siblings, and whether there is any dissociation between the affective and cognitive components of ToM. We adopted a family-based case-control design. Participants were 41 patients with first-episode schizophrenia, 43 unaffected siblings, and 42 healthy controls. The Yoni Task which measures the participants' ability to understand first- and second-order affective versus cognitive ToM and the Faux Pas Task which taps into integration of the affective and cognitive components of ToM were administered. Multivariate and univariate ANCOVAs were used to examine the group differences in ToM, while controlling for other neurocognitive functions. Compared with controls, patients with schizophrenia and their unaffected siblings performed poorer on the Faux Pas Task (p<0.001), with siblings having intermediate performance between patients and controls. Patients with schizophrenia performed worse than controls on second-order affective condition of the Yoni Task (p=0.004), but their unaffected siblings did not (p=0.063). We did not find any significant Group-by-Condition interaction in the Yoni Task (p=0.358). Patients with first-episode schizophrenia and their unaffected siblings exhibit ToM impairments, but no dissociation between affective and cognitive component of ToM was found. Our findings support the notion that ToM deficit may be a trait marker of schizophrenia. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Episodic, but not semantic, autobiographical memory is reduced in amnestic mild cognitive impairment

    PubMed Central

    Murphy, Kelly J.; Troyer, Angela K.; Levine, Brian; Moscovitch, Morris

    2008-01-01

    Amnestic mild cognitive impairment (aMCI) is characterized by decline in anterograde memory as measured by the ability to learn and remember new information. We investigated whether retrograde memory for autobiographical information was affected by aMCI. Eighteen control (age 66–84 years) and 17 aMCI (age 66–84 years) participants described a personal event from each of five periods across the lifespan. These events were transcribed and scored according to procedures that separate episodic (specific happenings) from semantic (general knowledge) elements of autobiographical memory. Although both groups generated protocols of similar length, the composition of autobiographical recall differentiated the groups. The aMCI group protocols were characterized by reduced episodic and increased semantic information relative to the control group. Both groups showed a similar pattern of recall across time periods, with no evidence that the aMCI group had more difficulty recalling recent, rather than remote, life events. These results indicate that episodic and semantic autobiographical memories are differentially affected by the early brain changes associated with aMCI. Reduced autobiographical episodic memories in aMCI may be the result of medial-temporal-lobe dysfunction, consistent with multiple trace theory, or alternatively, could be related to dysfunction of a wider related network of neocortical structures. In contrast, the preservation of autobiographical semantic memories in aMCI suggests neural systems, such as lateral temporal cortex, that support these memories, may remain relatively intact. PMID:18675285

  14. Stress administered prior to encoding impairs neutral but enhances emotional long-term episodic memories.

    PubMed

    Payne, Jessica D; Jackson, Eric D; Hoscheidt, Siobhan; Ryan, Lee; Jacobs, W Jake; Nadel, Lynn

    2007-12-01

    Stressful events frequently comprise both neutral and emotionally arousing information, yet the impact of stress on emotional and neutral events is still not fully understood. The hippocampus and frontal cortex have dense concentrations of receptors for stress hormones, such as cortisol, which at high levels can impair performance on hippocampally dependent memory tasks. Yet, the same stress hormones can facilitate memory for emotional information, which involves interactions between the hippocampus and amygdala. Here, we induced psychosocial stress prior to encoding and examined its long-term effects on memory for emotional and neutral episodes. The stress manipulation disrupted long-term memory for a neutral episode, but facilitated long-term memory for an equivalent emotional episode compared with a control condition. The stress manipulation also increased salivary cortisol, catecholamines as indicated by the presence of alpha-amylase, heart rate, and subjectively reported stress. Stressed subjects reported more false memories than nonstressed control subjects, and these false memories correlated positively with cortisol levels, providing evidence for a relationship between stress and false memory formation. Our results demonstrate that stress, when administered prior to encoding, produces different patterns of long-term remembering for neutral and emotional episodes. These differences likely emerge from differential actions of stress hormones on memory-relevant regions of the brain.

  15. Predictive value of symptoms for quality of life in first-episode schizophrenia.

    PubMed

    Chugh, Preeta Kaur; Rehan, Harmeet S; Unni, K E S; Sah, Ravinder K

    2013-06-01

    Management of the disease symptomatology impacts the long-term functioning and quality of life (QOL) in psychotic patients. The aim of this research was to study the association between psychiatric symptoms (positive, negative and general psychopathology symptoms) and QOL in first-episode schizophrenia patients. Fifty-five first-episode drug-naïve schizophrenia outpatients were recruited from a tertiary care hospital in New Delhi, India. WHOQOL-Bref (World Health Organization Quality of Life) Scale was used to assess multi-dimensional domains of QOL (physical, psychological, social and environmental health). The patients were evaluated clinically using PANSS and followed up for 6 months. Multivariate analyses were carried out to outline the symptoms which are predictive of QOL in these patients. Physical well-being as assessed with WHOQOL-Bref is significantly impacted by the positive, negative and general psychopathology symptoms of the disease. General psychopathology symptoms demonstrated a strong relationship with different facets of QOL. These symptoms are predictive of physical (P=0.025) and psychological health (P=0.026), social relationships (P=0.009) and environmental QOL (P=0.022). The general psychopathology symptoms significantly impact QOL in a diverse manner. Negative symptoms have a greater influence than positive symptoms on subjective QOL. The antipsychotics focus on primary positive and negative disease symptoms. There is a need to develop a holistic approach (target non-psychotic symptoms intensively) in the disease management to prevent further long-term impairment of QOL.

  16. Predicting Language Performance in Hearing Impaired Children.

    ERIC Educational Resources Information Center

    Monsees, Edna K.

    The 2-year study evaluated the language performance of 69 hearing impaired, preschool children born following the rubella epidemic of the early 1960's in order to develop an instrument for objectively assessing language achievement and a predictive index of language achievement. Two language rating scales were developed which were tied to the…

  17. Subjective memory complaint only relates to verbal episodic memory performance in mild cognitive impairment.

    PubMed

    Gifford, Katherine A; Liu, Dandan; Damon, Stephen M; Chapman, William G; Romano Iii, Raymond R; Samuels, Lauren R; Lu, Zengqi; Jefferson, Angela L

    2015-01-01

    A cognitive concern from the patient, informant, or clinician is required for the diagnosis of mild cognitive impairment (MCI); however, the cognitive and neuroanatomical correlates of complaint are poorly understood. We assessed how self-complaint relates to cognitive and neuroimaging measures in older adults with MCI. MCI participants were drawn from the Alzheimer's Disease Neuroimaging Initiative and dichotomized into two groups based on the presence of self-reported memory complaint (no complaint n = 191, 77 ± 7 years; complaint n = 206, 73 ± 8 years). Cognitive outcomes included episodic memory, executive functioning, information processing speed, and language. Imaging outcomes included regional lobar volumes (frontal, parietal, temporal, cingulate) and specific medial temporal lobe structures (hippocampal volume, entorhinal cortex thickness, parahippocampal gyrus thickness). Linear regressions, adjusting for age, gender, race, education, Mini-Mental State Examination score, mood, and apolipoprotein E4 status, found that cognitive complaint related to immediate (β = -1.07, p < 0.001) and delayed episodic memory performances assessed on a serial list learning task (β = -1.06, p = 0.001) but no other cognitive measures or neuroimaging markers. Self-reported memory concern was unrelated to structural neuroimaging markers of atrophy and measures of information processing speed, executive functioning, or language. In contrast, subjective memory complaint related to objective verbal episodic learning performance. Future research is warranted to better understand the relation between cognitive complaint and surrogate markers of abnormal brain aging, including Alzheimer's disease, across the cognitive aging spectrum.

  18. Neural correlates of episodic future thinking impairment in multiple sclerosis patients.

    PubMed

    Ernst, Alexandra; Noblet, Vincent; Gounot, Daniel; Blanc, Frédéric; de Seze, Jérôme; Manning, Liliann

    2015-01-01

    Recent clinical investigations showed impaired episodic future thinking (EFT) abilities in multiple sclerosis (MS) patients. On these bases, the aim of the current study was to explore the structural and functional correlates of EFT impairment in nondepressed MS patients. Twenty-one nondepressed MS patients and 20 matched healthy controls were assessed with the adapted Autobiographical Interview (AI), and patients were selected on the bases of an EFT impaired score criterion. The 41 participants underwent a functional magnetic resonance imaging (fMRI) session, distinguishing the construction and elaboration phases of the experimental EFT, and the categorical control tests. Structural images were also acquired. During the EFT fMRI task, increased cerebral activations were observed in patients (relative to healthy controls) within the EFT core network. These neural changes were particularly important during the construction phase of future events and involved mostly the prefrontal region. This was accompanied by an increased neural response mostly in anterior, and also posterior, cerebral regions, in association with the amount of detail produced by patients. In parallel, structural measures corroborated a main positive association between the prefrontal regions' volume and EFT performance. However, no association between the hippocampus and EFT performance was observed in patients, at both structural and functional levels. We have documented significant overlaps between the structural and functional underpinnings of EFT impairment, with a main role of the prefrontal region in its clinical expression in MS patients.

  19. Spatial navigation, episodic memory, episodic future thinking, and theory of mind in children with autism spectrum disorder: evidence for impairments in mental simulation?

    PubMed Central

    Lind, Sophie E.; Bowler, Dermot M.; Raber, Jacob

    2014-01-01

    This study explored spatial navigation alongside several other cognitive abilities that are thought to share common underlying neurocognitive mechanisms (e.g., the capacity for self-projection, scene construction, or mental simulation), and which we hypothesized may be impaired in autism spectrum disorder (ASD). Twenty intellectually high-functioning children with ASD (with a mean age of ~8 years) were compared to 20 sex, age, IQ, and language ability matched typically developing children on a series of tasks to assess spatial navigation, episodic memory, episodic future thinking (also known as episodic foresight or prospection), theory of mind (ToM), relational memory, and central coherence. This is the first study to explore these abilities concurrently within the same sample. Spatial navigation was assessed using the “memory island” task, which involves finding objects within a realistic, computer simulated, three-dimensional environment. Episodic memory and episodic future thinking were assessed using a past and future event description task. ToM was assessed using the “animations” task, in which children were asked to describe the interactions between two animated triangles. Relational memory was assessed using a recognition task involving memory for items (line drawings), patterned backgrounds, or combinations of items and backgrounds. Central coherence was assessed by exploring differences in performance across segmented and unsegmented versions of block design. Children with ASD were found to show impairments in spatial navigation, episodic memory, episodic future thinking, and central coherence, but not ToM or relational memory. Among children with ASD, spatial navigation was found to be significantly negatively related to the number of repetitive behaviors. In other words, children who showed more repetitive behaviors showed poorer spatial navigation. The theoretical and practical implications of the results are discussed. PMID:25538661

  20. Spatial navigation, episodic memory, episodic future thinking, and theory of mind in children with autism spectrum disorder: evidence for impairments in mental simulation?

    PubMed

    Lind, Sophie E; Bowler, Dermot M; Raber, Jacob

    2014-01-01

    This study explored spatial navigation alongside several other cognitive abilities that are thought to share common underlying neurocognitive mechanisms (e.g., the capacity for self-projection, scene construction, or mental simulation), and which we hypothesized may be impaired in autism spectrum disorder (ASD). Twenty intellectually high-functioning children with ASD (with a mean age of ~8 years) were compared to 20 sex, age, IQ, and language ability matched typically developing children on a series of tasks to assess spatial navigation, episodic memory, episodic future thinking (also known as episodic foresight or prospection), theory of mind (ToM), relational memory, and central coherence. This is the first study to explore these abilities concurrently within the same sample. Spatial navigation was assessed using the "memory island" task, which involves finding objects within a realistic, computer simulated, three-dimensional environment. Episodic memory and episodic future thinking were assessed using a past and future event description task. ToM was assessed using the "animations" task, in which children were asked to describe the interactions between two animated triangles. Relational memory was assessed using a recognition task involving memory for items (line drawings), patterned backgrounds, or combinations of items and backgrounds. Central coherence was assessed by exploring differences in performance across segmented and unsegmented versions of block design. Children with ASD were found to show impairments in spatial navigation, episodic memory, episodic future thinking, and central coherence, but not ToM or relational memory. Among children with ASD, spatial navigation was found to be significantly negatively related to the number of repetitive behaviors. In other words, children who showed more repetitive behaviors showed poorer spatial navigation. The theoretical and practical implications of the results are discussed.

  1. Neuropsychological impairments predict the clinical course in schizophrenia.

    PubMed

    Wölwer, Wolfgang; Brinkmeyer, Jürgen; Riesbeck, Mathias; Freimüller, Lena; Klimke, Ansgar; Wagner, Michael; Möller, Hans-Jürgen; Klingberg, Stefan; Gaebel, Wolfgang

    2008-11-01

    To add to the open question whether cognitive impairments predict clinical outcome in schizophrenia, a sample of 125 first episode patients was assessed at the onset and over one year of controlled long-term treatment within a study of the German Research Network on Schizophrenia. No relapse according to predefined criteria occurred within the first year, but a total of 29 patients fulfilled post-hoc criteria of "clinical deterioration". Impairments in cognitive functioning assessed by the Trail-Making Test B at the onset of long-term treatment differentiated between patients with vs. without later clinical deterioration and proved to be a significant predictor of the clinical course in a regression analysis outperforming initial clinical status as predictor. However, low sensitivity (72%) and specificity (51%) limit possibilities of a transfer to individual predictions. As a linear combination of neuropsychological and psychopathological variables obtained highest predictive validity, such a combination may improve the prediction of the course of schizophrenic disorders and may ultimately lead to a more efficient and comprehensive treatment planning.

  2. Gamma Oscillatory Power is Impaired During Cognitive Control Independent of Medication Status in First-Episode Schizophrenia

    PubMed Central

    Minzenberg, Michael J; Firl, Alana J; Yoon, Jong H; Gomes, Glenn C; Reinking, Celeste; Carter, Cameron S

    2010-01-01

    Schizophrenia is characterized by impaired cognitive control associated with prefrontal cortex dysfunction, but the underlying pathophysioloical mechanisms remain unknown. Higher cognitive processes are associated with cortical oscillations in the gamma range, which are also impaired in chronic schizophrenia. We tested whether cognitive control-related gamma deficits are observed in first-episode patients, and whether they are associated with antipsychotic medication exposure. Fifty-three first-episode schizophrenia patients (21 without antipsychotic medication treatment) and 29 healthy control subjects underwent electroencephalography (EEG) during performance of a preparatory cognitive control task (preparing to overcome prepotency or POP task). The first-episode schizophrenia patient group was impaired (relative to the control group) on task performance and on delay-period gamma power at each of the three subgroups of frontal electrodes. The unmedicated patient subgroup was similarly impaired compared with controls, and was not different on these measures compared with the medicated patient subgroup. In contrast, delay-period theta power was not impaired in the full patient group nor in the unmedicated patient subgroup. Impaired cognitive control-related gamma cortical oscillatory activity is present at the first psychotic episode in schizophrenia, and is independent of medication status. This suggests that altered local circuit function supporting high-frequency oscillatory activity in prefrontal cortex ensembles may serve as the pathophysiological substrate of cognitive control deficits in schizophrenia. PMID:20827271

  3. Gamma oscillatory power is impaired during cognitive control independent of medication status in first-episode schizophrenia.

    PubMed

    Minzenberg, Michael J; Firl, Alana J; Yoon, Jong H; Gomes, Glenn C; Reinking, Celeste; Carter, Cameron S

    2010-12-01

    Schizophrenia is characterized by impaired cognitive control associated with prefrontal cortex dysfunction, but the underlying pathophysiological mechanisms remain unknown. Higher cognitive processes are associated with cortical oscillations in the gamma range, which are also impaired in chronic schizophrenia. We tested whether cognitive control-related gamma deficits are observed in first-episode patients, and whether they are associated with antipsychotic medication exposure. Fifty-three first-episode schizophrenia patients (21 without antipsychotic medication treatment) and 29 healthy control subjects underwent electroencephalography (EEG) during performance of a preparatory cognitive control task (preparing to overcome prepotency or POP task). The first-episode schizophrenia patient group was impaired (relative to the control group) on task performance and on delay-period gamma power at each of the three subgroups of frontal electrodes. The unmedicated patient subgroup was similarly impaired compared with controls, and was not different on these measures compared with the medicated patient subgroup. In contrast, delay-period theta power was not impaired in the full patient group nor in the unmedicated patient subgroup. Impaired cognitive control-related gamma cortical oscillatory activity is present at the first psychotic episode in schizophrenia, and is independent of medication status. This suggests that altered local circuit function supporting high-frequency oscillatory activity in prefrontal cortex ensembles may serve as the pathophysiological substrate of cognitive control deficits in schizophrenia.

  4. Impairments in Component Processes of Executive Function and Episodic Memory in Alcoholism, HIV Infection, and HIV Infection with Alcoholism Comorbidity.

    PubMed

    Fama, Rosemary; Sullivan, Edith V; Sassoon, Stephanie A; Pfefferbaum, Adolf; Zahr, Natalie M

    2016-12-01

    Executive functioning and episodic memory impairment occur in HIV infection (HIV) and chronic alcoholism (ALC). Comorbidity of these conditions (HIV + ALC) is prevalent and heightens risk of vulnerability to separate and compounded deficits. Age and disease-related variables can also serve as mediators of cognitive impairment and should be considered, given the extended longevity of HIV-infected individuals in this era of improved pharmacological therapy. HIV, ALC, HIV + ALC, and normal controls (NC) were administered traditional and computerized tests of executive function and episodic memory. Test scores were expressed as age- and education-corrected Z-scores; selective tests were averaged to compute Executive Function and Episodic Memory Composite scores. Efficiency scores were calculated for tests with accuracy and response times. HIV, ALC, and HIV + ALC had lower scores than NC on Executive Function and Episodic Memory Composites, with HIV + ALC even lower than ALC and HIV on the Episodic Memory Composite. Impairments in planning and free recall of visuospatial material were observed in ALC, whereas impairments in psychomotor speed, sequencing, narrative free recall, and pattern recognition were observed in HIV. Lower decision-making efficiency scores than NC occurred in all 3 clinical groups. In ALC, age and lifetime alcohol consumption were each unique predictors of Executive Function and Episodic Memory Composite scores. In HIV + ALC, age was a unique predictor of Episodic Memory Composite score. Disease-specific and disease-overlapping patterns of impairment in HIV, ALC, and HIV + ALC have implications regarding brain systems disrupted by each disease and clinical ramifications regarding the complexities and compounded damping of cognitive functioning associated with dual diagnosis that may be exacerbated with aging. Copyright © 2016 by the Research Society on Alcoholism.

  5. Subjective memory complaint only relates to verbal episodic memory performance in mild cognitive impairment

    PubMed Central

    Gifford, Katherine A.; Liu, Dandan; Damon, Stephen M.; Chapman, William G.; Romano, Raymond R.; Samuels, Lauren R.; Lu, Zengqi; Jefferson, Angela L.

    2015-01-01

    Background A cognitive concern from the patient, informant, or clinician is required for the diagnosis of mild cognitive impairment (MCI); however, the cognitive and neuroanatomical correlates of complaint are poorly understood. Objective We assessed how self-complaint relates to cognitive and neuroimaging measures in older adults with MCI. Method MCI participants were drawn from the Alzheimer’s Disease Neuroimaging Initiative and dichotomized into two groups based on the presence of self-reported memory complaint (no complaint n=191, 77±7 years; complaint n=206, 73±8 years). Cognitive outcomes included episodic memory, executive functioning, information processing speed, and language. Imaging outcomes included regional lobar volumes (frontal, parietal, temporal, cingulate) and specific medial temporal lobe structures (hippocampal volume, entorhinal cortex thickness, parahippocampal gyrus thickness). Results Linear regressions, adjusting for age, gender, race, education, Mini-Mental State Examination score, mood, and apolipoprotein E-4 status, found that cognitive complaint related to immediate (β=−1.07, p<0.001) and delayed episodic memory performances assessed on a serial list learning task (β=−1.06, p=0.001) but no other cognitive measures or neuroimaging markers. Conclusions Self-reported memory concern was unrelated to structural neuroimaging markers of atrophy and measures of information processing speed, executive functioning, or language. In contrast, subjective memory complaint related to objective verbal episodic learning performance. Future research is warranted to better understand the relation between cognitive complaint and surrogate markers of abnormal brain aging, including Alzheimer’s disease, across the cognitive aging spectrum. PMID:25281602

  6. Episodic memory impairment in Addison's disease: results from a telephonic cognitive assessment.

    PubMed

    Henry, Michelle; Thomas, Kevin G F; Ross, Ian L

    2014-06-01

    Patients with Addison's disease frequently self-report memory and attention difficulties, even when on standard replacement therapy. However, few published studies examine, using objective measures and assessing across multiple domains, the cognitive functioning of Addison's disease patients relative to healthy controls. The primary aim of this study was to investigate whether the previously reported subjective cognitive deficits in Addison's disease are confirmed by objective measures. Conducting comprehensive neuropsychological assessments of patients with relatively rare clinical disorders, such as Addison's disease, is challenging because access to those patients is often limited, and because their medical condition might prevent extended testing sessions. Brief telephonic cognitive assessments are a useful tool in such circumstances. Hence, we administered the Brief Test of Adult Cognition by Telephone to 27 Addison's disease patients and 27 matched healthy controls. The instrument provides objective assessment of episodic memory, working memory, executive functioning, reasoning, and speed of processing. Statistical analyses confirmed that, as expected, patients performed significantly more poorly than controls on the episodic memory subtest. There were, however, no significant between-group differences on the attention, executive functioning, reasoning, and speed of processing subtests. Furthermore, patients with a longer duration of illness performed more poorly across all domains of cognition. We conclude that, for Addison's disease patients, previously reported subjective cognitive deficits are matched by objective impairment, but only in the domain of episodic memory. Future research might investigate (a) whether these memory deficits are material-specific (i.e., whether non-verbal memory is also affected), and (b) the neurobiological mechanisms underlying these deficits.

  7. CE verbal episodic memory impairment in schizophrenia: a comparison with frontal lobe lesion patients.

    PubMed

    Christensen, Bruce K; Patrick, Regan E; Stuss, Donald T; Gillingham, Susan; Zipursky, Robert B

    2013-01-01

    Schizophrenia (SCZ)-related verbal memory impairment is hypothesized to be mediated, in part, by frontal lobe (FTL) dysfunction. However, little research has contrasted the performance of SCZ patients with that of patients exhibiting circumscribed frontal lesions. The current study compared verbal episodic memory in patients with SCZ and focal FTL lesions (left frontal, LF; right frontal, RF; and bi-frontal, BF) on a four-trial list learning task consisting of three lists of varying semantic organizational structure. Each dependent variable was examined at two levels: scores collapsed across all four trials and learning scores (i.e., trial 4-trial 1). Performance deficits were observed in each patient group across most dependent measures at both levels. Regarding patient group differences, SCZ patients outperformed LF/BF patients (i.e., either learning scores or scores collapsed across trial) on free recall, primacy, primary memory, secondary memory, and subjective organization, whereas they only outperformed RF patients on the semantically blocked list on recency and primary memory. Collectively, these results indicate that the pattern of memory performance is largely similar between patients with SCZ and those with RF lesions. These data support tentative arguments that verbal episodic memory deficits in SCZ may be mediated by frontal dysfunction in the right hemisphere.

  8. F-18 Fluorodeoxyglucose Positron Emission Tomography study of Impaired Emotion Processing in First Episode Schizophrenia

    PubMed Central

    Choudhary, Mona; Kumar, Arvind; Tripathi, Madhavi; Bhatia, Triptish; Shivakumar, Venkataram; Beniwal, Ram Pratap; Gur, Ruben C.; Gur, Raquel E.; Nimgaonkar, Vishwajit L.

    2015-01-01

    Background Schizophrenia cases have consistently shown to have behavioural and neurofunctional abnormalities but studies during early course are scarce. The present work assesses the performance of acute first episode schizophrenia cases on correlation of a facial emotion perception task with brain function using Fluorine-18 Fluorodeoxyglucose (FDG) positron emission tomography (PET). Methods Twenty First episode schizophrenia cases and 20 matched healthy controls living in the community were enrolled. For cases, longest duration of illness was one year and treatment with neuroleptic did not exceed two weeks on the day of scan. To measure facial emotion perception (FEP) both groups were administered the Emotion battery from the Penn Computerized Battery followed by PET acquisition. SPM 8 analysis for group differences at p<0.001 was performed. Results Schizophrenia subjects showed hypoactivation of bilateral prefrontal cortices and fusiform gyrii, with significant hyperactivation of bilateral basal ganglia and left precuneus. Positive correlation of metabolism in prefrontal cortex and performance indices on emotions domain was seen. No correlation of CPZ equivalent days with metabolism in basal ganglia was observed. Conclusions The performance of schizophrenia cases on FEP task was significantly impaired in comparison to the control group. Brain regions implicated in emotion processing showed hypometabolism in cases as compared to controls. Failure of schizophrenia cases to optimally recruit brain circuitry may be contributing to deficits on FEP task. These findings suggest inherent deficits in neural circuitry of emotion processing in schizophrenia; devoid of confounding effects of neuroleptics and duration of illness. PMID:25655909

  9. Episodic memories predict adaptive value-based decision-making.

    PubMed

    Murty, Vishnu P; FeldmanHall, Oriel; Hunter, Lindsay E; Phelps, Elizabeth A; Davachi, Lila

    2016-05-01

    Prior research illustrates that memory can guide value-based decision-making. For example, previous work has implicated both working memory and procedural memory (i.e., reinforcement learning) in guiding choice. However, other types of memories, such as episodic memory, may also influence decision-making. Here we test the role for episodic memory-specifically item versus associative memory-in supporting value-based choice. Participants completed a task where they first learned the value associated with trial unique lotteries. After a short delay, they completed a decision-making task where they could choose to reengage with previously encountered lotteries, or new never before seen lotteries. Finally, participants completed a surprise memory test for the lotteries and their associated values. Results indicate that participants chose to reengage more often with lotteries that resulted in high versus low rewards. Critically, participants not only formed detailed, associative memories for the reward values coupled with individual lotteries, but also exhibited adaptive decision-making only when they had intact associative memory. We further found that the relationship between adaptive choice and associative memory generalized to more complex, ecologically valid choice behavior, such as social decision-making. However, individuals more strongly encode experiences of social violations-such as being treated unfairly, suggesting a bias for how individuals form associative memories within social contexts. Together, these findings provide an important integration of episodic memory and decision-making literatures to better understand key mechanisms supporting adaptive behavior.

  10. Multi-center MRI prediction models: Predicting sex and illness course in first episode psychosis patients.

    PubMed

    Nieuwenhuis, Mireille; Schnack, Hugo G; van Haren, Neeltje E; Lappin, Julia; Morgan, Craig; Reinders, Antje A; Gutierrez-Tordesillas, Diana; Roiz-Santiañez, Roberto; Schaufelberger, Maristela S; Rosa, Pedro G; Zanetti, Marcus V; Busatto, Geraldo F; Crespo-Facorro, Benedicto; McGorry, Patrick D; Velakoulis, Dennis; Pantelis, Christos; Wood, Stephen J; Kahn, René S; Mourao-Miranda, Janaina; Dazzan, Paola

    2017-01-15

    Structural Magnetic Resonance Imaging (MRI) studies have attempted to use brain measures obtained at the first-episode of psychosis to predict subsequent outcome, with inconsistent results. Thus, there is a real need to validate the utility of brain measures in the prediction of outcome using large datasets, from independent samples, obtained with different protocols and from different MRI scanners. This study had three main aims: 1) to investigate whether structural MRI data from multiple centers can be combined to create a machine-learning model able to predict a strong biological variable like sex; 2) to replicate our previous finding that an MRI scan obtained at first episode significantly predicts subsequent illness course in other independent datasets; and finally, 3) to test whether these datasets can be combined to generate multicenter models with better accuracy in the prediction of illness course. The multi-center sample included brain structural MRI scans from 256 males and 133 females patients with first episode psychosis, acquired in five centers: University Medical Center Utrecht (The Netherlands) (n=67); Institute of Psychiatry, Psychology and Neuroscience, London (United Kingdom) (n=97); University of São Paulo (Brazil) (n=64); University of Cantabria, Santander (Spain) (n=107); and University of Melbourne (Australia) (n=54). All images were acquired on 1.5-Tesla scanners and all centers provided information on illness course during a follow-up period ranging 3 to 7years. We only included in the analyses of outcome prediction patients for whom illness course was categorized as either "continuous" (n=94) or "remitting" (n=118). Using structural brain scans from all centers, sex was predicted with significant accuracy (89%; p<0.001). In the single- or multi-center models, illness course could not be predicted with significant accuracy. However, when reducing heterogeneity by restricting the analyses to male patients only, classification accuracy

  11. Cognitive impairments in patients with first episode psychosis: The relationship between neurophysiological and neuropsychological assessments.

    PubMed

    Morales-Muñoz, Isabel; Jurado-Barba, Rosa; Fernández-Guinea, Sara; Álvarez-Alonso, María José; Rodríguez-Jiménez, Roberto; Jiménez-Arriero, Miguel Angel; Rubio, Gabriel

    2017-02-01

    Cognitive deficits in schizophrenia have been widely reported. Neurophysiological and neuropsychological assessments have been conducted to study these impairments. Event-related potentials (ERPs) are relevant markers of cognitive deficits in schizophrenia, and reductions in specific ERP components have been found. The MATRICS Consensus Cognitive Battery (MCCB) was developed to obtain a consensus battery for the assessment of cognitive deficits in schizophrenia. Here, we aimed to study modulations of several ERP components in first episode psychosis (FEP). We also examined neuropsychological deficits using the MCCB, and correlations between ERP and MCCB impairments. Thirty-eight FEP patients were compared to thirty-eight healthy controls. The following ERP components were examined: P1, N1, MMN, P2, early-P3 and late-P3. We used an auditory three-stimulus oddball paradigm, with standard (60%), target (20%) and distractor (20%) stimuli. FEP patients showed significantly lower amplitudes of P2, early-P3 and late-P3 components. FEP patients also showed significant deficits in all the MCCB cognitive domains. Finally, correlational analyses found strong associations between amplitudes of P2, early-P3 and late-P3 components and MCCB tests for attention and speed of processing. These findings indicate that deficits in late auditory ERP components are present in FEP, whereas early components are preserved. These reductions in late ERP components were related to attentional deficits in FEP as assessed by MCCB. These findings indicate that MCCB is a valid battery for studying cognitive impairments in the initial stages of schizophrenia, and highlight the utility of converging neurophysiological and neuropsychological measures to examine attentional impairments in schizophrenia.

  12. Prediction of episodic acidification in North-eastern USA: An empirical/mechanistic approach

    USGS Publications Warehouse

    Davies, T.D.; Tranter, M.; Wigington, P.J.; Eshleman, K.N.; Peters, N.E.; Van Sickle, J.; DeWalle, David R.; Murdoch, Peter S.

    1999-01-01

    Observations from the US Environmental Protection Agency's Episodic Response Project (ERP) in the North-eastern United States are used to develop an empirical/mechanistic scheme for prediction of the minimum values of acid neutralizing capacity (ANC) during episodes. An acidification episode is defined as a hydrological event during which ANC decreases. The pre-episode ANC is used to index the antecedent condition, and the stream flow increase reflects how much the relative contributions of sources of waters change during the episode. As much as 92% of the total variation in the minimum ANC in individual catchments can be explained (with levels of explanation >70% for nine of the 13 streams) by a multiple linear regression model that includes pre-episode ANC and change in discharge as independent variable. The predictive scheme is demonstrated to be regionally robust, with the regional variance explained ranging from 77 to 83%. The scheme is not successful for each ERP stream, and reasons are suggested for the individual failures. The potential for applying the predictive scheme to other watersheds is demonstrated by testing the model with data from the Panola Mountain Research Watershed in the South-eastern United States, where the variance explained by the model was 74%. The model can also be utilized to assess 'chemically new' and 'chemically old' water sources during acidification episodes.Observations from the US Environmental Protection Agency's Episodic Response Project (ERP) in the Northeastern United States are used to develop an empirical/mechanistic scheme for prediction of the minimum values of acid neutralizing capacity (ANC) during episodes. An acidification episode is defined as a hydrological event during which ANC decreases. The pre-episode ANC is used to index the antecedent condition, and the stream flow increase reflects how much the relative contributions of sources of waters change during the episode. As much as 92% of the total variation in

  13. Individualized prediction of illness course at the first psychotic episode: a support vector machine MRI study

    PubMed Central

    Mourao-Miranda, J.; Reinders, A. A. T. S.; Rocha-Rego, V.; Lappin, J.; Rondina, J.; Morgan, C.; Morgan, K. D.; Fearon, P.; Jones, P. B.; Doody, G. A.; Murray, R. M.; Kapur, S.; Dazzan, P.

    2012-01-01

    Background To date, magnetic resonance imaging (MRI) has made little impact on the diagnosis and monitoring of psychoses in individual patients. In this study, we used a support vector machine (SVM) whole-brain classification approach to predict future illness course at the individual level from MRI data obtained at the first psychotic episode. Method One hundred patients at their first psychotic episode and 91 healthy controls had an MRI scan. Patients were re-evaluated 6.2 years (s.d.=2.3) later, and were classified as having a continuous, episodic or intermediate illness course. Twenty-eight subjects with a continuous course were compared with 28 patients with an episodic course and with 28 healthy controls. We trained each SVM classifier independently for the following contrasts: continuous versus episodic, continuous versus healthy controls, and episodic versus healthy controls. Results At baseline, patients with a continuous course were already distinguishable, with significance above chance level, from both patients with an episodic course (p=0.004, sensitivity=71, specificity=68) and healthy individuals (p=0.01, sensitivity=71, specificity=61). Patients with an episodic course could not be distinguished from healthy individuals. When patients with an intermediate outcome were classified according to the discriminating pattern episodic versus continuous, 74% of those who did not develop other episodes were classified as episodic, and 65% of those who did develop further episodes were classified as continuous (p=0.035). Conclusions We provide preliminary evidence of MRI application in the individualized prediction of future illness course, using a simple and automated SVM pipeline. When replicated and validated in larger groups, this could enable targeted clinical decisions based on imaging data. PMID:22059690

  14. Individualized prediction of illness course at the first psychotic episode: a support vector machine MRI study.

    PubMed

    Mourao-Miranda, J; Reinders, A A T S; Rocha-Rego, V; Lappin, J; Rondina, J; Morgan, C; Morgan, K D; Fearon, P; Jones, P B; Doody, G A; Murray, R M; Kapur, S; Dazzan, P

    2012-05-01

    To date, magnetic resonance imaging (MRI) has made little impact on the diagnosis and monitoring of psychoses in individual patients. In this study, we used a support vector machine (SVM) whole-brain classification approach to predict future illness course at the individual level from MRI data obtained at the first psychotic episode. One hundred patients at their first psychotic episode and 91 healthy controls had an MRI scan. Patients were re-evaluated 6.2 years (s.d.=2.3) later, and were classified as having a continuous, episodic or intermediate illness course. Twenty-eight subjects with a continuous course were compared with 28 patients with an episodic course and with 28 healthy controls. We trained each SVM classifier independently for the following contrasts: continuous versus episodic, continuous versus healthy controls, and episodic versus healthy controls. At baseline, patients with a continuous course were already distinguishable, with significance above chance level, from both patients with an episodic course (p=0.004, sensitivity=71, specificity=68) and healthy individuals (p=0.01, sensitivity=71, specificity=61). Patients with an episodic course could not be distinguished from healthy individuals. When patients with an intermediate outcome were classified according to the discriminating pattern episodic versus continuous, 74% of those who did not develop other episodes were classified as episodic, and 65% of those who did develop further episodes were classified as continuous (p=0.035). We provide preliminary evidence of MRI application in the individualized prediction of future illness course, using a simple and automated SVM pipeline. When replicated and validated in larger groups, this could enable targeted clinical decisions based on imaging data.

  15. Social and academic premorbid adjustment domains predict different functional outcomes among youth with first episode mania.

    PubMed

    Ratheesh, Aswin; Davey, Christopher G; Daglas, Rothanthi; Macneil, Craig; Hasty, Melissa; Filia, Kate; McGorry, Patrick D; Berk, Michael; Conus, Philippe; Cotton, Sue

    2017-09-01

    Premorbid characteristics may help predict the highly variable functional and illness outcomes of young people with early stage Bipolar Disorder (BD). We sought to examine the relationships between premorbid adjustment and short to medium-term outcomes after a first treated episode of mania. We examined the baseline and 18-month follow-up characteristics of 117 participants with first episode of mania, treated at two tertiary early intervention services in Melbourne, Australia. The baseline demographic, family history, diagnoses, comorbidity and clinical features were determined using unstructured questionnaires and structured diagnostic interviews. Premorbid adjustment was determined using the Premorbid Adjustment Scale (PAS), the components of which were identified using a principal component analysis. Eighteen-month follow-up outcome measures included the Clinical Global Impressions scale, Social and Occupational Functioning Assessment Scale and the Heinrichs' Quality of Life Scale (QLS). Correlations and linear regressions were utilised to examine the relationships between component scores and outcomes, while controlling for baseline and follow-up confounders. The social adjustment component of the PAS correlated with the interpersonal relations (rs = -0.46, p<0.001) domain of QLS while the academic adjustment component of the PAS correlated with the vocational functioning domain of QLS (rs =-0.39, p = 0.004). Premorbid adjustment did not predict illness severity or objective functioning. Lack of information on cognition, personality factors and prodromal symptoms limited the assessment of their impact on outcomes. Impairments in domains of premorbid adjustment may be early markers of persistent difficulties in social and vocational functioning and may benefit from targeted interventions. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Improving vocational outcomes in first-episode psychosis by addressing cognitive impairments using Cognitive Adaptation Training.

    PubMed

    Allott, Kelly A; Killackey, Eoin; Sun, Pamela; Brewer, Warrick J; Velligan, Dawn I

    2017-01-01

    Cognitive Adaptation Training (CAT) uses compensatory strategies and environmental supports to support cognitive impairments and improve functioning. CAT may be useful for addressing vocational recovery in first-episode psychosis (FEP) because cognitive impairments are common and vocational recovery is a key goal of young people with FEP. To describe clinical observations and practice experience when delivering CAT with FEP clients and explore potential benefits via objective outcome measures for improving vocational outcomes. In this pilot study, five FEP participants received 9 months of CAT. Participant goals and functional needs and clinical observations were recorded. Formal measures of functioning, quality of life and motivation were independently administered pre- and post-intervention. Vocational recovery (education, employment) was found to be a primary functional goal of FEP participants. Accordingly, CAT had a strong focus on vocational functioning, including functional domains required for successful work or educational outcomes, such as organization and planning, transportation and activities of daily living. Factors of clinical importance when delivering CAT with the FEP participants included cognitive heterogeneity, family involvement, flexibility in compensatory and environmental supports used, and experience of stigma. Improvements from baseline to post-intervention were observed on most measures, with the largest improvements seen in global functioning (including vocation), planning and organization, and quality of life. CAT is an intervention that appears well suited to addressing vocational functioning in FEP, but larger controlled trials are needed.

  17. Predicting heavy episodic drinking using an extended temporal self-regulation theory.

    PubMed

    Black, Nicola; Mullan, Barbara; Sharpe, Louise

    2017-10-01

    Alcohol consumption contributes significantly to the global burden from disease and injury, and specific patterns of heavy episodic drinking contribute uniquely to this burden. Temporal self-regulation theory and the dual-process model describe similar theoretical constructs that might predict heavy episodic drinking. The aims of this study were to test the utility of temporal self-regulation theory in predicting heavy episodic drinking, and examine whether the theoretical relationships suggested by the dual-process model significantly extend temporal self-regulation theory. This was a predictive study with 149 Australian adults. Measures were questionnaires (self-report habit index, cues to action scale, purpose-made intention questionnaire, timeline follow-back questionnaire) and executive function tasks (Stroop, Tower of London, operation span). Participants completed measures of theoretical constructs at baseline and reported their alcohol consumption two weeks later. Data were analysed using hierarchical multiple linear regression. Temporal self-regulation theory significantly predicted heavy episodic drinking (R(2)=48.0-54.8%, p<0.001) and the hypothesised extension significantly improved the prediction of heavy episodic drinking frequency (ΔR(2)=4.5%, p=0.001) but not peak consumption (ΔR(2)=1.4%, p=0.181). Intention and behavioural prepotency directly predicted heavy episodic drinking (p<0.01). Planning ability moderated the intention-behaviour relationship and inhibitory control moderated the behavioural prepotency-behaviour relationship (p<0.05). Both temporal self-regulation theory and the extended temporal self-regulation theory provide good prediction of heavy episodic drinking. Intention, behavioural prepotency, planning ability and inhibitory control may be good targets for interventions designed to decrease heavy episodic drinking. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Premorbid adjustment and clinical correlates of cognitive impairment in first-episode psychosis. The PEPsCog Study.

    PubMed

    Cuesta, Manuel J; Sánchez-Torres, Ana M; Cabrera, Bibiana; Bioque, Miquel; Merchán-Naranjo, Jessica; Corripio, Iluminada; González-Pinto, Ana; Lobo, Antonio; Bombín, Igor; de la Serna, Elena; Sanjuan, Julio; Parellada, Mara; Saiz-Ruiz, Jerónimo; Bernardo, Miquel

    2015-05-01

    The extent to which socio-demographic, clinical, and premorbid adjustment variables contribute to cognitive deficits in first-episode schizophrenia spectrum disorders remains to be ascertained. To examine the pattern and magnitude of cognitive impairment in first-episode psychosis patients, the profile of impairment across psychosis subtypes and the associations with premorbid adjustment. 226 first-episode psychosis patients and 225 healthy controls were assessed in the PEPsCog study, as part of the PEPs study. Patients showed slight to moderate cognitive impairment, verbal memory being the domain most impaired compared to controls. Broad affective spectrum patients had better premorbid IQ and outperformed the schizophrenia and other psychosis groups in executive function, and had better global cognitive function than the schizophrenia group. Adolescent premorbid adjustment together with age, gender, parental socio-economic status, and mean daily antipsychotic doses were the factors that best explained patients' cognitive performance. General and adolescent premorbid adjustment, age and parental socio-economic status were the best predictors of cognitive performance in controls. Poorer premorbid adjustment together with socio-demographic factors and higher daily antipsychotic doses were related to a generalized cognitive impairment and to a lower premorbid intellectual reserve, suggesting that neurodevelopmental impairment was present before illness onset. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Positive and negative emotional contexts unevenly predict episodic memory.

    PubMed

    Martínez-Galindo, Joyce Graciela; Cansino, Selene

    2015-09-15

    The aim of this study was to investigate whether the recognition of faces with neutral expressions differs when they are encoded under different emotional contexts (positive, negative or non-emotional). The effects of the emotional valence context on the subsequent memory effect (SME) and the autonomic responses were also examined. Twenty-eight participants performed a betting-game task in which the faces of their virtual opponents were presented in each trial. The probability of winning or losing was manipulated to generate positive or negative contexts, respectively. Additionally, the participants performed the same task without betting as a non-emotional condition. After the encoding phase, an old/new paradigm was performed for the faces of the virtual opponents. The recognition was superior for the faces encoded in the positive contexts than for the faces encoded in the non-emotional contexts. The skin conductance response amplitude was equivalent for both of the emotional contexts. The N170 and P300 components at occipital sites and the frontal slow wave manifested SMEs that were modulated by positive contexts; neither negative nor non-emotional contexts influenced these effects. The behavioral and neurophysiological data demonstrated that positive contexts are stronger predictors of episodic memory than negative or non-emotional contexts.

  20. Multiple cognitive deficits in patients during the mild cognitive impairment stage of Alzheimer's disease: how are cognitive domains other than episodic memory impaired?

    PubMed

    Matsuda, Osamu; Saito, Masahiko

    2009-10-01

    Little is known about how cognitive domains other than episodic memory are affected during the mild cognitive impairment (MCI) stage of Alzheimer's disease (AD). We attempted to clarify this issue in this study. Fifty-seven Japanese subjects were divided into two groups: one comprising people in the MCI stage of AD (MCI group, n = 28) and the other of normal controls (NC group, n = 29). Cognitive functions were assessed using the Japanese version of the neurobehavioral cognitive status examination (J-COGNISTAT). The MCI group performed significantly worse than the NC group on subtests that assessed orientation, confrontational naming, constructive ability, episodic memory, and abstract thinking. Three-quarters of the MCI group had deficits in memory and other non-mnemonic domains, particularly constructive ability and abstract thinking. However, within-subject comparisons showed that the MCI group performed significantly worse on the memory subtest compared to any other subtest. Besides episodic memory, multiple non-mnemonic cognitive domains, such as constructive ability and abstract thinking, are also impaired during the MCI stage of AD; however, these non-mnemonic deficits are smaller than episodic memory impairment.

  1. Computational Model-Based Prediction of Human Episodic Memory Performance Based on Eye Movements

    NASA Astrophysics Data System (ADS)

    Sato, Naoyuki; Yamaguchi, Yoko

    Subjects' episodic memory performance is not simply reflected by eye movements. We use a ‘theta phase coding’ model of the hippocampus to predict subjects' memory performance from their eye movements. Results demonstrate the ability of the model to predict subjects' memory performance. These studies provide a novel approach to computational modeling in the human-machine interface.

  2. Prediction of ENSO episodes using canonical correlation analysis

    SciTech Connect

    Barnston, A.G.; Ropelewski, C.F. )

    1992-11-01

    Canonical correlation analysis (CCA) is explored as a multivariate linear statistical methodology with which to forecast fluctuations of the El Nino/Southern Oscillation (ENSO) in real time. CCA is capable of identifying critical sequences of predictor patterns that tend to evolve into subsequent pattern that can be used to form a forecast. The CCA model is used to forecast the 3-month mean sea surface temperature (SST) in several regions of the tropical Pacific and Indian oceans for projection times of 0 to 4 seasons beyond the immediately forthcoming season. The predictor variables, representing the climate situation in the four consecutive 3-month periods ending at the time of the forecast, are (1) quasi-global seasonal mean sea level pressure (SLP) and (2) SST in the predicted regions themselves. Forecast skill is estimated using cross-validation, and persistence is used as the primary skill control measure. Results indicate that a large region in the eastern equatorial Pacific (120[degrees]-170[degrees] W longitude) has the highest overall predictability, with excellent skill realized for winter forecasts made at the end of summer. CCA outperforms persistence in this region under most conditions, and does noticeably better with the SST included as a predictor in addition to the SLP. It is demonstrated that better forecast performance at the longer lead times would be obtained if some significantly earlier (i.e., up to 4 years) predictor data were included, because the ability to predict the lower-frequency ENSO phase changes would increase. The good performance of the current system at shorter lead times appears to be based largely on the ability to predict ENSO evolution for events already in progress. The forecasting of the eastern tropical Pacific SST using CCA is now done routinely on a monthly basis for a O-, 1-, and 2-season lead at the Climate Analysis Center.

  3. Specific impairment of "what-where-when" episodic-like memory in experimental models of temporal lobe epilepsy.

    PubMed

    Inostroza, Marion; Brotons-Mas, Jorge R; Laurent, François; Cid, Elena; de la Prida, Liset Menendez

    2013-11-06

    Episodic memory deficit is a common cognitive disorder in human temporal lobe epilepsy (TLE). However, no animal model of TLE has been shown to specifically replicate this cognitive dysfunction, which has limited its translational appeal. Here, using a task that tests for nonverbal correlates of episodic-like memory in rats, we show that kainate-treated TLE rats exhibit a selective impairment of the "what-where-when" memory while preserving other forms of hippocampal-dependent memories. Assisted by multisite silicon probes, we recorded from the dorsal hippocampus of behaving animals to control for seizure-related factors and to look for electrophysiological signatures of cognitive impairment. Analyses of hippocampal local field potentials showed that both the power of theta rhythm and its coordination across CA1 and the DG-measured as theta coherence and phase locking-were selectively disrupted. This disruption represented a basal condition of the chronic epileptic hippocampus that was linked to different features of memory impairment. Theta power was more correlated with the spatial than with the temporal component of the task, while measures of theta coordination correlated with the temporal component. We conclude that episodic-like memory, as tested in the what-where-when task, is specifically affected in experimental TLE and that the impairment of hippocampal theta activity might be central to this dysfunction.

  4. Prediction of episodic acidification in Maryland Coastal Plain streams. Final report

    SciTech Connect

    Gerritsen, J.; Dietz, J.; Wilson, H.T.; Janicki, A.J.

    1989-12-01

    Episodic acidification from acidic precipitation in Coastal Plain streams of the Chesapeake Bay watershed is a potential threat to spawning and survival of anadromous fish species. The study is part of a process of selection of streams for mitigation of acidic episodes to increase the spawning success of anadromous fish stocks. It describes the development of practical, empirical models to predict the chemical response of Coastal Plain streams during precipitation events. One of the design criteria for the models was that they predict the response of a stream to precipitation events using data that are relatively easy to obtain. Data used to build and test the models were from several intensive studies of episodic acidification in the Maryland Coastal Plain. Regression models were developed to predict minimum pH during an event, change in pH during an event and minimum ANC (alkalinity) during an event. Two models were developed for each dependent variable.

  5. Prediction of the period of psychotic episode in individual schizophrenics by simulation-data construction approach.

    PubMed

    Huang, Chun-Jung; Wang, Hsiao-Fan; Chiu, Hsien-Jane; Lan, Tsuo-Hung; Hu, Tsung-Ming; Loh, El-Wui

    2010-10-01

    Although schizophrenia can be treated, most patients still experience inevitable psychotic episodes from time to time. Precautious actions can be taken if the next onset can be predicted. However, sufficient information is always lacking in the clinical scenario. A possible solution is to use the virtual data generated from limited of original data. Data construction method (DCM) has been shown to generate the virtual felt earthquake data effectively and used in the prediction of further events. Here we investigated the performance of DCM in deriving the membership functions and discrete-event simulations (DES) in predicting the period embracing the initiation and termination time-points of the next psychotic episode of 35 individual schizophrenic patients. The results showed that 21 subjects had a success of simulations (RSS) ≥70%. Further analysis demonstrated that the co-morbidity of coronary heart diseases (CHD), risks of CHD, and the frequency of previous psychotic episodes increased the RSS.

  6. Predicting goals in action episodes attenuates BOLD response in inferior frontal and occipitotemporal cortex.

    PubMed

    Wurm, Moritz F; Hrkać, Mari; Morikawa, Yuka; Schubotz, Ricarda I

    2014-11-01

    Actions are usually made of several action steps gearing towards an overarching goal. During observation of such action episodes the overarching action goal becomes more and more clear and upcoming action steps can be predicted with increasing precision. To tap this process, the present fMRI study investigated the dynamic changes of neural activity during the observation of distinct action steps that cohere by an overarching goal. Our hypotheses specifically addressed the role of the inferior frontal gyrus (IFG), a region assumed to be a key hub for integration functions during action processing, as well as the role of regions involved in action perception (often referred to as action observation network or AON) that should benefit from the predictability of forthcoming action steps. Participants watched separate action steps that formed a coherent action goal or not (factor goal coherence) and were performed by a single actor or not (factor actor coherence). Independent of actor coherence, neural activity in IFG and occipitotemporal cortex decreased as a function of goal predictability during the unfolding of goal-coherent episodes. In addition, we identified a network (precuneus, dorsolateral prefrontal and orbitofrontal cortex, angular gyrus, and middle temporal gyrus) that showed increased activity for goal coherence. We conclude that IFG fosters the integration of action steps to build overarching goals. Identifying the unifying goal of an action episode allows anticipation, and thus efficient processing, of forthcoming action steps. To this end, past action steps of the action episode are buffered and recollected with recourse to episodic memory.

  7. Youth meeting symptom and impairment criteria for mania-like episodes lasting less than four days: an epidemiological enquiry

    PubMed Central

    Stringaris, Argyris; Santosh, Paramala; Leibenluft, Ellen; Goodman, Robert

    2009-01-01

    Background Little is known about short-duration episodes of mania-like symptoms in youth. Here we determine the prevalence, morbid associations, and contribution to social impairment of a phenotype characterised by episodes during which symptom and impairment criteria for mania are met, but DSM-IV duration criteria are not (Bipolar not otherwise specified; BP-NOS). Methods A cross-sectional national survey of a sample (N=5326) of 8-19 year olds from the general population using information from parents and youth. Outcome measures were prevalence rates and morbid associations assessed by the Developmental and Well-Being Assessment, and social impairment assessed by the impact scale of the Strengths and Difficulties Questionnaire. Results While only seven individuals (0.1%) met definite or probable DSM-IV criteria for BPI or BPII, the prevalence of BP-NOS was 10-fold higher, 1.1% by parent report and 1.5% by youth report. Parent-youth agreement was very low: κ=0.02, p>0.05 for BP-NOS. Prevalence and episode duration for BP-NOS did not vary by age. BP-NOS showed strong associations with externalising disorders. After adjusting for a dimensional measure of general psychopathology, self-reported (but not parent-reported) BP-NOS remained associated with overall social impairment. Conclusions BP meeting full DSM-IV criteria is rare in youth. BP-NOS, defined by episodes shorter than those required by DSM-IV, but during which DSM-IV symptom and impairment criteria are met, is commoner and may be associated with social impairment that is beyond what can be accounted for by other psychopathology. These findings support the importance of research into these short episodes during which manic symptoms are met in youth but they also call into question the extent to which BP-NOS in youth is a variant of DSM-IV BP - superficially similar symptoms may not necessarily imply deeper similarities in aetiology or treatment response. PMID:19686330

  8. Impaired neuroendocrine and immune response to acute stress in medication-naive patients with a first episode of psychosis.

    PubMed

    van Venrooij, Janine A E M; Fluitman, Sjoerd B A H A; Lijmer, Jeroen G; Kavelaars, Annemieke; Heijnen, Cobi J; Westenberg, Herman G M; Kahn, René S; Gispen-de Wied, Christine C

    2012-03-01

    Little is known about how the biological stress response systems--the autonomic nervous system (ANS), the hypothalamic-pituitary-adrenal (HPA) axis, and the immune system--function during psychosis. Results of studies on the effect of stress on the immune and autonomic system in patients with schizophrenia are inconsistent. The present study investigates whether the stress response is impaired in medication-naive patients with a first episode of psychosis. Ten male patients with a first episode of psychosis and 15 controls were exposed to the stress of public speaking. Parameters of the ANS (heart rate and catecholamines), the HPA axis (plasma adrenocorticotropic hormone [ACTH] and cortisol), and the immune system (number and activity of natural killer [NK] cells) were measured. Peak responses were calculated to examine the relationship between stress-induced activation of the different systems. Subjective stress and anxiety before and during the task were assessed. Patients and controls displayed similar autonomic responses to acute stress. However, there was an impaired HPA axis response, slow onset and return of ACTH, and flattened cortisol response and a reduced increase in number NK cells and NK cell activity in patients with a first episode of psychosis. Furthermore, in patients, the relationship between the different stress response systems was weaker or absent compared with controls. These findings indicate that impairments in stress processing are associated with the endophenotype of psychosis and are not a result of illness progression or antipsychotic medication.

  9. Abnormal insula functional network is associated with episodic memory decline in amnestic mild cognitive impairment.

    PubMed

    Xie, Chunming; Bai, Feng; Yu, Hui; Shi, Yongmei; Yuan, Yonggui; Chen, Gang; Li, Wenjun; Chen, Guangyu; Zhang, Zhijun; Li, Shi-Jiang

    2012-10-15

    Abnormalities of functional connectivity in the default mode network (DMN) recently have been reported in patients with amnestic mild cognitive impairment (aMCI), Alzheimer's disease (AD) or other psychiatric diseases. As such, these abnormalities may be epiphenomena instead of playing a causal role in AD progression. To date, few studies have investigated specific brain networks, which extend beyond the DMN involved in the early AD stages, especially in aMCI. The insula is one site affected by early pathological changes in AD and is a crucial hub of the human brain networks. Currently, we explored the contribution of the insula networks to cognitive performance in aMCI patients. Thirty aMCI and 26 cognitively normal (CN) subjects participated in this study. Intrinsic connectivity of the insula networks was measured, using the resting-state functional connectivity fMRI approach. We examined the differential connectivity of insula networks between groups, and the neural correlation between the altered insula networks connectivity and the cognitive performance in aMCI patients and CN subjects, respectively. Insula subregional volumes were also investigated. AMCI subjects, when compared to CN subjects, showed significantly reduced right posterior insula volumes, cognitive deficits and disrupted intrinsic connectivity of the insula networks. Specifically, decreased intrinsic connectivity was primarily located in the frontal-parietal network and the cingulo-opercular network, including the anterior prefrontal cortex (aPFC), anterior cingulate cortex, operculum, inferior parietal cortex and precuneus. Increased intrinsic connectivity was primarily situated in the visual-auditory pathway, which included the posterior superior temporal gyrus and middle occipital gyrus. Conjunction analysis was performed; and significantly decreased intrinsic connectivity in the overlapping regions of the anterior and posterior insula networks, including the bilateral aPFC, left

  10. The chemotherapeutic agent paclitaxel selectively impairs reversal learning while sparing prior learning, new learning and episodic memory.

    PubMed

    Panoz-Brown, Danielle; Carey, Lawrence M; Smith, Alexandra E; Gentry, Meredith; Sluka, Christina M; Corbin, Hannah E; Wu, Jie-En; Hohmann, Andrea G; Crystal, Jonathon D

    2017-10-01

    Chemotherapy is widely used to treat patients with systemic cancer. The efficacy of cancer therapies is frequently undermined by adverse side effects that have a negative impact on the quality of life of cancer survivors. Cancer patients who receive chemotherapy often experience chemotherapy-induced cognitive impairment across a variety of domains including memory, learning, and attention. In the current study, the impact of paclitaxel, a taxane derived chemotherapeutic agent, on episodic memory, prior learning, new learning, and reversal learning were evaluated in rats. Neurogenesis was quantified post-treatment in the dentate gyrus of the same rats using immunostaining for 5-Bromo-2'-deoxyuridine (BrdU) and Ki67. Paclitaxel treatment selectively impaired reversal learning while sparing episodic memory, prior learning, and new learning. Furthermore, paclitaxel-treated rats showed decreases in markers of hippocampal cell proliferation, as measured by markers of cell proliferation assessed using immunostaining for Ki67 and BrdU. This work highlights the importance of using multiple measures of learning and memory to identify the pattern of impaired and spared aspects of chemotherapy-induced cognitive impairment. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Impaired cue identification and intention retrieval underlie prospective memory deficits in patients with first-episode schizophrenia.

    PubMed

    Liu, Dengtang; Ji, Chengfeng; Zhuo, Kaiming; Song, Zhenhua; Wang, Yingchan; Mei, Li; Zhu, Dianming; Xiang, Qiong; Chen, Tianyi; Yang, Zhilei; Zhu, Guang; Wang, Ya; Cheung, Eric Fc; Xiang, Yu-Tao; Fan, Xiaoduo; Chan, Raymond Ck; Xu, Yifeng; Jiang, Kaida

    2017-03-01

    Schizophrenia is associated with impairment in prospective memory, the ability to remember to carry out an intended action in the future. It has been established that cue identification (detection of the cue event signaling that an intended action should be performed) and intention retrieval (retrieval of an intention from long-term memory following the recognition of a prospective cue) are two important processes underlying prospective memory. The purpose of this study was to examine prospective memory deficit and underlying cognitive processes in patients with first-episode schizophrenia. This study examined cue identification and intention retrieval components of event-based prospective memory using a dual-task paradigm in 30 patients with first-episode schizophrenia and 30 healthy controls. All participants were also administered a set of tests assessing working memory and retrospective memory. Both cue identification and intention retrieval were impaired in patients with first-episode schizophrenia compared with healthy controls ( ps < 0.05), with a large effect size for cue identification (Cohen's d = 0.98) and a medium effect size for intention retrieval (Cohen's d = 0.62). After controlling for working memory and retrospective memory, the difference in cue identification between patients and healthy controls remained significant. However, the difference in intention retrieval between the two groups was no longer significant. In addition, there was a significant inverse relationship between cue identification and negative symptoms ( r = -0.446, p = 0.013) in the patient group. These findings suggest that both cue identification and intention retrieval in event-based prospective memory are impaired in patients with first-episode schizophrenia. Cue identification and intention retrieval could be potentially used as biomarkers for early detection and treatment prognosis of schizophrenia. In addition, addressing cue identification deficit

  12. Wireless Wearable Multisensory Suite and Real-Time Prediction of Obstructive Sleep Apnea Episodes.

    PubMed

    Le, Trung Q; Cheng, Changqing; Sangasoongsong, Akkarapol; Wongdhamma, Woranat; Bukkapatnam, Satish T S

    2013-01-01

    Obstructive sleep apnea (OSA) is a common sleep disorder found in 24% of adult men and 9% of adult women. Although continuous positive airway pressure (CPAP) has emerged as a standard therapy for OSA, a majority of patients are not tolerant to this treatment, largely because of the uncomfortable nasal air delivery during their sleep. Recent advances in wireless communication and advanced ("bigdata") preditive analytics technologies offer radically new point-of-care treatment approaches for OSA episodes with unprecedented comfort and afforadability. We introduce a Dirichlet process-based mixture Gaussian process (DPMG) model to predict the onset of sleep apnea episodes based on analyzing complex cardiorespiratory signals gathered from a custom-designed wireless wearable multisensory suite. Extensive testing with signals from the multisensory suite as well as PhysioNet's OSA database suggests that the accuracy of offline OSA classification is 88%, and accuracy for predicting an OSA episode 1-min ahead is 83% and 3-min ahead is 77%. Such accurate prediction of an impending OSA episode can be used to adaptively adjust CPAP airflow (toward improving the patient's adherence) or the torso posture (e.g., minor chin adjustments to maintain steady levels of the airflow).

  13. Wireless Wearable Multisensory Suite and Real-Time Prediction of Obstructive Sleep Apnea Episodes

    PubMed Central

    Cheng, Changqing; Sangasoongsong, Akkarapol; Wongdhamma, Woranat; Bukkapatnam, Satish T. S.

    2013-01-01

    Obstructive sleep apnea (OSA) is a common sleep disorder found in 24% of adult men and 9% of adult women. Although continuous positive airway pressure (CPAP) has emerged as a standard therapy for OSA, a majority of patients are not tolerant to this treatment, largely because of the uncomfortable nasal air delivery during their sleep. Recent advances in wireless communication and advanced (“bigdata”) preditive analytics technologies offer radically new point-of-care treatment approaches for OSA episodes with unprecedented comfort and afforadability. We introduce a Dirichlet process-based mixture Gaussian process (DPMG) model to predict the onset of sleep apnea episodes based on analyzing complex cardiorespiratory signals gathered from a custom-designed wireless wearable multisensory suite. Extensive testing with signals from the multisensory suite as well as PhysioNet's OSA database suggests that the accuracy of offline OSA classification is 88%, and accuracy for predicting an OSA episode 1-min ahead is 83% and 3-min ahead is 77%. Such accurate prediction of an impending OSA episode can be used to adaptively adjust CPAP airflow (toward improving the patient's adherence) or the torso posture (e.g., minor chin adjustments to maintain steady levels of the airflow). PMID:27170854

  14. Is the Ultimate Treatment Response Predictable with Early Response in Major Depressive Episode?

    PubMed Central

    ÇİFTÇİ, Aslı; ULAŞ, Halis; TOPUZOĞLU, Ahmet; TUNCA, Zeliha

    2016-01-01

    Introduction New evidence suggests that the efficacy of antidepressants occurs within the first weeks of treatment and this early response predicts the later response. The purpose of the present study was to investigate if the partial response in the first week predicts the response at the end of treatment in patients with major depressive disorder who are treated with either antidepressant medication or electroconvulsive therapy. Methods Inpatients from Dokuz Eylül University Hospital with a major depressive episode, treated with antidepressant medication (n=52) or electroconvulsive therapy (ECT) (n=48), were recruited for the study. The data were retrospectively collected to decide whether a 25% decrease in the Hamilton Depression Rating Scale (HDRS) score at the first week of treatment predicts a 50% decrease at the third week using validity analysis. In addition, the effects of socio-demographic and clinical variables on the treatment response were assessed. Results A 25% decrease in the HDRS score in the first week of treatment predicted a 50% decrease in the HDRS score in the third week with a 78.3% positive predictive value, 62.1% negative predictive value, 62.1% sensitivity, and 78.3% specificity for antidepressant medications and an 88% positive predictive value, 52.2% negative predictive value, 66.7% sensitivity, and 80% specificity for ECT. The number of previous hospitalizations, comorbid medical illnesses, number of depressive episodes, duration of illness, and duration of the current episode were related to the treatment response. Conclusion Treatment response in the first week predicted the response in the third week with a high specificity and a high positive predictive value. Close monitoring of the response from the first week of treatment may thus help the clinician to predict the subsequent response. PMID:28373802

  15. Episodic memory encoding interferes with reward learning and decreases striatal prediction errors.

    PubMed

    Wimmer, G Elliott; Braun, Erin Kendall; Daw, Nathaniel D; Shohamy, Daphna

    2014-11-05

    Learning is essential for adaptive decision making. The striatum and its dopaminergic inputs are known to support incremental reward-based learning, while the hippocampus is known to support encoding of single events (episodic memory). Although traditionally studied separately, in even simple experiences, these two types of learning are likely to co-occur and may interact. Here we sought to understand the nature of this interaction by examining how incremental reward learning is related to concurrent episodic memory encoding. During the experiment, human participants made choices between two options (colored squares), each associated with a drifting probability of reward, with the goal of earning as much money as possible. Incidental, trial-unique object pictures, unrelated to the choice, were overlaid on each option. The next day, participants were given a surprise memory test for these pictures. We found that better episodic memory was related to a decreased influence of recent reward experience on choice, both within and across participants. fMRI analyses further revealed that during learning the canonical striatal reward prediction error signal was significantly weaker when episodic memory was stronger. This decrease in reward prediction error signals in the striatum was associated with enhanced functional connectivity between the hippocampus and striatum at the time of choice. Our results suggest a mechanism by which memory encoding may compete for striatal processing and provide insight into how interactions between different forms of learning guide reward-based decision making.

  16. Episodic Memory Encoding Interferes with Reward Learning and Decreases Striatal Prediction Errors

    PubMed Central

    Braun, Erin Kendall; Daw, Nathaniel D.

    2014-01-01

    Learning is essential for adaptive decision making. The striatum and its dopaminergic inputs are known to support incremental reward-based learning, while the hippocampus is known to support encoding of single events (episodic memory). Although traditionally studied separately, in even simple experiences, these two types of learning are likely to co-occur and may interact. Here we sought to understand the nature of this interaction by examining how incremental reward learning is related to concurrent episodic memory encoding. During the experiment, human participants made choices between two options (colored squares), each associated with a drifting probability of reward, with the goal of earning as much money as possible. Incidental, trial-unique object pictures, unrelated to the choice, were overlaid on each option. The next day, participants were given a surprise memory test for these pictures. We found that better episodic memory was related to a decreased influence of recent reward experience on choice, both within and across participants. fMRI analyses further revealed that during learning the canonical striatal reward prediction error signal was significantly weaker when episodic memory was stronger. This decrease in reward prediction error signals in the striatum was associated with enhanced functional connectivity between the hippocampus and striatum at the time of choice. Our results suggest a mechanism by which memory encoding may compete for striatal processing and provide insight into how interactions between different forms of learning guide reward-based decision making. PMID:25378157

  17. Modifiable impairments predict progressive disability among older persons.

    PubMed

    Tinetti, Mary E; Allore, Heather; Araujo, Katy L B; Seeman, Teresa

    2005-04-01

    Our purpose was to determine the extent to which a predetermined set of modifiable impairments predicted progression of disability. We conducted a 3-year follow-up of two community-based cohorts of older adults. The impairment areas included lower extremity, upper extremity, hearing, vision, and affect. Home management and social or productive activities were the domains of function investigated. All five impairments were of at least borderline significance in predicting decline in both functional domains in both cohorts with the exception of hearing for home management activities. The five impairments together explained from 17% to 23% of the decline seen in the functional outcomes (partial R(2)s 0.17 to 0.23). Five prevalent and potentially modifiable impairments explained much of the progressive disability experienced. Given the priority that older patients place on function as a health outcome, these impairments should be routinely assessed and modified.

  18. Individual differences in acute alcohol impairment of inhibitory control predict ad libitum alcohol consumption

    PubMed Central

    Weafer, Jessica

    2015-01-01

    Rationale Research has begun to examine how acute cognitive impairment from alcohol could contribute to alcohol abuse. Specifically, alcohol-induced impairment of inhibitory control could compromise the drinker’s ability to stop the self-administration of alcohol, increasing the risk of binge drinking. Objective The present study was designed to test this hypothesis by examining the relation between acute alcohol impairment of inhibitory control and alcohol consumption during a single drinking episode. Materials and methods Twenty-six healthy adults performed a cued go/no-go task that measured inhibitory control. The study tested the degree to which their inhibitory control was impaired by a moderate dose of alcohol (0.65 g/kg) versus a placebo and the extent to which individual differences in this impairment predicted levels of alcohol consumption as assessed by ad lib drinking in the laboratory. Results In accord with the hypothesis, greater impairment of inhibitory control from alcohol was associated with increased ad lib consumption. Conclusion Acute impairment of inhibitory control might be an important cognitive effect that contributes to abuse in addition to the positive rewarding effects of the drug. PMID:18758758

  19. Impairments in Episodic-Autobiographical Memory and Emotional and Social Information Processing in CADASIL during Mid-Adulthood.

    PubMed

    Staniloiu, Angelica; Woermann, Friedrich G; Markowitsch, Hans J

    2014-01-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) - is the most common genetic source of vascular dementia in adults, being caused by a mutation in NOTCH3 gene. Spontaneous de novo mutations may occur, but their frequency is largely unknown. Ischemic strokes and cognitive impairments are the most frequent manifestations, but seizures affect up to 10% of the patients. Herein, we describe a 47-year-old male scholar with a genetically confirmed diagnosis of CADASIL (Arg133Cys mutation in the NOTCH3 gene) and a seemingly negative family history of CADASIL illness, who was investigated with a comprehensive neuropsychological testing battery and neuroimaging methods. The patient demonstrated on one hand severe and accelerated deteriorations in multiple cognitive domains such as concentration, long-term memory (including the episodic-autobiographical memory domain), problem solving, cognitive flexibility and planning, affect recognition, discrimination and matching, and social cognition (theory of mind). Some of these impairments were even captured by abbreviated instruments for investigating suspicion of dementia. On the other hand the patient still possessed high crystallized (verbal) intelligence and a capacity to put forth a façade of well-preserved intellectual functioning. Although no definite conclusions can be drawn from a single case study, our findings point to the presence of additional cognitive changes in CADASIL in middle adulthood, in particular to impairments in the episodic-autobiographical memory domain and social information processing (e.g., social cognition). Whether these identified impairments are related to the patient's specific phenotype or to an ascertainment bias (e.g., a paucity of studies investigating these cognitive functions) requires elucidation by larger scale research.

  20. Impairments in Episodic-Autobiographical Memory and Emotional and Social Information Processing in CADASIL during Mid-Adulthood

    PubMed Central

    Staniloiu, Angelica; Woermann, Friedrich G.; Markowitsch, Hans J.

    2014-01-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) – is the most common genetic source of vascular dementia in adults, being caused by a mutation in NOTCH3 gene. Spontaneous de novo mutations may occur, but their frequency is largely unknown. Ischemic strokes and cognitive impairments are the most frequent manifestations, but seizures affect up to 10% of the patients. Herein, we describe a 47-year-old male scholar with a genetically confirmed diagnosis of CADASIL (Arg133Cys mutation in the NOTCH3 gene) and a seemingly negative family history of CADASIL illness, who was investigated with a comprehensive neuropsychological testing battery and neuroimaging methods. The patient demonstrated on one hand severe and accelerated deteriorations in multiple cognitive domains such as concentration, long-term memory (including the episodic-autobiographical memory domain), problem solving, cognitive flexibility and planning, affect recognition, discrimination and matching, and social cognition (theory of mind). Some of these impairments were even captured by abbreviated instruments for investigating suspicion of dementia. On the other hand the patient still possessed high crystallized (verbal) intelligence and a capacity to put forth a façade of well-preserved intellectual functioning. Although no definite conclusions can be drawn from a single case study, our findings point to the presence of additional cognitive changes in CADASIL in middle adulthood, in particular to impairments in the episodic-autobiographical memory domain and social information processing (e.g., social cognition). Whether these identified impairments are related to the patient’s specific phenotype or to an ascertainment bias (e.g., a paucity of studies investigating these cognitive functions) requires elucidation by larger scale research. PMID:25009481

  1. Improvement of episodic memory in persons with mild cognitive impairment and healthy older adults: evidence from a cognitive intervention program.

    PubMed

    Belleville, Sylvie; Gilbert, Brigitte; Fontaine, Francine; Gagnon, Lise; Ménard, Edith; Gauthier, Serge

    2006-01-01

    The efficacy of cognitive training was assessed in persons with mild cognitive impairment (MCI) and persons with normal cognitive aging. Forty-seven participants were included in this study: 28 with MCI and 17 controls. Twenty-one participants received intervention (20 MCI and 9 controls) and 16 participants (8 MCI and 8 controls) received no intervention (waiting-list group). The intervention focused on teaching episodic memory strategies. Three tasks of episodic memory (list recall, face-name association, text memory) were used as primary outcome measures. Results were analyzed using analyses of variance. The intervention effect (pre- and post-intervention difference) was significant on two of the primary outcome measures (delayed list recall and face-name association). A significant pre-post-effect was also found on measures of subjective memory and well-being. There was no improvement in the performance of groups of individuals with MCI and normal elderly persons who did not receive the intervention. These results suggest that persons with MCI can improve their performance on episodic memory when provided with cognitive training.

  2. Entorhinal cortex volume is associated with episodic memory related brain activation in normal aging and amnesic mild cognitive impairment.

    PubMed

    Trivedi, Mehul A; Stoub, Travis R; Murphy, Christopher M; George, Sarah; deToledo-Morrell, Leyla; Shah, Raj C; Whitfield-Gabrieli, Susan; Gabrieli, John D E; Stebbins, Glenn T

    2011-06-01

    The present study examined the relationship between entorhinal cortex and hippocampal volume with fMRI activation during episodic memory function in elderly controls with no cognitive impairment and individuals with amnesic mild cognitive impairment (aMCI). Both groups displayed limited evidence for a relationship between hippocampal volume and fMRI activation. Smaller right entorhinal cortex volume was correlated with reduced activation in left and right medial frontal cortex (BA 8) during incidental encoding for both aMCI and elderly controls. However, during recognition, smaller left entorhinal cortex volume correlated with reduced activation in right BA 8 for the control group, but greater activation for the aMCI group. There was no significant relationship between entorhinal cortex volume and activation during intentional encoding in either group. The recognition-related dissociation in structure/function relationships in aMCI paralleled our behavioral findings, where individuals with aMCI displayed poorer performance relative to controls during recognition, but not encoding. Taken together, these results suggest that the relationship between entorhinal cortex volume and fMRI activation during episodic memory function is altered in individuals with aMCI.

  3. Entorhinal cortex volume is associated with episodic memory related brain activation in normal aging and amnesic mild cognitive impairment

    PubMed Central

    Trivedi, Mehul A.; Stoub, Travis R.; Murphy, Christopher M.; George, Sarah; deToledo-Morrell, Leyla; Shah, Raj C.; Whitfield-Gabrieli, Susan; Gabrieli, John D.E.; Stebbins, Glenn T.

    2011-01-01

    The present study examined the relationship between entorhinal cortex and hippocampal volume with fMRI activation during episodic memory function in elderly controls with no cognitive impairment and individuals with amnesic mild cognitive impairment (aMCI). Both groups displayed limited evidence for a relationship between hippocampal volume and fMRI activation. Smaller right entorhinal cortex volume was correlated with reduced activation in left and right medial frontal cortex (BA 8) during incidental encoding for both aMCI and elderly controls. However, during recognition, smaller left entorhinal cortex volume correlated with reduced activation in right BA 8 for the control group, but greater activation for the aMCI group. There was no significant relationship between entorhinal cortex volume and activation during intentional encoding in either group. The recognition-related dissociation in structure/function relationships in aMCI paralleled our behavioral findings, where individuals with aMCI displayed poorer performance relative to controls during recognition, but not encoding. Taken together, these results suggest that the relationship between entorhinal cortex volume and fMRI activation during episodic memory function is altered in individuals with aMCI. PMID:21328083

  4. Improving prediction of binge episodes by modelling chronicity of dietary restriction.

    PubMed

    Holmes, Millicent; Fuller-Tyszkiewicz, Matthew; Skouteris, Helen; Broadbent, Jaclyn

    2014-11-01

    This study evaluates the influences of chronicity of, and time lag between, dietary restriction and binge outcome for predicting binge episode onset. Sixty-two women aged 18 to 40 years old completed an online survey at random intervals seven times daily for a 7-day period. Participants self-reported engagement in dietary restriction and/or binging, and temptation to binge. Consecutive instances of reported dietary restriction better predicted subsequent binges than single instances. As the time lag between the first report of dietary restriction and binge onset increased, a clear linear trend emerged, such that the value of restriction for predicting binges increased with the number of consecutive assessments in which they reported dietary restriction. A similar pattern was found when predicting temptation to binge. Present findings suggest that duration of restriction is a crucial determinant of binge onset. These findings have implications for clinical practice by highlighting the time course from dietary restriction to binging.

  5. Depressive symptoms predict incident cognitive impairment in cognitive healthy older women

    PubMed Central

    Rosenberg, Paul B.; Mielke, Michelle M.; Xue, Qian-Li; Carlson, Michelle C.

    2009-01-01

    OBJECTIVES There is increasing evidence that depressive symptoms are associated with the development of cognitive impairment and dementia in late life. We sought to examine whether depression increased the risk of incident cognitive impairment in a longitudinal study of older women. DESIGN observational study, up to 6 examinations spanning up to 9 years. SETTING university-based Division of Geriatric Medicine PARTICIPANTS community-based sample of 436 older, non-demented women MEASUREMENTS Participants were followed with regular medical and neuropsychiatric evaluations. Cognitive assessment included episodic immediate and delayed memory, psychomotor speed, and executive functioning. Participants were characterized as having incident impairment on a cognitive test when scores fell below the tenth percentile on age-adjusted norms. Baseline depressive symptoms were measured using the Geriatric Depression Scale (GDS) (30-item). Discrete-time Cox Proportional hazards regression with generalized linear models were used to determine whether baseline risk factors predicted incident impairment on each cognitive test, defined as performance below the tenth percentile on age-adjusted norms. RESULTS Baseline GDS was highly associated with incident impairment on all cognitive tests (p <.03). These associations were unaffected by vascular conditions except diabetes, which was associated with incident impairment in delayed recall and psychomotor speed. CONCLUSIONS These data suggest that depression may be risk factors for cognitive decline, and thus a potential target for diagnostic and therapeutic interventions. PMID:20224517

  6. Stress Administered Prior to Encoding Impairs Neutral but Enhances Emotional Long-Term Episodic Memories

    ERIC Educational Resources Information Center

    Payne, Jessica D.; Jackson, Eric D.; Hoscheidt, Siobhan; Ryan, Lee; Jacobs, W. Jake; Nadel, Lynn

    2007-01-01

    Stressful events frequently comprise both neutral and emotionally arousing information, yet the impact of stress on emotional and neutral events is still not fully understood. The hippocampus and frontal cortex have dense concentrations of receptors for stress hormones, such as cortisol, which at high levels can impair performance on hippocampally…

  7. Stress Administered Prior to Encoding Impairs Neutral but Enhances Emotional Long-Term Episodic Memories

    ERIC Educational Resources Information Center

    Payne, Jessica D.; Jackson, Eric D.; Hoscheidt, Siobhan; Ryan, Lee; Jacobs, W. Jake; Nadel, Lynn

    2007-01-01

    Stressful events frequently comprise both neutral and emotionally arousing information, yet the impact of stress on emotional and neutral events is still not fully understood. The hippocampus and frontal cortex have dense concentrations of receptors for stress hormones, such as cortisol, which at high levels can impair performance on hippocampally…

  8. Risk of severe asthma episodes predicted from fluctuation analysis of airway function.

    PubMed

    Frey, Urs; Brodbeck, Tanja; Majumdar, Arnab; Taylor, D Robin; Town, G Ian; Silverman, Michael; Suki, Béla

    2005-12-01

    Asthma is an increasing health problem worldwide, but the long-term temporal pattern of clinical symptoms is not understood and predicting asthma episodes is not generally possible. We analyse the time series of peak expiratory flows, a standard measurement of airway function that has been assessed twice daily in a large asthmatic population during a long-term crossover clinical trial. Here we introduce an approach to predict the risk of worsening airflow obstruction by calculating the conditional probability that, given the current airway condition, a severe obstruction will occur within 30 days. We find that, compared with a placebo, a regular long-acting bronchodilator (salmeterol) that is widely used to improve asthma control decreases the risk of airway obstruction. Unexpectedly, however, a regular short-acting beta2-agonist bronchodilator (albuterol) increases this risk. Furthermore, we find that the time series of peak expiratory flows show long-range correlations that change significantly with disease severity, approaching a random process with increased variability in the most severe cases. Using a nonlinear stochastic model, we show that both the increased variability and the loss of correlations augment the risk of unstable airway function. The characterization of fluctuations in airway function provides a quantitative basis for objective risk prediction of asthma episodes and for evaluating the effectiveness of therapy.

  9. Platelets miRNA as a Prediction Marker of Thrombotic Episodes

    PubMed Central

    Dzieciol, Malgorzata

    2016-01-01

    The blood platelets are crucial for the coagulation physiology to maintain haemostatic balance and are involved in various pathologies such as atherosclerosis and thrombosis. The studies of recent years have shown that anucleated platelets are able to succeed protein synthesis. Additionally, mRNA translation in blood platelets is regulated by miRNA molecules. Recent works postulate the possibility of using miRNAs as biomarkers of atherosclerosis and ischemic episodes. This review article describes clinical studies that presented blood platelets miRNAs expression profile changes in different thrombotic states, which suggest use of these molecules as predictive biomarkers. PMID:28042196

  10. Decreased glutathione levels and impaired antioxidant enzyme activities in drug-naive first-episode schizophrenic patients

    PubMed Central

    2011-01-01

    Background The aim of this study was to determine glutathione levels and antioxidant enzyme activities in the drug-naive first-episode patients with schizophrenia in comparison with healthy control subjects. Methods It was a case-controlled study carried on twenty-three patients (20 men and 3 women, mean age = 29.3 ± 7.5 years) recruited in their first-episode of schizophrenia and 40 healthy control subjects (36 men and 9 women, mean age = 29.6 ± 6.2 years). In patients, the blood samples were obtained prior to the initiation of neuroleptic treatments. Glutathione levels: total glutathione (GSHt), reduced glutathione (GSHr) and oxidized glutathione (GSSG) and antioxidant enzyme activities: superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) were determined by spectrophotometry. Results GSHt and reduced GSHr were significantly lower in patients than in controls, whereas GSSG was significantly higher in patients. GPx activity was significantly higher in patients compared to control subjects. CAT activity was significantly lower in patients, whereas the SOD activity was comparable to that of controls. Conclusion This is a report of decreased plasma levels of GSHt and GSHr, and impaired antioxidant enzyme activities in drug-naive first-episode patients with schizophrenia. The GSH deficit seems to be implicated in psychosis, and may be an important indirect biomarker of oxidative stress in schizophrenia early in the course of illness. Finally, our results provide support for further studies of the possible role of antioxidants as neuroprotective therapeutic strategies for schizophrenia from early stages. PMID:21810251

  11. A digit symbol coding task as a screening instrument for cognitive impairment in first-episode psychosis.

    PubMed

    González-Blanch, César; Pérez-Iglesias, Rocío; Rodríguez-Sánchez, José Manuel; Pardo-García, Gema; Martínez-García, Obdulia; Vázquez-Barquero, José Luis; Crespo-Facorro, Benedicto

    2011-02-01

    Cognitive impairment may be detected largely by examining the performance on a single neuropsychological measure. The purpose of the present study was to evaluate the validity and diagnostic accuracy of a coding task in comparison with other related tasks. One hundred thirty-one first-episode psychosis patients were administered five cognitive tasks related to a "speed of processing and executive functioning" dimension (Digit Symbol, Trail Making Test [TMT] parts A and B, Cancellation Test, and Digit Span-backward) and an additional measure of functional outcome. Digit Symbol provided good indices of accuracy and correlations with the global composite score of a comprehensive neuropsychological assessment represented large effect sizes. Correlations with a functional outcome were modest. Similar results were observed with the TMT. The processing speed, as measured by Digit Symbol, may be particularly good in capturing the generalized dysfunction which may be causing the widespread cognitive failures in schizophrenia spectrum disorders.

  12. Deviant functional activation and connectivity of the right insula are associated with lack of awareness of episodic memory impairment in nonamnesic alcoholism.

    PubMed

    Le Berre, Anne-Pascale; Müller-Oehring, Eva M; Schulte, Tilman; Serventi, Matthew R; Pfefferbaum, Adolf; Sullivan, Edith V

    2017-10-01

    A disorder of metamemory, expressed as unawareness of mnemonic ability, is typically associated with the profound amnesia of Korsakoff's Syndrome (KS). A similar but less severe type of limited awareness can also occur in non-KS alcoholism and is observed as an impairment in generating Feeling-of-Knowing (FOK) predictions about future recognition performance. We previously found that FOK accuracy was selectively related to volumes of the insula in alcoholics involved in the present study. Unknown, however, are the neural substrates of unawareness of memory impairment in alcoholism. A task-activated fMRI paradigm served to identify neural nodes and networks implicated in inaccurate self-estimation of mnemonic ability in sober alcoholics while they made prospective FOK judgments in an episodic memory paradigm. Lower activation in the right insula correlated with greater overestimations of future memory abilities in alcoholics. Weaker connectivity of the right insula with the left dorsal anterior cingulate cortex, a node of the salience network, and stronger connectivity of the right insula with the right ventromedial prefrontal cortex (vmPFC), a node of the default mode network (DMN), co-occurred in alcoholics relative to the controls. Specifically, alcoholics, who failed to desynchronize insula-vmPFC activity, had greater overestimation of their memory predictions and poorer recognition performance. This study provides novel support that deviant functional activation and connectivity involving the right insula, a hub of the salience network, appears to participate in disrupting metamemory functioning in alcoholics. Compromised FOK performance might result from disturbance of the switching mechanism between brain networks serving self-referential processes (i.e., DMN network) and networks serving externally-driven activities like memory monitoring (i.e., fronto-parietal network). Thus, compromise in insular network coupling could be a neural mechanism underlying

  13. Predicting cognitive impairment and accident risk.

    PubMed

    Raslear, Thomas G; Hursh, Steven R; Van Dongen, Hans P A

    2011-01-01

    Sleep and cognition are temporally regulated by a homeostatic process generating pressure for sleep as a function of sleep/wake history, and a circadian process generating pressure for wakefulness as a function of time of day. Under normal nocturnal sleep conditions, these two processes are aligned in such a manner as to provide optimal daytime performance and consolidated nighttime sleep. Under conditions of sleep deprivation, shift work or transmeridian travel, the two processes are misaligned, resulting in fatigue and cognitive deficits. Mathematical models of fatigue and performance have been developed to predict these cognitive deficits. Recent studies showing long-term effects on performance of chronic sleep restriction suggest that the homeostatic process undergoes gradual changes that are slow to recover. New developments in mathematical modeling of performance are focused on capturing these gradual changes and their effects on fatigue. Accident risk increases as a function of fatigue severity as well as the duration of exposure to fatigue. Work schedule and accident rate information from an operational setting can thus be used to calibrate a mathematical model of fatigue and performance to predict accident risk. This provides a fatigue risk management tool that helps to direct mitigation resources to where they would have the greatest mitigating effect. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Decoding episodic memory in ageing: A Bayesian analysis of activity patterns predicting memory

    PubMed Central

    Morcom, Alexa M.; Friston, Karl J.

    2012-01-01

    Normal ageing is associated with a decline in episodic memory, and neuroimaging studies in older adults have shown reduced activity in prefrontal cortex and other regions critical for memory function in the young. However, older adults also activate additional regions, suggesting a degree of functional reorganisation that has been attributed variously to detrimental and adaptive changes. Evaluation of these competing hypotheses depends critically upon inferences about the relative location and distribution of activity that are not well supported by current univariate or multivariate analyses. Here, we employed a recently developed model-based multivariate ‘decoding’ approach (Friston et al., 2008) to re-analyse a rich episodic encoding dataset and examine directly how the patterns of activity change in ageing. We assessed which spatial activity patterns, within lateral prefrontal cortex, best predict successful memory formation. Bayesian model comparison showed that the older adults had more distributed and bilateral (fragmented) predictive patterns of activity in anterior inferior frontal gyrus and middle frontal gyrus. With this direct multivariate test for changes in patterns of activity, we replicate and extend earlier findings of reduced prefrontal lateralisation in ageing. These findings extend conclusions based on conventional analyses, and support the notion that ageing alters the spatial deployment of neuronal activity, to render it less spatially coherent and regionally specific. This greater distribution of activity in older adults was also linked to poorer individual memory performance, suggesting that it reflects neural ageing, rather than adaptive compensatory responses. PMID:21907810

  15. Discovery of serum biomarkers predicting development of a subsequent depressive episode in social anxiety disorder.

    PubMed

    Gottschalk, M G; Cooper, J D; Chan, M K; Bot, M; Penninx, B W J H; Bahn, S

    2015-08-01

    Although social anxiety disorder (SAD) is strongly associated with the subsequent development of a depressive disorder (major depressive disorder or dysthymia), no underlying biological risk factors are known. We aimed to identify biomarkers which predict depressive episodes in SAD patients over a 2-year follow-up period. One hundred sixty-five multiplexed immunoassay analytes were investigated in blood serum of 143 SAD patients without co-morbid depressive disorders, recruited within the Netherlands Study of Depression and Anxiety (NESDA). Predictive performance of identified biomarkers, clinical variables and self-report inventories was assessed using receiver operating characteristics curves (ROC) and represented by the area under the ROC curve (AUC). Stepwise logistic regression resulted in the selection of four serum analytes (AXL receptor tyrosine kinase, vascular cell adhesion molecule 1, vitronectin, collagen IV) and four additional variables (Inventory of Depressive Symptomatology, Beck Anxiety Inventory somatic subscale, depressive disorder lifetime diagnosis, BMI) as optimal set of patient parameters. When combined, an AUC of 0.86 was achieved for the identification of SAD individuals who later developed a depressive disorder. Throughout our analyses, biomarkers yielded superior discriminative performance compared to clinical variables and self-report inventories alone. We report the discovery of a serum marker panel with good predictive performance to identify SAD individuals prone to develop subsequent depressive episodes in a naturalistic cohort design. Furthermore, we emphasise the importance to combine biological markers, clinical variables and self-report inventories for disease course predictions in psychiatry. Following replication in independent cohorts, validated biomarkers could help to identify SAD patients at risk of developing a depressive disorder, thus facilitating early intervention. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. A Long-Term Prediction Model of Beijing Haze Episodes Using Time Series Analysis

    PubMed Central

    Zhang, Zhongqiu; Sun, Liren; Xu, Cui

    2016-01-01

    The rapid industrial development has led to the intermittent outbreak of pm2.5 or haze in developing countries, which has brought about great environmental issues, especially in big cities such as Beijing and New Delhi. We investigated the factors and mechanisms of haze change and present a long-term prediction model of Beijing haze episodes using time series analysis. We construct a dynamic structural measurement model of daily haze increment and reduce the model to a vector autoregressive model. Typical case studies on 886 continuous days indicate that our model performs very well on next day's Air Quality Index (AQI) prediction, and in severely polluted cases (AQI ≥ 300) the accuracy rate of AQI prediction even reaches up to 87.8%. The experiment of one-week prediction shows that our model has excellent sensitivity when a sudden haze burst or dissipation happens, which results in good long-term stability on the accuracy of the next 3–7 days' AQI prediction. PMID:27597861

  17. Attentional episodes in visual perception

    PubMed Central

    Wyble, Brad; Potter, Mary C; Bowman, Howard; Nieuwenstein, Mark

    2011-01-01

    Is one's temporal perception of the world truly as seamless as it appears? This paper presents a computationally motivated theory suggesting that visual attention samples information from temporal episodes (episodic Simultaneous Type/ Serial Token model or eSTST; Wyble et al 2009a). Breaks between these episodes are punctuated by periods of suppressed attention, better known as the attentional blink (Raymond, Shapiro & Arnell 1992). We test predictions from this model and demonstrate that subjects are able to report more letters from a sequence of four targets presented in a dense temporal cluster, than from a sequence of four targets that are interleaved with non-targets. However, this superior report accuracy comes at a cost in impaired temporal order perception. Further experiments explore the dynamics of multiple episodes, and the boundary conditions that trigger episodic breaks. Finally, we contrast the importance of attentional control, limited resources and memory capacity constructs in the model. PMID:21604913

  18. Impaired Social and Role Function in Ultra-High Risk for Psychosis and First-Episode Schizophrenia: Its Relations with Negative Symptoms

    PubMed Central

    Lee, So Jung; Kim, Kyung Ran; Lee, Su Young

    2017-01-01

    Objective Psychosocial dysfunction was a nettlesome of schizophrenia even in their prodromal phase as well as first episode and its relations with psychopathology were not determined. The aim of the present study was to examine whether the social and role function impairment was found in ultra-high risk for psychosis (UHR) individuals as well as first-episode schizophrenia patients and to explore its relations with psychopathology. Methods Thirty-seven normal controls, 63 UHR participants and 28 young, first-episode schizophrenia patients were recruited. Psychosocial functioning was examined by using Global function: Social and Role scale. Psychopathologies of positive, negative and depressive symptom were also measured. Results Social and role functioning in UHR were compromised at the equivalent level of those of first-episode schizophrenia patients. Multiple linear regression analysis revealed that social and role dysfunction was associated with negative symptoms in each UHR and first-episode schizophrenia group. Conclusion These findings suggest that the significant impairment of social and role function may be appeared before the active psychosis onset at the level of extent to those of first-episode schizophrenia patients. The psychosocial intervention strategy especially targeting the negative symptoms should be developed and provided to individuals from their prepsychotic stage of schizophrenia. PMID:28326117

  19. Pyogenic liver abscess: current status and predictive factors for recurrence and mortality of first episodes.

    PubMed

    Czerwonko, Matías E; Huespe, Pablo; Bertone, Santiago; Pellegrini, Pablo; Mazza, Oscar; Pekolj, Juan; de Santibañes, Eduardo; Hyon, Sung Ho; de Santibañes, Martín

    2016-12-01

    In times of modern surgery, transplantation and percutaneous techniques, pyogenic liver abscess (PLA) has essentially become a problem of biliary or iatrogenic origin. In the current scenario, diagnostic approach, clinical behavior and therapeutic outcomes have not been profoundly studied. This study analyzes the clinical and microbiological features, diagnostic methods, therapeutic management and predictive factors for recurrence and mortality of first episodes of PLA. A retrospective single-center study was conducted including 142 patients admitted to the Hospital Italiano de Buenos Aires, between 2005 and 2015 with first episodes of PLA. Prevailing identifiable causes were biliary diseases (47.9%) followed by non-biliary percutaneous procedures (NBIPLA, 15.5%). Seventeen patients (12%) were liver recipients. Eleven patients (7.8%) died and 18 patients (13.7%) had recurrence in the first year of follow up. The isolation of multiresistant organisms (p = 0.041) and a history of cholangitis (p < 0.001) were independent risk factors for recurrence. Mortality was associated with serum bilirubin >5 mg/dL (p = 0.022) and bilateral involvement (p = 0.014) in the multivariate analysis. NBPLA and PLA after transplantation may be increasing among the population of PLA in referral centers. History of cholangitis is a strong predictor for recurrence. Mortality is associated to hiperbilirrubinemia and anatomical distribution of the lesions. Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

  20. Metamemory ratings predict long-term changes in reactivated episodic memories

    PubMed Central

    Yacoby, Amnon; Dudai, Yadin; Mendelsohn, Avi

    2015-01-01

    Reactivation of long-term memory can render the memory item temporarily labile, offering an opportunity to modify it via behavioral or pharmacological intervention. Declarative memory reactivation is accompanied by a metamemory ability to subjectively assess the knowledge available concerning the target item (Feeling of knowing, FOK). We set out to examine whether FOK can predict the extent of change of long-term episodic memories by post-retrieval manipulations. To this end, participants watched a short movie and were immediately thereafter tested on their memory for it. A day later, they were reminded of that movie, and either immediately or 1 day later, were presented with a second movie. The reminder phase consisted of memory cues to which participants were asked to judge their FOK regarding the original movie. The memory performance of participants to whom new information was presented immediately after reactivating the original episode corresponded to the degree of FOK ratings upon reactivation such that the lower their FOK, the less their memory declined. In contrast, no relation was found between FOK and memory strength for those who learned new information 1 day after the reminder phase. Our findings suggest that the subjective accessibility of reactivated memories may determine the extent to which new information might modify those memories. PMID:25709571

  1. Multi-voxel patterns of visual category representation during episodic encoding are predictive of subsequent memory

    PubMed Central

    Kuhl, Brice A.; Rissman, Jesse; Wagner, Anthony D.

    2012-01-01

    Successful encoding of episodic memories is thought to depend on contributions from prefrontal and temporal lobe structures. Neural processes that contribute to successful encoding have been extensively explored through univariate analyses of neuroimaging data that compare mean activity levels elicited during the encoding of events that are subsequently remembered vs. those subsequently forgotten. Here, we applied pattern classification to fMRI data to assess the degree to which distributed patterns of activity within prefrontal and temporal lobe structures elicited during the encoding of word-image pairs were diagnostic of the visual category (Face or Scene) of the encoded image. We then assessed whether representation of category information was predictive of subsequent memory. Classification analyses indicated that temporal lobe structures contained information robustly diagnostic of visual category. Information in prefrontal cortex was less diagnostic of visual category, but was nonetheless associated with highly reliable classifier-based evidence for category representation. Critically, trials associated with greater classifier-based estimates of category representation in temporal and prefrontal regions were associated with a higher probability of subsequent remembering. Finally, consideration of trial-by-trial variance in classifier-based measures of category representation revealed positive correlations between prefrontal and temporal lobe representations, with the strength of these correlations varying as a function of the category of image being encoded. Together, these results indicate that multi-voxel representations of encoded information can provide unique insights into how visual experiences are transformed into episodic memories. PMID:21925190

  2. Mild Cognitive Impairment Is Not “Mild” at All in Altered Activation of Episodic Memory Brain Networks: Evidence from ALE Meta-Analysis

    PubMed Central

    Wang, Pengyun; Li, Juan; Li, Hui-Jie; Huo, Lijuan; Li, Rui

    2016-01-01

    The present study conducted a quantitative meta-analysis aiming at assessing consensus across the functional neuroimaging studies of episodic memory in individuals with amnestic mild cognitive impairment (aMCI) and elucidating consistent activation patterns. An activation likelihood estimation (ALE) was conducted on the functional neuroimaging studies of episodic encoding and retrieval in aMCI individuals published up to March 31, 2015. Analyses covered 24 studies, which yielded 770 distinct foci. Compared to healthy controls, aMCI individuals showed statistically significant consistent activation differences in a widespread episodic memory network, not only in the bilateral medial temporal lobe and prefrontal cortex, but also in the angular gyrus, precunes, posterior cingulate cortex, and even certain more basic structures. The present ALE meta-analysis revealed that the abnormal patterns of widespread episodic memory network indicated that individuals with aMCI may not be completely “mild” in nature. PMID:27872591

  3. Bidirectional changes to hippocampal theta-gamma comodulation predict memory for recent spatial episodes.

    PubMed

    Shirvalkar, Prasad R; Rapp, Peter R; Shapiro, Matthew L

    2010-04-13

    Episodic memory requires the hippocampus, which is thought to bind cortical inputs into conjunctive codes. Local field potentials (LFPs) reflect dendritic and synaptic oscillations whose temporal structure may coordinate cellular mechanisms of plasticity and memory. We now report that single-trial spatial memory performance in rats was predicted by the power comodulation of theta (4-10 Hz) and low gamma (30-50 Hz) rhythms in the hippocampus. Theta-gamma comodulation (TGC) was prominent during successful memory retrieval but was weak when memory failed or was unavailable during spatial exploration in sample trials. Muscimol infusion into medial septum reduced the probability of TGC and successful memory retrieval. In contrast, patterned electrical stimulation of the fimbria-fornix increased TGC in amnestic animals and partially rescued memory performance in the water maze. The results suggest that TGC accompanies memory retrieval in the hippocampus and that patterned brain stimulation may inform therapeutic strategies for cognitive disorders.

  4. Cognitive dysfunction at baseline predicts symptomatic 1-year outcome in first-episode schizophrenics.

    PubMed

    Moritz, S; Krausz, M; Gottwalz, E; Lambert, M; Perro, C; Ganzer, S; Naber, D

    2000-01-01

    The present study addresses the consequences of cognitive disturbances on symptomatic outcome. Fifty-three first-episode schizophrenics were reassessed (n = 32) 1 year after admission. Simple regression analyses revealed that several self-perceived cognitive deficits at baseline as measured with the Frankfurt Complaint Questionnaire significantly predicted increased Brief Psychiatric Rating Scale global scores at follow-up (p = 0.05 to p = 0.005). A stepwise regression analysis proved memory dysfunction to be the strongest predictor of symptomatic worsening (p = 0.005). It is suggested that the exploration and treatment of neuropsychological deficits in schizophrenia is of great clinical importance with regard to its impact on both functional and symptomatic outcome in schizophrenia.

  5. The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment.

    PubMed

    Papma, Janne M; Smits, Marion; de Groot, Marius; Mattace Raso, Francesco U; van der Lugt, Aad; Vrooman, Henri A; Niessen, Wiro J; Koudstaal, Peter J; van Swieten, John C; van der Veen, Frederik M; Prins, Niels D

    2017-09-01

    Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer's disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the relationship between hippocampus function, volume and structural connectivity, and PCC activation during an episodic memory task-related fMRI study in mild cognitive impairment (MCI). MCI patients (n = 27) underwent episodic memory task-related fMRI, 3D-T1w MRI, 2D T2-FLAIR MRI and diffusion tensor imaging. Stepwise linear regression analysis was performed to examine the relationship between PCC activation and hippocampal activation, hippocampal volume and diffusion measures within the cingulum along the hippocampus. We found a significant relationship between PCC and hippocampus activation during successful episodic memory encoding and correct recognition in MCI patients. We found no relationship between the PCC and structural hippocampal predictors. Our results indicate a relationship between PCC and hippocampus activation during episodic memory engagement in MCI. This may suggest that during episodic memory, functional network deterioration is the most important predictor of PCC functioning in MCI. • PCC functioning during episodic memory relates to hippocampal functioning in MCI. • PCC functioning during episodic memory does not relate to hippocampal structure in MCI. • Functional network changes are an important predictor of PCC functioning in MCI.

  6. Cognitive Impairment Precedes and Predicts Functional Impairment in Mild Alzheimer’s Disease

    PubMed Central

    Liu-Seifert, Hong; Siemers, Eric; Price, Karen; Han, Baoguang; Selzler, Katherine J.; Henley, David; Sundell, Karen; Aisen, Paul; Cummings, Jeffrey; Raskin, Joel; Mohs, Richard

    2015-01-01

    Abstract Background: The temporal relationship of cognitive deficit and functional impairment in Alzheimer’s disease (AD) is not well characterized. Recent analyses suggest cognitive decline predicts subsequent functional decline throughout AD progression. Objective: To better understand the relationship between cognitive and functional decline in mild AD using autoregressive cross-lagged (ARCL) panel analyses in several clinical trials. Methods: Data included placebo patients with mild AD pooled from two multicenter, double-blind, Phase 3 solanezumab (EXPEDITION/2) or semagacestat (IDENTITY/2) studies, and from AD patients participating in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Cognitive and functional outcomes were assessed using AD Assessment Scale-Cognitive subscale (ADAS-Cog), AD Cooperative Study-Activities of Daily Living instrumental subscale (ADCS-iADL), or Functional Activities Questionnaire (FAQ), respectively. ARCL panel analyses evaluated relationships between cognitive and functional impairment over time. Results: In EXPEDITION, ARCL panel analyses demonstrated cognitive scores significantly predicted future functional impairment at 5 of 6 time points, while functional scores predicted subsequent cognitive scores in only 1 of 6 time points. Data from IDENTITY and ADNI programs yielded consistent results whereby cognition predicted subsequent function, but not vice-versa. Conclusions: Analyses from three databases indicated cognitive decline precedes and predicts subsequent functional decline in mild AD dementia, consistent with previously proposed hypotheses, and corroborate recent publications using similar methodologies. Cognitive impairment may be used as a predictor of future functional impairment in mild AD dementia and can be considered a critical target for prevention strategies to limit future functional decline in the dementia process. PMID:26402769

  7. Metacognitive functioning predicts positive and negative symptoms over 12 months in first episode psychosis.

    PubMed

    McLeod, Hamish J; Gumley, Andrew I; Macbeth, Angus; Schwannauer, Matthias; Lysaker, Paul H

    2014-07-01

    The negative symptoms of schizophrenia are a major source of impairment and distress but both pharmacological and psychological treatment options provide only modest benefit. Developing more effective psychological treatments for negative symptoms will require a more sophisticated understanding of the psychological processes that are implicated in their development and maintenance. We extended previous work by demonstrating that metacognitive functioning is related to negative symptom expression across the first 12 months of first episode psychosis (FEP). Previous studies in this area have either been cross-sectional or have used much older participants with long-standing symptoms. In this study, forty-five FEP participants were assessed three times over 12 months and provided data on PANSS rated symptoms, premorbid adjustment, metacognitive functioning, and DUP. Step-wise linear regression showed that adding metacognition scores to known predictors of negative symptoms (baseline symptom severity, gender, DUP, and premorbid academic and social adjustment) accounted for 62% of the variance in PANSS negative symptom scores at six months and 38% at 12 months. The same predictors also explained 47% of the variance in positive symptoms at both six and 12 months. However, exploration of the simple correlations between PANSS symptom scores and metacognition suggests a stronger univariate relationship between metacognition and negative symptoms. Overall, the results indicate that problems with mental state processing may be important determinants of negative symptom expression from the very early stages of psychosis. These results provide further evidence that metacognitive functioning is a potentially relevant target for psychological interventions.

  8. Hippocampal Volume Reduction in Humans Predicts Impaired Allocentric Spatial Memory in Virtual-Reality Navigation

    PubMed Central

    Dzieciol, Anna M.; Gadian, David G.; Jentschke, Sebastian; Doeller, Christian F.; Burgess, Neil; Mishkin, Mortimer

    2015-01-01

    The extent to which navigational spatial memory depends on hippocampal integrity in humans is not well documented. We investigated allocentric spatial recall using a virtual environment in a group of patients with severe hippocampal damage (SHD), a group of patients with “moderate” hippocampal damage (MHD), and a normal control group. Through four learning blocks with feedback, participants learned the target locations of four different objects in a circular arena. Distal cues were present throughout the experiment to provide orientation. A circular boundary as well as an intra-arena landmark provided spatial reference frames. During a subsequent test phase, recall of all four objects was tested with only the boundary or the landmark being present. Patients with SHD were impaired in both phases of this task. Across groups, performance on both types of spatial recall was highly correlated with memory quotient (MQ), but not with intelligence quotient (IQ), age, or sex. However, both measures of spatial recall separated experimental groups beyond what would be expected based on MQ, a widely used measure of general memory function. Boundary-based and landmark-based spatial recall were both strongly related to bilateral hippocampal volumes, but not to volumes of the thalamus, putamen, pallidum, nucleus accumbens, or caudate nucleus. The results show that boundary-based and landmark-based allocentric spatial recall are similarly impaired in patients with SHD, that both types of recall are impaired beyond that predicted by MQ, and that recall deficits are best explained by a reduction in bilateral hippocampal volumes. SIGNIFICANCE STATEMENT In humans, bilateral hippocampal atrophy can lead to profound impairments in episodic memory. Across species, perhaps the most well-established contribution of the hippocampus to memory is not to episodic memory generally but to allocentric spatial memory. However, the extent to which navigational spatial memory depends on

  9. Hippocampal Volume Reduction in Humans Predicts Impaired Allocentric Spatial Memory in Virtual-Reality Navigation.

    PubMed

    Guderian, Sebastian; Dzieciol, Anna M; Gadian, David G; Jentschke, Sebastian; Doeller, Christian F; Burgess, Neil; Mishkin, Mortimer; Vargha-Khadem, Faraneh

    2015-10-21

    The extent to which navigational spatial memory depends on hippocampal integrity in humans is not well documented. We investigated allocentric spatial recall using a virtual environment in a group of patients with severe hippocampal damage (SHD), a group of patients with "moderate" hippocampal damage (MHD), and a normal control group. Through four learning blocks with feedback, participants learned the target locations of four different objects in a circular arena. Distal cues were present throughout the experiment to provide orientation. A circular boundary as well as an intra-arena landmark provided spatial reference frames. During a subsequent test phase, recall of all four objects was tested with only the boundary or the landmark being present. Patients with SHD were impaired in both phases of this task. Across groups, performance on both types of spatial recall was highly correlated with memory quotient (MQ), but not with intelligence quotient (IQ), age, or sex. However, both measures of spatial recall separated experimental groups beyond what would be expected based on MQ, a widely used measure of general memory function. Boundary-based and landmark-based spatial recall were both strongly related to bilateral hippocampal volumes, but not to volumes of the thalamus, putamen, pallidum, nucleus accumbens, or caudate nucleus. The results show that boundary-based and landmark-based allocentric spatial recall are similarly impaired in patients with SHD, that both types of recall are impaired beyond that predicted by MQ, and that recall deficits are best explained by a reduction in bilateral hippocampal volumes. In humans, bilateral hippocampal atrophy can lead to profound impairments in episodic memory. Across species, perhaps the most well-established contribution of the hippocampus to memory is not to episodic memory generally but to allocentric spatial memory. However, the extent to which navigational spatial memory depends on hippocampal integrity in humans is

  10. Understanding the importance of episodic acidification on fish predator-prey interactions: does weak acidification impair predator recognition?

    PubMed

    Brown, Grant E; Elvidge, Chris K; Ferrari, Maud C O; Chivers, Douglas P

    2012-11-15

    The ability of prey to recognize predators is a fundamental prerequisite to avoid being eaten. Indeed, many prey animals learn to distinguish species that pose a threat from those that do not. Once the prey has learned the identity of one predator, it may generalize this recognition to similar predators with which the prey has no experience. The ability to generalize reduces the costs associated with learning and further enhances the ability of the prey to avoid relevant threats. For many aquatic organisms, recognition of predators is based on odor signatures, consequently any anthropogenic alteration in water chemistry has the potential to impair recognition and learning of predators. Here we explored whether episodic acidification could influence the ability of juvenile rainbow trout to learn to recognize an unknown predator and then generalize this recognition to a closely related predator. Trout were conditioned to recognize the odor of pumpkinseed sunfish under circumneutral (~pH 7) conditions, and then tested for recognition of pumpkinseed or longear sunfish under both neutral or weakly acidic (~pH 6) conditions. When tested for a response to pumpkinseed odor, we found no significant effect of predator odor pH: trout responded similarly regardless of pH. Moreover, under neutral conditions, trout were able to generalize their recognition to the odor of longear sunfish. However, the trout could not generalize their recognition of the longear sunfish under acidic conditions. Given the widespread occurrence of anthropogenic acidification, acid-mediated impairment of predator recognition and generalization may be a pervasive problem for freshwater salmonid populations and other aquatic organisms. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Impacts of episodic acidification on in-stream survival and physiological impairment of Atlantic salmon (Salmo salar) smolts

    USGS Publications Warehouse

    McCormick, S.D.; Keyes, A.; Nislow, K.H.; Monette, M.Y.

    2009-01-01

    We conducted field studies to determine the levels of acid and aluminum (Al) that affect survival, smolt development, ion homeostasis, and stress in Atlantic salmon (Salmo salar) smolts in restoration streams of the Connecticut River in southern Vermont, USA. Fish were held in cages in five streams encompassing a wide range of acid and Al levels for two 6-day intervals during the peak of smolt development in late April and early May. Physiological parameters were unchanged from initial sampling at the hatchery and the high water quality reference site (pH > 7.0, inorganic Al < 12 μg·L-1). Mortality, substantial loss of plasma chloride, and gill Na+/K+-ATPase activity, and elevated gill Al occurred at sites with the lowest pH (5.4-5.6) and highest inorganic Al (50-80 μg·L-1). Moderate loss of plasma chloride, increased plasma cortisol and glucose, and moderately elevated gill Al occurred at less severely impacted sites. Gill Al was a better predictor of integrated physiological impacts than water chemistry alone. The results indicate that Al and low pH under field conditions in some New England streams can cause mortality and impair smolt development in juvenile Atlantic salmon and provide direct evidence that episodic acidification is impacting conservation and recovery of Atlantic salmon in the northeastern USA.

  12. Auditory evoked fields predict language ability and impairment in children.

    PubMed

    Oram Cardy, Janis E; Flagg, Elissa J; Roberts, Wendy; Roberts, Timothy P L

    2008-05-01

    Recent evidence suggests that a subgroup of children with autism show similarities to children with Specific Language Impairment (SLI) in the pattern of their linguistic impairments, but the source of this overlap is unclear. We examined the ability of auditory evoked magnetic fields to predict language and other developmental abilities in children and adolescents. Following standardized assessment of language ability, nonverbal IQ, and autism-associated behaviors, 110 trails of a tone were binaurally presented to 45 7-18 year olds who had typical development, autism (with LI), Asperger Syndrome (i.e., without LI), or SLI. Using a 151-channel MEG system, latency of left hemisphere (LH) and right hemisphere (RH) auditory M50 and M100 peaks was recorded. RH M50 latency (and to a lesser extent, RH M100 latency) predicted overall oral language ability, accounting for 36% of the variance. Nonverbal IQ and autism behavior ratings were not predicted by any of the evoked fields. Latency of the RH M50 was the best predictor of clinical LI (i.e., irrespective of autism diagnosis), and demonstrated 82% accuracy in predicting Receptive LI; a cutoff of 84.6 ms achieved 92% specificity and 70% sensitivity in classifying children with and without Receptive LI. Auditory evoked responses appear to reflect language functioning and impairment rather than non-specific brain (dys)function (e.g., IQ, behavior). RH M50 latency proved to be a relatively useful indicator of impaired language comprehension, suggesting that delayed auditory perceptual processing in the RH may be a key neural dysfunction underlying the overlap between subgroups of children with autism and SLI.

  13. Sleep architecture as correlate and predictor of symptoms and impairment in inter-episode bipolar disorder: taking on the challenge of medication effects.

    PubMed

    Eidelman, Polina; Talbot, Lisa S; Gruber, June; Hairston, Ilana; Harvey, Allison G

    2010-12-01

    This study was designed to clarify the association between inter-episode bipolar disorder (BD) and sleep architecture. Participants completed a baseline symptom and sleep assessment and, 3 months later, an assessment of symptoms and impairment. The effects of psychiatric medications on sleep architecture were also considered. Participants included 22 adults with BD I or II (inter-episode) and 22 non-psychiatric controls. The sleep assessment was conducted at the Sleep and Psychological Disorders Laboratory at the University of California, Berkeley. Follow-up assessments 3 months later were conducted over the phone. Results indicate that, at the sleep assessment, BD participants exhibited greater rapid eye movement sleep (REM) density than control participants with no other group differences in sleep architecture. Sleep architecture was not correlated with concurrent mood symptoms in either group. In the BD group, duration of the first REM period and slow-wave sleep (SWS) amount were positively correlated with manic symptoms and impairment at 3 months, while REM density was positively correlated with depressive symptoms and impairment at 3 months. The amount of Stage 2 sleep was negatively correlated with manic symptoms and impairment at 3 months. In contrast, for the control group, REM density was negatively correlated with impairment at 3 months. SWS and Stage 2 sleep were not correlated with symptoms or impairment. Study findings suggest that inter-episode REM sleep, SWS and Stage 2 sleep are correlated with future manic and depressive symptoms and impairment in BD. This is consistent with the proposition that sleep architecture may be a mechanism of illness maintenance in BD.

  14. Sleep Architecture as Correlate and Predictor of Symptoms and Impairment in Inter-episode Bipolar Disorder: Taking on the Challenge of Medication Effects

    PubMed Central

    Eidelman, Polina; Talbot, Lisa S.; Gruber, June; Hairston, Ilana; Harvey, Allison G.

    2010-01-01

    This study was designed to clarify the association between inter-episode bipolar disorder and sleep architecture. Participants completed a baseline symptom and sleep assessment and, 3 months later, an assessment of symptoms and impairment. The effects of psychiatric medications on sleep architecture were also considered. Participants included 22 adults with bipolar I or II (inter-episode) and 22 non-psychiatric controls. The sleep assessment was conducted at the Sleep and Psychological Disorders Laboratory at the University of California, Berkeley. Follow-up assessments 3 months later were conducted over the phone. Results indicate that, at the sleep assessment, bipolar participants exhibited greater REM density than control participants with no other group differences in sleep architecture. Sleep architecture was not correlated with concurrent mood symptoms in either group. In the bipolar group, duration of the first REM period and Slow Wave Sleep (SWS) amount were positively correlated with manic symptoms and impairment at 3 months, while REM density was positively correlated with depressive symptoms and impairment at 3 months. The amount of Stage 2 sleep was negatively correlated with manic symptoms and impairment at 3 months. In contrast, for the control group, REM density was negatively correlated with impairment at 3 months. SWS and Stage 2 sleep were not correlated with symptoms or impairment. Study findings suggest that inter-episode REM sleep, SWS and Stage 2 sleep are correlated with future manic and depressive symptoms and impairment in bipolar disorder. This is consistent with the proposition that sleep architecture may be a mechanism of illness maintenance in bipolar disorder. PMID:20408930

  15. Can Recurrence After an Acute Episode of Low Back Pain Be Predicted?

    PubMed

    Machado, Gustavo C; Maher, Chris G; Ferreira, Paulo H; Latimer, Jane; Koes, Bart W; Steffens, Daniel; Ferreira, Manuela L

    2017-09-01

    Although recurrence is common after an acute episode of low back pain, estimates of recurrence rates vary widely and predictors of recurrence remain largely unknown. The purposes of the study were to determine the 1-year incidence of recurrence in participants who recovered from an acute episode of low back pain and to identify predictors of recurrence. The design was an inception cohort study nested in a case-crossover study. For 12 months, 832 of the 999 participants who initially presented to primary care within the first 7 days of an episode of low back pain were followed. Of these participants, 469 recovered (1 month pain free) from the index episode within 6 weeks and were included in this study. Recurrence was defined as a new episode lasting more than 1 day, or as an episode of care seeking. Putative predictors were assessed at baseline and chosen a priori. Multivariable regression analysis was used to calculate odds ratios (OR) and 95% confidence intervals (CI). The 1-year incidence of recurrence of low back pain was 33%, and the 1-year incidence of recurrence of low back pain with care seeking was 18%. Participants reporting more than 2 previous episodes of low back pain had increased odds of future recurrences (OR = 3.18, CI = 2.11-4.78). This factor was also associated with recurrent episodes that led to care seeking (OR = 2.87, CI = 1.73-4.78). No other factors were associated with recurrences. There are limitations inherent in reliance on recall. After an acute episode of low back pain, one-third of patients will experience a recurrent episode, and approximately half of those will seek care. Experiencing more than 2 previous episodes of low back pain triples the odds of a recurrence within 1 year.

  16. Atrial high-rate episodes predict clinical outcome in patients with cardiac resynchronization therapy.

    PubMed

    Jacobsson, Jonatan; Platonov, Pyotr G; Reitan, Christian; Carlsson, Jonas; Borgquist, Rasmus

    2017-04-01

    Up to 50% of patients qualified for cardiac resynchronization therapy (CRT) have documented atrial fibrillation (AF) prior to CRT-implantation. This finding is associated with worse prognosis but few studies have evaluated the importance of post-implant device-detected AF. This study aimed to assess the prognostic impact of device-detected atrial high-rate episodes (AHRE), as a surrogate for AF. Data were retrospectively obtained from consecutive patients receiving CRT. Baseline clinical data and data from CRT device-interrogations, performed at a median of 12.2 months after CRT-implantation, were evaluated with regard to prediction of the composite endpoint of death, heart transplant or appropriate shock therapy. Median follow-up time was 51 months post-implant. The study included 377 patients. Preoperative AF was present in 49% and associated with worse outcome. The cumulative burden of AHRE at 12 months post-implant was an independent predictor of the primary endpoint. During the first 12 months after CRT-implantation, AHRE were detected in 25% of the patients with no preoperative diagnosis of AF. This finding was not associated with worse outcome. In CRT recipients, the cumulative burden of AHRE during the first year of follow-up was associated with worse long-term clinical outcome. Prospective trials are needed to determine if a rhythm control strategy is to be preferred in patients with CRT.

  17. An Examination of Polygenic Score Risk Prediction in Individuals With First-Episode Psychosis.

    PubMed

    Vassos, Evangelos; Di Forti, Marta; Coleman, Jonathan; Iyegbe, Conrad; Prata, Diana; Euesden, Jack; O'Reilly, Paul; Curtis, Charles; Kolliakou, Anna; Patel, Hamel; Newhouse, Stephen; Traylor, Matthew; Ajnakina, Olesya; Mondelli, Valeria; Marques, Tiago Reis; Gardner-Sood, Poonam; Aitchison, Katherine J; Powell, John; Atakan, Zerrin; Greenwood, Kathryn E; Smith, Shubulade; Ismail, Khalida; Pariante, Carmine; Gaughran, Fiona; Dazzan, Paola; Markus, Hugh S; David, Anthony S; Lewis, Cathryn M; Murray, Robin M; Breen, Gerome

    2017-03-15

    Polygenic risk scores (PRSs) have successfully summarized genome-wide effects of genetic variants in schizophrenia with significant predictive power. In a clinical sample of first-episode psychosis (FEP) patients, we estimated the ability of PRSs to discriminate case-control status and to predict the development of schizophrenia as opposed to other psychoses. The sample (445 case and 265 control subjects) was genotyped on the Illumina HumanCore Exome BeadChip with an additional 828 control subjects of African ancestry genotyped on the Illumina Multi-Ethnic Genotyping Array. To calculate PRSs, we used the results from the latest Psychiatric Genomics Consortium schizophrenia meta-analysis. We examined the association of PRSs with case-control status and with schizophrenia versus other psychoses in European and African ancestry FEP patients and in a second sample of 248 case subjects with chronic psychosis. PRS had good discriminative ability of case-control status in FEP European ancestry individuals (9.4% of the variance explained, p < 10(-6)), but lower in individuals of African ancestry (R(2) = 1.1%, p = .004). Furthermore, PRS distinguished European ancestry case subjects who went on to acquire a schizophrenia diagnosis from those who developed other psychotic disorders (R(2) = 9.2%, p = .002). PRS was a powerful predictor of case-control status in a European sample of patients with FEP, even though a large proportion did not have an established diagnosis of schizophrenia at the time of assessment. PRS was significantly different between those case subjects who developed schizophrenia from those who did not, although the discriminative accuracy may not yet be sufficient for clinical utility in FEP. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  18. Within-person Changes in Individual Symptoms of Depression Predict Subsequent Depressive Episodes in Adolescents: A Prospective Study

    PubMed Central

    Kouros, Chrystyna D.; Morris, Matthew C.; Garber, Judy

    2015-01-01

    The current longitudinal study examined which individual symptoms of depression uniquely predicted a subsequent Major Depressive Episode (MDE) in adolescents, and whether these relations differed by sex. Adolescents (N=240) were first interviewed in grade 6 (M=11.86 years old; SD = 0.56; 54% female; 81.5% Caucasian) and then annually through grade 12 regarding their individual symptoms of depression as well as the occurrence of MDEs. Individual symptoms of depression were assessed with the Children’s Depression Rating Scale-Revised (CDRS-R) and depressive episodes were assessed with the Longitudinal Interval Follow-up Evaluation (LIFE). Results showed that within-person changes in sleep problems and low self-esteem/excessive guilt positively predicted an increased likelihood of an MDE for both boys and girls. Significant sex differences also were found. Within-person changes in anhedonia predicted an increased likelihood of a subsequent MDE among boys, whereas irritability predicted a decreased likelihood of a future MDE among boys, and concentration difficulties predicted a decreased likelihood of an MDE in girls. These results identified individual depressive symptoms that predicted subsequent depressive episodes in male and female adolescents, and may be used to guide the early detection, treatment, and prevention of depressive disorders in youth. PMID:26105209

  19. Interpersonal predictive coding, not action perception, is impaired in autism

    PubMed Central

    von der Lühe, T.; Manera, V.; Barisic, I.; Becchio, C.; Vogeley, K.

    2016-01-01

    This study was conducted to examine interpersonal predictive coding in individuals with high-functioning autism (HFA). Healthy and HFA participants observed point-light displays of two agents (A and B) performing separate actions. In the ‘communicative’ condition, the action performed by agent B responded to a communicative gesture performed by agent A. In the ‘individual’ condition, agent A's communicative action was substituted by a non-communicative action. Using a simultaneous masking-detection task, we demonstrate that observing agent A's communicative gesture enhanced visual discrimination of agent B for healthy controls, but not for participants with HFA. These results were not explained by differences in attentional factors as measured via eye-tracking, or by differences in the recognition of the point-light actions employed. Our findings, therefore, suggest that individuals with HFA are impaired in the use of social information to predict others' actions and provide behavioural evidence that such deficits could be closely related to impairments of predictive coding. PMID:27069050

  20. Learning temporal statistics for sensory predictions in mild cognitive impairment.

    PubMed

    Di Bernardi Luft, Caroline; Baker, Rosalind; Bentham, Peter; Kourtzi, Zoe

    2015-08-01

    Training is known to improve performance in a variety of perceptual and cognitive skills. However, there is accumulating evidence that mere exposure (i.e. without supervised training) to regularities (i.e. patterns that co-occur in the environment) facilitates our ability to learn contingencies that allow us to interpret the current scene and make predictions about future events. Recent neuroimaging studies have implicated fronto-striatal and medial temporal lobe brain regions in the learning of spatial and temporal statistics. Here, we ask whether patients with mild cognitive impairment due to Alzheimer's disease (MCI-AD) that are characterized by hippocampal dysfunction are able to learn temporal regularities and predict upcoming events. We tested the ability of MCI-AD patients and age-matched controls to predict the orientation of a test stimulus following exposure to sequences of leftwards or rightwards orientated gratings. Our results demonstrate that exposure to temporal sequences without feedback facilitates the ability to predict an upcoming stimulus in both MCI-AD patients and controls. However, our fMRI results demonstrate that MCI-AD patients recruit an alternate circuit to hippocampus to succeed in learning of predictive structures. In particular, we observed stronger learning-dependent activations for structured sequences in frontal, subcortical and cerebellar regions for patients compared to age-matched controls. Thus, our findings suggest a cortico-striatal-cerebellar network that may mediate the ability for predictive learning despite hippocampal dysfunction in MCI-AD.

  1. Social cognition in schizophrenia, Part 2: 12-month stability and prediction of functional outcome in first-episode patients.

    PubMed

    Horan, William P; Green, Michael F; DeGroot, Michael; Fiske, Alan; Hellemann, Gerhard; Kee, Kimmy; Kern, Robert S; Lee, Junghee; Sergi, Mark J; Subotnik, Kenneth L; Sugar, Catherine A; Ventura, Joseph; Nuechterlein, Keith H

    2012-06-01

    This study evaluated the longitudinal stability and functional correlates of social cognition during the early course of schizophrenia. Fifty-five first-episode schizophrenia patients completed baseline and 12-month follow-up assessments of 3 key domains of social cognition (emotional processing, theory of mind, and social/relationship perception), as well as clinical ratings of real-world functioning and symptoms. Scores on all 3 social cognitive tests demonstrated good longitudinal stability with test-retest correlations exceeding .70. Higher baseline and 12-month social cognition scores were both robustly associated with significantly better work functioning, independent living, and social functioning at the 12-month follow-up assessment. Furthermore, cross-lagged panel analyses were consistent with a causal model in which baseline social cognition drove later functional outcome in the domain of work, above and beyond the contribution of symptoms. Social cognitive impairments are relatively stable, functionally relevant features of early schizophrenia. These results extend findings from a companion study, which showed stable impairments across patients in prodromal, first-episode, and chronic phases of illness on the same measures. Social cognitive impairments may serve as useful vulnerability indicators and early clinical intervention targets.

  2. Predicting the onset and persistence of episodes of depression in primary health care. The predictD-Spain study: Methodology

    PubMed Central

    Bellón, Juan Ángel; Moreno-Küstner, Berta; Torres-González, Francisco; Montón-Franco, Carmen; GildeGómez-Barragán, María Josefa; Sánchez-Celaya, Marta; Díaz-Barreiros, Miguel Ángel; Vicens, Catalina; de Dios Luna, Juan; Cervilla, Jorge A; Gutierrez, Blanca; Martínez-Cañavate, María Teresa; Oliván-Blázquez, Bárbara; Vázquez-Medrano, Ana; Sánchez-Artiaga, María Soledad; March, Sebastia; Motrico, Emma; Ruiz-García, Victor Manuel; Brangier-Wainberg, Paulette Renée; del Mar Muñoz-García, María; Nazareth, Irwin; King, Michael

    2008-01-01

    Background The effects of putative risk factors on the onset and/or persistence of depression remain unclear. We aim to develop comprehensive models to predict the onset and persistence of episodes of depression in primary care. Here we explain the general methodology of the predictD-Spain study and evaluate the reliability of the questionnaires used. Methods This is a prospective cohort study. A systematic random sample of general practice attendees aged 18 to 75 has been recruited in seven Spanish provinces. Depression is being measured with the CIDI at baseline, and at 6, 12, 24 and 36 months. A set of individual, environmental, genetic, professional and organizational risk factors are to be assessed at each follow-up point. In a separate reliability study, a proportional random sample of 401 participants completed the test-retest (251 researcher-administered and 150 self-administered) between October 2005 and February 2006. We have also checked 118,398 items for data entry from a random sample of 480 patients stratified by province. Results All items and questionnaires had good test-retest reliability for both methods of administration, except for the use of recreational drugs over the previous six months. Cronbach's alphas were good and their factorial analyses coherent for the three scales evaluated (social support from family and friends, dissatisfaction with paid work, and dissatisfaction with unpaid work). There were 191 (0.16%) data entry errors. Conclusion The items and questionnaires were reliable and data quality control was excellent. When we eventually obtain our risk index for the onset and persistence of depression, we will be able to determine the individual risk of each patient evaluated in primary health care. PMID:18657275

  3. Prediction of P300 BCI Aptitude in Severe Motor Impairment

    PubMed Central

    Halder, Sebastian; Ruf, Carolin Anne; Furdea, Adrian; Pasqualotto, Emanuele; De Massari, Daniele; van der Heiden, Linda; Bogdan, Martin; Rosenstiel, Wolfgang; Birbaumer, Niels; Kübler, Andrea; Matuz, Tamara

    2013-01-01

    Brain-computer interfaces (BCIs) provide a non-muscular communication channel for persons with severe motor impairments. Previous studies have shown that the aptitude with which a BCI can be controlled varies from person to person. A reliable predictor of performance could facilitate selection of a suitable BCI paradigm. Eleven severely motor impaired participants performed three sessions of a P300 BCI web browsing task. Before each session auditory oddball data were collected to predict the BCI aptitude of the participants exhibited in the current session. We found a strong relationship of early positive and negative potentials around 200 ms (elicited with the auditory oddball task) with performance. The amplitude of the P2 (r  =  −0.77) and of the N2 (r  =  −0.86) had the strongest correlations. Aptitude prediction using an auditory oddball was successful. The finding that the N2 amplitude is a stronger predictor of performance than P3 amplitude was reproduced after initially showing this effect with a healthy sample of BCI users. This will reduce strain on the end-users by minimizing the time needed to find suitable paradigms and inspire new approaches to improve performance. PMID:24204597

  4. Evidence for Trait Related Theory of Mind Impairment in First Episode Psychosis Patients and Its Relationship with Processing Speed: A 3 Year Follow-up Study.

    PubMed

    Ayesa-Arriola, Rosa; Setién-Suero, Esther; Neergaard, Karl D; Ferro, Adele; Fatjó-Vilas, Mar; Ríos-Lago, Marcos; Otero, Soraya; Rodríguez-Sánchez, Jose M; Crespo-Facorro, Benedicto

    2016-01-01

    This study aimed to confirm whether first-episode psychosis patients present a stable trait impairment in theory of mind (ToM) and to examine the potential relationship between ToM and clinical symptomatology and neurocognition. Patients with a first episode of psychosis (N = 160) and healthy controls (N = 159) were assessed with an extensive neuropsychological test battery, which included a mental state decoding task known as "The Reading the Mind in the Eyes" (Eyes test), at baseline and reassessed after 1 and 3 years. The clinical group performed below healthy controls on the Eyes test while not showing test-retest differences between baseline and follow-up administrations. Analyses revealed age, education and premorbid IQ as potential moderators. Poorer performance on the Eyes test was not linked to clinical symptomatology but was associated with greater neurocognitive deficit, particularly related to processing speed. The persistence of ToM deficits in patients suggests that there are trait related metalizing impairments in first episode psychosis. This study shows the influence of processing speed and moderator variables on efficient ToM.

  5. Evidence for Trait Related Theory of Mind Impairment in First Episode Psychosis Patients and Its Relationship with Processing Speed: A 3 Year Follow-up Study

    PubMed Central

    Ayesa-Arriola, Rosa; Setién-Suero, Esther; Neergaard, Karl D.; Ferro, Adele; Fatjó-Vilas, Mar; Ríos-Lago, Marcos; Otero, Soraya; Rodríguez-Sánchez, Jose M.; Crespo-Facorro, Benedicto

    2016-01-01

    This study aimed to confirm whether first-episode psychosis patients present a stable trait impairment in theory of mind (ToM) and to examine the potential relationship between ToM and clinical symptomatology and neurocognition. Patients with a first episode of psychosis (N = 160) and healthy controls (N = 159) were assessed with an extensive neuropsychological test battery, which included a mental state decoding task known as “The Reading the Mind in the Eyes” (Eyes test), at baseline and reassessed after 1 and 3 years. The clinical group performed below healthy controls on the Eyes test while not showing test-retest differences between baseline and follow-up administrations. Analyses revealed age, education and premorbid IQ as potential moderators. Poorer performance on the Eyes test was not linked to clinical symptomatology but was associated with greater neurocognitive deficit, particularly related to processing speed. The persistence of ToM deficits in patients suggests that there are trait related metalizing impairments in first episode psychosis. This study shows the influence of processing speed and moderator variables on efficient ToM. PMID:27199826

  6. Impact of avolition and cognitive impairment on functional outcome in first-episode schizophrenia-spectrum disorder: a prospective one-year follow-up study.

    PubMed

    Chang, Wing Chung; Hui, Christy Lai Ming; Chan, Sherry Kit Wa; Lee, Edwin Ho Ming; Chen, Eric Yu Hai

    2016-02-01

    Previous research investigating the relationships between avolition, cognition and functioning in schizophrenia mostly focused on chronic samples and were cross-sectional in design. Impacts of avolition and cognition on longitudinal functional outcome in first-episode patients are under-studied. We assessed 114 Chinese aged 18-55 years presenting with first-episode schizophrenia-spectrum disorder aiming to identify baseline predictors of 1-year functional outcome. Results showed that both avolition and global cognition independently predicted functioning, with avolition being the strongest predictor above and beyond cognition and other symptom dimensions. Our findings indicate the central role of in determining longitudinal functional status in the early illness stage.

  7. Episodic Memory Does Not Add Up: Verbatim-Gist Superposition Predicts Violations of the Additive Law of Probability

    PubMed Central

    Brainerd, C. J.; Wang, Zheng; Reyna, Valerie. F.; Nakamura, K.

    2015-01-01

    Fuzzy-trace theory’s assumptions about memory representation are cognitive examples of the familiar superposition property of physical quantum systems. When those assumptions are implemented in a formal quantum model (QEMc), they predict that episodic memory will violate the additive law of probability: If memory is tested for a partition of an item’s possible episodic states, the individual probabilities of remembering the item as belonging to each state must sum to more than 1. We detected this phenomenon using two standard designs, item false memory and source false memory. The quantum implementation of fuzzy-trace theory also predicts that violations of the additive law will vary in strength as a function of reliance on gist memory. That prediction, too, was confirmed via a series of manipulations (e.g., semantic relatedness, testing delay) that are thought to increase gist reliance. Surprisingly, an analysis of the underlying structure of violations of the additive law revealed that as a general rule, increases in remembering correct episodic states do not produce commensurate reductions in remembering incorrect states. PMID:26236091

  8. Mucosal host immune response predicts the severity and duration of herpes simplex virus-2 genital tract shedding episodes

    PubMed Central

    Schiffer, Joshua T.; Abu-Raddad, Laith; Mark, Karen E.; Zhu, Jia; Selke, Stacy; Koelle, David M.; Wald, Anna; Corey, Lawrence

    2010-01-01

    Herpes simplex virus-2 (HSV-2) shedding episodes in humans vary markedly in duration and virologic titer within an infected person over time, an observation that is unexplained. To evaluate whether host or virological factors more closely accounted for this variability, we combined measures of viral replication and CD8+ lymphocyte density in genital biopsies, with a stochastic mathematical model of HSV-2 infection. Model simulations reproduced quantities of virus and duration of shedding detected in 1,003 episodes among 386 persons. In the simulations, local CD8+ lymphocyte density in the mucosa at episode onset predicted peak HSV DNA copy number and whether genital lesions or subclinical shedding occurred. High density of CD8+ T cells in the mucosa correlated with decreased infected cell lifespan and fewer infected epithelial cells before episode clearance. If infected cell lifespan increased by 15 min because of CD8+ lymphocyte decay, then there was potential for a thousandfold increase in the number of infected cells. The model suggests that the rate of containment of infected cells by the peripheral mucosal immune system is the major driver of duration and severity of HSV-2 reactivation in the immunocompetent host. PMID:20956313

  9. Impaired predictive motor timing in patients with cerebellar disorders.

    PubMed

    Bares, Martin; Lungu, Ovidiu; Liu, Tao; Waechter, Tobias; Gomez, Christopher M; Ashe, James

    2007-06-01

    The ability to precisely time events is essential for both perception and action. There is evidence that the cerebellum is important for the neural representation of time in a variety of behaviors including time perception, the tapping of specific time intervals, and eye-blink conditioning. It has been difficult to assess the contribution of the cerebellum to timing during more dynamic motor behavior because the component movements themselves may be abnormal or any motor deficit may be due to an inability to combine the component movements into a complete action rather than timing per se. Here we investigated the performance of subjects with cerebellar disease in predictive motor timing using a task that involved mediated interception of a moving target, and we tested the effect of movement type (acceleration, deceleration, constant), speed (slow, medium, fast), and angle (0 degrees , 15 degrees and 30 degrees) on performance. The subjects with cerebellar damage were significantly worse at interception than healthy controls even when we controlled for basic motor impairments such as response time. Our data suggest that subjects with damage to the cerebellum have a fundamental problem with predictive motor timing and indicate that the cerebellum plays an essential role in integrating incoming visual information with motor output when making predictions about upcoming actions. The findings demonstrate that the cerebellum may have properties that would facilitate the processing or storage of internal models of motor behavior.

  10. Prediction of dementia by subjective memory impairment: effects of severity and temporal association with cognitive impairment.

    PubMed

    Jessen, Frank; Wiese, Birgitt; Bachmann, Cadja; Eifflaender-Gorfer, Sandra; Haller, Franziska; Kölsch, Heike; Luck, Tobias; Mösch, Edelgard; van den Bussche, Hendrik; Wagner, Michael; Wollny, Anja; Zimmermann, Thomas; Pentzek, Michael; Riedel-Heller, Steffi G; Romberg, Heinz-Peter; Weyerer, Siegfried; Kaduszkiewicz, Hanna; Maier, Wolfgang; Bickel, Horst

    2010-04-01

    Subjective memory impairment (SMI) is receiving increasing attention as a pre-mild cognitive impairment (MCI) condition in the course of the clinical manifestation of Alzheimer disease (AD). To determine the risk for conversion to any dementia, dementia in AD, or vascular dementia by SMI, graded by the level of SMI-related worry and by the temporal association of SMI and subsequent MCI. Longitudinal cohort study with follow-up examinations at 1(1/2) and 3 years after baseline. Primary care medical record registry sample. A total of 2415 subjects without cognitive impairment 75 years or older in the German Study on Aging, Cognition and Dementia in Primary Care Patients. Conversion to any dementia, dementia in AD, or vascular dementia at follow-up 1 or follow-up 2 predicted by SMI with or without worry at baseline and at follow-up 2 predicted by different courses of SMI at baseline and MCI at follow-up 1. In the first analysis, SMI with worry at baseline was associated with greatest risk for conversion to any dementia (hazard ratio [HR], 3.53; 95% confidence interval [CI], 2.07-6.03) or dementia in AD (6.54; 2.82-15.20) at follow-up 1 or follow-up 2. The sensitivity was 69.0% and the specificity was 74.3% conversion to dementia in AD. In the second analysis, SMI at baseline and MCI at follow-up 1 were associated with greatest risk for conversion to any dementia (odds ratio [OR], 8.92; 95% CI, 3.69-21.60) or dementia in AD (19.33; 5.29-70.81) at follow-up 2. Furthermore, SMI at baseline and amnestic MCI at follow-up 1 increased the risk for conversion to any dementia (OR, 29.24; 95% CI, 8.75-97.78) or dementia in AD (60.28; 12.23-297.10), with a sensitivity of 66.7% and a specificity of 98.3% for conversion to dementia in AD. The prediction of dementia in AD by SMI with subsequent amnestic MCI supports the model of a consecutive 3-stage clinical manifestation of AD from SMI via MCI to dementia.

  11. Why Am I Remembering This Now? Predicting the Occurrence of Involuntary (Spontaneous) Episodic Memories

    ERIC Educational Resources Information Center

    Berntsen, Dorthe; Staugaard, Soren Rislov; Sorensen, Louise Maria Torp

    2013-01-01

    Involuntary episodic memories are memories of events that come to mind spontaneously, that is, with no preceding retrieval attempts. They are common in daily life and observed in a range of clinical disorders in the form of negative, intrusive recollections or flashbacks. However, little is known about their underlying mechanisms. Here we report a…

  12. Why Am I Remembering This Now? Predicting the Occurrence of Involuntary (Spontaneous) Episodic Memories

    ERIC Educational Resources Information Center

    Berntsen, Dorthe; Staugaard, Soren Rislov; Sorensen, Louise Maria Torp

    2013-01-01

    Involuntary episodic memories are memories of events that come to mind spontaneously, that is, with no preceding retrieval attempts. They are common in daily life and observed in a range of clinical disorders in the form of negative, intrusive recollections or flashbacks. However, little is known about their underlying mechanisms. Here we report a…

  13. Are All Judgments Created Equal? An fMRI Study of Semantic and Episodic Metamemory Predictions

    ERIC Educational Resources Information Center

    Reggev, Niv; Zuckerman, Maya; Maril, Anat

    2011-01-01

    Metamemory refers to the ability of individuals to monitor and control their own memory performance. Although little theoretical consideration of the possible differences between the monitoring of episodic and of semantic knowledge has been published, results from patient and drug studies that used the "feeling of knowing" (FOK) paradigm show a…

  14. Are All Judgments Created Equal? An fMRI Study of Semantic and Episodic Metamemory Predictions

    ERIC Educational Resources Information Center

    Reggev, Niv; Zuckerman, Maya; Maril, Anat

    2011-01-01

    Metamemory refers to the ability of individuals to monitor and control their own memory performance. Although little theoretical consideration of the possible differences between the monitoring of episodic and of semantic knowledge has been published, results from patient and drug studies that used the "feeling of knowing" (FOK) paradigm show a…

  15. Predicting Conversion from Mild Cognitive Impairment to Alzheimer’s Disease Using Neuropsychological Tests and Multivariate Methods

    PubMed Central

    Chapman, Robert M.; Mapstone, Mark; McCrary, John W.; Gardner, Margaret N.; Porsteinsson, Anton; Sandoval, Tiffany C.; Guillily, Maria D.; DeGrush, Elizabeth; Reilly, Lindsey A.

    2011-01-01

    Behavioral markers measured through neuropsychological testing in Mild Cognitive Impairment (MCI) were analyzed and combined in multivariate ways to predict conversion to Alzheimer’s disease (AD) in a longitudinal study of 43 MCI patients. The test measures taken at a baseline evaluation were first reduced to underlying components (Principal Components Analysis, PCA) and then the component scores were used in discriminant analysis to classify MCI individuals as likely to convert or not. When empirically weighted and combined, episodic memory, speeded executive functioning, recognition memory (false and true positives), visuospatial memory processing speed, and visuospatial episodic memory were together strong predictors of conversion to AD. These multivariate combinations of the test measures achieved through the PCA were good, statistically significant predictors of MCI conversion to AD (84% accuracy, 86% sensitivity, and 83% specificity). Importantly, the posterior probabilities of group membership that accompanied the binary prediction for each participant indicated the confidence of the prediction. Most of the subjects (81%) were in the highly confident probability bins (0.70 – 1.00), where the obtained prediction accuracy was more than 90%. The strength and reliability of this multivariate prediction method were tested by cross-validation and randomized resampling. PMID:20711906

  16. Predicting microbiologically defined infection in febrile neutropenic episodes in children: global individual participant data multivariable meta-analysis

    PubMed Central

    Phillips, Robert S; Sung, Lillian; Amman, Roland A; Riley, Richard D; Castagnola, Elio; Haeusler, Gabrielle M; Klaassen, Robert; Tissing, Wim J E; Lehrnbecher, Thomas; Chisholm, Julia; Hakim, Hana; Ranasinghe, Neil; Paesmans, Marianne; Hann, Ian M; Stewart, Lesley A

    2016-01-01

    Background: Risk-stratified management of fever with neutropenia (FN), allows intensive management of high-risk cases and early discharge of low-risk cases. No single, internationally validated, prediction model of the risk of adverse outcomes exists for children and young people. An individual patient data (IPD) meta-analysis was undertaken to devise one. Methods: The ‘Predicting Infectious Complications in Children with Cancer' (PICNICC) collaboration was formed by parent representatives, international clinical and methodological experts. Univariable and multivariable analyses, using random effects logistic regression, were undertaken to derive and internally validate a risk-prediction model for outcomes of episodes of FN based on clinical and laboratory data at presentation. Results: Data came from 22 different study groups from 15 countries, of 5127 episodes of FN in 3504 patients. There were 1070 episodes in 616 patients from seven studies available for multivariable analysis. Univariable analyses showed associations with microbiologically defined infection (MDI) in many items, including higher temperature, lower white cell counts and acute myeloid leukaemia, but not age. Patients with osteosarcoma/Ewings sarcoma and those with more severe mucositis were associated with a decreased risk of MDI. The predictive model included: malignancy type, temperature, clinically ‘severely unwell', haemoglobin, white cell count and absolute monocyte count. It showed moderate discrimination (AUROC 0.723, 95% confidence interval 0.711–0.759) and good calibration (calibration slope 0.95). The model was robust to bootstrap and cross-validation sensitivity analyses. Conclusions: This new prediction model for risk of MDI appears accurate. It requires prospective studies assessing implementation to assist clinicians and parents/patients in individualised decision making. PMID:26954719

  17. Alcohol abstinence in patients surviving an episode of alcoholic hepatitis: Prediction and impact on long-term survival.

    PubMed

    Altamirano, José; López-Pelayo, Hugo; Michelena, Javier; Jones, Patricia D; Ortega, Lluisa; Ginès, Pere; Caballería, Juan; Gual, Antoni; Bataller, Ramón; Lligoña, Anna

    2017-06-23

    Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease. Most studies have focused on short-term prognosis, while factors associated with long-term survival are largely unknown. 1) to determine the impact of complete abstinence from alcohol on long-term survival and 2) to identify prognostic factors at admission capable of predicting abstinence during long-term follow-up in patients with AH. One hundred and forty-two patients with biopsy-proven AH that survived the first episode were included. Demographic, psychiatric and biochemical variables at admission and drinking status during follow-up were obtained. Cox regression, logistic regression and classification and regression trees (CART) analyses were used for statistical analysis. Overall mortality was 38% with a median follow-up of 55 months. During follow-up, complete abstinence was reported in 39% and was associated with better long-term survival (HR 0.53; p=0.03). After adjustment for baseline prognostic scoring systems (MELD and ABIC scores), complete abstinence was independently associated with survival (p<0.05). Age and lack of prior alcoholism treatments were independently associated with complete abstinence (p<0.001 and p=0.02, respectively) during follow-up. CART analysis generated a simple and practical algorithm based-on the combination of prior alcoholism treatments and age. Using CART analysis we stratified 2 subgroups of patients with high (65%) and low (26-29%) rates of complete abstinence after an episode of AH. Complete abstinence after an episode of AH positively impacts long-term survival. The combination of 2 variables easily obtained at admission might be useful to predict long-term abstinence after an episode of AH. Strategies aimed at promoting alcohol abstinence in these patients are mandatory. This article is protected by copyright. All rights reserved. © 2017 by the American Association for the Study of Liver Diseases.

  18. Early maladaptive schema-related impairment and co-occurring current major depressive episode-related enhancement of mental state decoding ability in borderline personality disorder.

    PubMed

    Unoka, Zsolt Szabolcs; Fogd, Dóra; Seres, Imola; Kéri, Szabolcs; Csukly, Gábor

    2015-04-01

    Disturbed interpersonal relationships specific to borderline personality disorder (BPD) suggest biased processing of social information. The goal of this study was to examine alterations in mental state decoding (MSD) and their associations with early maladaptive schemas (EMS) that may lead to the misinterpretation of incoming information. In addition, the authors' aim was to evaluate the effects of a co-occurring current major depressive episode (MDE) on the MSD performance of BPD patients. Seventy-eight BPD patients (34 with MDE) and 76 matched healthy controls (HC) were assessed for Reading the Mind in the Eyes Test (RMET) and the level of EMS. The authors found that impairment in the total RMET performance, as well as specific impairment regarding the recognition of positive and neutral items, was associated with EMS, and enhanced vigilance to negative mental states was characteristic to BPD with MDE. Results suggest that MSD ability is altered in two independent ways in BPD.

  19. Cognition and the prediction of functioning in patients with a first treated episode of psychosis: a prospective study.

    PubMed

    Norman, Ross M G; Carr, Jason; Manchanda, Rahul

    2015-03-01

    Past research on the role of cognitive performance in predicting later psychosocial functioning for individuals with first treated episode of a psychotic disorder has yielded inconsistent results. Several factors have been suggested as determining the strength of any such relationship including the type of functioning measured, time of the cognitive assessment, covariates included and the use of global versus specific measures of cognitive functioning. In the current study, we examined the importance of these factors in a five year prospective study of individuals with first episode psychotic disorders. Just over 80% of the sample had a schizophrenia spectrum disorder. Cognitive assessments were carried out after initiation of treatment on 113 patients, and at one year for 79 patients. There was evidence that cognition predicted occupational functioning and use of a disability pension, but not a summary index of functioning or use of supervised housing, at follow-up. Overall I.Q. was a more consistent predictor than measures of specific cognitive functions, and there was evidence that cognition assessed after presentation for treatment, particularly after a year of treatment, was more predictive of later functioning than premorbid I.Q. Cognitive functioning, however, did not add to the prediction of outcomes beyond the level possible using past educational achievement or academic premorbid adjustment.

  20. fMRI Activation Changes during Successful Episodic Memory Encoding and Recognition in Amnestic Mild Cognitive Impairment Relative to Cognitively Healthy Older Adults

    PubMed Central

    Trivedi, Mehul A.; Murphy, Christopher M.; Goetz, Celine; Shah, Raj C.; Gabrieli, John D.E.; Whitfield-Gabrieli, Susan; Turner, David A.; Stebbins, Glenn T.

    2009-01-01

    Background/Aims Previous functional MRI studies in individuals with amnestic mild cognitive impairment (AMCI), a putative, prodromal form of Alzheimer’s disease, reveal substantial regional changes in brain activation during episodic memory function. Methods Functional MRI was applied to examine changes in brain activation during different stages of episodic memory function using a subsequent memory task in individuals with AMCI relative to older normal controls. Results We found that the AMCI group displayed greater activation in the right hippocampus but less activation in the frontal cortex relative to the older normal control group during intentional encoding of items that were subsequently recognized. We observed nearly the opposite pattern of results for successful recognition. The AMCI group displayed less activation in the medial temporal cortex but greater activation in the frontal cortex. In addition, the AMCI group showed reduced activation in the medial temporal and frontal cortices during incidental encoding of novel information during recognition. Conclusion The results of the present study suggest that brain activation differences in individuals with AMCI are modulated by the stage of episodic memory examined (i.e. intentional vs. incidental encoding vs. recognition). These observations may help to clarify some of the conflicting findings regarding brain activation changes in AMCI. PMID:18663302

  1. Can artificial neural networks be used to predict the origin of ozone episodes?

    PubMed

    Fontes, T; Silva, L M; Silva, M P; Barros, N; Carvalho, A C

    2014-08-01

    Tropospheric ozone is a secondary pollutant having a negative impact on health and environment. To control and minimize such impact the European Community established regulations to promote a clean air all over Europe. However, when an episode is related with natural mechanisms as Stratosphere-Troposphere Exchanges (STE), the benefits of an action plan to minimize precursor emissions are inefficient. Therefore, this work aims to develop a tool to identify the sources of ozone episodes in order to minimize misclassification and thus avoid the implementation of inappropriate air quality plans. For this purpose, an artificial neural network model - the Multilayer Perceptron - is used as a binary classifier of the source of an ozone episode. Long data series, between 2001 and 2010, considering the ozone precursors, (7)Be activity and meteorological conditions were used. With this model, 2-7% of a mean error was achieved, which is considered as a good generalization. Accuracy measures for imbalanced data are also discussed. The MCC values show a good performance of the model (0.65-0.92). Precision and F1-measure indicate that the model specifies a little better the rare class. Thus, the results demonstrate that such a tool can be used to help authorities in the management of ozone, namely when its thresholds are exceeded due natural causes, as the above mentioned STE. Therefore, the resources used to implement an action plan to minimize ozone precursors could be better managed avoiding the implementation of inappropriate measures. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Grammar Predicts Procedural Learning and Consolidation Deficits in Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Hedenius, Martina; Persson, Jonas; Tremblay, Antoine; Adi-Japha, Esther; Verissimo, Joao; Dye, Cristina D.; Alm, Per; Jennische, Margareta; Tomblin, J. Bruce; Ullman, Michael T.

    2011-01-01

    The Procedural Deficit Hypothesis (PDH) posits that Specific Language Impairment (SLI) can be largely explained by abnormalities of brain structures that subserve procedural memory. The PDH predicts impairments of procedural memory itself, and that such impairments underlie the grammatical deficits observed in the disorder. Previous studies have…

  3. Grammar Predicts Procedural Learning and Consolidation Deficits in Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Hedenius, Martina; Persson, Jonas; Tremblay, Antoine; Adi-Japha, Esther; Verissimo, Joao; Dye, Cristina D.; Alm, Per; Jennische, Margareta; Tomblin, J. Bruce; Ullman, Michael T.

    2011-01-01

    The Procedural Deficit Hypothesis (PDH) posits that Specific Language Impairment (SLI) can be largely explained by abnormalities of brain structures that subserve procedural memory. The PDH predicts impairments of procedural memory itself, and that such impairments underlie the grammatical deficits observed in the disorder. Previous studies have…

  4. Language impairment from 4 to 12 years: prediction and etiology.

    PubMed

    Hayiou-Thomas, Marianna E; Dale, Philip S; Plomin, Robert

    2014-06-01

    The authors of this article examined the etiology of developmental language impairment (LI) at 4 and 12 years of age, as well as the relationship between the 2. Phenotypic and quantitative genetic analyses using longitudinal data from the Twins Early Development Study (Oliver & Plomin, 2007) were conducted. A total of 2,923 pairs of twins (1,075 monozygotic [MZ]; 975 dizygotic same sex [DZss]; and 873 dizygotic opposite sex [DZos]) provided data at 4 and 12 years. At 4 years, (a) psychometric LI was defined on the basis of a low parent-reported expressive vocabulary score (-1.25 SDs; 226 MZ and 115 DZss probands for genetic analysis); and (b) parent referral was defined as having seen a medical professional or speech-language pathologist following parental concern (112 MZ and 104 DZss probands). The 12-year language measure was a composite of 4 web-administered receptive language tests. (a) Psychometric LI at 4 years is more predictive than parent referral of poor language performance at age 12 years, and (b) parent referral is substantially and significantly more heritable than psychometric LI. Parents' concern about their child's language development seems to be the marker of a more heritable disorder than poor expressive language skills alone. However, the language difficulties that arouse parental concern in preschool children, although more heritable, are not predictive of language difficulties in early adolescence. Rather, poor expressive language skills at age 4 years, psychometrically defined, are a better predictor than parent referral of continuing language difficulties at age 12 years.

  5. Language Impairment From 4 to 12 Years: Prediction and Etiology

    PubMed Central

    Hayiou-Thomas, Marianna E.; Dale, Philip S.; Plomin, Robert

    2014-01-01

    Purpose The authors of this article examined the etiology of developmental language impairment (LI) at 4 and 12 years of age, as well as the relationship between the 2. Method Phenotypic and quantitative genetic analyses using longitudinal data from the Twins Early Development Study (Oliver & Plomin, 2007) were conducted. A total of 2,923 pairs of twins (1,075 monozygotic [MZ]; 975 dizygotic same sex [DZss]; and 873 dizygotic opposite sex [DZos]) provided data at 4 and 12 years. At 4 years, (a) psychometric LI was defined on the basis of a low parent-reported expressive vocabulary score (−1.25 SDs; 226 MZ and 115 DZss probands for genetic analysis); and (b) parent referral was defined as having seen a medical professional or speech-language pathologist following parental concern (112 MZ and 104 DZss probands). The 12-year language measure was a composite of 4 web-administered receptive language tests. Results (a) Psychometric LI at 4 years is more predictive than parent referral of poor language performance at age 12 years, and (b) parent referral is substantially and significantly more heritable than psychometric LI. Conclusions Parents’ concern about their child’s language development seems to be the marker of a more heritable disorder than poor expressive language skills alone. However, the language difficulties that arouse parental concern in preschool children, although more heritable, are not predictive of language difficulties in early adolescence. Rather, poor expressive language skills at age 4 years, psychometrically defined, are a better predictor than parent referral of continuing language difficulties at age 12 years. PMID:24167234

  6. Impairments in perceptual competency and maintenance on a visual delayed match-to-sample test in first-episode schizophrenia.

    PubMed

    Lencz, Todd; Bilder, Robert M; Turkel, Elihu; Goldman, Robert S; Robinson, Delbert; Kane, John M; Lieberman, Jeffrey A

    2003-03-01

    Deficits in working memory (WM) have been reported in patients with schizophrenia, but WM is a complex construct dependent on several subprocesses, including input representation (perceptual competency) and holding stimuli on-line (maintenance). A visual delayed match-to-sample task (DMST) was developed to isolate perceptual competency from maintenance during delays. It was hypothesized that patients in the first episode of schizophrenia would exhibit dissociable deficits in both WM domains. Performance on the DMST was assessed in 57 patients in the first episode of schizophrenia or schizoaffective disorder and 22 healthy comparison subjects. In phase 1 of the DMST, a complex visual stimulus (target) was followed immediately by a forced choice between 2 test stimuli, and item difficulty (differences between the test stimuli) was titrated until each subject achieved a consistent accuracy (80%-90%) in this no-delay condition. In phase 2, a delay of 4 or 8 seconds with a mask of randomly illuminated pixels was introduced between target and test stimuli; test stimuli were fixed in difficulty level based on phase 1 titration. Main outcome measures were mean item difficulty attained in the no-delay condition and mean accuracy in matching after delay. Compared with controls, patients attained a lower level of difficulty in the no-delay condition (P =.001) and significantly lower accuracy with delay (P =.002). Deficits in both domains of WM suggest abnormality in the posterior and prefrontal cortexes. These deficits can be observed in a task involving complex visual pattern stimuli using only a brief delay and are present even in unmedicated patients in the first episode of illness.

  7. Learning impairments identified early in life are predictive of future impairments associated with aging

    PubMed Central

    Hullinger, Rikki; Burger, Corinna

    2016-01-01

    The Morris water maze (MWM) behavioral paradigm is commonly used to measure spatial learning and memory in rodents. It is widely accepted that performance in the MWM declines with age. However, young rats ubiquitously perform very well on established versions of the water maze, suggesting that more challenging tasks may be required to reveal subtle differences in young animals. Therefore, we have used a one-day water maze and novel object recognition to test whether more sensitive paradigms of memory in young animals could identify subtle cognitive impairments early in life that might become accentuated later with senescence. We have found that these two tasks reliably separate young rats into inferior and superior learners, are highly correlated, and that performance on these tasks early in life is predictive of performance at 12 months of age. Furthermore, we have found that repeated training in this task selectively improves the performance of inferior learners, suggesting that behavioral training from an early age may provide a buffer against age-related cognitive decline. PMID:26283528

  8. A Two-Component Mixing Model for Predicting Regional Episodic Acidification of Surface Waters During Spring Snowmelt Periods

    NASA Astrophysics Data System (ADS)

    Eshleman, Keith N.; Davies, Trevor D.; Tranter, Martyn; Wigington, Parker J.

    1995-04-01

    A two-component mixing model of acid neutralizing capacity (ANC) is proposed for explaining two observed features related to the episodic acidification of surface waters during snowmelt periods: (1) maximum episodic declines in ANC are largest in high ANC systems and increase linearly with antecedent ANC and (2) relative depressions in ANC attributable to increases in nitric acid concentrations are larger in low ANC systems, while relative depressions in ANC attributable to dilution of base cations are larger in high ANC systems. Conceptually, the model represents the physical mixing of two hydrochemical end-members within a surface water environment, although the physical sources of water in the model are undefined. The model is shown to explain 55-72% of the total variation of these characteristics among various surface water systems within the Catskill and Adirondack mountain regions of New York. In addition, the model also explains 11-47% of the relative depression in ANC attributable to natural organic acidity in surface waters in these regions. The model is subsequently linked to an empirical equilibrium acidification model for predicting the long-term episodic acidification response of Adirondack lakes during snowmelt periods. Model predictions suggest that percentage decreases in sulfuric acid concentrations of the magnitude mandated by the 1990 Clean Air Act Amendments (40%) will not restore to positive values the ANC of all Adirondack lakes which are currently acidic (ANC < 0) during spring snowmelt periods. Long-term increases in nitric acid concentrations may counterbalance the expected increases in ANC attributable to reductions in sulfur deposition.

  9. DRD2 promoter region variation predicts antipsychotic-induced weight gain in first episode schizophrenia.

    PubMed

    Lencz, Todd; Robinson, Delbert G; Napolitano, Barbara; Sevy, Serge; Kane, John M; Goldman, David; Malhotra, Anil K

    2010-09-01

    Many antipsychotic medications carry a substantial liability for weight gain, and one mechanism common to all antipsychotics is binding to the dopamine D2 receptor. We therefore examined the relationship between -141C Ins/Del (rs1799732), a functional promoter region polymorphism in DRD2, and antipsychotic-induced weight gain in 58 first episode schizophrenia patients enrolled in a randomized trial of risperidone versus olanzapine. Carriers of the deletion allele (n=29) were compared with Ins/Ins homozygotes (noncarriers, n=29) in a mixed model encompassing 10 weight measurements over 16 weeks. Deletion allele carriers showed significantly more weight gain after 6 weeks of treatment regardless of assigned medication. Although deletion carriers were prescribed higher doses of olanzapine (but not risperidone), dose did not seem to account for the genotype effects on weight gain. Given earlier evidence that deletion carriers show reduced symptom response to medication, additional study of appropriate treatment options for these patients seems warranted.

  10. Prediction and prevention of the first psychotic episode: new directions and opportunities

    PubMed Central

    Piras, Sara; Casu, Gianluca; Casu, Maria Antonietta; Orrù, Alessandro; Ruiu, Stefania; Pilleri, Antonio; Manca, Gabriella; Marchese, Giorgio

    2014-01-01

    In the last few decades, substantial research has focused on the possibility of early detection and prevention of the first psychotic episode in young individuals at risk of developing this mental disturbance; however, unresolved clinical and ethical issues still call for further investigations. New perspectives and opportunities may come from the identification of selective psychopathological and instrumental markers linking the appearance of subtle psychotic symptoms with the clinical outcome of specific mental pathologies. Furthermore, empirically derived algorithms and risk staging models should facilitate the identification of targeted prevention therapies, possibly improving the efficacy of well-tolerated therapeutic approaches, such as psychological interventions and natural compound supplementations. To date, the collected evidence on the efficacy and tolerability of pharmacological prevention therapies raises more doubts than hopes. A very early detection of risk and appropriate symptomatic pattern classifications may provide a chance to better match prevention strategies with the development of psychosis. PMID:24729711

  11. Prediction of bacteremia in children with febrile episodes during chemotherapy for acute lymphoblastic leukemia.

    PubMed

    Lücking, Vibeke; Rosthøj, Steen

    2013-03-01

    The purpose was to identify risk factors for bacteremia in febrile episodes occurring during chemotherapy for acute lymphoblastic leukemia (ALL) in children, and to develop a risk score permitting risk-adapted antibiotic therapy. We reviewed a total of 172 febrile episodes occurring during chemotherapy in 31 children and adolescents with ALL. Temperature, hematological parameters, culture findings, and antibiotic therapy were recorded. Bacteremias were classified as transmucosal or CVC-dependent. Blood cultures were positive with mucosal pathogens in 15 cases (9%) and with skin/environmental bacteria in 34 (20%). CVC-dependent infections occurred throughout the treatment phases, while transmucosal primarily during induction therapy. Transmucosal bacteremia was associated with induction therapy, leukocyte count ≤0.5 × 10(9)/L, neutrophil count ≤0.1 × 10(9)/L, monocyte count ≤0.01 × 10(9)/L, and platelet count ≤50 × 10(9)/L. Based on logistic conversion of the odds ratios for the five factors, a weight of 2 was assigned to induction therapy and leukocyte count ≤0.5 × 10(9)/L, and a weight of 1 to the remaining three parameters. The weights were included in a simple additive score ranging from 0 to 7, which defined groups with 4%, 6%, 24%, and 40% risk of transmucosal bacteremia. CVC-dependent bacteremia was not associated with markers of poor bone marrow function. In conclusion, transmucosal bacteremia in children with ALL is related to infiltration or suppression of the bone marrow. A score reflecting the condition of the marrow can define low-risk and high-risk groups and may prove clinically useful.

  12. Predicting the vulnerability of streams to episodic acidification and potential effects on aquatic biota in Shenandoah National Park, Virginia

    USGS Publications Warehouse

    Rice, Karen C.; Deviney, Frank A.; Hornberger, George M.; Webb, James R.

    2006-01-01

    Acidic deposition is one of the most serious environmental problems affecting Shenandoah National Park in north-central Virginia. The park is the third most contaminated park in the National Park System because of the deposition of acid rain. Acid rain affects headwater streams in the park by temporarily reducing the acid-neutralizing capacity (ANC) of the water, a process termed episodic acidification. In turn, the increase in acidic components in streamwater can have deleterious effects on the aquatic biota.Although acidic deposition to the park is relatively uniform across its land area, the water-quality response of streamwater during rain events varies substantially. This response is a function of the underlying geology and topographic attributes of watersheds.Geologic and topographic data for the park's 231 watersheds are readily available; however, long-term (years and tens of years) measurements of streamwater ANC and accompanying discharge are not and would be prohibitively expensive to collect. Modeled predictions of the vulnerability of the park's streams to episodic acidification are an alternative to long-term water-quality monitoring. These predictions can aid park officials in making management decisions.

  13. Norms for change in episodic memory as a prerequisite for the diagnosis of mild cognitive impairment (MCI).

    PubMed

    Bläsi, Stefan; Zehnder, Antoinette E; Berres, Manfred; Taylor, Kirsten I; Spiegel, René; Monsch, Andreas U

    2009-03-01

    The new diagnostic criteria for mild cognitive impairment (MCI) from the International Working Group on Mild Cognitive Impairment (Winblad et al., 2004, p. 243) list "evidence of decline over time in objective cognitive tasks" as one diagnostic sign, implying the repeated neuropsychological testing. This study aimed to compare different assessment methods of longitudinal change based on the performances of 366 cognitively healthy participants (237 men, 129 women) examined with a German version of the California Verbal Learning Test (Delis, Kramer, Kaplan, & Ober, 1987) at baseline and 2 years later. Age, education, gender, and baseline performance were taken into account. Results revealed marked practice effects after 2 years. Normal ranges for change that controls for practice effects and regression to the mean proved to be superior to other reliable change indexes. This new method allows for more valid interpretation of change in neuropsychological functioning and thus diagnosis of MCI.

  14. Comparison of semantic and episodic memory BOLD fMRI activation in predicting cognitive decline in older adults

    PubMed Central

    Hantke, Nathan; Nielson, Kristy A.; Woodard, John L.; Guidotti Breting, Leslie M.; Butts, Alissa; Seidenberg, Michael; Smith, J. Carson; Durgerian, Sally; Lancaster, Melissa; Matthews, Monica; Sugarman, Michael A.; Rao, Stephen M.

    2013-01-01

    Previous studies suggest that task-activated fMRI can predict future cognitive decline among healthy older adults. The present fMRI study examined the relative sensitivity of semantic memory (SM) versus episodic memory (EM) activation tasks for predicting cognitive decline. Seventy-eight cognitively intact elders underwent neuropsychological testing at entry and after an 18-month interval, with participants classified as cognitively “Stable” or “Declining” based on ≥1.0 SD decline in performance. Baseline fMRI scanning involved SM (famous name discrimination) and EM (name recognition) tasks. SM and EM fMRI activation, along with APOE ε4 status, served as predictors of cognitive outcome using a logistic regression analysis. Twenty-seven (34.6%) participants were classified as Declining and 51 (65.4%) as Stable. APOE ε4 status alone significantly predicted cognitive decline (R2 = .106; C index = .642). Addition of SM activation significantly improved prediction accuracy (R2 = .285; C index = .787), whereas the addition of EM did not (R2 = .212; C index = .711). In combination with APOE status, SM task activation predicts future cognitive decline better than EM activation. These results have implications for use of fMRI in prevention clinical trials involving the identification of persons at-risk for age-associated memory loss and Alzheimer’s disease. PMID:23199565

  15. Mismatch Negativity Encoding of Prediction Errors Predicts S-ketamine-Induced Cognitive Impairments

    PubMed Central

    Schmidt, André; Bachmann, Rosilla; Kometer, Michael; Csomor, Philipp A; Stephan, Klaas E; Seifritz, Erich; Vollenweider, Franz X

    2012-01-01

    Psychotomimetics like the N-methyl--aspartate receptor (NMDAR) antagonist ketamine and the 5-hydroxytryptamine2A receptor (5-HT2AR) agonist psilocybin induce psychotic symptoms in healthy volunteers that resemble those of schizophrenia. Recent theories of psychosis posit that aberrant encoding of prediction errors (PE) may underlie the expression of psychotic symptoms. This study used a roving mismatch negativity (MMN) paradigm to investigate whether the encoding of PE is affected by pharmacological manipulation of NMDAR or 5-HT2AR, and whether the encoding of PE under placebo can be used to predict drug-induced symptoms. Using a double-blind within-subject placebo-controlled design, S-ketamine and psilocybin, respectively, were administrated to two groups of healthy subjects. Psychological alterations were assessed using a revised version of the Altered States of Consciousness (ASC-R) questionnaire. As an index of PE, we computed changes in MMN amplitudes as a function of the number of preceding standards (MMN memory trace effect) during a roving paradigm. S-ketamine, but not psilocybin, disrupted PE processing as expressed by a frontally disrupted MMN memory trace effect. Although both drugs produced positive-like symptoms, the extent of PE processing under placebo only correlated significantly with the severity of cognitive impairments induced by S-ketamine. Our results suggest that the NMDAR, but not the 5-HT2AR system, is implicated in PE processing during the MMN paradigm, and that aberrant PE signaling may contribute to the formation of cognitive impairments. The assessment of the MMN memory trace in schizophrenia may allow detecting early phases of the illness and might also serve to assess the efficacy of novel pharmacological treatments, in particular of cognitive impairments. PMID:22030715

  16. Mismatch negativity encoding of prediction errors predicts S-ketamine-induced cognitive impairments.

    PubMed

    Schmidt, André; Bachmann, Rosilla; Kometer, Michael; Csomor, Philipp A; Stephan, Klaas E; Seifritz, Erich; Vollenweider, Franz X

    2012-03-01

    Psychotomimetics like the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine and the 5-hydroxytryptamine2A receptor (5-HT(2A)R) agonist psilocybin induce psychotic symptoms in healthy volunteers that resemble those of schizophrenia. Recent theories of psychosis posit that aberrant encoding of prediction errors (PE) may underlie the expression of psychotic symptoms. This study used a roving mismatch negativity (MMN) paradigm to investigate whether the encoding of PE is affected by pharmacological manipulation of NMDAR or 5-HT(2A)R, and whether the encoding of PE under placebo can be used to predict drug-induced symptoms. Using a double-blind within-subject placebo-controlled design, S-ketamine and psilocybin, respectively, were administrated to two groups of healthy subjects. Psychological alterations were assessed using a revised version of the Altered States of Consciousness (ASC-R) questionnaire. As an index of PE, we computed changes in MMN amplitudes as a function of the number of preceding standards (MMN memory trace effect) during a roving paradigm. S-ketamine, but not psilocybin, disrupted PE processing as expressed by a frontally disrupted MMN memory trace effect. Although both drugs produced positive-like symptoms, the extent of PE processing under placebo only correlated significantly with the severity of cognitive impairments induced by S-ketamine. Our results suggest that the NMDAR, but not the 5-HT(2A)R system, is implicated in PE processing during the MMN paradigm, and that aberrant PE signaling may contribute to the formation of cognitive impairments. The assessment of the MMN memory trace in schizophrenia may allow detecting early phases of the illness and might also serve to assess the efficacy of novel pharmacological treatments, in particular of cognitive impairments.

  17. Abnormal Stress‐Related Measures of Arterial Stiffness in Middle‐Aged and Elderly Men and Women With Impaired Fasting Glucose at Risk for a First Episode of Symptomatic Heart Failure

    PubMed Central

    Vasu, Sujethra; Morgan, Timothy M.; Kitzman, Dalane W.; Bertoni, Alain; Stacey, Richard B.; Hamilton, Craig; Chiles, Caroline; Thohan, Vinay; Hundley, W. Gregory

    2015-01-01

    Background Abnormal resting arterial stiffness is present in middle‐aged and elderly persons with abnormalities of fasting glucose (diabetes or impaired fasting glucose) and is associated with exercise intolerance. We sought to determine whether these same persons exhibited stress‐related abnormalities of arterial stiffness. Methods and Results We analyzed dobutamine magnetic resonance stress imaging results from 373 consecutively recruited persons aged 55 to 85 years with normal fasting glucose, impaired fasting glucose, or diabetes who were at risk for but without symptomatic heart failure. Personnel blinded to participant identifiers measured arterial stiffness (brachial pulse pressure/left ventricular stroke volume indexed to body surface area, the aortic elastance index [brachial end‐systolic pressure/left ventricular stroke volume indexed to body surface area], and thoracic aortic distensibility) at 80% of the maximum predicted heart rate response for age. Participants averaged 69±8 years of age; 79% were white, 92% were hypertensive, and 66% were women. After accounting for hypertension, sex, coronary artery disease, smoking, medications, hypercholesterolemia, and visceral fat, we observed an effect of glycemic status for stress measures of arterial stiffness in those with diabetes and impaired fasting glucose relative to those with normal fasting glucose (P=0.002, P=0.02, and P=0.003, respectively). Conclusion Middle‐ and older‐aged individuals with diabetes or impaired fasting glucose have higher stress measures of arterial stiffness than those with normal fasting glucose. These data emphasize the need for future studies with larger sample sizes to determine whether stress‐related elevations in arterial stiffness are related to exercise intolerance and future episodes of heart failure experienced by those with abnormalities of fasting glucose. Clinical Trial Registration URL: http://clinicaltrials.gov/. Unique identifier: NCT00542503. PMID

  18. DRD2 Promoter Region Variation Predicts Antipsychotic-Induced Weight Gain in First Episode Schizophrenia

    PubMed Central

    Lencz, Todd; Robinson, Delbert G.; Napolitano, Barbara; Sevy, Serge; Kane, John M.; Goldman, David; Malhotra, Anil K.

    2010-01-01

    Many antipsychotic medications carry a substantial liability for weight gain, and one mechanism common to all antipsychotics is binding to the dopamine D2 receptor. We therefore examined the relationship between −141C Ins/Del (rs1799732), a functional promoter region polymorphism in DRD2, and antipsychotic-induced weight gain in 58 first episode schizophrenia patients enrolled in a randomized trial of risperidone (RIS) vs. olanzapine (OLZ). Carriers of the deletion allele (n=29) were compared to Ins/Ins homozygotes (non-carriers, n=29) in a mixed model encompassing 10 weight measurements over 16 weeks. Deletion allele carriers demonstrated significantly more weight gain after 6 weeks of treatment regardless of assigned medication. While deletion carriers were prescribed higher doses of OLZ (but not RIS), dose did not appear to account for the genotype effects on weight gain. Given previous evidence that deletion carriers demonstrate reduced symptom response to medication, additional study of appropriate treatment options for these patients appears warranted. PMID:20664489

  19. Personality Disorders Predict Relapse after Remission from an Episode of Major Depressive Disorder: A Six-year Prospective Study

    PubMed Central

    Grilo, Carlos M.; Stout, Robert L.; Markowitz, John C.; Sanislow, Charles A.; Ansell, Emily B.; Skodol, Andrew E.; Bender, Donna S.; Pinto, Anthony; Shea, M. Tracie; Yen, Shirley; Gunderson, John G.; Morey, Leslie C.; Hopwood, Christopher J.; McGlashan, Thomas H.

    2015-01-01

    Objective To examine prospectively the course of major depressive disorder (MDD) and to test for the moderating effects of personality disorder (PD) co-morbidity on relapse after remission from an episode of MDD. Method Participants were 303 patients (196 women and 107 men) with current MDD at baseline enrollment in the Collaborative Longitudinal Personality Disorders Study. MDD and Axis I psychiatric disorders were assessed with the Structured Clinical Interview for DSM-IV and Axis II PDs were assessed with the Diagnostic Interview for DSM-IV PD. The course of MDD was assessed with the Longitudinal Interval Follow-up Evaluation at 6- and 12-months and then yearly through 6 years. Survival analyses were used to analyze time to remission and time to relapse. Results 260 (86%) of 303 patients remitted from MDD; lifetable survival analyses revealed that patients with MDD who had PDs at baseline had significantly longer time to remission from MDD than patients without PDs. Among the 260 patients whose MDD remitted, 183 (70%) relapsed. MDD patients with PDs -- specifically those with borderline and obsessive-compulsive PDs -- at baseline had significantly shorter time to relapse than MDD patients without PDs. Cox proportional hazards regression analyses revealed that the presence of PDs at baseline (hazard ratio 1.5) and recurrent-type MDD (hazard ratio 2.2), but not gender (hazard ratio 1.03) or dysthymic disorder (hazard ratio 0.97), significantly predicted time to relapse. Conclusions PDs at baseline were robust predictors prospectively of accelerated relapse after remission from an episode of MDD. PDs at baseline significantly moderated eventual time to relapse in MDD among patients who remitted from an episode of MDD, even when controlling for other potential negative prognostic predictors. PMID:20584514

  20. Cognitive impairments in first-episode drug-naive and chronic medicated schizophrenia: MATRICS consensus cognitive battery in a Chinese Han population.

    PubMed

    Wu, Jing Qin; Chen, Da Chun; Tan, Yun Long; Xiu, Mei Hong; De Yang, Fu; Soares, Jair C; Zhang, Xiang Yang

    2016-04-30

    Cognitive deficits are a core feature of schizophrenia and we examined the cognitive profile of first-episode and chronic schizophrenia in a Chinese Han population using the MATRICS Consensus Cognitive Battery (MCCB). We recruited 79 first-episode drug-naïve (FEDN) schizophrenia, 132 chronic medicated schizophrenia inpatients and 124 healthy controls. We assessed patient psychopathology using the Positive and Negative Syndrome Scale (PANSS). MCCB total score (p<0.01) and index scores of category fluency, trail making A, digital sequence, Hopkins Verbal Learning Test (HVLT), mazes, and Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) were significantly higher in FEDN than in chronic patients (all p<0.05). FEDN exhibited relative weakness in continuous performance, whereas chronic patients exhibited relative weakness in mazes. Multiple regression analysis confirmed that in FEDN and chronic patients, total score and negative symptom of PANSS were independent contributors to MCCB total score, respectively. Our results not only demonstrate the applicability of the MCCB as a sensitive measure of cognitive impairment for schizophrenia patients in a Chinese Han population, but also suggest that the compromised cognition is present in the early stage of schizophrenia, some of which could be more severe in the chronic stage of illness. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Time series and recurrence interval models to predict the vulnerability of streams to episodic acidification in Shenandoah National Park, Virginia

    USGS Publications Warehouse

    Deviney, F.A.; Rice, Karen C.; Hornberger, G.M.

    2006-01-01

    Acid rain affects headwater streams by temporarily reducing the acid-neutralizing capacity (ANC) of the water, a process termed episodic acidification. The increase in acidic components in stream water can have deleterious effects on the aquatic biota. Although acidic deposition is uniform across Shenandoah National Park (SNP) in north central Virginia, the stream water quality response during rain events varies substantially. This response is a function of the catchment's underlying geology and topography. Geologic and topographic data for SNP's 231 catchments are readily available; however, long-term measurements (tens of years) of ANC and accompanying discharge are not and would be prohibitively expensive to collect. Transfer function time series models were developed to predict hourly ANC from discharge for five SNP catchments with long-term water-quality and discharge records. Hourly ANC predictions over short time periods (≤1 week) were averaged, and distributions of the recurrence intervals of annual water-year minimum ANC values were model-simulated for periods of 6, 24, 72, and 168 hours. The distributions were extrapolated to the rest of the SNP catchments on the basis of catchment geology and topography. On the basis of the models, large numbers of SNP streams have 6- to 168-hour periods of low-ANC values, which may stress resident fish populations. Smaller catchments are more vulnerable to episodic acidification than larger catchments underlain by the same bedrock. Catchments with similar topography and size are more vulnerable if underlain by less basaltic/carbonate bedrock. Many catchments are predicted to have successive years of low-ANC values potentially sufficient to extirpate some species.

  2. Theta band power increases in the posterior hippocampus predict successful episodic memory encoding in humans.

    PubMed

    Lin, Jui-Jui; Rugg, Michael D; Das, Sandhitsu; Stein, Joel; Rizzuto, Daniel S; Kahana, Michael J; Lega, Bradley C

    2017-10-01

    Functional differences in the anterior and posterior hippocampus during episodic memory processing have not been examined in human electrophysiological data. This is in spite of strong evidence for such differences in rodent data, including greater place cell specificity in the dorsal hippocampus, greater sensitivity to the aversive or motivational content of memories in ventral regions, connectivity analyses identifying preferential ventral hippocampal connections with the amygdala, and gene expression analyses identifying a dorsal-ventral gradient. We asked if memory-related oscillatory patterns observed in human hippocampal recordings, including the gamma band and slow-theta (2.5-5 Hz) subsequent memory effects, would exhibit differences along the longitudinal axis and between hemispheres. We took advantage of a new dataset of stereo electroencephalography patients with simultaneous, robotically targeted anterior, and posterior hippocampal electrodes to directly compare oscillatory subsequent memory effects during item encoding. This same data set allowed us to examine left-right connectivity and hemispheric differences in hippocampal oscillatory patterns. Our data suggest that a power increase during successful item encoding in the 2.5-5 Hz slow-theta frequency range preferentially occurs in the posterior hippocampus during the first 1,000 ms after item presentation, while a gamma band power increase is stronger in the dominant hemisphere. This dominant-nondominant pattern in the gamma range appears to reverse during item retrieval, however. Intrahippocampal phase coherence was found to be stronger during successful item encoding. Our phase coherence data are also consistent with existing reports of a traveling wave for theta oscillations propagating along the septotemporal (longitudinal) axis of the human hippocampus. We examine how our findings fit with theories of functional specialization along the hippocampal axis. © 2017 Wiley Periodicals, Inc.

  3. Abnormal white matter connections between medial frontal regions predict symptoms in patients with first episode schizophrenia.

    PubMed

    Ohtani, Toshiyuki; Bouix, Sylvain; Lyall, Amanda E; Hosokawa, Taiga; Saito, Yukiko; Melonakos, Eric; Westin, Carl-Fredrik; Seidman, Larry J; Goldstein, Jill; Mesholam-Gately, Raquelle; Petryshen, Tracey; Wojcik, Joanne; Kubicki, Marek

    2015-10-01

    The medial orbitofrontal cortex (mOFC) and rostral part of anterior cingulate cortex (rACC) have been suggested to be involved in the neural network of salience and emotional processing, and associated with specific clinical symptoms in schizophrenia. Considering the schizophrenia dysconnectivity hypothesis, the connectivity abnormalities between mOFC and rACC might be associated with clinical characteristics in first episode schizophrenia patients (FESZ). After parcellating mOFC into the anterior and posterior part, diffusion properties of the mOFC-rACC white matter connections for 21 patients with FESZ and 21 healthy controls (HCs) were examined using stochastic tractography, one of the most effective Diffusion Tensor Imaging (DTI) methods for examining tracts between adjacent gray matter (GM) regions. Fractional anisotropy (FA) reductions were observed in bilateral posterior, but not anterior mOFC-rACC connections (left: p < .0001; right: p < .0001) in FESZ compared to HCs. In addition, reduced FA in the left posterior mOFC-rACC connection was associated with more severe anhedonia-asociality (rho = -.633, p = .006) and total score (rho = -.520, p = .032) in the Scale for the Assessment of Negative Symptoms (SANS); reduced FA in the right posterior mOFC-rACC connection was associated with more severe affective flattening (rho = -.644, p = .005), total score (rho = -.535, p = .027) in SANS, hallucinations (rho = -.551, p = .018), delusions (rho = -.632, p = .005) and total score (rho = -.721, p = .001) in the Scale for the Assessment of Positive Symptoms (SAPS) in FESZ. The observed white matter abnormalities within the connections between mOFC and rACC might be associated with the psychopathology of the early stage of schizophrenia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Abnormal White Matter Connections Between Medial Frontal Regions Predict Symptoms in Patients with First Episode Schizophrenia

    PubMed Central

    Ohtani, Toshiyuki; Bouix, Sylvain; Lyall, Amanda E; Hosokawa, Taiga; Saito, Yukiko; Melonakos, Eric; Westin, Carl-Fredrik; Seidman, Larry J.; Goldstein, Jill; Mesholam-Gately, Raquelle; Petryshen, Tracey; Wojcik, Joanne; Kubicki, Marek

    2015-01-01

    Introduction The medial orbitofrontal cortex (mOFC) and rostral part of anterior cingulate cortex (rACC) have been suggested to be involved in the neural network of salience and emotional processing, and associated with specific clinical symptoms in schizophrenia. Considering the schizophrenia dysconnectivity hypothesis, the connectivity abnormalities between mOFC and rACC might be associated with clinical characteristics in first episode schizophrenia patients (FESZ). Methods After parcellating mOFC into the anterior and posterior part, diffusion properties of the mOFC-rACC white matter connections for 21 patients with FESZ and 21 healthy controls (HCs) were examined using stochastic tractography, one of the most effective Diffusion Tensor Imaging methods for examining tracts between adjacent gray matter regions. Results Fractional anisotropy (FA) reductions were observed in bilateral posterior, but not anterior mOFC-rACC connections (left: p<0.0001; right: p<0.0001) in FESZ compared to HCs. In addition, reduced FA in the left posterior mOFC-rACC connection was associated with more severe anhedonia-asociality (rho=−0.633, p=0.006) and total score (rho=−0.520, p=0.032) in the Scale for the Assessment of Negative Symptoms (SANS); reduced FA in the right posterior mOFC-rACC connection was associated with more severe affective flattening (rho=−0.644, p=0.005), total score (rho=−0.535, p=0.027) in SANS, hallucinations (rho=−0.551, p=0.018), delusions (rho=−0.632, p=0.005) and total score (rho=−0.721, p=0.001) in the Scale for the Assessment of Positive Symptoms (SAPS) in FESZ. Conclusions The observed white matter abnormalities within the connections between mOFC and rACC might be associated with the psychopathology of the early stage of schizophrenia. PMID:26277547

  5. Impact of hippocampal subfield histopathology in episodic memory impairment in mesial temporal lobe epilepsy and hippocampal sclerosis.

    PubMed

    Comper, Sandra Mara; Jardim, Anaclara Prada; Corso, Jeana Torres; Gaça, Larissa Botelho; Noffs, Maria Helena Silva; Lancellotti, Carmen Lúcia Penteado; Cavalheiro, Esper Abrão; Centeno, Ricardo Silva; Yacubian, Elza Márcia Targas

    2017-10-01

    The objective of the study was to analyze preoperative visual and verbal episodic memories in a homogeneous series of patients with mesial temporal lobe epilepsy (MTLE) and unilateral hippocampal sclerosis (HS) submitted to corticoamygdalohippocampectomy and its association with neuronal cell density of each hippocampal subfield. The hippocampi of 72 right-handed patients were collected and prepared for histopathological examination. Hippocampal sclerosis patterns were determined, and neuronal cell density was calculated. Preoperatively, two verbal and two visual memory tests (immediate and delayed recalls) were applied, and patients were divided into two groups, left and right MTLE (36/36). There were no statistical differences between groups regarding demographic and clinical data. Cornu Ammonis 4 (CA4) neuronal density was significantly lower in the right hippocampus compared with the left (p=0.048). The groups with HS presented different memory performance - the right HS were worse in visual memory test [Complex Rey Figure, immediate (p=0.001) and delayed (p=0.009)], but better in one verbal task [RAVLT delayed (p=0.005)]. Multiple regression analysis suggested that the verbal memory performance of the group with left HS was explained by CA1 neuronal density since both tasks were significantly influenced by CA1 [Logical Memory immediate recall (p=0.050) and Logical Memory and RAVLT delayed recalls (p=0.004 and p=0.001, respectively)]. For patients with right HS, both CA1 subfield integrity (p=0.006) and epilepsy duration (p=0.012) explained Complex Rey Figure immediate recall performance. Ultimately, epilepsy duration also explained the performance in the Complex Rey Figure delayed recall (p<0.001). Cornu Ammonis 1 (CA1) hippocampal subfield was related to immediate and delayed recalls of verbal memory tests in left HS, while CA1 and epilepsy duration were associated with visual memory performance in patients with right HS. Copyright © 2017 Elsevier Inc. All

  6. Language Impairment from 4 to 12 Years: Prediction and Etiology

    ERIC Educational Resources Information Center

    Hayiou-Thomas, Marianna E.; Dale, Philip S.; Plomin, Robert

    2014-01-01

    Purpose: The authors of this article examined the etiology of developmental language impairment (LI) at 4 and 12 years of age, as well as the relationship between the 2. Method: Phenotypic and quantitative genetic analyses using longitudinal data from the Twins Early Development Study (Oliver & Plomin, 2007) were conducted. A total of 2,923…

  7. Language Impairment from 4 to 12 Years: Prediction and Etiology

    ERIC Educational Resources Information Center

    Hayiou-Thomas, Marianna E.; Dale, Philip S.; Plomin, Robert

    2014-01-01

    Purpose: The authors of this article examined the etiology of developmental language impairment (LI) at 4 and 12 years of age, as well as the relationship between the 2. Method: Phenotypic and quantitative genetic analyses using longitudinal data from the Twins Early Development Study (Oliver & Plomin, 2007) were conducted. A total of 2,923…

  8. Mediation of episodic memory performance by the executive function network in patients with amnestic mild cognitive impairment: a resting-state functional MRI study

    PubMed Central

    Yuan, Baoyu; Chen, Jiu; Gong, Liang; Shu, Hao; Liao, Wenxiang; Wang, Zan; Liu, Duan; Xie, Chunming; Zhang, Zhijun

    2016-01-01

    Deficits in episodic memory (EM) are a hallmark clinical symptom of patients with amnestic mild cognitive impairment (aMCI). Impairments in executive function (EF) are widely considered to exacerbate memory deficits and to increase the risk of conversion from aMCI to Alzheimer's disease (AD). However, the specific mechanisms underlying the interaction between executive dysfunction and memory deficits in aMCI patients remain unclear. Thus, the present study utilized resting-state functional magnetic resonance imaging (fMRI) scans of the EF network and the EM network to investigate this relationship in 79 aMCI patients and 119 healthy controls (HC). The seeds were obtained from the results of a regional homogeneity (ReHo) analysis. Functional connectivity (FC) within the EM network was determined using a seed in the right retrosplenial cortex (RSC), and FC within EF network was assessed using seeds in the right dorsolateral prefrontal cortex (DLPFC). There was a significant negative correlation between EM scores and EF scores in both the aMCI and HC groups. Compared to the HC group, aMCI patients had reduced right RSC connectivity but enhanced right DLPFC connectivity. The overlapping brain regions between the EM and EF networks were associated with FC in the right inferior parietal lobule (IPL) in the right RSC network, and in the bilateral middle cingulate cortex (MCC) and left IPL in the right DLPFC network. A mediation analysis revealed that the EF network had an indirect positive effect on EM performance in the aMCI patients. The present findings provide new insights into the neural mechanisms underlying the interaction between impaired EF and memory deficits in aMCI patients and suggest that the EF network may mediate EM performance in this population. PMID:27589839

  9. Predicting episodic memory performance using different biomarkers: results from Argentina-Alzheimer’s Disease Neuroimaging Initiative

    PubMed Central

    Russo, María Julieta; Cohen, Gabriela; Chrem Mendez, Patricio; Campos, Jorge; Nahas, Federico E; Surace, Ezequiel I; Vazquez, Silvia; Gustafson, Deborah; Guinjoan, Salvador; Allegri, Ricardo F; Sevlever, Gustavo

    2016-01-01

    Purpose Argentina-Alzheimer’s Disease Neuroimaging Initiative (Arg-ADNI) is the first ADNI study to be performed in Latin America at a medical center with the appropriate infrastructure. Our objective was to describe baseline characteristics and to examine whether biomarkers related to Alzheimer’s disease (AD) physiopathology were associated with worse memory performance. Patients and methods Fifteen controls and 28 mild cognitive impairment and 13 AD dementia subjects were included. For Arg-ADNI, all biomarker parameters and neuropsychological tests of ADNI-II were adopted. Results of positron emission tomography (PET) with fluorodeoxyglucose and 11C-Pittsburgh compound-B (PIB-PET) were available from all participants. Cerebrospinal fluid biomarker results were available from 39 subjects. Results A total of 56 participants were included and underwent baseline evaluation. The three groups were similar with respect to years of education and sex, and they differed in age (F=5.10, P=0.01). Mean scores for the baseline measurements of the neuropsychological evaluation differed significantly among the three groups at P<0.001, showing a continuum in their neuropsychological performance. No significant correlations were found between the principal measures (long-delay recall, C-Pittsburgh compound-B scan, left hippocampal volume, and APOEε4) and either age, sex, or education (P>0.1). Baseline amyloid deposition and left hippocampal volume separated the three diagnostic groups and correlated with the memory performance (P<0.001). Conclusion Cross-sectional analysis of baseline data revealed links between cognition, structural changes, and biomarkers. Follow-up of a larger and more representative cohort, particularly analyzing cerebrospinal fluid and brain biomarkers, will allow better characterization of AD in our country. PMID:27695331

  10. Self-blame-Selective Hyperconnectivity Between Anterior Temporal and Subgenual Cortices and Prediction of Recurrent Depressive Episodes.

    PubMed

    Lythe, Karen E; Moll, Jorge; Gethin, Jennifer A; Workman, Clifford I; Green, Sophie; Lambon Ralph, Matthew A; Deakin, John F W; Zahn, Roland

    2015-11-01

    Patients with remitted major depressive disorder (MDD) were previously found to display abnormal functional magnetic resonance imaging connectivity (fMRI) between the right superior anterior temporal lobe (RSATL) and the subgenual cingulate cortex and adjacent septal region (SCSR) when experiencing self-blaming emotions relative to emotions related to blaming others (eg, "indignation or anger toward others"). This finding provided the first neural signature of biases toward overgeneralized self-blaming emotions (eg, "feeling guilty for everything"), known to have a key role in cognitive vulnerability to MDD. It is unknown whether this neural signature predicts risk of recurrence, a crucial step in establishing its potential as a prognostic biomarker, which is urgently needed for stratification into pathophysiologically more homogeneous subgroups and for novel treatments. To use fMRI in remitted MDD at baseline to test the hypothesis that RSATL-SCSR connectivity for self-blaming relative to other-blaming emotions predicts subsequent recurrence of depressive episodes. A prospective cohort study from June 16, 2011, to October 10, 2014, in a clinical research facility completed by 75 psychotropic medication-free patients with remitted MDD and no relevant comorbidity. In total, 31 remained in stable remission, and 25 developed a recurring episode over the 14 months of clinical follow-up and were included in the primary analysis. Thirty-nine control participants with no personal or family history of MDD were recruited for further comparison. Between-group difference (recurring vs stable MDD) in RSATL connectivity, with an a priori SCSR region of interest for self-blaming vs other-blaming emotions. We corroborated our hypothesis that during the experience of self-blaming vs other-blaming emotions, RSATL-SCSR connectivity predicted risk of subsequent recurrence. The recurring MDD group showed higher connectivity than the stable MDD group (familywise error-corrected P

  11. Why Is It Difficult to Predict Language Impairment and Outcome in Patients with Aphasia after Stroke?

    PubMed Central

    Kasselimis, Dimitrios; Varkanitsa, Maria; Selai, Caroline; Potagas, Constantin; Evdokimidis, Ioannis

    2014-01-01

    One of the most devastating consequences of stroke is aphasia. Communication problems after stroke can severely impair the patient's quality of life and make even simple everyday tasks challenging. Despite intense research in the field of aphasiology, the type of language impairment has not yet been localized and correlated with brain damage, making it difficult to predict the language outcome for stroke patients with aphasia. Our primary objective is to present the available evidence that highlights the difficulties of predicting language impairment after stroke. The different levels of complexity involved in predicting the lesion site from language impairment and ultimately predicting the long-term outcome in stroke patients with aphasia were explored. Future directions and potential implications for research and clinical practice are highlighted. PMID:24829592

  12. Neural oscillatory deficits in schizophrenia predict behavioral and neurocognitive impairments

    PubMed Central

    Martínez, Antígona; Gaspar, Pablo A.; Hillyard, Steven A.; Bickel, Stephan; Lakatos, Peter; Dias, Elisa C.; Javitt, Daniel C.

    2015-01-01

    Paying attention to visual stimuli is typically accompanied by event-related desynchronizations (ERD) of ongoing alpha (7–14 Hz) activity in visual cortex. The present study used time-frequency based analyses to investigate the role of impaired alpha ERD in visual processing deficits in schizophrenia (Sz). Subjects viewed sinusoidal gratings of high (HSF) and low (LSF) spatial frequency (SF) designed to test functioning of the parvo- vs. magnocellular pathways, respectively. Patients with Sz and healthy controls paid attention selectively to either the LSF or HSF gratings which were presented in random order. Event-related brain potentials (ERPs) were recorded to all stimuli. As in our previous study, it was found that Sz patients were selectively impaired at detecting LSF target stimuli and that ERP amplitudes to LSF stimuli were diminished, both for the early sensory-evoked components and for the attend minus unattend difference component (the Selection Negativity), which is generally regarded as a specific index of feature-selective attention. In the time-frequency domain, the differential ERP deficits to LSF stimuli were echoed in a virtually absent theta-band phase locked response to both unattended and attended LSF stimuli (along with relatively intact theta-band activity for HSF stimuli). In contrast to the theta-band evoked responses which were tightly stimulus locked, stimulus-induced desynchronizations of ongoing alpha activity were not tightly stimulus locked and were apparent only in induced power analyses. Sz patients were significantly impaired in the attention-related modulation of ongoing alpha activity for both HSF and LSF stimuli. These deficits correlated with patients’ behavioral deficits in visual information processing as well as with visually based neurocognitive deficits. These findings suggest an additional, pathway-independent, mechanism by which deficits in early visual processing contribute to overall cognitive impairment in Sz. PMID

  13. External validation of the international risk prediction algorithm for major depressive episode in the US general population: the PredictD-US study.

    PubMed

    Nigatu, Yeshambel T; Liu, Yan; Wang, JianLi

    2016-07-22

    Multivariable risk prediction algorithms are useful for making clinical decisions and for health planning. While prediction algorithms for new onset of major depression in the primary care attendees in Europe and elsewhere have been developed, the performance of these algorithms in different populations is not known. The objective of this study was to validate the PredictD algorithm for new onset of major depressive episode (MDE) in the US general population. Longitudinal study design was conducted with approximate 3-year follow-up data from a nationally representative sample of the US general population. A total of 29,621 individuals who participated in Wave 1 and 2 of the US National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) and who did not have an MDE in the past year at Wave 1 were included. The PredictD algorithm was directly applied to the selected participants. MDE was assessed by the Alcohol Use Disorder and Associated Disabilities Interview Schedule, based on the DSM-IV criteria. Among the participants, 8 % developed an MDE over three years. The PredictD algorithm had acceptable discriminative power (C-statistics = 0.708, 95 % CI: 0.696, 0.720), but poor calibration (p < 0.001) with the NESARC data. In the European primary care attendees, the algorithm had a C-statistics of 0.790 (95 % CI: 0.767, 0.813) with a perfect calibration. The PredictD algorithm has acceptable discrimination, but the calibration capacity was poor in the US general population despite of re-calibration. Therefore, based on the results, at current stage, the use of PredictD in the US general population for predicting individual risk of MDE is not encouraged. More independent validation research is needed.

  14. Linear regression analysis of Hospital Episode Statistics predicts a large increase in demand for elective hand surgery in England.

    PubMed

    Bebbington, Emily; Furniss, Dominic

    2015-02-01

    We integrated two factors, demographic population shifts and changes in prevalence of disease, to predict future trends in demand for hand surgery in England, to facilitate workforce planning. We analysed Hospital Episode Statistics data for Dupuytren's disease, carpal tunnel syndrome, cubital tunnel syndrome, and trigger finger from 1998 to 2011. Using linear regression, we estimated trends in both diagnosis and surgery until 2030. We integrated this regression with age specific population data from the Office for National Statistics in order to estimate how this will contribute to a change in workload over time. There has been a significant increase in both absolute numbers of diagnoses and surgery for all four conditions. Combined with future population data, we calculate that the total operative burden for these four conditions will increase from 87,582 in 2011 to 170,166 (95% confidence interval 144,517-195,353) in 2030. The prevalence of these diseases in the ageing population, and increasing prevalence of predisposing factors such as obesity and diabetes, may account for the predicted increase in workload. The most cost effective treatments must be sought, which requires high quality clinical trials. Our methodology can be applied to other sub-specialties to help anticipate the need for future service provision. Copyright © 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  15. Overgeneral autobiographical memory at baseline predicts depressive symptoms at follow-up in patients with first-episode depression.

    PubMed

    Liu, Yansong; Zhang, Fuquan; Wang, Zhiqiang; Cao, Leiming; Wang, Jun; Na, Aiguo; Sun, Yujun; Zhao, Xudong

    2016-09-30

    Previous studies have shown that overgeneral autobiographical memory (OGM) is a characteristic of depression. However, there are no studies to explore the association between baseline OGM and depressive symptoms at follow-up in patients with first-episode depression (FE). This study investigated whether baseline OGM predicts depressive symptoms at follow-up in patients with FE. We recruited 125 patients with FE. The participants were divided into remitted group and non-remitted group according to the severity of their depression at 12 months follow-up. The measures consisted of the 17-item Hamilton Depression Rating Scale, Ruminative Response Scale, and Autobiographical Memory Test. Hierarchical linear regression analyses and bootstrap mediation analyses were conducted. The results showed that non-remitted patients had more OGM at baseline. Baseline OGM predicted depressive symptoms at follow-up in patients with FE. Rumination mediated the relationship between baseline OGM and depressive symptoms at follow-up. Our findings highlight OGM as a vulnerability factor involved in the maintenance of depression in patients with FE.

  16. Utilising symptom dimensions with diagnostic categories improves prediction of time to first remission in first-episode psychosis.

    PubMed

    Ajnakina, Olesya; Lally, John; Di Forti, Marta; Stilo, Simona A; Kolliakou, Anna; Gardner-Sood, Poonam; Dazzan, Paola; Pariante, Carmine; Reis Marques, Tiago; Mondelli, Valeria; MacCabe, James; Gaughran, Fiona; David, Anthony S; Stamate, Daniel; Murray, Robin M; Fisher, Helen L

    2017-07-25

    There has been much recent debate concerning the relative clinical utility of symptom dimensions versus conventional diagnostic categories in patients with psychosis. We investigated whether symptom dimensions rated at presentation for first-episode psychosis (FEP) better predicted time to first remission than categorical diagnosis over a four-year follow-up. The sample comprised 193 FEP patients aged 18-65years who presented to psychiatric services in South London, UK, between 2006 and 2010. Psychopathology was assessed at baseline with the Positive and Negative Syndrome Scale and five symptom dimensions were derived using Wallwork/Fortgang's model; baseline diagnoses were grouped using DSM-IV codes. Time to start of first remission was ascertained from clinical records. The Bayesian Information Criterion (BIC) was used to find the best fitting accelerated failure time model of dimensions, diagnoses and time to first remission. Sixty percent of patients remitted over the four years following first presentation to psychiatric services, and the average time to start of first remission was 18.3weeks (SD=26.0, median=8). The positive (BIC=166.26), excited (BIC=167.30) and disorganised/concrete (BIC=168.77) symptom dimensions, and a diagnosis of schizophrenia (BIC=166.91) predicted time to first remission. However, a combination of the DSM-IV diagnosis of schizophrenia with all five symptom dimensions led to the best fitting model (BIC=164.35). Combining categorical diagnosis with symptom dimension scores in FEP patients improved the accuracy of predicting time to first remission. Thus our data suggest that the decision to consign symptom dimensions to an annexe in DSM-5 should be reconsidered at the earliest opportunity. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Episodic Memories

    ERIC Educational Resources Information Center

    Conway, Martin A.

    2009-01-01

    An account of episodic memories is developed that focuses on the types of knowledge they represent, their properties, and the functions they might serve. It is proposed that episodic memories consist of "episodic elements," summary records of experience often in the form of visual images, associated to a "conceptual frame" that provides a…

  18. Episodic Memories

    ERIC Educational Resources Information Center

    Conway, Martin A.

    2009-01-01

    An account of episodic memories is developed that focuses on the types of knowledge they represent, their properties, and the functions they might serve. It is proposed that episodic memories consist of "episodic elements," summary records of experience often in the form of visual images, associated to a "conceptual frame" that provides a…

  19. Neurocognitive impairment on motor imagery associated with positive symptoms in patients with first-episode schizophrenia: evidence from event-related brain potentials.

    PubMed

    Chen, Jiu; Wei, Dunhong; Yang, Laiqi; Wu, Xingqu; Ma, Wentao; Fu, Qinghai; Wang, Haun; Liu, Guangxiong; Deng, Zihe; Ye, Ming; Zhang, Yan; Zhang, Zhijun

    2015-03-30

    Motor imagery provides direct insight into an anatomically interconnected system involved in the integration of sensory information with motor actions, a process that is associated with positive symptoms in schizophrenia (SCZ). However, very little is known about the electrophysiological processing of motor imagery in first episode SCZ. In the current study, we used a visual hand mental rotation (MR) paradigm to manipulate the processing of motor imagery while event-related brain potentials (ERPs) were recorded in 42 SCZ participants and 40 healthy controls (HC). The 400-600 ms window was measured and analyzed for peak latencies and amplitudes. Participants with SCZ had slower reaction time (RT) and made more errors than did HC participants. Moreover, SCZ participants had lower amplitudes in the 400-600 ms window and the typical MR function for amplitudes of MR was lacking. Interestingly, the scalp activity maps for MR in SCZ exhibited an absence of activation in the left parietal site as shown in HC. Furthermore, deficits of amplitude for MR were positively correlated with positive symptom scores in SCZ. These results provide novel evidence for relationships between the electrophysiological processing of motor imagery and positive symptoms in SCZ. They further suggest that the impaired information processing of motor imagery indexed by amplitudes and specific topographic characteristics of the EEG during MR tasks may be a potentially useful and early defining biomarker for SCZ. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Neonatal white matter abnormality predicts childhood motor impairment in very preterm children.

    PubMed

    Spittle, Alicia J; Cheong, Jeanie; Doyle, Lex W; Roberts, Gehan; Lee, Katherine J; Lim, Jeremy; Hunt, Rod W; Inder, Terrie E; Anderson, Peter J

    2011-11-01

    Children born very preterm are at risk for impaired motor performance ranging from cerebral palsy (CP) to milder abnormalities, such as developmental coordination disorder. White matter abnormalities (WMA) at term have been associated with CP in very preterm children; however, little is known about the impact of WMA on the range of motor impairments. The aim of this study was to assess whether WMA were predictive of all levels of motor impairments in very preterm children. Two hundred and twenty-seven very preterm infants (< 30 wks gestational age or birthweight < 1250 g) had brain magnetic resonance imaging at term-equivalent age to assess for WMA, which were categorized as nil, mild, or moderate to severe. At 5 years of age children were classified as having a moderate to severe motor impairment if they were below the 5th centile or mild to severe motor impairment if their score placed them no higher than the 15th centile on the Movement Assessment Battery for Children (MABC). WMA (nil vs mild and nil vs moderate-severe) were explored as predictors of motor impairment using logistic regression. Analyses were repeated adjusting for the effects of other perinatal variables and excluding children with CP. Of the 193 very preterm children (97 males, 96 females) assessed with the MABC, 53 (27%) were classified as having a moderate to severe motor impairment and 96 (50%) a mild to severe motor impairment. WMA were predictive of motor impairment in very preterm children, with mild versus no WMA increasing the odds of moderate to severe motor impairment by over fivefold (odds ratio [OR] 5.6; 95% confidence interval [CI] 1.9-16.1; p=0.002) and mild to severe impairment by twofold (OR 2.2; 95% CI 1.1-4.2; p=0.02). Compared with no WMA, moderate to severe WMA increased the odds for moderate to severe impairment 19-fold (OR 19.4; 95% CI 5.6-66.7; p<0.001) and for mild to severe motor impairment ninefold (OR 9.4; 95% CI 3.2-28.1; p<0.001). Results remained similar after

  1. A flood episode in Northern Italy: multi-model and single-model mesoscale meteorological ensembles for hydrological predictions

    NASA Astrophysics Data System (ADS)

    Davolio, S.; Miglietta, M. M.; Diomede, T.; Marsigli, C.; Montani, A.

    2012-12-01

    Numerical weather prediction models can be coupled with hydrological models to generate streamflow forecasts. Several ensemble approaches have been recently developed in order to take into account the different sources of errors and provide probabilistic forecasts feeding a flood forecasting system. Within this framework, the present study aims at comparing two high-resolution limited-area meteorological ensembles, covering short and medium range, obtained via different methodologies, but implemented with similar number of members, horizontal resolution (about 7 km), and driving global ensemble prediction system. The former is a multi-model ensemble, based on three mesoscale models (BOLAM, COSMO, and WRF), while the latter, following a single-model approach, is the operational ensemble forecasting system developed within the COSMO consortium, COSMO-LEPS (Limited-area Ensemble Prediction System). The meteorological models are coupled with a distributed rainfall-runoff model (TOPKAPI) to simulate the discharge of the Reno River (Northern Italy), for a recent severe weather episode affecting Northern Apennines. The evaluation of the ensemble systems is performed both from a meteorological perspective over the entire Northern Italy and in terms of discharge prediction over the Reno River basin during two periods of heavy precipitation between 29 November and 2 December 2008. For each period, ensemble performance has been compared at two different forecast ranges. It is found that both mesoscale model ensembles remarkably outperform the global ensemble for application at basin scale as the horizontal resolution plays a relevant role in modulating the precipitation distribution. Moreover, the multi-model ensemble provides more informative probabilistic predictions with respect to COSMO-LEPS, since it is characterized by a larger spread especially at short lead times. A thorough analysis of the multi-model results shows that this behaviour is due to the different

  2. Factors Predicting Post-High School Employment for Young Adults with Visual Impairments

    ERIC Educational Resources Information Center

    McDonnall, Michele Capella

    2010-01-01

    Although low levels of employment among transition-age youth with visual impairments (VI) have long been a concern, empirical research in this area is very limited. The purpose of this study was to identify factors that predict future employment for this population and to compare these factors to the factors that predict employment for the general…

  3. Factors Predicting Post-High School Employment for Young Adults with Visual Impairments

    ERIC Educational Resources Information Center

    McDonnall, Michele Capella

    2010-01-01

    Although low levels of employment among transition-age youth with visual impairments (VI) have long been a concern, empirical research in this area is very limited. The purpose of this study was to identify factors that predict future employment for this population and to compare these factors to the factors that predict employment for the general…

  4. Predicting imminent episodes of ventricular tachyarrhythmia--retrospective analysis of short R-R records from ICD.

    PubMed

    Thong, Tran

    2008-01-01

    A predictor of an imminent episode of ventricular tachyarrhythmia, namely ventricular tachycardia and ventricular fibrillation has been developed. It only uses R-R records. The previous work was based on long R-R records stored in the memory of implantable cardioverter-defibrillators. With 1.8 hour of data, sensitivity of 53-83% can be achieved with corresponding specificity of 57-91%, depending on which set of criteria are used. The Medtronic ICD data series was made available to us. This consists of 135 pairs of files with 1024 R-R intervals. Each pair consists of a record that ends with the detection of the tachyarrhythmia, and a 'most recent' record just prior to the interrogation of the device. It was hoped that the 'most recent' record can be used to improve the specificity of the prediction algorithm. The predictor pattern was found in 29% of the arrhythmic records, and in 38% of the records with heart rate variability, namely SDNN, greater than 20 ms. This is comparable to the 40% results for similar conditions found earlier for records only 0.2 hr long. Unfortunately, due to a 'white coat effect', the predictor pattern was found in 40% of the 'most recent' records. While this new set of data has confirmed the sensitivity of the arrhythmia predictor, a fault in the data collection process this data set did not add to our understanding of the predictor behavior with a normal heart rhythm.

  5. A flood episode in northern Italy: multi-model and single-model mesoscale meteorological ensembles for hydrological predictions

    NASA Astrophysics Data System (ADS)

    Davolio, S.; Miglietta, M. M.; Diomede, T.; Marsigli, C.; Montani, A.

    2013-06-01

    Numerical weather prediction models can be coupled with hydrological models to generate streamflow forecasts. Several ensemble approaches have been recently developed in order to take into account the different sources of errors and provide probabilistic forecasts feeding a flood forecasting system. Within this framework, the present study aims at comparing two high-resolution limited-area meteorological ensembles, covering short and medium range, obtained via different methodologies, but implemented with similar number of members, horizontal resolution (about 7 km), and driving global ensemble prediction system. The former is a multi-model ensemble, based on three mesoscale models (BOLAM, COSMO, and WRF), while the latter, following a single-model approach, is the operational ensemble forecasting system developed within the COSMO consortium, COSMO-LEPS (limited-area ensemble prediction system). The meteorological models are coupled with a distributed rainfall-runoff model (TOPKAPI) to simulate the discharge of the Reno River (northern Italy), for a recent severe weather episode affecting northern Apennines. The evaluation of the ensemble systems is performed both from a meteorological perspective over northern Italy and in terms of discharge prediction over the Reno River basin during two periods of heavy precipitation between 29 November and 2 December 2008. For each period, ensemble performance has been compared at two different forecast ranges. It is found that, for the intercomparison undertaken in this specific study, both mesoscale model ensembles outperform the global ensemble for application at basin scale. Horizontal resolution is found to play a relevant role in modulating the precipitation distribution. Moreover, the multi-model ensemble provides a better indication concerning the occurrence, intensity and timing of the two observed discharge peaks, with respect to COSMO-LEPS. This seems to be ascribable to the different behaviour of the involved

  6. Higher Self-Control Capacity Predicts Lower Anxiety-Impaired Cognition during Math Examinations

    PubMed Central

    Bertrams, Alex; Baumeister, Roy F.; Englert, Chris

    2016-01-01

    We assumed that self-control capacity, self-efficacy, and self-esteem would enable students to keep attentional control during tests. Therefore, we hypothesized that the three personality traits would be negatively related to anxiety-impaired cognition during math examinations. Secondary school students (N = 158) completed measures of self-control capacity, self-efficacy, and self-esteem at the beginning of the school year. Five months later, anxiety-impaired cognition during math examinations was assessed. Higher self-control capacity, but neither self-efficacy nor self-esteem, predicted lower anxiety-impaired cognition 5 months later, over and above baseline anxiety-impaired cognition. Moreover, self-control capacity was indirectly related to math grades via anxiety-impaired cognition. The findings suggest that improving self-control capacity may enable students to deal with anxiety-related problems during school tests. PMID:27065013

  7. A Study of Impairing Injuries in Real World Crashes Using the Injury Impairment Scale (IIS) and the Predicted Functional Capacity Index (PFCI-AIS)

    PubMed Central

    Barnes, Jo; Morris, Andrew

    2009-01-01

    The ability to predict impairment outcomes in large databases using a simplified technique allows researchers to focus attention on preventing costly impairing injuries. The dilemma that exists for researchers is to determine which method is the most reliable and valid. This study examines available methods to predict impairment and explores the differences between the IIS and pFCI applied to real world crash injury data. Occupant injury data from the UK Co-operative Crash Injury Study (CCIS) database have been coded using AIS 1990 and AIS 2005. The data have subsequently been recoded using the associated impairment scales namely the Injury Impairment Scale (IIS) and the predicted Functional Capacity Index (pFCI) to determine the predicted impairment levels of injuries at one year post crash. Comparisons between the levels of impairment were made and any differences further explored. Injury data for the period February 2006 to September 2008 from the CCIS database were used in the analysis which involved a dataset of 2,437 occcupants who sustained over 8000 injuries. This study found some differences between the impairment scales for injuries coded to the AIS 1990 and AIS 2005 coding dictionaries. The pFCI predicts 31.5% of injuries to be impairing in AIS 2005, less than the IIS (38.5%) using AIS 1990. Using CCIS data the pFCI predicted that only 6% of the occupants with a coded injury would have an impairing injury compared to 24% of occupants using the IIS. The main body regions identified as having the major differences between the two impairment scales for car occupants were the head and spine. Follow up data were then used for a small number of cases (n=31, lower extremity and whiplash injuries) to examine any differences in predicted impairment versus perceived impairment. These data were selected from a previous study conducted between 2003 and 2006 and identified the discrepancy between predicted impairment and actual perceived impairment as defined by the

  8. A study of impairing injuries in real world crashes using the Injury Impairment Scale (IIS) and the predicted Functional Capacity Index (PFCI-AIS).

    PubMed

    Barnes, Jo; Morris, Andrew

    2009-10-01

    The ability to predict impairment outcomes in large databases using a simplified technique allows researchers to focus attention on preventing costly impairing injuries. The dilemma that exists for researchers is to determine which method is the most reliable and valid. This study examines available methods to predict impairment and explores the differences between the IIS and pFCI applied to real world crash injury data. Occupant injury data from the UK Co-operative Crash Injury Study (CCIS) database have been coded using AIS 1990 and AIS 2005. The data have subsequently been recoded using the associated impairment scales namely the Injury Impairment Scale (IIS) and the predicted Functional Capacity Index (pFCI) to determine the predicted impairment levels of injuries at one year post crash. Comparisons between the levels of impairment were made and any differences further explored. Injury data for the period February 2006 to September 2008 from the CCIS database were used in the analysis which involved a dataset of 2,437 occcupants who sustained over 8000 injuries. This study found some differences between the impairment scales for injuries coded to the AIS 1990 and AIS 2005 coding dictionaries. The pFCI predicts 31.5% of injuries to be impairing in AIS 2005, less than the IIS (38.5%) using AIS 1990. Using CCIS data the pFCI predicted that only 6% of the occupants with a coded injury would have an impairing injury compared to 24% of occupants using the IIS. The main body regions identified as having the major differences between the two impairment scales for car occupants were the head and spine. Follow up data were then used for a small number of cases (n=31, lower extremity and whiplash injuries) to examine any differences in predicted impairment versus perceived impairment. These data were selected from a previous study conducted between 2003 and 2006 and identified the discrepancy between predicted impairment and actual perceived impairment as defined by the

  9. Personality disorder symptom severity predicts onset of mood episodes and conversion to bipolar I disorder in individuals with bipolar spectrum disorder.

    PubMed

    Ng, Tommy H; Burke, Taylor A; Stange, Jonathan P; Walshaw, Patricia D; Weiss, Rachel B; Urosevic, Snezana; Abramson, Lyn Y; Alloy, Lauren B

    2017-04-01

    Although personality disorders (PDs) are highly comorbid with bipolar spectrum disorders (BSDs), little longitudinal research has been conducted to examine the prospective impact of PD symptoms on the course of BSDs. The aim of this study is to examine whether PD symptom severity predicts shorter time to onset of bipolar mood episodes and conversion to bipolar I disorder over time among individuals with less severe BSDs. Participants (n = 166) with bipolar II disorder, cyclothymia, or bipolar disorder not otherwise specified completed diagnostic interview assessments of PD symptoms and self-report measures of mood symptoms at baseline. They were followed prospectively with diagnostic interviews every 4 months for an average of 3.02 years. Cox proportional hazard regression analyses indicated that overall PD symptom severity significantly predicted shorter time to onset of hypomanic (hazard ratio [HR] = 1.42; p < .001) and major depressive episodes (HR = 1.51; p < .001) and conversion to bipolar I disorder (HR = 2.51; p < .001), after controlling for mood symptoms. Results also suggested that cluster B severity predicted shorter time to onset of hypomanic episodes (HR = 1.38; p = .002) and major depressive episodes (HR = 1.35; p = .01) and conversion to bipolar I disorder (HR = 2.77; p < .001), whereas cluster C severity (HR = 1.56; p < .001) predicted shorter time to onset of major depressive episodes. These results support predisposition models in suggesting that PD symptoms may act as a risk factor for a more severe course of BSDs. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  10. MRI-Based Classification Models in Prediction of Mild Cognitive Impairment and Dementia in Late-Life Depression

    PubMed Central

    Lebedeva, Aleksandra K.; Westman, Eric; Borza, Tom; Beyer, Mona K.; Engedal, Knut; Aarsland, Dag; Selbaek, Geir; Haberg, Asta K.

    2017-01-01

    Objective: Late-life depression (LLD) is associated with development of different types of dementia. Identification of LLD patients, who will develop cognitive decline, i.e., the early stage of dementia would help to implement interventions earlier. The purpose of this study was to assess whether structural brain magnetic resonance imaging (MRI) in LLD patients can predict mild cognitive impairment (MCI) or dementia 1 year prior to the diagnosis. Methods: LLD patients underwent brain MRI at baseline and repeated clinical assessment after 1-year. Structural brain measurements were obtained using Freesurfer software (v. 5.1) from the T1W brain MRI images. MRI-based Random Forest classifier was used to discriminate between LLD who developed MCI or dementia after 1-year follow-up and cognitively stable LLD. Additionally, a previously established Random Forest model trained on 185 patients with Alzheimer’s disease (AD) vs. 225 cognitively normal elderly from the Alzheimer’s disease Neuroimaging Initiative was tested on the LLD data set (ADNI model). Results: MCI and dementia diagnoses were predicted in LLD patients with 76%/68%/84% accuracy/sensitivity/specificity. Adding the baseline Mini-Mental State Examination (MMSE) scores to the models improved accuracy/sensitivity/specificity to 81%/75%/86%. The best model predicted MCI status alone using MRI and baseline MMSE scores with accuracy/sensitivity/specificity of 89%/85%/90%. The most important region for all the models was right ventral diencephalon, including hypothalamus. Its volume correlated negatively with the number of depressive episodes. ADNI model trained on AD vs. Controls using SV could predict MCI-DEM patients with 67% accuracy. Conclusion: LDD patients developing MCI and dementia can be discriminated from LLD patients remaining cognitively stable with good accuracy based on baseline structural MRI alone. Baseline MMSE score improves prediction accuracy. Ventral diencephalon, including the hypothalamus

  11. Cortisol Responses to Psychosocial Stress Predict Depression Trajectories: Social-Evaluative Threat and Prior Depressive Episodes as Moderators

    PubMed Central

    Morris, Matthew C.; Rao, Uma; Garber, Judy

    2012-01-01

    Background Alterations of hypothalamic-pituitary-adrenal (HPA) function are well-established in adults with current depression. HPA alterations may persist into remission and confer increased risk for recurrence. Methods A modified version of the Trier Social Stress Test (TSST) was administered at baseline to 32 young adults with remitted major depressive disorder and 36 never-depressed controls. Participants were randomly assigned to either a ‘high–stress’ condition involving social evaluation or a ‘low-stress’ control condition. Cortisol concentrations were measured in saliva samples throughout the TSST. Participants were assessed again after 6 months for the occurrence of stressful life events and depressive symptoms/disorders during the follow-up period. Results Participants who exhibited enhanced cortisol reactivity in the low-stress condition showed increases in depressive symptoms over follow-up, after controlling for stressful life events during the follow-up period. Anticipatory stress cortisol and cortisol reactivity each interacted with history of depressive episodes to predict depression trajectories. Limitations The single TSST administration limits conclusions about whether alterations of cortisol reactivity represent trait-like vulnerability factors or consequences (“scars’) of past depression. Conclusions These results extend previous findings on stress sensitivity in depression and suggest that altered HPA function during remission could reflect an endophenotype for vulnerability to depression recurrence. Findings support interactive models of risk for depression recurrence implicating HPA function, depression history, and sensitivity to minor stressors. Results may have implications for interventions that match treatment approaches to profiles of HPA function. PMID:22858210

  12. Insomnia brings soldiers into mental health treatment, predicts treatment engagement, and outperforms other suicide-related symptoms as a predictor of major depressive episodes.

    PubMed

    Hom, Melanie A; Lim, Ingrid C; Stanley, Ian H; Chiurliza, Bruno; Podlogar, Matthew C; Michaels, Matthew S; Buchman-Schmitt, Jennifer M; Silva, Caroline; Ribeiro, Jessica D; Joiner, Thomas E

    2016-08-01

    Given the high rates of suicide among military personnel and the need to characterize suicide risk factors associated with mental health service use, this study aimed to identify suicide-relevant factors that predict: (1) treatment engagement and treatment adherence, and (2) suicide attempts, suicidal ideation, and major depressive episodes in a military sample. Army recruiters (N = 2596) completed a battery of self-report measures upon study enrollment. Eighteen months later, information regarding suicide attempts, suicidal ideation, major depressive episodes, and mental health visits were obtained from participants' military medical records. Suicide attempts and suicidal ideation were very rare in this sample; negative binomial regression analyses with robust estimation were used to assess correlates and predictors of mental health treatment visits and major depressive episodes. More severe insomnia and agitation were significantly associated with mental health visits at baseline and over the 18-month study period. In contrast, suicide-specific hopelessness was significantly associated with fewer mental health visits. Insomnia severity was the only significant predictor of major depressive episodes. Findings suggest that assessment of sleep problems might be useful in identifying at-risk military service members who may engage in mental health treatment. Additional research is warranted to examine the predictive validity of these suicide-related symptom measures in a more representative, higher suicide risk military sample.

  13. Perspectives on Episodic-Like and Episodic Memory

    PubMed Central

    Pause, Bettina M.; Zlomuzica, Armin; Kinugawa, Kiyoka; Mariani, Jean; Pietrowsky, Reinhard; Dere, Ekrem

    2013-01-01

    Episodic memory refers to the conscious recollection of a personal experience that contains information on what has happened and also where and when it happened. Recollection from episodic memory also implies a kind of first-person subjectivity that has been termed autonoetic consciousness. Episodic memory is extremely sensitive to cerebral aging and neurodegenerative diseases. In Alzheimer’s disease deficits in episodic memory function are among the first cognitive symptoms observed. Furthermore, impaired episodic memory function is also observed in a variety of other neuropsychiatric diseases including dissociative disorders, schizophrenia, and Parkinson disease. Unfortunately, it is quite difficult to induce and measure episodic memories in the laboratory and it is even more difficult to measure it in clinical populations. Presently, the tests used to assess episodic memory function do not comply with even down-sized definitions of episodic-like memory as a memory for what happened, where, and when. They also require sophisticated verbal competences and are difficult to apply to patient populations. In this review, we will summarize the progress made in defining behavioral criteria of episodic-like memory in animals (and humans) as well as the perspectives in developing novel tests of human episodic memory which can also account for phenomenological aspects of episodic memory such as autonoetic awareness. We will also define basic behavioral, procedural, and phenomenological criteria which might be helpful for the development of a valid and reliable clinical test of human episodic memory. PMID:23616754

  14. Do CSF Biomarkers Predict Progression to Cognitive Impairment in Parkinson's disease patients? A Systematic Review.

    PubMed

    Leaver, Katherine; Poston, Kathleen L

    2015-12-01

    Many patients with Parkinson's disease (PD) will develop cognitive impairment. Cross-sectional studies have shown that certain protein levels are altered in the cerebrospinal fluid (CSF) of PD patients with dementia and are thought to represent potential biomarkers of underlying pathogenesis. Recent studies suggest that CSF biomarker levels may be predictive of future risk of cognitive decline in non-demented PD patients. However, the strength of this evidence and difference between specific CSF biomarkers is not well delineated. We therefore performed a systematic review to assess if levels of specific CSF protein biomarkers are predictive of progression to cognitive impairment. Nine articles were identified that met inclusion criteria for the review. Findings from the review suggest a convergence of evidence that a low baseline Aβ42 in the CSF of non-demented PD patients predicts development of cognitive impairment over time. Conversely, there is limited evidence that CSF levels of tau, either total tau or phosphorylated tau, is a useful predictive biomarker. There are mixed results for other CSF biomarkers such as α-synuclein, Neurofilament light chain, and Heart fatty acid-binding protein. Overall the results of this review show that certain CSF biomarkers have better predictive ability to identify PD patients who are at risk for developing cognitive impairment. Given the interest in developing disease-modifying therapies, identifying this group will be important for clinical trials as initiation of therapy prior to the onset of cognitive decline is likely to be more efficacious.

  15. Disruptions of network connectivity predict impairment in multiple behavioral domains after stroke.

    PubMed

    Siegel, Joshua Sarfaty; Ramsey, Lenny E; Snyder, Abraham Z; Metcalf, Nicholas V; Chacko, Ravi V; Weinberger, Kilian; Baldassarre, Antonello; Hacker, Carl D; Shulman, Gordon L; Corbetta, Maurizio

    2016-07-26

    Deficits following stroke are classically attributed to focal damage, but recent evidence suggests a key role of distributed brain network disruption. We measured resting functional connectivity (FC), lesion topography, and behavior in multiple domains (attention, visual memory, verbal memory, language, motor, and visual) in a cohort of 132 stroke patients, and used machine-learning models to predict neurological impairment in individual subjects. We found that visual memory and verbal memory were better predicted by FC, whereas visual and motor impairments were better predicted by lesion topography. Attention and language deficits were well predicted by both. Next, we identified a general pattern of physiological network dysfunction consisting of decrease of interhemispheric integration and intrahemispheric segregation, which strongly related to behavioral impairment in multiple domains. Network-specific patterns of dysfunction predicted specific behavioral deficits, and loss of interhemispheric communication across a set of regions was associated with impairment across multiple behavioral domains. These results link key organizational features of brain networks to brain-behavior relationships in stroke.

  16. Disruptions of network connectivity predict impairment in multiple behavioral domains after stroke

    PubMed Central

    Ramsey, Lenny E.; Metcalf, Nicholas V.; Chacko, Ravi V.; Weinberger, Kilian; Baldassarre, Antonello; Hacker, Carl D.; Shulman, Gordon L.; Corbetta, Maurizio

    2016-01-01

    Deficits following stroke are classically attributed to focal damage, but recent evidence suggests a key role of distributed brain network disruption. We measured resting functional connectivity (FC), lesion topography, and behavior in multiple domains (attention, visual memory, verbal memory, language, motor, and visual) in a cohort of 132 stroke patients, and used machine-learning models to predict neurological impairment in individual subjects. We found that visual memory and verbal memory were better predicted by FC, whereas visual and motor impairments were better predicted by lesion topography. Attention and language deficits were well predicted by both. Next, we identified a general pattern of physiological network dysfunction consisting of decrease of interhemispheric integration and intrahemispheric segregation, which strongly related to behavioral impairment in multiple domains. Network-specific patterns of dysfunction predicted specific behavioral deficits, and loss of interhemispheric communication across a set of regions was associated with impairment across multiple behavioral domains. These results link key organizational features of brain networks to brain–behavior relationships in stroke. PMID:27402738

  17. Using Virtual Reality to Characterize Episodic Memory Profiles in Amnestic Mild Cognitive Impairment and Alzheimer's Disease: Influence of Active and Passive Encoding

    ERIC Educational Resources Information Center

    Plancher, G.; Tirard, A.; Gyselinck, V.; Nicolas, S.; Piolino, P.

    2012-01-01

    Most neuropsychological assessments of episodic memory bear little similarity to the events that patients actually experience as memories in daily life. The first aim of this study was to use a virtual environment to characterize episodic memory profiles in an ecological fashion, which includes memory for central and perceptual details,…

  18. Using Virtual Reality to Characterize Episodic Memory Profiles in Amnestic Mild Cognitive Impairment and Alzheimer's Disease: Influence of Active and Passive Encoding

    ERIC Educational Resources Information Center

    Plancher, G.; Tirard, A.; Gyselinck, V.; Nicolas, S.; Piolino, P.

    2012-01-01

    Most neuropsychological assessments of episodic memory bear little similarity to the events that patients actually experience as memories in daily life. The first aim of this study was to use a virtual environment to characterize episodic memory profiles in an ecological fashion, which includes memory for central and perceptual details,…

  19. American Spinal Injury Association Impairment Scale Predicts the Need for Tracheostomy After Cervical Spinal Cord Injury.

    PubMed

    Childs, Benjamin R; Moore, Timothy A; Como, John J; Vallier, Heather A

    2015-09-15

    Retrospective review. The objective of this study was to evaluate the ability of the American Spinal Injury Association (ASIA) Impairment Scale and neurological level of injury to predict the need for mechanical ventilation as well as tracheostomy. High-level cervical spinal cord injuries, high Injury Severity Score, and low Glasgow Coma Scale have been shown to predict tracheostomy. A total of 383 patients with fractures, dislocations, or ligamentous injury of the cervical spine were included in the study. Charts were reviewed to determine demographics, Injury Severity Score, Glasgow Coma Scale, presence and severity of chest injuries, length of hospital stay, intensive care unit stay, mechanical ventilation time, and mortality. Fifty-nine patients (15.4%) underwent tracheostomy. An ASIA Impairment Scale of A had a specificity of 98.8% and sensitivity of 32.2% for predicting the need for tracheostomy. This yielded a 1.2% false-positive rate. The ASIA Impairment Scale remained the most significant predictor after regression for Injury Severity Score, Glasgow Coma Scale, and Chest Abbreviated Injury Scale. Neurological level of injury was not a significant predictor of tracheostomy. An ASIA Impairment Scale of A at any level of injury is a specific predictor of the need for tracheostomy with a low false-positive rate. Given the relatively low risk of early tracheostomy and the potential benefits, an ASIA Impairment Scale of A would be a sensible early criterion to determine the need for tracheostomy. 3.

  20. Theory of mind impairments in first-episode psychosis, individuals at ultra-high risk for psychosis and in first-degree relatives of schizophrenia: systematic review and meta-analysis.

    PubMed

    Bora, Emre; Pantelis, Christos

    2013-03-01

    Theory of mind (ToM) deficit is a well-established feature of schizophrenia and has been suggested as a vulnerability marker of this disorder. However, as most of this evidence is based on studies in chronic patients, it is less clear whether ToM is impaired prior to or following the onset of a first-episode and whether it is evident in unaffected relatives of patients. In this meta-analysis, ToM performance of 3005 individuals with first-episode psychosis (FEP), individuals at ultra-high risk for psychosis (UHR) and unaffected relatives were compared with 1351 healthy controls. ToM was substantially impaired in first-episode psychosis (Cohen d=1.0) and this deficit was comparable to findings in chronic patients. ToM was also impaired in unaffected relatives (d=0.37) and UHR subjects (d=0.45) and performances of these groups were intermediate between FES and healthy controls. Severity of ToM deficits in unaffected relatives and UHR subjects was similar to other cognitive deficits observed in these groups. Longitudinal studies of clinical and genetic high-risk subjects are necessary to investigate the trajectory of development of ToM deficits in schizophrenia. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Use of the binomial distribution to predict impairment: application in a nonclinical sample.

    PubMed

    Axelrod, Bradley N; Wall, Jacqueline R; Estes, Bradley W

    2008-01-01

    A mathematical model based on the binomial theory was developed to illustrate when abnormal score variations occur by chance in a multitest battery (Ingraham & Aiken, 1996). It has been successfully used as a comparison for obtained test scores in clinical samples, but not in nonclinical samples. In the current study, this model has been applied to demographically corrected scores on the Halstead-Reitan Neuropsychological Test Battery, obtained from a sample of 94 nonclinical college students. Results found that 15% of the sample had impairments suggested by the Halstead Impairment Index, using criteria established by Reitan and Wolfson (1993). In addition, one-half of the sample obtained impaired scores on one or two tests. These results were compared to that predicted by the binomial model and found to be consistent. The model therefore serves as a useful resource for clinicians considering the probability of impaired test performance.

  2. Predicting academic performance in children with language impairment: the role of parent report.

    PubMed

    Hall, Nancy E; Segarra, Veronica Rosa

    2007-01-01

    This study examines the ability of preschool speech-language measures and parent report in predicting later academic performance. Preschool measures of speech, language and communication for 35 children with language impairment were analyzed for their ability to predict reading, writing, spelling, and mathematics in these same children at age nine. Regression analyses revealed that scores from the Vineland Adaptive Behavior Scales Communication Domain (a parent report instrument) were the best predictors of scores on measures of reading, writing, and math, while the scores from the Photo Articulation Test best predicted spelling outcomes. The results are discussed relative to the value of parent report in assessing and managing language impairment, and predicting scholastic performance in preschool children.

  3. Multivariate Analysis of MRI Biomarkers for Predicting Neurologic Impairment in Cervical Spinal Cord Injury.

    PubMed

    Haefeli, J; Mabray, M C; Whetstone, W D; Dhall, S S; Pan, J Z; Upadhyayula, P; Manley, G T; Bresnahan, J C; Beattie, M S; Ferguson, A R; Talbott, J F

    2017-03-01

    Acute markers of spinal cord injury are essential for both diagnostic and prognostic purposes. The goal of this study was to assess the relationship between early MR imaging biomarkers after acute cervical spinal cord injury and to evaluate their predictive validity of neurologic impairment. We performed a retrospective cohort study of 95 patients with acute spinal cord injury and preoperative MR imaging within 24 hours of injury. The American Spinal Injury Association Impairment Scale was used as our primary outcome measure to define neurologic impairment. We assessed several MR imaging features of injury, including axial grade (Brain and Spinal Injury Center score), sagittal grade, length of injury, maximum canal compromise, and maximum spinal cord compression. Data-driven nonlinear principal component analysis was followed by correlation and optimal-scaled multiple variable regression to predict neurologic impairment. Nonlinear principal component analysis identified 2 clusters of MR imaging variables related to 1) measures of intrinsic cord signal abnormality and 2) measures of extrinsic cord compression. Neurologic impairment was best accounted for by MR imaging measures of intrinsic cord signal abnormality, with axial grade representing the most accurate predictor of short-term impairment, even when correcting for surgical decompression and degree of cord compression. This study demonstrates the utility of applying nonlinear principal component analysis for defining the relationship between MR imaging biomarkers in a complex clinical syndrome of cervical spinal cord injury. Of the assessed imaging biomarkers, the intrinsic measures of cord signal abnormality were most predictive of neurologic impairment in acute spinal cord injury, highlighting the value of axial T2 MR imaging. © 2017 by American Journal of Neuroradiology.

  4. Predicting Social Impairment and ASD Diagnosis in Younger Siblings of Children with Autism Spectrum Disorder

    PubMed Central

    Stone, Wendy L.; Walden, Tedra; Malesa, Elizabeth

    2014-01-01

    Later-born siblings of children with autism spectrum disorder (Sibs-ASD) are at elevated risk for social impairments. Two putative predictors of later social impairment—measures of responding to joint attention and weighted triadic communication—were examined in a sample of 43 Sibs-ASD who were followed from 15 to 34 months of age. Results revealed that initial level of responding to joint attention and growth rate of weighted triadic communication predicted the degree of social impairment at the final measurement period. Additionally, both predictors were associated with later ASD diagnosis. In contrast, unweighted triadic communication, age of entry into the study, and initial language level did not predict later social impairment. The importance of considering social outcome as a continuous variable in prospective studies of Sibs-ASD is discussed. PMID:19449096

  5. Conversion from mild cognitive impairment to probable Alzheimer's disease predicted by brain magnetic resonance spectroscopy.

    PubMed

    Modrego, Pedro J; Fayed, Nicolás; Pina, Miguel A

    2005-04-01

    Mild cognitive impairment has been regarded as a pre-Alzheimer condition, but some patients do not develop dementia. Given the available therapies for Alzheimer's disease, early diagnosis is of paramount importance. The authors' objective was to determine whether findings from magnetic resonance spectroscopy (MRS) of the hippocampus and other cortical areas would predict conversion from amnestic mild cognitive impairment to probable Alzheimer's disease. A longitudinal inception cohort of 53 consecutive and incident subjects fulfilling the criteria of amnestic mild cognitive impairment was followed for a mean period of 3 years. At baseline, a neuropsychological examination (Mini-Mental State Examination, Blessed Dementia Rating Scale, Clinical Dementia Rating, verbal fluency test, and memory tests) and standard blood tests were performed, and three cortical areas were examined by proton MRS: left hippocampus, right parietal cortex, and left occipital cortex. The patients were evaluated periodically to detect conversion to probable Alzheimer's disease. The statistical analysis of predictions was based on receiver operating characteristic curves. By the follow-up assessment that occurred on average after 3 years, 29 patients (55%) had developed probable Alzheimer's disease. An occipital cortex N-acetylaspartate/creatine ratio < or =1.61 predicted dementia at 100% sensitivity and 75% specificity (area under the curve=0.91, 95% CI=0.80-0.97). The positive predictive value was 83%, and the negative predictive value was 100%, with an overall cross-validated classification accuracy of 88.7%. None of the values in the hippocampus and parietal cortex had significant predictive value. MRS of the brain performed on patients with mild cognitive impairment is a valuable tool in predicting conversion to probable Alzheimer's disease. Occipital values were more reliable than hippocampal values in this prediction.

  6. Predicting Word Decoding and Word Spelling Development in Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    van Weerdenburg, Marjolijn; Verhoeven, Ludo; Bosman, Anna; van Balkom, Hans

    2011-01-01

    This longitudinal investigation on Dutch children with Specific Language Impairment (SLI) aimed at determining the predictive value of statistically uncorrelated language proficiencies on later reading and spelling skills in Dutch. Language abilities, tested with an extensive test battery at the onset of formal reading instruction, were…

  7. Predicting Efficiency of Travel in Young, Visually Impaired Children from Their Other Spatial Skills.

    ERIC Educational Resources Information Center

    Hill, Anita; And Others

    1985-01-01

    To test ways of predicting how efficiently visually impaired children learn travel skills, a criteria checklist of spatial skills was developed for close-body space, local space, and geographical/travel space. Comparison was made between predictors of efficient learning including subjective ratings of teachers, personal qualities and factors of…

  8. Predicting Efficiency of Travel in Young, Visually Impaired Children from Their Other Spatial Skills.

    ERIC Educational Resources Information Center

    Hill, Anita; And Others

    1985-01-01

    To test ways of predicting how efficiently visually impaired children learn travel skills, a criteria checklist of spatial skills was developed for close-body space, local space, and geographical/travel space. Comparison was made between predictors of efficient learning including subjective ratings of teachers, personal qualities and factors of…

  9. Learning to predict is spared in mild cognitive impairment due to Alzheimer's disease.

    PubMed

    Baker, Rosalind; Bentham, Peter; Kourtzi, Zoe

    2015-10-01

    Learning the statistics of the environment is critical for predicting upcoming events. However, little is known about how we translate previous knowledge about scene regularities to sensory predictions. Here, we ask whether patients with mild cognitive impairment due to Alzheimer's disease (MCI-AD) that are known to have spared implicit but impaired explicit recognition memory are able to learn temporal regularities and predict upcoming events. We tested the ability of MCI-AD patients and age-matched controls to predict the orientation of a test stimulus following exposure to sequences of leftwards or rightwards oriented gratings. Our results demonstrate that exposure to temporal sequences without feedback facilitates the ability to predict an upcoming stimulus in both MCI-AD patients and controls. Further, we show that executive cognitive control may account for individual variability in predictive learning. That is, we observed significant positive correlations of performance in attentional and working memory tasks with post-training performance in the prediction task. Taken together, these results suggest a mediating role of circuits involved in cognitive control (i.e. frontal circuits) that may support the ability for predictive learning in MCI-AD.

  10. Predicting brain-age from multimodal imaging data captures cognitive impairment.

    PubMed

    Liem, Franziskus; Varoquaux, Gaël; Kynast, Jana; Beyer, Frauke; Kharabian Masouleh, Shahrzad; Huntenburg, Julia M; Lampe, Leonie; Rahim, Mehdi; Abraham, Alexandre; Craddock, R Cameron; Riedel-Heller, Steffi; Luck, Tobias; Loeffler, Markus; Schroeter, Matthias L; Witte, Anja Veronica; Villringer, Arno; Margulies, Daniel S

    2017-03-01

    The disparity between the chronological age of an individual and their brain-age measured based on biological information has the potential to offer clinically relevant biomarkers of neurological syndromes that emerge late in the lifespan. While prior brain-age prediction studies have relied exclusively on either structural or functional brain data, here we investigate how multimodal brain-imaging data improves age prediction. Using cortical anatomy and whole-brain functional connectivity on a large adult lifespan sample (N=2354, age 19-82), we found that multimodal data improves brain-based age prediction, resulting in a mean absolute prediction error of 4.29 years. Furthermore, we found that the discrepancy between predicted age and chronological age captures cognitive impairment. Importantly, the brain-age measure was robust to confounding effects: head motion did not drive brain-based age prediction and our models generalized reasonably to an independent dataset acquired at a different site (N=475). Generalization performance was increased by training models on a larger and more heterogeneous dataset. The robustness of multimodal brain-age prediction to confounds, generalizability across sites, and sensitivity to clinically-relevant impairments, suggests promising future application to the early prediction of neurocognitive disorders.

  11. Validity of hearing impairment calculation methods for prediction of self-reported hearing handicap.

    PubMed

    John, Andrew B; Kreisman, Brian M; Pallett, Stephen

    2012-01-01

    Worker's compensation for hearing loss caused by occupational noise exposure is calculated by varying methods, from state to state within the United States (US), with many employing arithmetic formulas based on the pure-tone audiogram, to quantify hearing loss. Several assumptions unsupported or weakly supported by empirical data underlie these formulas. The present study evaluated the ability of various arithmetic hearing impairment calculations to predict a self-reported hearing handicap in a sample of presenting with sensorineural hearing loss. 204 adults (127 male, 77 female) ranging in age from 18 to 94 served as participants. The sample was selected to exclude patients who had been referred for hearing testing for a medicolegal examination or a hearing conservation appointment. A hearing handicap was measured by the Hearing Handicap Inventory for Adults/for the Elderly (HHIA/E). The covariance analysis of linear structural equations was used to assess the relative strength of correlation with the HHIA/E score among the six formulas and various forms of pure-tone average. The results revealed that all the hearing impairment calculations examined were significantly, but weakly, correlated with the self-reported hearing impairment scores. No significant differences among the predictive abilities of the impairment calculations were evident; however, the average binaural impairment assigned differed significantly among the six calculations examined. Individuals who demonstrated 0% impairment had significantly lower (i.e., better) HHIA/E scores compared to those with non-zero impairment for each formula. These results supported the idea that audiometric data provided an insufficient explanation for real-world hearing difficulties.

  12. Leg and Trunk Impairments Predict Participation in Life Roles in Older Adults: Results From Boston RISE

    PubMed Central

    Jette, Alan M.; Ni, Pengsheng; Latham, Nancy K.; Ward, Rachel E.; Kurlinski, Laura A.; Percac-Lima, Sanja; Leveille, Suzanne G.; Bean, Jonathan F.

    2016-01-01

    Background: The physical impairments that affect participation in life roles among older adults have not been identified. Using the International Classification of Functioning Disability and Health as a conceptual framework, we aimed to determine the leg and trunk impairments that predict participation over 2 years, both directly and indirectly through mediation by changes in activities. Methods: We analyzed 2 years of data from the Boston Rehabilitative Impairment Study of the Elderly, a cohort study of 430 primary care patients with self-reported mobility limitation (mean age 77 years; 68% female; average of four chronic conditions). Frequency of and limitations in participation were examined using the Late-Life Disability Instrument. Baseline physical impairments included: leg strength, leg speed of movement, knee range of motion (ROM), ankle ROM, leg strength asymmetry, kyphosis, and trunk extensor endurance. Structural equation modeling with latent growth curve analysis was used to identify the impairments that predicted participation at year 2, mediated by changes in activities. Models were adjusted for baseline participation, age, and gender. Results: Leg speed and ankle ROM directly influenced participation in life roles during follow-up (βdirect = 1.39–4.53 and 4.70, respectively). Additionally, ankle ROM and trunk extensor endurance contributed indirectly to participation score at follow-up via effects on changes in activities (βindirect = −1.06 to −4.24 and 1.01 to 4.18, respectively). Conclusions: Leg speed, ankle ROM, and trunk extensor endurance are key physical impairments predicting participation in life roles in older adults. These results have implications for the development of exercise interventions to enhance participation. PMID:26369668

  13. Prediction of motor recovery using initial impairment and fMRI 48 h poststroke.

    PubMed

    Zarahn, Eric; Alon, Leeor; Ryan, Sophia L; Lazar, Ronald M; Vry, Magnus-Sebastian; Weiller, Cornelius; Marshall, Randolph S; Krakauer, John W

    2011-12-01

    There is substantial interpatient variation in recovery from upper limb impairment after stroke in patients with severe initial impairment. Defining recovery as a change in the upper limb Fugl-Meyer score (ΔFM), we predicted ΔFM with its conditional expectation (i.e., posterior mean) given upper limb Fugl-Meyer initial impairment (FM(ii)) and a putative functional magnetic resonance imaging (fMRI) recovery measure. Patients with first time, ischemic stroke were imaged at 2.5 ± 2.2 days poststroke with 1.5-T fMRI during a hand closure task alternating with rest (fundamental frequency = 0.025 Hz, scan duration = 172 s). Confirming a previous finding, we observed that the prediction of ΔFM by FM(ii) alone is good in patients with nonsevere initial hemiparesis but is not good in patients with severe initial hemiparesis (96% and 16% of the total sum of squares of ΔFM explained, respectively). In patients with severe initial hemiparesis, prediction of ΔFM by the combination of FM(ii) and the putative fMRI recovery measure nonsignificantly increased predictive explanation from 16% to 47% of the total sum of squares of ΔFM explained. The implications of this preliminary negative result are discussed.

  14. Prediction of Motor Recovery Using Initial Impairment and fMRI 48 h Poststroke

    PubMed Central

    Alon, Leeor; Ryan, Sophia L.; Lazar, Ronald M.; Vry, Magnus-Sebastian; Weiller, Cornelius; Marshall, Randolph S.

    2011-01-01

    There is substantial interpatient variation in recovery from upper limb impairment after stroke in patients with severe initial impairment. Defining recovery as a change in the upper limb Fugl-Meyer score (ΔFM), we predicted ΔFM with its conditional expectation (i.e., posterior mean) given upper limb Fugl-Meyer initial impairment (FMii) and a putative functional magnetic resonance imaging (fMRI) recovery measure. Patients with first time, ischemic stroke were imaged at 2.5 ± 2.2 days poststroke with 1.5-T fMRI during a hand closure task alternating with rest (fundamental frequency = 0.025 Hz, scan duration = 172 s). Confirming a previous finding, we observed that the prediction of ΔFM by FMii alone is good in patients with nonsevere initial hemiparesis but is not good in patients with severe initial hemiparesis (96% and 16% of the total sum of squares of ΔFM explained, respectively). In patients with severe initial hemiparesis, prediction of ΔFM by the combination of FMii and the putative fMRI recovery measure nonsignificantly increased predictive explanation from 16% to 47% of the total sum of squares of ΔFM explained. The implications of this preliminary negative result are discussed. PMID:21527788

  15. Cognitive impairment predicts worse short-term response to spinal tap test in normal pressure hydrocephalus.

    PubMed

    Wolfsegger, Thomas; Topakian, Raffi

    2017-08-15

    In patients with idiopathic normal pressure hydrocephalus (iNPH), the spinal tap test (STT) is commonly used to predict ventriculoperitoneal shunt responsiveness. Clinical improvement following STT usually is measured by testing gait function. In our study, we investigated the impact of cognitive impairment on gait improvement after STT. 22 patients with the clinical and radiological diagnosis of iNPH underwent gait analyses (mobile measuring system Medilogic) before and 2-4h after STT in self-paced gait velocity over 7m. Prior to STT, cognition was evaluated by the Mini Mental State Examination (MMSE). MMSE<24/30 points was used to define the subgroup of patients with cognitive impairment (iNPH-CI). Spatio-temporal parameters of gait before STT vs. after STT were analyzed with ANOVA with repeated measures. 1. Baseline gait parameters did not differ between the two groups: patients with iNPH and normal cognition (n=11) and patients with iNPH-CI (n=11). 2. Following STT, there was significant improvement of gait parameters in patients without cognitive impairment, while patients with iNPH-CI did not benefit from STT. Subjects with iNPH have a higher probability of lack of gait improvement 2-4h following STT, if cognitive impairment is present. Further studies are needed to elucidate the associations of cognitive impairment and quantitative gait parameters measured early and at later time points after STT. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Clinical usefulness of the clock drawing test applying rasch analysis in predicting of cognitive impairment.

    PubMed

    Yoo, Doo Han; Lee, Jae Shin

    2016-07-01

    [Purpose] This study examined the clinical usefulness of the clock drawing test applying Rasch analysis for predicting the level of cognitive impairment. [Subjects and Methods] A total of 187 stroke patients with cognitive impairment were enrolled in this study. The 187 patients were evaluated by the clock drawing test developed through Rasch analysis along with the mini-mental state examination of cognitive evaluation tool. An analysis of the variance was performed to examine the significance of the mini-mental state examination and the clock drawing test according to the general characteristics of the subjects. Receiver operating characteristic analysis was performed to determine the cutoff point for cognitive impairment and to calculate the sensitivity and specificity values. [Results] The results of comparison of the clock drawing test with the mini-mental state showed significant differences in according to gender, age, education, and affected side. A total CDT of 10.5, which was selected as the cutoff point to identify cognitive impairement, showed a sensitivity, specificity, Youden index, positive predictive, and negative predicive values of 86.4%, 91.5%, 0.8, 95%, and 88.2%. [Conclusion] The clock drawing test is believed to be useful in assessments and interventions based on its excellent ability to identify cognitive disorders.

  17. Adding Recognition Discriminability Index to the Delayed Recall Is Useful to Predict Conversion from Mild Cognitive Impairment to Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative.

    PubMed

    Russo, María J; Campos, Jorge; Vázquez, Silvia; Sevlever, Gustavo; Allegri, Ricardo F

    2017-01-01

    Background: Ongoing research is focusing on the identification of those individuals with mild cognitive impairment (MCI) who are most likely to convert to Alzheimer's disease (AD). We investigated whether recognition memory tasks in combination with delayed recall measure of episodic memory and CSF biomarkers can predict MCI to AD conversion at 24-month follow-up. Methods: A total of 397 amnestic-MCI subjects from Alzheimer's disease Neuroimaging Initiative were included. Logistic regression modeling was done to assess the predictive value of all RAVLT measures, risk factors such as age, sex, education, APOE genotype, and CSF biomarkers for progression to AD. Estimating adjusted odds ratios was used to determine which variables would produce an optimal predictive model, and whether adding tests of interaction between the RAVLT Delayed Recall and recognition measures (traditional score and d-prime) would improve prediction of the conversion from a-MCI to AD. Results: 112 (28.2%) subjects developed dementia and 285 (71.8%) subjects did not. Of the all included variables, CSF Aβ1-42 levels, RAVLT Delayed Recall, and the combination of RAVLT Delayed Recall and d-prime were predictive of progression to AD (χ(2) = 38.23, df = 14, p < 0.001). Conclusions: The combination of RAVLT Delayed Recall and d-prime measures may be predictor of conversion from MCI to AD in the ADNI cohort, especially in combination with amyloid biomarkers. A predictive model to help identify individuals at-risk for dementia should include not only traditional episodic memory measures (delayed recall or recognition), but also additional variables (d-prime) that allow the homogenization of the assessment procedures in the diagnosis of MCI.

  18. Adding Recognition Discriminability Index to the Delayed Recall Is Useful to Predict Conversion from Mild Cognitive Impairment to Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative

    PubMed Central

    Russo, María J.; Campos, Jorge; Vázquez, Silvia; Sevlever, Gustavo; Allegri, Ricardo F.; Weiner, Michael W.

    2017-01-01

    Background: Ongoing research is focusing on the identification of those individuals with mild cognitive impairment (MCI) who are most likely to convert to Alzheimer's disease (AD). We investigated whether recognition memory tasks in combination with delayed recall measure of episodic memory and CSF biomarkers can predict MCI to AD conversion at 24-month follow-up. Methods: A total of 397 amnestic-MCI subjects from Alzheimer's disease Neuroimaging Initiative were included. Logistic regression modeling was done to assess the predictive value of all RAVLT measures, risk factors such as age, sex, education, APOE genotype, and CSF biomarkers for progression to AD. Estimating adjusted odds ratios was used to determine which variables would produce an optimal predictive model, and whether adding tests of interaction between the RAVLT Delayed Recall and recognition measures (traditional score and d-prime) would improve prediction of the conversion from a-MCI to AD. Results: 112 (28.2%) subjects developed dementia and 285 (71.8%) subjects did not. Of the all included variables, CSF Aβ1-42 levels, RAVLT Delayed Recall, and the combination of RAVLT Delayed Recall and d-prime were predictive of progression to AD (χ2 = 38.23, df = 14, p < 0.001). Conclusions: The combination of RAVLT Delayed Recall and d-prime measures may be predictor of conversion from MCI to AD in the ADNI cohort, especially in combination with amyloid biomarkers. A predictive model to help identify individuals at-risk for dementia should include not only traditional episodic memory measures (delayed recall or recognition), but also additional variables (d-prime) that allow the homogenization of the assessment procedures in the diagnosis of MCI. PMID:28344552

  19. Regional functional connectivity predicts distinct cognitive impairments in Alzheimer's disease spectrum.

    PubMed

    Ranasinghe, Kamalini G; Hinkley, Leighton B; Beagle, Alexander J; Mizuiri, Danielle; Dowling, Anne F; Honma, Susanne M; Finucane, Mariel M; Scherling, Carole; Miller, Bruce L; Nagarajan, Srikantan S; Vossel, Keith A

    2014-01-01

    Understanding neural network dysfunction in neurodegenerative disease is imperative to effectively develop network-modulating therapies. In Alzheimer's disease (AD), cognitive decline associates with deficits in resting-state functional connectivity of diffuse brain networks. The goal of the current study was to test whether specific cognitive impairments in AD spectrum correlate with reduced functional connectivity of distinct brain regions. We recorded resting-state functional connectivity of alpha-band activity in 27 patients with AD spectrum--22 patients with probable AD (5 logopenic variant primary progressive aphasia, 7 posterior cortical atrophy, and 10 early-onset amnestic/dysexecutive AD) and 5 patients with mild cognitive impairment due to AD. We used magnetoencephalographic imaging (MEGI) to perform an unbiased search for regions where patterns of functional connectivity correlated with disease severity and cognitive performance. Functional connectivity measured the strength of coherence between a given region and the rest of the brain. Decreased neural connectivity of multiple brain regions including the right posterior perisylvian region and left middle frontal cortex correlated with a higher degree of disease severity. Deficits in executive control and episodic memory correlated with reduced functional connectivity of the left frontal cortex, whereas visuospatial impairments correlated with reduced functional connectivity of the left inferior parietal cortex. Our findings indicate that reductions in region-specific alpha-band resting-state functional connectivity are strongly correlated with, and might contribute to, specific cognitive deficits in AD spectrum. In the future, MEGI functional connectivity could be an important biomarker to map and follow defective networks in the early stages of AD.

  20. Predicting quality of life impairment in chronic schizophrenia from cognitive variables.

    PubMed

    Ritsner, Michael S

    2007-08-01

    The aim of this study was to see whether and how cognition deficit predicts quality of life impairments in schizophrenia patients. The Computerized Cambridge Automated Neuropsychological Test Battery, the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and the Quality of Life Scale (QLS) were used to assess 62 patients with chronic schizophrenia. Step-wise multiple regression analysis was used in order to determine cognitive variables that would predict the scores of each Q-LES-Q and QLS domain scores. Regression analysis revealed a significant association of the cognitive deficits with both general and domain-specific quality of life impairment measured with Q-LES-Q and QLS. Deficits in executive functions, visual sustained attention, memory and motor skills have been found to be valid predictors both before and after controlling for the severity of symptoms, emotional distress, side effects, age, education, and illness duration. This study suggests that deficits in executive functioning, attention, memory and motor skills substantially contributes to predicting impairments across a wide range of HRQL domains, and, consequently, to quality of life appraisal in schizophrenia. Cognitive predictors cannot be attributed to illness-related and background variables. It can be concluded that, when aiming at the improvement of quality of life in schizophrenia patients, cognitive functioning should be targeted.

  1. Attention/processing speed prospectively predicts social impairment 18 years later in mood disorders.

    PubMed

    Sarapas, Casey; Shankman, Stewart A; Harrow, Martin; Faull, Robert N

    2013-09-01

    Cross-sectional studies suggest that cognitive deficits contribute to psychosocial impairment among individuals with mood disorders. However, studies examining whether cognition prospectively predicts psychosocial outcome are few, have used short follow-up periods, and have not demonstrated incremental validity (i.e., that cognition predicts future functioning even when controlling for baseline functioning). In a sample of 51 individuals with unipolar depression or bipolar disorder, we investigated whether attention/processing speed (APS) performance predicted social functioning 18 years later. Baseline APS predicted 18-year social functioning even after controlling for baseline social functioning and depressive symptoms, demonstrating incremental validity. Individuals with high baseline APS had stable social functioning over 18 years, whereas functioning deteriorated among those with low APS. This finding helps clarify the temporal order of cognitive and psychosocial deficits associated with mood disorders and suggests the clinical utility of cognitive measures in identifying those at risk of deterioration in social functioning.

  2. Preschool impairments in auditory processing and speech perception uniquely predict future reading problems.

    PubMed

    Boets, Bart; Vandermosten, Maaike; Poelmans, Hanne; Luts, Heleen; Wouters, Jan; Ghesquière, Pol

    2011-01-01

    Developmental dyslexia is characterized by severe reading and spelling difficulties that are persistent and resistant to the usual didactic measures and remedial efforts. It is well established that a major cause of these problems lies in poorly specified phonological representations. Many individuals with dyslexia also present impairments in auditory temporal processing and speech perception, but it remains debated whether these more basic perceptual impairments play a role in causing the reading problem. Longitudinal studies may help clarifying this issue by assessing preschool children before they receive reading instruction and by following them up through literacy development. The current longitudinal study shows impairments in auditory frequency modulation (FM) detection, speech perception and phonological awareness in kindergarten and in grade 1 in children who receive a dyslexia diagnosis in grade 3. FM sensitivity and speech-in-noise perception in kindergarten uniquely contribute to growth in reading ability, even after controlling for letter knowledge and phonological awareness. These findings indicate that impairments in auditory processing and speech perception are not merely an epiphenomenon of reading failure. Although no specific directional relations were observed between auditory processing, speech perception and phonological awareness, the highly significant concurrent and predictive correlations between all these variables suggest a reciprocal association and corroborate the evidence for the auditory deficit theory of dyslexia. Copyright © 2010 Elsevier Ltd. All rights reserved.

  3. Neurologic impairment following closed head injury predicts post-traumatic neurogenesis

    PubMed Central

    Villasana, L.E.; Westbrook, G.L.; Schnell, E.

    2014-01-01

    In the mammalian hippocampus, neurogenesis persists into adulthood, and increased generation of newborn neurons could be of clinical benefit following concussive head injuries. Post-traumatic neurogenesis has been well documented using “open” traumatic brain injury (TBI) models in rodents; however, human TBI most commonly involves closed head injury. Here we used a closed head injury (CHI) model to examine post-traumatic hippocampal neurogenesis in mice. All mice were subjected to the same CHI protocol, and a gross-motor based injury severity score was used to characterize neurologic impairment one hour after the injury. When analyzed 2 weeks later, post-traumatic neurogenesis was significantly increased only in mice with a high degree of transient neurologic impairment immediately after injury. This increase was associated with an early increase in c-fos activity, and subsequent reactive astrocytosis and microglial activation in the dentate gyrus. Our results demonstrate that the initial degree of neurologic impairment after closed head injury predicts the induction of secondary physiologic and pathophysiologic processes, and that animals with severe neurologic impairment early after injury manifest an increase in post-traumatic neurogenesis in the absence of gross anatomic pathology. PMID:24861442

  4. Impairment variables predicting activity limitation in individuals with lower limb amputation.

    PubMed

    Raya, Michele A; Gailey, Robert S; Fiebert, Ira M; Roach, Kathyrn E

    2010-03-01

    The purpose of this study was to determine whether measures of impairment (i.e., muscle strength, balance), personal factors (i.e., comorbidities, demographic information) and amputation specific variables (i.e., time since amputation, cause of amputation, level of amputation) were able to predict performance on the six-minute walk test, a measure of activity limitation, in individuals with lower limb amputation. A total of 72 individuals with lower limb amputation ranging in age from 21-83 were tested for balance, limb muscle strength and function. Medical comorbidities were recorded and activity limitation was measured using the six-minute walk test. Data were analyzed and multivariate relationships were examined using multiple linear regression. Impairment variables of strength, balance, subject demographics, time since amputation, cause of amputation and level of amputation were all significant predictors and explained 72% of the variance in the outcome variable. Strength of the hip extensors was the strongest predictor, accounting for 30.9% of the total variance. Multiple factors impact six minute walk scores in individuals with lower limb amputation. Impairments in hip strength and balance appear to be the two most significant. The findings of this study support the use of the six-minute walk test to underscore impairments of the musculoskeletal system that can affect ambulation ability in the amputee.

  5. Predicting word decoding and word spelling development in children with Specific Language Impairment.

    PubMed

    van Weerdenburg, Marjolijn; Verhoeven, Ludo; Bosman, Anna; van Balkom, Hans

    2011-01-01

    This longitudinal investigation on Dutch children with Specific Language Impairment (SLI) aimed at determining the predictive value of statistically uncorrelated language proficiencies on later reading and spelling skills in Dutch. Language abilities, tested with an extensive test battery at the onset of formal reading instruction, were represented by four statistically uncorrelated factors: lexical-semantic abilities, auditory perception, verbal-sequential processing, and speech production. All factors contributed significantly to the prediction of word reading and spelling development seven months later. Verbal-sequential processing was the strongest predictor for both word decoding and spelling. Furthermore, autoregression effects of word decoding and spelling were strong and verbal-sequential processing had predictive value on word spelling nineteen months later when pre-existing spelling abilities were accounted for. Children with SLI and normal literacy skills performed better on most of the language and language-related measures than children with SLI and poor literacy skills. As a result of this activity, readers will describe four language domains that are related to later literacy skills in children with Specific Language Impairment (SLI). As a result of this activity, readers will recognize the predictive value of each of these language domains and the important role of verbal-sequential processing in learning to decode and writing words for children with SLI. As a result of this activity, readers will recall the differences in language proficiencies between children with SLI who develop normal literacy skills and those who encounter literacy problems. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. Do CSF biomarkers help clinicians predict the progression of mild cognitive impairment to dementia?

    PubMed

    Mitchell, Alex J; Monge-Argilés, J A; Sánchez-Paya, J

    2010-08-01

    There is increasing interest in the value of CSF biomarkers to predict those individuals with mild cognitive impairment who will progress to dementia. However, lumbar puncture is not routine in these patients and biomarker assays are not universally available. To change clinical practice there must be very good evidence that biomarkers are helpful over and above clinical impression. Here we discuss the merits of CSF biomarkers compared with clinicians using simple bedside cognitive tests. Although every biomarker has a superior positive predictive value, most have inferior negative predictive values. When predicting the progression of mild cognitive impairment, the overall misclassification rate by clinicians using bedside cognitive tests is approximately 38% but this could be reduced to approximately 30% by using Abeta1-42 and to 24% with phosphorylated tau or total tau (or a combination of CSF biomarkers). Clinicians and patients together should decide whether this is sufficient to warrant the additional burden of a lumbar puncture, and the cost of the test, or whether further studies are needed before useful and clinically practical conclusions can be reached.

  7. Sentence Recognition Prediction for Hearing-impaired Listeners in Stationary and Fluctuation Noise With FADE

    PubMed Central

    Schädler, Marc René; Warzybok, Anna; Meyer, Bernd T.; Brand, Thomas

    2016-01-01

    To characterize the individual patient’s hearing impairment as obtained with the matrix sentence recognition test, a simulation Framework for Auditory Discrimination Experiments (FADE) is extended here using the Attenuation and Distortion (A+D) approach by Plomp as a blueprint for setting the individual processing parameters. FADE has been shown to predict the outcome of both speech recognition tests and psychoacoustic experiments based on simulations using an automatic speech recognition system requiring only few assumptions. It builds on the closed-set matrix sentence recognition test which is advantageous for testing individual speech recognition in a way comparable across languages. Individual predictions of speech recognition thresholds in stationary and in fluctuating noise were derived using the audiogram and an estimate of the internal level uncertainty for modeling the individual Plomp curves fitted to the data with the Attenuation (A-) and Distortion (D-) parameters of the Plomp approach. The “typical” audiogram shapes from Bisgaard et al with or without a “typical” level uncertainty and the individual data were used for individual predictions. As a result, the individualization of the level uncertainty was found to be more important than the exact shape of the individual audiogram to accurately model the outcome of the German Matrix test in stationary or fluctuating noise for listeners with hearing impairment. The prediction accuracy of the individualized approach also outperforms the (modified) Speech Intelligibility Index approach which is based on the individual threshold data only. PMID:27604782

  8. Grammar Predicts Procedural Learning and Consolidation Deficits in Children with Specific Language Impairment

    PubMed Central

    Hedenius, Martina; Persson, Jonas; Tremblay, Antoine; Adi-Japha, Esther; Veríssimo, João; Dye, Cristina D.; Alm, Per; Jennische, Margareta; Tomblin, J. Bruce; Ullman, Michael T.

    2011-01-01

    The Procedural Deficit Hypothesis (PDH) posits that Specific Language Impairment (SLI) can be largely explained by abnormalities of brain structures that subserve procedural memory. The PDH predicts impairments of procedural memory itself, and that such impairments underlie the grammatical deficits observed in the disorder. Previous studies have indeed reported procedural learning impairments in SLI, and have found that these are associated with grammatical difficulties. The present study extends this research by examining the consolidation and longer-term procedural sequence learning in children with SLI. The Alternating Serial Reaction Time (ASRT) task was given to children with SLI and typically-developing (TD) children in an initial learning session and an average of three days later to test for consolidation and longer-term learning. Although both groups showed evidence of initial sequence learning, only the TD children showed clear signs of consolidation, even though the two groups did not differ in longer-term learning. When the children were re-categorized on the basis of grammar deficits rather than broader language deficits, a clearer pattern emerged. Whereas both the grammar impaired and normal grammar groups showed evidence of initial sequence learning, only those with normal grammar showed consolidation and longer-term learning. Indeed, the grammar-impaired group appeared to lose any sequence knowledge gained during the initial testing session. These findings held even when controlling for vocabulary or a broad non-grammatical language measure, neither of which were associated with procedural memory. When grammar was examined as a continuous variable over all children, the same relationships between procedural memory and grammar, but not vocabulary or the broader language measure, were observed. Overall, the findings support and further specify the PDH. They suggest that consolidation and longer-term procedural learning are impaired in SLI, but that

  9. Grammar predicts procedural learning and consolidation deficits in children with Specific Language Impairment.

    PubMed

    Hedenius, Martina; Persson, Jonas; Tremblay, Antoine; Adi-Japha, Esther; Veríssimo, João; Dye, Cristina D; Alm, Per; Jennische, Margareta; Bruce Tomblin, J; Ullman, Michael T

    2011-01-01

    The Procedural Deficit Hypothesis (PDH) posits that Specific Language Impairment (SLI) can be largely explained by abnormalities of brain structures that subserve procedural memory. The PDH predicts impairments of procedural memory itself, and that such impairments underlie the grammatical deficits observed in the disorder. Previous studies have indeed reported procedural learning impairments in SLI, and have found that these are associated with grammatical difficulties. The present study extends this research by examining consolidation and longer-term procedural sequence learning in children with SLI. The Alternating Serial Reaction Time (ASRT) task was given to children with SLI and typically developing (TD) children in an initial learning session and an average of three days later to test for consolidation and longer-term learning. Although both groups showed evidence of initial sequence learning, only the TD children showed clear signs of consolidation, even though the two groups did not differ in longer-term learning. When the children were re-categorized on the basis of grammar deficits rather than broader language deficits, a clearer pattern emerged. Whereas both the grammar impaired and normal grammar groups showed evidence of initial sequence learning, only those with normal grammar showed consolidation and longer-term learning. Indeed, the grammar-impaired group appeared to lose any sequence knowledge gained during the initial testing session. These findings held even when controlling for vocabulary or a broad non-grammatical language measure, neither of which were associated with procedural memory. When grammar was examined as a continuous variable over all children, the same relationships between procedural memory and grammar, but not vocabulary or the broader language measure, were observed. Overall, the findings support and further specify the PDH. They suggest that consolidation and longer-term procedural learning are impaired in SLI, but that these

  10. Neural correlates of out-group bias predict social impairment in patients with schizophrenia.

    PubMed

    Blackford, J U; Williams, L E; Heckers, S

    2015-05-01

    responses during out-group processing predicted degree of social impairment in patients with schizophrenia; thus, neural responses to opposite-gender faces may provide a novel measure for studies of treatment response and disease outcome. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Predicting falls in elderly receiving home care: the role of malnutrition and impaired mobility.

    PubMed

    Meijers, J M; Halfens, R J; Neyens, J C; Luiking, Y C; Verlaan, G; Schols, J M

    2012-07-01

    To investigate the role of malnutrition, impaired mobility and care dependency in predicting fallers in older Dutch home care clients. This study is a secondary analysis of data of the annual independent national prevalence measurement of care problems of Maastricht University. The design involves a cross-sectional, multicentre point prevalence measurement (malnutrition, mobility), and a 30 days incidence measurement (falls). Dutch home care organisations. 2971 clients (older than 65 years) from 22 home care organizations participated. A standardized questionnaire was used to register amongst others data of weight, height, number and type of diseases (like for example neurologic diseases, dementia, CVA, COPD, eye/ear disorders, musculoskeletal disorders), nutritional intake, use of psychopharmaca, undesired weight loss, fall history, mobility, and care dependency. The study was able to show that fallers are more often malnourished than non-fallers in the univariate analysis. Most importantly the study indicated by multivariate analysis that fallers could be predicted by the risk factors immobility ((OR 2.516 95% CI 1.144-5.532), high care dependency (OR 1.684 95% CI 1.121-2.532) and malnutrition (OR 1.978 95% CI 1.340-2.920). The findings of this study stress that malnutrition, impaired mobility and care dependency are potential reversible factors related to falls. Therefore early identification and management of nutritional status, impaired mobility and care dependency are important aspects for a possible fall prevention strategy.

  12. Prediction of lithium response in first-episode mania using the LITHium Intelligent Agent (LITHIA): Pilot data and proof-of-concept.

    PubMed

    Fleck, David E; Ernest, Nicholas; Adler, Caleb M; Cohen, Kelly; Eliassen, James C; Norris, Matthew; Komoroski, Richard A; Chu, Wen-Jang; Welge, Jeffrey A; Blom, Thomas J; DelBello, Melissa P; Strakowski, Stephen M

    2017-06-01

    Individualized treatment for bipolar disorder based on neuroimaging treatment targets remains elusive. To address this shortcoming, we developed a linguistic machine learning system based on a cascading genetic fuzzy tree (GFT) design called the LITHium Intelligent Agent (LITHIA). Using multiple objectively defined functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy ((1) H-MRS) inputs, we tested whether LITHIA could accurately predict the lithium response in participants with first-episode bipolar mania. We identified 20 subjects with first-episode bipolar mania who received an adequate trial of lithium over 8 weeks and both fMRI and (1) H-MRS scans at baseline pre-treatment. We trained LITHIA using 18 (1) H-MRS and 90 fMRI inputs over four training runs to classify treatment response and predict symptom reductions. Each training run contained a randomly selected 80% of the total sample and was followed by a 20% validation run. Over a different randomly selected distribution of the sample, we then compared LITHIA to eight common classification methods. LITHIA demonstrated nearly perfect classification accuracy and was able to predict post-treatment symptom reductions at 8 weeks with at least 88% accuracy in training and 80% accuracy in validation. Moreover, LITHIA exceeded the predictive capacity of the eight comparator methods and showed little tendency towards overfitting. The results provided proof-of-concept that a novel GFT is capable of providing control to a multidimensional bioinformatics problem-namely, prediction of the lithium response-in a pilot data set. Future work on this, and similar machine learning systems, could help assign psychiatric treatments more efficiently, thereby optimizing outcomes and limiting unnecessary treatment. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Multisite prediction of 4-week and 52-week treatment outcomes in patients with first-episode psychosis: a machine learning approach.

    PubMed

    Koutsouleris, Nikolaos; Kahn, René S; Chekroud, Adam M; Leucht, Stefan; Falkai, Peter; Wobrock, Thomas; Derks, Eske M; Fleischhacker, Wolfgang W; Hasan, Alkomiet

    2016-10-01

    At present, no tools exist to estimate objectively the risk of poor treatment outcomes in patients with first-episode psychosis. Such tools could improve treatment by informing clinical decision-making before the commencement of treatment. We tested whether such a tool could be successfully built and validated using routinely available, patient-reportable information. By applying machine learning to data from 334 patients in the European First Episode Schizophrenia Trial (EUFEST; International Clinical Trials Registry Platform number, ISRCTN68736636), we developed a tool to predict poor versus good treatment outcome (Global Assessment of Functioning [GAF] score ≥65 vs GAF <65, respectively) after 4 weeks and 52 weeks of treatment. To enable the unbiased estimation of the predictive system's generalisability to new patients, we used repeated nested cross-validation to prevent information leaking between patients used for training and validating the models. In pursuit of everyday clinical applicability, we retrained the 4-week outcome predictor with only the top ten predictors of the pooled prediction system and then tested this tool in 108 independent patients with 4-week outcome labels. Discontinuation and readmission to hospital events in patients with predicted poor versus good outcomes were assessed with Kaplan-Meier log-rank analyses, whereas generalised linear mixed-effects models were used to investigate the GAF-based predictions against several clinically meaningful outcome indicators, including treatment adherence, symptom remission, and quality of life. The generalisability of our outcome predictions were estimated with cross-validation (test-fold balanced accuracy [BAC] of 75·0% for 4-week outcomes and 73·8% for and 52-week outcomes), and leave-site-out validation across 44 European sites (BAC of 72·1% for 4-week outcomes and 71·1% for 52-week outcomes). We identified a smaller group of ten predictors still providing a BAC of 71·7% in 108 patients

  14. Dominant-negative mutation p.Arg324Thr in KCNA1 impairs Kv1.1 channel function in episodic ataxia.

    PubMed

    Tristán-Clavijo, Enriqueta; Scholl, Francisco G; Macaya, Alfons; Iglesias, Gemma; Rojas, Ana M; Lucas, Miguel; Castellano, Antonio; Martinez-Mir, Amalia

    2016-11-01

    Episodic ataxia type 1 is a rare autosomal dominant neurological disorder caused by mutations in the KCNA1 gene that encodes the α subunit of voltage-gated potassium channel Kv1.1. The functional consequences of identified mutations on channel function do not fully correlate with the clinical phenotype of patients. A clinical and genetic study was performed in a family with 5 patients with episodic ataxia type 1, with concurrent epilepsy in 1 of them. Protein expression, modeling, and electrophysiological analyses were performed to study Kv1.1 function. Whole-genome linkage and candidate gene analyses revealed the novel heterozygous mutation p.Arg324Thr in the KCNA1 gene. The encoded mutant Kv1.1 channel displays reduced currents and altered activation and inactivation. Taken together, we provide genetic and functional evidence that mutation p.Arg324Thr in the KCNA1 gene is pathogenic and results in episodic ataxia type 1 through a dominant-negative effect. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

  15. Specific, personally meaningful cues can benefit episodic prospection in medial temporal lobe amnesia.

    PubMed

    Kwan, Donna; Kurczek, Jake; Rosenbaum, R Shayna

    2016-06-01

    instead provide more structured and personally meaningful cues to guide responses Further research is needed to determine case-specific characteristics that best predict benefit from specific, personal cues. These might include extent of MTL damage and overall severity of episodic memory and prospection impairment. © 2015 The British Psychological Society.

  16. Impaired Sleep Predicts Cognitive Decline in Old People: Findings from the Prospective KORA Age Study.

    PubMed

    Johar, Hamimatunnisa; Kawan, Rasmila; Emeny, Rebecca Thwing; Ladwig, Karl-Heinz

    2016-01-01

    To investigate the association between sleep-related characteristics and cognitive change over 3 years of follow up in an aged population. Sleep characteristics and covariates were assessed at baseline in a standardized interview and clinical examination of the population-based KORA Age Study (n = 740, mean age = 75 years). Cognitive score (determined by telephone interview for cognitive status, TICS-m) was recorded at baseline and 3 years later. At baseline, 82.83% (n = 613) of participants had normal cognitive status, 13.51% (n = 100) were classified with mild cognitive impairment (MCI), and 3.64% (n = 27) with probable dementia. The effect of three distinct patterns of poor sleep (difficulties initiating [DIS] or maintaining sleep [DMS], daytime sleepiness [DS] or sleep duration) were considered on a change in cognitive score with adjustments for potential confounders in generalized linear regression models. Cognitive decline was more pronounced in individuals with DMS compared to those with no DMS (β = 1.33, 95% CI = 0.41-2.24, P < 0.001). However, the predictive power of DMS was only significant in individuals with normal cognition and not impaired subjects at baseline. Prolonged sleep duration increased the risk for cognitive decline in cognitively impaired elderly (β = 1.86, 95% CI = 0.15-3.57, P = 0.03). Other sleep characteristics (DIS and DS) were not significantly associated with cognitive decline. DMS and long sleep duration were associated with cognitive decline in normal and cognitively impaired elderly, respectively. The identification of impaired sleep quality may offer intervention strategies to deter cognitive decline in the elderly with normal cognitive function. © 2016 Associated Professional Sleep Societies, LLC.

  17. Mild cognitive impairment predicts death and readmission within 30days of discharge for heart failure.

    PubMed

    Huynh, Quan L; Negishi, Kazuaki; Blizzard, Leigh; Saito, Makoto; De Pasquale, Carmine G; Hare, James L; Leung, Dominic; Stanton, Tony; Sanderson, Kristy; Venn, Alison J; Marwick, Thomas H

    2016-10-15

    Cognitive impairment is highly prevalent in heart failure (HF), and may be associated with short-term readmission. This study investigated the role of cognition, incremental to other clinical and non-clinical factors, independent of depression and anxiety, in predicting 30-day readmission or death in HF. This study followed 565 patients from an Australia-wide HF longitudinal study. Cognitive function (MoCA score) together with standard clinical and non-clinical factors, mental health and 2D echocardiograms were collected before hospital discharge. The study outcomes were death and readmission within 30days of discharge. Logistic regression, Harrell's C-statistic, integrated discrimination improvement (IDI) and net reclassification index were used for analysis. Among 565 patients, 255 (45%) had at least mild cognitive impairment (MoCA≤22). Death (n=43, 8%) and readmission (n=122, 21%) within 30days of discharge were more likely to occur among patients with mild cognitive impairment (OR=2.00, p=0.001). MoCA score was also negatively associated with 30-day readmission or death (OR=0.91, p<0.001) independent of other risk factors. Adding MoCA score to an existing prediction model of 30-day readmission significantly improved discrimination (C-statistic=0.715 vs. 0.617, IDI estimate 0.077, p<0.001). From prediction models developed from our study, adding MoCA score (C-statistic=0.83) provided incremental value to that of standard clinical and non-clinical factors (C-statistic=0.76) and echocardiogram parameters (C-statistic=0.81) in predicting 30-day readmission or death. Reclassification analysis suggests that addition of MoCA score improved classification for a net of 12% of patients with 30-day readmission or death and of 6% of patients without (p=0.002). Mild cognitive impairment predicts short-term outcomes in HF, independent of clinical and non-clinical factors. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Episodic foresight and aging.

    PubMed

    Lyons, Amanda D; Henry, Julie D; Rendell, Peter G; Corballis, Michael C; Suddendorf, Thomas

    2014-12-01

    Decline in episodic memory is one of the most prominent cognitive deficits seen in late adulthood. It is therefore surprising that few studies have examined how the related capacity for episodic foresight might also be affected in this age group. Preliminary evidence suggests that older adults show deficits in generating phenomenological characteristics of future events, but the critical question of whether such deficits extend to generating and executing appropriate future intentions remains to be addressed. Here, we present 2 studies. In Study 1, we report the results of our pilot testing, which was used to develop and validate stimuli for the first measure of this construct that is appropriate for use in adult populations. In Study 2, we administer this measure to 40 older and 40 younger adults. The results indicate that, relative to their younger counterparts, older adults are less likely to spontaneously acquire items that would later allow a problem to be solved, and are also less likely to subsequently use these items to solve the problems. These data provide important initial evidence that the capacity to apply episodic foresight in a functionally adaptive way is impaired in late adulthood. The results also provide important validation data for a novel measure of episodic foresight that has potential application to many other groups, including clinical groups known to have difficulties anticipating and planning for the future. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

  19. Utility of a Language Screening Measure for Predicting Risk for Language Impairment in Bilinguals

    PubMed Central

    Peña, Elizabeth D.; Bedore, Lisa M.; Gillam, Ronald B.

    2015-01-01

    Purpose This study evaluated the accuracy of an experimental version of the Bilingual English Spanish Oral Screener (BESOS; Peña, Bedore, Iglesias, Gutiérrez-Clellen, & Goldstein, 2008) for predicting the long-term risk for language impairment (LI) for a matched group of preschool-aged Spanish–English bilingual children with and without LI. Method A total of 1,029 Spanish–English bilingual children completed the BESOS before entering kindergarten. A subset of 167 participants completed a follow-up language evaluation in 1st grade. Twenty-one of these children were identified as having LI and were matched to a group of 21 typically developing peers from the larger sample. A series of discriminant analyses were used to determine the combination of scores on the BESOS that most accurately predicted 2 years later which children presented with and without LI. Results The linear combination of the semantics and morphosyntax scores in the best language resulted in predictive sensitivity of 95.2% and predictive specificity of 71.4%, with an overall accuracy of 81% for predicting risk for LI. Conclusion A bilingual language screener administered before kindergarten can be useful for predicting risk for LI in bilingual children in 1st grade. PMID:25885932

  20. Mild cognitive impairment in different functional domains and incident Alzheimer's disease

    PubMed Central

    Aggarwal, N; Wilson, R; Beck, T; Bienias, J; Bennett, D

    2005-01-01

    Background: Little is known about factors that predict transition from mild cognitive impairment to Alzheimer's disease (AD). Objective: To examine the relation of impairment in different cognitive systems to risk of developing AD in persons with mild cognitive impairment. Methods: Participants are 218 older Catholic clergy members from the Religious Orders Study. At baseline, they met criteria for mild cognitive impairment based on a uniform clinical evaluation that included detailed cognitive testing. Evaluations were repeated annually for up to 10 years. Analyses were controlled for age, sex, and education. Results: Eighty two persons (37.6%) developed AD. In separate analyses, episodic memory, semantic memory, working memory, and perceptual speed, but not visuospatial ability, were associated with risk of AD, but when analysed together only episodic memory and perceptual speed were associated with AD incidence, with the effect for episodic memory especially strong. Overall, those with impaired episodic memory were more than twice as likely to develop AD as those with impairment in other cognitive domains (relative risk (RR) = 2.45; 95% confidence interval (CI): 1.53 to 3.92), and they experienced more rapid cognitive decline. Lower episodic memory performance was associated with increased risk of AD throughout the observation period, whereas impairment in other cognitive domains was primarily associated with risk during the following year but not thereafter. Conclusion: Among persons with mild cognitive impairment, episodic memory impairment is associated with a substantial and persistent elevation in risk of developing AD compared to impairment in other cognitive systems. PMID:16227534

  1. Do Personality Traits Predict Functional Impairment and Quality of Life in Adult ADHD? A Controlled Study.

    PubMed

    He, J Allison; Antshel, Kevin M; Biederman, Joseph; Faraone, Stephen V

    2015-11-25

    To examine the association of personality traits and characteristics on quality of life and functioning in adults with ADHD. Participants were adults with (n = 206) and without ADHD (n = 123) who completed the Temperament and Character Inventory (TCI), the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), and the Social Adjustment Scale-Self-Report (SAS-SR). Participants also provided information on academic, motor vehicle operation, legal, social, familial, and occupational functioning. Outcomes were examined using stepwise linear regression, logistic regression (for binary outcomes), and negative binomial regression (for count outcomes) controlling for ADHD symptoms, psychiatric comorbidity, and executive dysfunction. Adults with ADHD significantly differed from controls across nearly all TCI personality domains. On average, adults with ADHD endorsed more novelty seeking, harm avoidance, and self-transcendence, and less reward dependence, persistence, self-directedness, and cooperativeness. Personality traits and characteristics, especially self-directedness, significantly predicted functional impairments even after controlling for ADHD symptoms, executive function deficits, and current psychiatric comorbidities. In adults with ADHD, personality traits exert unique associations on quality of life and functional impairment across major life domains, beyond the relations expected of and associated with ADHD symptoms and other associated psychiatric conditions and cognitive vulnerabilities. Addressing personality traits in adults with ADHD may lead to improvements in quality of life and reductions in functional impairment. © The Author(s) 2015.

  2. In your eyes: does theory of mind predict impaired life functioning in bipolar disorder?

    PubMed

    Purcell, Amanda L; Phillips, Mary; Gruber, June

    2013-12-01

    Deficits in emotion perception and social functioning are strongly implicated in bipolar disorder (BD). Examining theory of mind (ToM) may provide one potential mechanism to explain observed socio-emotional impairments in this disorder. The present study prospectively investigated the relationship between theory of mind performance and life functioning in individuals diagnosed with BD compared to unipolar depression and healthy control groups. Theory of mind (ToM) performance was examined in 26 individuals with remitted bipolar I disorder (BD), 29 individuals with remitted unipolar depression (UD), and 28 healthy controls (CTL) using a well-validated advanced theory of mind task. Accuracy and response latency scores were calculated from the task. Life functioning was measured during a 12 month follow-up session. No group differences for ToM accuracy emerged. However, the BD group exhibited significantly shorter response times than the UD and CTL groups. Importantly, quicker response times in the BD group predicted greater life functioning impairment at a 12-month follow-up, even after controlling for baseline symptoms. The stimuli were static representations of emotional states and do not allow for evaluating the appropriateness of context during emotional communication; due to sample size, neither specific comorbidities nor medication effects were analyzed for the BD and UD groups; preliminary status of theory of mind as a construct. Results suggest that quickened socio-emotional decision making may represent a risk factor for future functional impairment in BD. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Fusing Functional MRI and Diffusion Tensor Imaging Measures of Brain Function and Structure to Predict Working Memory and Processing Speed Performance among Inter-episode Bipolar Patients.

    PubMed

    McKenna, Benjamin S; Theilmann, Rebecca J; Sutherland, Ashley N; Eyler, Lisa T

    2015-05-01

    Evidence for abnormal brain function as measured with diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) and cognitive dysfunction have been observed in inter-episode bipolar disorder (BD) patients. We aimed to create a joint statistical model of white matter integrity and functional response measures in explaining differences in working memory and processing speed among BD patients. Medicated inter-episode BD (n=26; age=45.2±10.1 years) and healthy comparison (HC; n=36; age=46.3±11.5 years) participants completed 51-direction DTI and fMRI while performing a working memory task. Participants also completed a processing speed test. Tract-based spatial statistics identified common white matter tracts where fractional anisotropy was calculated from atlas-defined regions of interest. Brain responses within regions of interest activation clusters were also calculated. Least angle regression was used to fuse fMRI and DTI data to select the best joint neuroimaging predictors of cognitive performance for each group. While there was overlap between groups in which regions were most related to cognitive performance, some relationships differed between groups. For working memory accuracy, BD-specific predictors included bilateral dorsolateral prefrontal cortex from fMRI, splenium of the corpus callosum, left uncinate fasciculus, and bilateral superior longitudinal fasciculi from DTI. For processing speed, the genu and splenium of the corpus callosum and right superior longitudinal fasciculus from DTI were significant predictors of cognitive performance selectively for BD patients. BD patients demonstrated unique brain-cognition relationships compared to HC. These findings are a first step in discovering how interactions of structural and functional brain abnormalities contribute to cognitive impairments in BD.

  4. Automated hippocampal shape analysis predicts the onset of dementia in mild cognitive impairment.

    PubMed

    Costafreda, Sergi G; Dinov, Ivo D; Tu, Zhuowen; Shi, Yonggang; Liu, Cheng-Yi; Kloszewska, Iwona; Mecocci, Patrizia; Soininen, Hilkka; Tsolaki, Magda; Vellas, Bruno; Wahlund, Lars-Olof; Spenger, Christian; Toga, Arthur W; Lovestone, Simon; Simmons, Andrew

    2011-05-01

    The hippocampus is involved at the onset of the neuropathological pathways leading to Alzheimer's disease (AD). Individuals with mild cognitive impairment (MCI) are at increased risk of AD. Hippocampal volume has been shown to predict which MCI subjects will convert to AD. Our aim in the present study was to produce a fully automated prognostic procedure, scalable to high throughput clinical and research applications, for the prediction of MCI conversion to AD using 3D hippocampal morphology. We used an automated analysis for the extraction and mapping of the hippocampus from structural magnetic resonance scans to extract 3D hippocampal shape morphology, and we then applied machine learning classification to predict conversion from MCI to AD. We investigated the accuracy of prediction in 103 MCI subjects (mean age 74.1 years) from the longitudinal AddNeuroMed study. Our model correctly predicted MCI conversion to dementia within a year at an accuracy of 80% (sensitivity 77%, specificity 80%), a performance which is competitive with previous predictive models dependent on manual measurements. Categorization of MCI subjects based on hippocampal morphology revealed more rapid cognitive deterioration in MMSE scores (p<0.01) and CERAD verbal memory (p<0.01) in those subjects who were predicted to develop dementia relative to those predicted to remain stable. The pattern of atrophy associated with increased risk of conversion demonstrated initial degeneration in the anterior part of the cornus ammonis 1 (CA1) hippocampal subregion. We conclude that automated shape analysis generates sensitive measurements of early neurodegeneration which predates the onset of dementia and thus provides a prognostic biomarker for conversion of MCI to AD. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Automated hippocampal shape analysis predicts the onset of dementia in Mild Cognitive Impairment

    PubMed Central

    Costafreda, Sergi G.; Dinov, Ivo D.; Tu, Zhuowen; Shi, Yonggang; Liu, Cheng-Yi; Kloszewska, Iwona; Mecocci, Patrizia; Soininen, Hilkka; Tsolaki, Magda; Vellas, Bruno; Wahlund, Lars-Olof; Spenger, Christian; Toga, Arthur W.; Lovestone, Simon; Simmons, Andrew

    2011-01-01

    The hippocampus is involved at the onset of the neuropathological pathways leading to Alzheimer’s disease (AD). Individuals with Mild Cognitive Impairment (MCI) are at increased risk of AD. Hippocampal volume has been shown to predict which MCI subjects will convert to AD. Our aim in the present study was to produce a fully automated prognostic procedure, scalable to high throughput clinical and research applications, for the prediction of MCI conversion to AD using 3D hippocampal morphology. We used an automated analysis for the extraction and mapping of the hippocampus from structural magnetic resonance scans to extract 3D hippocampal shape morphology, and we then applied machine learning classification to predict conversion from MCI to AD. We investigated the accuracy of prediction in 103 MCI subjects (mean age 74.1 years) from the longitudinal AddNeuroMed study. Our model correctly predicted MCI conversion to dementia within a year at an accuracy of 80% (sensitivity 77%, specificity 80%), a performance which is competitive with previous predictive models dependent on manual measurements. Categorization of MCI subjects based on hippocampal morphology revealed more rapid cognitive deterioration in MMSE scores (p < 0.01) and CERAD verbal memory (p < 0.01) in those subjects who were predicted to develop dementia relative to those predicted to remain stable. The pattern of atrophy associated with increased risk of conversion demonstrated initial degeneration in the anterior part of the cornus ammonis 1 (CA1) hippocampal subregion. We conclude that automated shape analysis generates sensitive measurements of early neurodegeneration which predates the onset of dementia and thus provides a prognostic biomarker for conversion of MCI to AD. PMID:21272654

  6. Predicting progression from mild cognitive impairment to Alzheimer's disease using longitudinal callosal atrophy.

    PubMed

    Lee, Sang Han; Bachman, Alvin H; Yu, Donghyeon; Lim, Johan; Ardekani, Babak A

    2016-01-01

    We investigate whether longitudinal callosal atrophy could predict conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Longitudinal (baseline + 1-year follow-up) MRI scans of 132 MCI subjects from the Alzheimer's Disease Neuroimaging Initiative were used. A total of 54 subjects did not convert to AD over an average (±SD) follow-up of 5.46 (±1.63) years, whereas 78 converted to AD with an average conversion time of 2.56 (±1.65) years. Annual change in the corpus callosum thickness profile was calculated from the baseline and 1-year follow-up MRI. A logistic regression model with fused lasso regularization for prediction was applied to the annual changes. We found a sex difference. The accuracy of prediction was 84% in females and 61% in males. The discriminating regions of corpus callosum differed between sexes. In females, the genu, rostrum, and posterior body had predictive power, whereas the genu and splenium were relevant in males. Annual callosal atrophy predicts MCI-to-AD conversion in females more accurately than in males.

  7. Modeled changes of cerebellar activity in mutant mice are predictive of their learning impairments

    PubMed Central

    Badura, Aleksandra; Clopath, Claudia; Schonewille, Martijn; De Zeeuw, Chris I.

    2016-01-01

    Translating neuronal activity to measurable behavioral changes has been a long-standing goal of systems neuroscience. Recently, we have developed a model of phase-reversal learning of the vestibulo-ocular reflex, a well-established, cerebellar-dependent task. The model, comprising both the cerebellar cortex and vestibular nuclei, reproduces behavioral data and accounts for the changes in neural activity during learning in wild type mice. Here, we used our model to predict Purkinje cell spiking as well as behavior before and after learning of five different lines of mutant mice with distinct cell-specific alterations of the cerebellar cortical circuitry. We tested these predictions by obtaining electrophysiological data depicting changes in neuronal spiking. We show that our data is largely consistent with the model predictions for simple spike modulation of Purkinje cells and concomitant behavioral learning in four of the mutants. In addition, our model accurately predicts a shift in simple spike activity in a mutant mouse with a brainstem specific mutation. This combination of electrophysiological and computational techniques opens a possibility of predicting behavioral impairments from neural activity. PMID:27805050

  8. Modeled changes of cerebellar activity in mutant mice are predictive of their learning impairments

    NASA Astrophysics Data System (ADS)

    Badura, Aleksandra; Clopath, Claudia; Schonewille, Martijn; de Zeeuw, Chris I.

    2016-11-01

    Translating neuronal activity to measurable behavioral changes has been a long-standing goal of systems neuroscience. Recently, we have developed a model of phase-reversal learning of the vestibulo-ocular reflex, a well-established, cerebellar-dependent task. The model, comprising both the cerebellar cortex and vestibular nuclei, reproduces behavioral data and accounts for the changes in neural activity during learning in wild type mice. Here, we used our model to predict Purkinje cell spiking as well as behavior before and after learning of five different lines of mutant mice with distinct cell-specific alterations of the cerebellar cortical circuitry. We tested these predictions by obtaining electrophysiological data depicting changes in neuronal spiking. We show that our data is largely consistent with the model predictions for simple spike modulation of Purkinje cells and concomitant behavioral learning in four of the mutants. In addition, our model accurately predicts a shift in simple spike activity in a mutant mouse with a brainstem specific mutation. This combination of electrophysiological and computational techniques opens a possibility of predicting behavioral impairments from neural activity.

  9. Prediction of probable Alzheimer's disease in memory-impaired patients: A prospective longitudinal study.

    PubMed

    Tierney, M C; Szalai, J P; Snow, W G; Fisher, R H; Nores, A; Nadon, G; Dunn, E; St George-Hyslop, P H

    1996-03-01

    We determined whether a battery of neuropsychological tests could predict who would develop Alzheimer's disease (AD) in a group of 123 memory-impaired nondemented patients. Patients were followed longitudinally for 2 years with a research battery of neuropsychological tests. After 2 years, 29 developed probable AD, and 94 did not develop dementia. We used logistic regression analyses to examine the classification accuracy of subjects' performance at entry to the study on the research battery. The logistic regression model was significant with an accuracy of 89%, sensitivity of 76%, and specificity of 94%. Two tests contributed significantly to this model: the delayed recall from the Rey Auditory Verbal Learning Test and the Mental Control subtest of the Wechsler Memory Scale. These two tests alone produced the same accuracy, sensitivity, and specificity as the larger model. These results demonstrate that probable AD can be predicted with a high degree of accuracy and with a relatively brief battery of neuropsychological tests.

  10. Anosognosia, neglect, extinction and lesion site predict impairment of daily living after right-hemispheric stroke.

    PubMed

    Vossel, Simone; Weiss, Peter H; Eschenbeck, Philipp; Fink, Gereon R

    2013-01-01

    Right-hemispheric stroke can give rise to manifold neuropsychological deficits, in particular, impairments of spatial perception which are often accompanied by reduced self-awareness of these deficits (anosognosia). To date, the specific contribution of these deficits to a patient's difficulties in daily life activities remains to be elucidated. In 55 patients with right-hemispheric stroke we investigated the predictive value of different neglect-related symptoms, visual extinction and anosognosia for the performance of standardized activities of daily living (ADL). The additional impact of lesion location was examined using voxel-based lesion-symptom mapping. Step-wise linear regression revealed that anosognosia for visuospatial deficits was the most important predictor for performance in standardized ADL. In addition, motor-intentional and perceptual-attentional neglect, extinction and cancellation task performance significantly predicted ADL performance. Lesions comprising the right frontal and cingulate cortex and adjacent white matter explained additional variance in the performance of standardized ADL, in that damage to these areas was related to lower performance than predicted by the regression model only. Our data show a decisive role of anosognosia for visuospatial deficits for impaired ADL and therefore outcome/disability after stroke. The findings further demonstrate that the severity of neglect and extinction also predicts ADL performance. Our results thus strongly suggest that right-hemispheric stroke patients should not only be routinely assessed for neglect and extinction but also for anosognosia to initiate appropriate rehabilitative treatment. The observation that right frontal lesions explain additional variance in ADL most likely reflects that dysfunction of the supervisory system also significantly impacts upon rehabilitation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Systematic review and meta-analysis of the discriminatory performance of risk prediction rules in febrile neutropaenic episodes in children and young people

    PubMed Central

    Phillips, Bob; Wade, Ros; Stewart, Lesley A.; Sutton, Alex J.

    2010-01-01

    Introduction Febrile neutropaenia is a frequently occurring and occasionally life-threatening complication of treatment for childhood cancer, yet many children are aggressively over-treated. We aimed to undertake a systematic review and meta-analysis to summarise evidence on the discriminatory ability and predictive accuracy of clinical decision rules (CDR) of risk stratification in febrile neutropaenic episodes. Methods The review was conducted in accordance with Centre for Reviews and Dissemination methods, using random effects models to undertake meta-analysis. It was registered with the HTA Registry of systematic reviews, CRD32009100453. Results We found 20 studies describing 16 different CDR assessed in 8388 episodes of FNP. No study compared different approaches and only one CDR had been subject to testing across multiple datasets. This review cannot conclude that any system is more effective or reliable than any other. Conclusion To maximise the value of the information already collected by these and other cohorts of children with febrile neutropaenia, an individual-patient-data (IPD) meta-analysis is required to develop and test new and existing CDR to improve stratification and optimise therapy. PMID:20621468

  12. Dependent stressful life events and prior depressive episodes in the prediction of major depression: the problem of causal inference in psychiatric epidemiology.

    PubMed

    Kendler, Kenneth S; Gardner, Charles O

    2010-11-01

    Most environmental risk factors for psychiatric disorders cannot be studied experimentally, making causal attributions difficult. Can we address this question by using together 2 major methods for causal inference: natural experiments and specialized statistical methods? To determine the causal relationship between dependent stressful life events (dSLEs) and prior depressive episodes (PDEs) and major depression (MD). Assessment of risk factors and episodes of MD at interview. Statistical analyses used the co-twin control and propensity score-matching methods. General community. Four thousand nine hundred ten male and female twins from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Episodes of MD. We found that dSLEs were strongly associated with risk for MD in female (odds ratio [OR], 5.85) and male (4.55) twins in the entire sample and, at considerably lower levels, in female (2.29) and male (2.19) monozygotic twins discordant for dSLE exposure. A case-control sample matched on propensity score showed a moderate association in female (OR, 1.79) and male (1.53) twins. A PDE strongly predicted risk for MD in female (OR, 3.68) and male (5.20) twins in the entire sample. In monozygotic pairs discordant for exposure, the association was weaker in male (OR, 1.41) and absent in female (1.00) twins. A case-control sample matched on propensity score showed a moderate association between PDE and depressive episodes in male (OR, 1.58) and female twins (1.66). Although dSLEs have a modest causal effect on the risk for MD, a large proportion of the observed association is noncausal. The same pattern is seen for PDEs, although the causal impact is somewhat more tenuous. For environmental exposures in psychiatry that cannot be studied experimentally, co-twin control and propensity scoring methods--which have complementary strengths and weaknesses--can provide similar results, suggesting their joint use can help with the critical question of causal

  13. Predicting the occurrence of embolic events: an analysis of 1456 episodes of infective endocarditis from the Italian Study on Endocarditis (SEI)

    PubMed Central

    2014-01-01

    Background Embolic events are a major cause of morbidity and mortality in patients with infective endocarditis. We analyzed the database of the prospective cohort study SEI in order to identify factors associated with the occurrence of embolic events and to develop a scoring system for the assessment of the risk of embolism. Methods We retrospectively analyzed 1456 episodes of infective endocarditis from the multicenter study SEI. Predictors of embolism were identified. Risk factors identified at multivariate analysis as predictive of embolism in left-sided endocarditis, were used for the development of a risk score: 1 point was assigned to each risk factor (total risk score range: minimum 0 points; maximum 2 points). Three categories were defined by the score: low (0 points), intermediate (1 point), or high risk (2 points); the probability of embolic events per risk category was calculated for each day on treatment (day 0 through day 30). Results There were 499 episodes of infective endocarditis (34%) that were complicated by ≥ 1 embolic event. Most embolic events occurred early in the clinical course (first week of therapy: 15.5 episodes per 1000 patient days; second week: 3.7 episodes per 1000 patient days). In the total cohort, the factors associated with the occurrence of embolism at multivariate analysis were prosthetic valve localization (odds ratio, 1.84), right-sided endocarditis (odds ratio, 3.93), Staphylococcus aureus etiology (odds ratio, 2.23) and vegetation size ≥ 13 mm (odds ratio, 1.86). In left-sided endocarditis, Staphylococcus aureus etiology (odds ratio, 2.1) and vegetation size ≥ 13 mm (odds ratio, 2.1) were independently associated with embolic events; the 30-day cumulative incidence of embolism varied with risk score category (low risk, 12%; intermediate risk, 25%; high risk, 38%; p < 0.001). Conclusions Staphylococcus aureus etiology and vegetation size are associated with an increased risk of embolism. In left

  14. Impaired fear inhibition learning predicts the persistence of symptoms of posttraumatic stress disorder (PTSD).

    PubMed

    Sijbrandij, Marit; Engelhard, Iris M; Lommen, Miriam J J; Leer, Arne; Baas, Johanna M P

    2013-12-01

    Recent cross-sectional studies have shown that the inability to suppress fear under safe conditions is a key problem in people with posttraumatic stress disorder (PTSD). The current longitudinal study examined whether individual differences in fear inhibition predict the persistence of PTSD symptoms. Approximately 2 months after deployment to Afghanistan, 144 trauma-exposed Dutch soldiers were administered a conditional discrimination task (AX+/BX-). In this paradigm, A, B, and X are neutral stimuli. X combined with A is paired with a shock (AX+ trials); X combined with B is not (BX- trials). Fear inhibition was measured (AB trials). Startle electromyogram responses and shock expectancy ratings were recorded. PTSD symptoms were measured at 2 months and at 9 months after deployment. Results showed that greater startle responses during AB trials in individuals who discriminated between danger (AX+) and safety (BX-) during conditioning, predicted higher PTSD symptoms at 2 months and 9 months post-deployment. The predictive effect at 9 months remained significant after controlling for critical incidents during previous deployments and PTSD symptoms at 2 months. Responses to AX+ or BX- trials, or discrimination learning (AX+ minus BX-) did not predict PTSD symptoms. It is concluded that impaired fear inhibition learning seems to be involved in the persistence of PTSD symptoms.

  15. Comparison of neuroimaging modalities for the prediction of conversion from mild cognitive impairment to Alzheimer's dementia.

    PubMed

    Trzepacz, Paula T; Yu, Peng; Sun, Jia; Schuh, Kory; Case, Michael; Witte, Michael M; Hochstetler, Helen; Hake, Ann

    2014-01-01

    In this study we compared Pittsburgh compound-B (PIB) positron emission tomography (PET) amyloid imaging, fluorodeoxyglucose PET for metabolism, and magnetic resonance imaging (MRI) for structure to predict conversion from amnestic mild cognitive impairment (MCI) to Alzheimer's dementia using data from the Alzheimer's Disease Neuroimaging Initiative cohort. Numeric neuroimaging variables generated by the Alzheimer's Disease Neuroimaging Initiative-funded laboratories for each neuroimaging modality along with apolipoprotein-E genotype (n = 29) were analyzed. Performance of these biomarkers for predicting conversion from MCI to Alzheimer's dementia at 2 years was evaluated in 50 late amnestic MCI subjects, 20 of whom converted. Multivariate modeling found that among individual modalities, MRI had the highest predictive accuracy (67%) which increased by 9% to 76% when combined with PIB-PET, producing the highest accuracy among any biomarker combination. Individually, PIB-PET generated the best sensitivity, and fluorodeoxyglucose PET had the lowest. Among individual brain regions, the temporal cortex was found to be most predictive for MRI and PIB-PET. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Caudate nucleus-dependent response strategies in a virtual navigation task are associated with lower basal cortisol and impaired episodic memory.

    PubMed

    Bohbot, Véronique D; Gupta, Melini; Banner, Harrison; Dahmani, Louisa

    2011-09-01

    The present research examined the relationship between endogenous glucocorticoids, navigational strategies in a virtual navigation task, and performance on standard neuropsychological assessments of memory. Healthy young adult participants (N=66, mean age: 21.7) were tested on the 4 on 8 virtual maze (4/8 VM) and standard neuropsychological tests such as the Rey-Osterrieth Complex Figure (RO) and the Rey Auditory Verbal Learning Task (RAVLT), which measure episodic memory. The 4/8 VM differentiates between navigational strategies, where participants either use a hippocampal-dependent spatial strategy by building relationships between landmarks, or a caudate nucleus-dependent stimulus-response strategy by automatizing a pattern of open and closed arms to learn the location of objects within the maze. Degree of stress was assessed by administering the Perceived Stress Scale (PSS) questionnaire. Cortisol samples were taken on two consecutive days upon waking, 30 min after waking, at 11 am, 4 pm, and 9 pm. There was a significant difference in basal levels of cortisol between spatial and response learners. Interestingly, response learners had significantly lower cortisol levels throughout the day. The two groups did not differ in terms of perceived stress as measured with the PSS questionnaire. Moreover, there was no significant correlation between PSS scores and salivary cortisol levels, indicating that the higher cortisol levels in the spatial group were not associated with greater perceived stress. In addition, participants who spontaneously used a spatial strategy performed significantly better on the RAVLT and RO. These data indicate that the cortisol levels in the spatial group may be optimal in terms of episodic memory performance whereas the cortisol levels in the response group may be associated with poorer memory. These results are suggestive of an inverted U-shaped curve describing the effects of basal levels of circulating cortisol on memory in young adults.

  17. Impaired white matter connectivity between regions containing mirror neurons, and relationship to negative symptoms and social cognition, in patients with first-episode schizophrenia.

    PubMed

    Saito, Yukiko; Kubicki, Marek; Koerte, Inga; Otsuka, Tatsui; Rathi, Yogesh; Pasternak, Ofer; Bouix, Sylvain; Eckbo, Ryan; Kikinis, Zora; von Hohenberg, Christian Clemm; Roppongi, Tomohide; Del Re, Elisabetta; Asami, Takeshi; Lee, Sang-Hyuk; Karmacharya, Sarina; Mesholam-Gately, Raquelle I; Seidman, Larry J; Levitt, James; McCarley, Robert W; Shenton, Martha E; Niznikiewicz, Margaret A

    2017-02-28

    In schizophrenia, abnormalities in structural connectivity between brain regions known to contain mirror neurons and their relationship to negative symptoms related to a domain of social cognition are not well understood. Diffusion tensor imaging (DTI) scans were acquired in 16 patients with first episode schizophrenia and 16 matched healthy controls. FA and Trace of the tracts interconnecting regions known to be rich in mirror neurons, i.e., anterior cingulate cortex (ACC), inferior parietal lobe (IPL) and premotor cortex (PMC) were evaluated. A significant group effect for Trace was observed in IPL-PMC white matter fiber tract (F (1, 28) = 7.13, p = .012), as well as in the PMC-ACC white matter fiber tract (F (1, 28) = 4.64, p = .040). There were no group differences in FA. In addition, patients with schizophrenia showed a significant positive correlation between the Trace of the left IPL-PMC white matter fiber tract, and the Ability to Feel Intimacy and Closeness score (rho = .57, p = 0.034), and a negative correlation between the Trace of the left PMC-ACC and the Relationships with Friends and Peers score (rho = remove -.54, p = 0.049). We have demonstrated disrupted white mater microstructure within the white matter tracts subserving brain regions containing mirror neurons. We further showed that such structural disruptions might impact negative symptoms and, more specifically, contribute to the inability to feel intimacy (a measure conceptually related to theory of mind) in first episode schizophrenia. Further studies are needed to understand the potential of our results for diagnosis, prognosis and therapeutic interventions.

  18. Multidimensional Analysis of Magnetic Resonance Imaging Predicts Early Impairment in Thoracic and Thoracolumbar Spinal Cord Injury

    PubMed Central

    Mabray, Marc C.; Whetstone, William D.; Dhall, Sanjay S.; Phillips, David B.; Pan, Jonathan Z.; Manley, Geoffrey T.; Bresnahan, Jacqueline C.; Beattie, Michael S.; Haefeli, Jenny

    2016-01-01

    Abstract Literature examining magnetic resonance imaging (MRI) in acute spinal cord injury (SCI) has focused on cervical SCI. Reproducible systems have been developed for MRI-based grading; however, it is unclear how they apply to thoracic SCI. Our hypothesis is that MRI measures will group as coherent multivariate principal component (PC) ensembles, and that distinct PCs and individual variables will show discriminant validity for predicting early impairment in thoracic SCI. We undertook a retrospective cohort study of 25 patients with acute thoracic SCI who underwent MRI on admission and had American Spinal Injury Association Impairment Scale (AIS) assessment at hospital discharge. Imaging variables of axial grade, sagittal grade, length of injury, thoracolumbar injury classification system (TLICS), maximum canal compromise (MCC), and maximum spinal cord compression (MSCC) were collected. We performed an analytical workflow to detect multivariate PC patterns followed by explicit hypothesis testing to predict AIS at discharge. All imaging variables loaded positively on PC1 (64.3% of variance), which was highly related to AIS at discharge. MCC, MSCC, and TLICS also loaded positively on PC2 (22.7% of variance), while variables concerning cord signal abnormality loaded negatively on PC2. PC2 was highly related to the patient undergoing surgical decompression. Variables of signal abnormality were all negatively correlated with AIS at discharge with the highest level of correlation for axial grade as assessed with the Brain and Spinal Injury Center (BASIC) score. A multiple variable model identified BASIC as the only statistically significant predictor of AIS at discharge, signifying that BASIC best captured the variance in AIS within our study population. Our study provides evidence of convergent validity, construct validity, and clinical predictive validity for the sampled MRI measures of SCI when applied in acute thoracic and thoracolumbar SCI. PMID:26414451

  19. Diabetes and Impaired Fasting Glucose Prediction Using Anthropometric Indices in Adults from Maracaibo City, Venezuela.

    PubMed

    Bermúdez, Valmore; Salazar, Juan; Rojas, Joselyn; Calvo, María; Rojas, Milagros; Chávez-Castillo, Mervin; Añez, Roberto; Cabrera, Mayela

    2016-12-01

    To determine the predictive power of various anthropometric indices for the identification of dysglycemic states in Maracaibo, Venezuela. A cross-sectional study with randomized, multi-staged sampling was realized in 2230 adult subjects of both genders who had their body mass index (BMI), waist circumference (WC) and waist-height ratio (WHR) determined. Diagnoses of type 2 diabetes mellitus (DM2) and impaired fasting glucose (IFG) were made following ADA 2015 criteria. ROC curves were used to evaluate the predictive power of each anthropometric parameter. Area under the curve (AUC) values were compared through Delong's test. Of the total 2230 individuals (52.6 % females), 8.4 % were found to have DM2, and 19.5 % had IFG. Anthropometric parameters displayed greater predictive power regarding newly diagnosed diabetics, where WHR was the most important predictor in both females (AUC = 0.808; CI 95 % 0.715-0.900. Sensitivity: 82.8 %; specificity: 76.2 %) and males (AUC = 0.809; CI 95 % 0.736-0.882. Sensitivity: 78.6 %; specificity: 68.1 %), although all three parameters appeared to have comparable predictive power in this subset. In previously diagnosed diabetic subjects, WHR was superior to both WC and BMI in females, and WHR and WC were both superior to BMI in males. Lower predictive values were found for IFG in both genders. Accumulation of various altered anthropometric measurements was associated with increased odds ratios for both newly and previously diagnosed DM2. The predictive power of anthropometric measurements was greater for DM2 than IFG. We suggest assessment of as many available parameters as possible in the clinical setting.

  20. Predictive validity of a MK-801-induced cognitive impairment model in mice: implications on the potential limitations and challenges of modeling cognitive impairment associated with schizophrenia preclinically.

    PubMed

    Brown, Jordan W; Rueter, Lynne E; Zhang, Min

    2014-03-03

    Cognitive impairment associated with schizophrenia (CIAS) is a major and disabling symptom domain of the disease that is generally unresponsive to current pharmacotherapies. Critically important to the discovery of novel therapeutics for CIAS is the utilization of preclinical models with robust predictive validity. We investigated the predictive validity of MK-801-induced memory impairments in mouse inhibitory avoidance (MK-IA) as a preclinical model for CIAS by investigating compounds that have been tested in humans, including antipsychotics, sodium channel blocker mood stabilizers, and putative cognitive enhancers. The atypical antipsychotic clozapine, as well as risperidone and olanzapine (see Brown et al., 2013), had no effect on MK-801-induced memory impairments. For sodium channel blockers, carbamazepine significantly attenuated memory impairments induced by MK-801, whereas lamotrigine had no effect. Nicotine, donepezil, modafinil, and xanomeline all significantly attenuated MK-801-induced memory impairments, but the magnitude of effects and the dose-responses observed varied across compounds. Clinically, only acute administration of nicotine has demonstrated consistent positive effects on CIAS, while inconsistent results have been reported for lamotrigine, donepezil, and modafinil; atypical antipsychotics produce only moderate improvements at best. A positive clinical signal has been observed with xanomeline, but only in a small pilot trial. The results presented here suggest that the MK-IA model lacks robust predictive validity for CIAS as the model is likely permissive and may indicate false positive signals for compounds and mechanisms that lack clear clinical efficacy for CIAS. Our findings also highlight the potential limitations and challenges of using NMDA receptor antagonists in rodents to model CIAS. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. BrainAGE in Mild Cognitive Impaired Patients: Predicting the Conversion to Alzheimer’s Disease

    PubMed Central

    Klöppel, Stefan; Koutsouleris, Nikolaos; Sauer, Heinrich

    2013-01-01

    Alzheimer’s disease (AD), the most common form of dementia, shares many aspects of abnormal brain aging. We present a novel magnetic resonance imaging (MRI)-based biomarker that predicts the individual progression of mild cognitive impairment (MCI) to AD on the basis of pathological brain aging patterns. By employing kernel regression methods, the expression of normal brain-aging patterns forms the basis to estimate the brain age of a given new subject. If the estimated age is higher than the chronological age, a positive brain age gap estimation (BrainAGE) score indicates accelerated atrophy and is considered a risk factor for conversion to AD. Here, the BrainAGE framework was applied to predict the individual brain ages of 195 subjects with MCI at baseline, of which a total of 133 developed AD during 36 months of follow-up (corresponding to a pre-test probability of 68%). The ability of the BrainAGE framework to correctly identify MCI-converters was compared with the performance of commonly used cognitive scales, hippocampus volume, and state-of-the-art biomarkers derived from cerebrospinal fluid (CSF). With accuracy rates of up to 81%, BrainAGE outperformed all cognitive scales and CSF biomarkers in predicting conversion of MCI to AD within 3 years of follow-up. Each additional year in the BrainAGE score was associated with a 10% greater risk of developing AD (hazard rate: 1.10 [CI: 1.07–1.13]). Furthermore, the post-test probability was increased to 90% when using baseline BrainAGE scores to predict conversion to AD. The presented framework allows an accurate prediction even with multicenter data. Its fast and fully automated nature facilitates the integration into the clinical workflow. It can be exploited as a tool for screening as well as for monitoring treatment options. PMID:23826273

  2. BrainAGE in Mild Cognitive Impaired Patients: Predicting the Conversion to Alzheimer's Disease.

    PubMed

    Gaser, Christian; Franke, Katja; Klöppel, Stefan; Koutsouleris, Nikolaos; Sauer, Heinrich

    2013-01-01

    Alzheimer's disease (AD), the most common form of dementia, shares many aspects of abnormal brain aging. We present a novel magnetic resonance imaging (MRI)-based biomarker that predicts the individual progression of mild cognitive impairment (MCI) to AD on the basis of pathological brain aging patterns. By employing kernel regression methods, the expression of normal brain-aging patterns forms the basis to estimate the brain age of a given new subject. If the estimated age is higher than the chronological age, a positive brain age gap estimation (BrainAGE) score indicates accelerated atrophy and is considered a risk factor for conversion to AD. Here, the BrainAGE framework was applied to predict the individual brain ages of 195 subjects with MCI at baseline, of which a total of 133 developed AD during 36 months of follow-up (corresponding to a pre-test probability of 68%). The ability of the BrainAGE framework to correctly identify MCI-converters was compared with the performance of commonly used cognitive scales, hippocampus volume, and state-of-the-art biomarkers derived from cerebrospinal fluid (CSF). With accuracy rates of up to 81%, BrainAGE outperformed all cognitive scales and CSF biomarkers in predicting conversion of MCI to AD within 3 years of follow-up. Each additional year in the BrainAGE score was associated with a 10% greater risk of developing AD (hazard rate: 1.10 [CI: 1.07-1.13]). Furthermore, the post-test probability was increased to 90% when using baseline BrainAGE scores to predict conversion to AD. The presented framework allows an accurate prediction even with multicenter data. Its fast and fully automated nature facilitates the integration into the clinical workflow. It can be exploited as a tool for screening as well as for monitoring treatment options.

  3. Impaired Oculomotor Behavior of Children with Developmental Dyslexia in Antisaccades and Predictive Saccades Tasks

    PubMed Central

    Lukasova, Katerina; Silva, Isadora P.; Macedo, Elizeu C.

    2016-01-01

    Analysis of eye movement patterns during tracking tasks represents a potential way to identify differences in the cognitive processing and motor mechanisms underlying reading in dyslexic children before the occurrence of school failure. The current study aimed to evaluate the pattern of eye movements in antisaccades, predictive saccades and visually guided saccades in typical readers and readers with developmental dyslexia. The study included 30 children (age M = 11; SD = 1.67), 15 diagnosed with developmental dyslexia (DG) and 15 regular readers (CG), matched by age, gender and school grade. Cognitive assessment was performed prior to the eye-tracking task during which both eyes were registered using the Tobii® 1750 eye-tracking device. The results demonstrated a lower correct antisaccades rate in dyslexic children compared to the controls (p < 0.001, DG = 25%, CC = 37%). Dyslexic children also made fewer saccades in predictive latency (p < 0.001, DG = 34%, CG = 46%, predictive latency within −300–120 ms with target as 0 point). No between-group difference was found for visually guided saccades. In this task, both groups showed shorter latency for right-side targets. The results indicated altered oculomotor behavior in dyslexic children, which has been reported in previous studies. We extend these findings by demonstrating impaired implicit learning of target's time/position patterns in dyslexic children. PMID:27445945

  4. Impaired Oculomotor Behavior of Children with Developmental Dyslexia in Antisaccades and Predictive Saccades Tasks.

    PubMed

    Lukasova, Katerina; Silva, Isadora P; Macedo, Elizeu C

    2016-01-01

    Analysis of eye movement patterns during tracking tasks represents a potential way to identify differences in the cognitive processing and motor mechanisms underlying reading in dyslexic children before the occurrence of school failure. The current study aimed to evaluate the pattern of eye movements in antisaccades, predictive saccades and visually guided saccades in typical readers and readers with developmental dyslexia. The study included 30 children (age M = 11; SD = 1.67), 15 diagnosed with developmental dyslexia (DG) and 15 regular readers (CG), matched by age, gender and school grade. Cognitive assessment was performed prior to the eye-tracking task during which both eyes were registered using the Tobii® 1750 eye-tracking device. The results demonstrated a lower correct antisaccades rate in dyslexic children compared to the controls (p < 0.001, DG = 25%, CC = 37%). Dyslexic children also made fewer saccades in predictive latency (p < 0.001, DG = 34%, CG = 46%, predictive latency within -300-120 ms with target as 0 point). No between-group difference was found for visually guided saccades. In this task, both groups showed shorter latency for right-side targets. The results indicated altered oculomotor behavior in dyslexic children, which has been reported in previous studies. We extend these findings by demonstrating impaired implicit learning of target's time/position patterns in dyslexic children.

  5. Severity of specific language impairment predicts delayed development in number skills

    PubMed Central

    Durkin, Kevin; Mok, Pearl L. H.; Conti-Ramsden, Gina

    2013-01-01

    The extent to which mathematical development is dependent upon language is controversial. This longitudinal study investigates the role of language ability in children's development of number skills. Participants were 229 children with specific language impairment (SLI) who were assessed initially at age 7 and again 1 year later. All participants completed measures of psycholinguistic development (expressive and receptive), performance IQ, and the Basic Number Skills subtest of the British Ability Scales. Number skills data for this sample were compared with normative population data. Consistent with predictions that language impairment would impact on numerical development, average standard scores were more than 1 SD below the population mean at both ages. Although the children showed improvements in raw scores at the second wave of the study, the discrepancy between their scores and the population data nonetheless increased over time. Regression analyses showed that, after controlling for the effect of PIQ, language skills explained an additional 19 and 17% of the variance in number skills for ages 7 and 8, respectively. Furthermore, logistic regression analyses revealed that less improvement in the child's language ability over the course of the year was associated with a greater odds of a drop in performance in basic number skills from 7 to 8 years. The results are discussed in relation to the interaction of linguistic and cognitive factors in numerical development and the implications for mathematical education. PMID:24027548

  6. Severity of specific language impairment predicts delayed development in number skills.

    PubMed

    Durkin, Kevin; Mok, Pearl L H; Conti-Ramsden, Gina

    2013-01-01

    The extent to which mathematical development is dependent upon language is controversial. This longitudinal study investigates the role of language ability in children's development of number skills. Participants were 229 children with specific language impairment (SLI) who were assessed initially at age 7 and again 1 year later. All participants completed measures of psycholinguistic development (expressive and receptive), performance IQ, and the Basic Number Skills subtest of the British Ability Scales. Number skills data for this sample were compared with normative population data. Consistent with predictions that language impairment would impact on numerical development, average standard scores were more than 1 SD below the population mean at both ages. Although the children showed improvements in raw scores at the second wave of the study, the discrepancy between their scores and the population data nonetheless increased over time. Regression analyses showed that, after controlling for the effect of PIQ, language skills explained an additional 19 and 17% of the variance in number skills for ages 7 and 8, respectively. Furthermore, logistic regression analyses revealed that less improvement in the child's language ability over the course of the year was associated with a greater odds of a drop in performance in basic number skills from 7 to 8 years. The results are discussed in relation to the interaction of linguistic and cognitive factors in numerical development and the implications for mathematical education.

  7. Prediction of brain injury severity by subscales of the alternative impairment index.

    PubMed

    Horton, A M

    2000-11-01

    A new screening index, the Alternative Impairment Index (AII) reflects the severity of brain damage with hit rates of 60% with the Halstead Impairment Index (HII) and 64% with the General Neuropsychological Deficit Scale (GNDS) and a cross-validation study found a hit rate between the AII and the HII of 66%. This paper explores the use of demographic corrections (e.g., age, education and sex) to enable Cognitive (Cog) and Motor (Mot) Subscales of the AII to predict the severity of brain damage. A sample of 40 normal, psychiatric and brain-damaged subjects with Halstead-Reitan Neuropsychological Test Battery results was selected. The GNDS, HII, Cog and Mot were calculated for each brain-damaged patient. There were 36 males and four women in the subject group. Ages ranged from 19-66 and years of education ranged from 8-22. Demographic corrections produced worse than chance level results (Cog vs. GNDS = 42.5%, Cog vs. HII = 42.5%/Mot vs. GNDS = 42.5%, Mot vs. HII = 35%).

  8. Short-term test for predicting the potential of xenobiotics to impair reproductive success in fish

    SciTech Connect

    Landner, L.; Neilson, A.H.; Soerensen, L.T.; Taernholm, A.V.; Viktor, T.

    1985-06-01

    Short-term screening tests with the zebra fish (Brachydanio rerio) have been developed for predicting the potential of xenobiotics to impair reproductive success in fish. The aim was to find simple and sensitive test parameters and to simulate exposure situations typical for anadromous fish species (salmonids), which generally cross heavily polluted coastal areas or estuaries before they reach uncontaminated upstream spawning areas. Therefore, particular attention was directed to tests designed to assess adverse effects induced during gametogenesis in adult fish. The test protocol involves exposure of adults prior to, but not during, spawning and the effects are measured in the offspring as alterations in hatching frequency and hatching rate of eggs, and survival and stress tolerance of embryos and larvae. Some representative examples of the application of these tests are given, and it is shown that impairment of reproductive success can be induced by exposure of parent fish prior to spawning at concentrations of xenobiotics at least five times lower than those yielding effects during direct exposure of embryos and larvae. It is suggested that, in hazard assessment programs, tests of the effect of xenobiotics on the offspring of preexposed adults be routinely incorporated.

  9. Distinguishing between persistent and transient impaired glucose tolerance using a prediction model.

    PubMed

    Bourn, D M; Williams, S M; Mann, J I

    1992-10-01

    Screening for impaired glucose tolerance (IGT) and Type 2 (non-insulin dependent) diabetes was carried out in 777 people and those with high blood glucose levels completed three 2-h oral glucose tolerance tests (OGTT). Blood lipid levels, fasting and 2-h insulin levels, body mass index, and blood pressure were also measured and family history of Type 2 diabetes recorded. Fifty people were identified with IGT and of these 21 were found to have persistent IGT and 29 transient IGT. A model including the variables body mass index, fasting and 2-h insulin levels, fasting triglycerides and family history of Type 2 diabetes was developed using the Speigelhalter-Knill-Jones weighting method to predict subjects with persistent IGT. This model could be useful in identifying people with persistent IGT and therefore eliminate the need for repeat OGTTs which are time consuming and expensive.

  10. The Role of Occupational Voice Demand and Patient-Rated Impairment in Predicting Voice Therapy Adherence.

    PubMed

    Ebersole, Barbara; Soni, Resha S; Moran, Kathleen; Lango, Miriam; Devarajan, Karthik; Jamal, Nausheen

    2017-07-11

    Examine the relationship among the severity of patient-perceived voice impairment, perceptual dysphonia severity, occupational voice demand, and voice therapy adherence. Identify clinical predictors of increased risk for therapy nonadherence. A retrospective cohort study of patients presenting with a chief complaint of persistent dysphonia at an interdisciplinary voice center was done. The Voice Handicap Index-10 (VHI-10) and the Voice-Related Quality of Life (V-RQOL) survey scores, clinician rating of dysphonia severity using the Grade score from the Grade, Roughness Breathiness, Asthenia, and Strain scale, occupational voice demand, and patient demographics were tested for associations with therapy adherence, defined as completion of the treatment plan. Classification and Regression Tree (CART) analysis was performed to establish thresholds for nonadherence risk. Of 166 patients evaluated, 111 were recommended for voice therapy. The therapy nonadherence rate was 56%. Occupational voice demand category, VHI-10, and V-RQOL scores were the only factors significantly correlated with therapy adherence (P < 0.0001, P = 0.018, and P = 0.008, respectively). CART analysis found that patients with low or no occupational voice demand are significantly more likely to be nonadherent with therapy than those with high occupational voice demand (P < 0.001). Furthermore, a VHI-10 score of ≤29 or a V-RQOL score of >40 is a significant cutoff point for predicting therapy nonadherence (P < 0.011 and P < 0.004, respectively). Occupational voice demand and patient perception of impairment are significantly and independently correlated with therapy adherence. A VHI-10 score of ≤9 or a V-RQOL score of >40 is a significant cutoff point for predicting nonadherence risk. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  11. Early Functional Limitations in Cognitively Normal Older Adults Predict Diagnostic Conversion to Mild Cognitive Impairment.

    PubMed

    Farias, Sarah Tomaszewski; Lau, Karen; Harvey, Danielle; Denny, Katherine G; Barba, Cheyanne; Mefford, Anthony N

    2017-06-01

    To examine whether specific types of early functional limitations in cognitively normal older adults are associated with subsequent development of mild cognitive impairment (MCI), as well as the relative predictive value of self versus informant report in predicting diagnostic conversion to MCI. As a part of a longitudinal study design, participants underwent baseline and annual multidisciplinary clinical evaluations, including a physical and neurological examination, imaging, laboratory work, and neuropsychological testing. Data used in this study were collected as part of longitudinal research at the University of California, Davis Alzheimer's Disease Center. Individuals diagnosed as having normal cognition at study baseline who had an informant who could complete informant-based ratings and at least one follow-up visit (N = 324). Participants and informants each completed the Everyday Cognition Scale (ECog), an instrument designed to measure everyday function in six cognitively relevant domains. Self- and informant-reported functional limitations on the ECog were associated with significantly greater risk of diagnostic conversion to MCI (informant: hazard ratio (HR) = 2.0, 95% confidence interval (CI) = 1.3-3.2, P = .002), with self-report having a slightly higher hazard (HR = 2.3, 95% CI = 1.4-3.6, P < .001). When controlling for baseline cognitive abilities, the effect remained significant for self- and informant-reported functional limitations. Deficits in everyday memory and executive function domains were the strongest predictors of diagnostic conversion to MCI. Detection of early functional limitations may be clinically useful in assessing the future risk of developing cognitive impairment in cognitively normal older adults. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

  12. Background rhythm frequency and theta power of quantitative EEG analysis: predictive biomarkers for cognitive impairment post-cerebral infarcts.

    PubMed

    Song, Yang; Zang, Da-Wei; Jin, Yan-Yu; Wang, Zhi-Jun; Ni, Hong-Yan; Yin, Jian-Zhong; Ji, Dong-Xu

    2015-04-01

    In clinical settings, cerebral infarct is a common disease of older adults, which usually increases the risk of cognitive impairment. This study aims to assess the quantitative electroencephalography (qEEG) as a predictive biomarker for the development of cognitive impairment, post-cerebral infarcts, in subjects from the Department of Neurology. They underwent biennial EEG recording. Cerebral infarct subjects, with follow-up cognitive evaluation, were analyzed for qEEG measures of background rhythm frequency (BRF) and relative δ, θ, α, and β band power. The relationship between cognitive impairment and qEEG, and other possible predictors, was assessed by Cox regression. The results showed that the risk hazard of developing cognitive impairment was 14 times higher for those with low BRF than for those with high BRF (P < .001). Hazard ratio (HR) was also significant for more than median θ band power (HR = 5, P = .002) compared with less than median θ band power. The HRs for δ, α, and β bands were equal to the baseline demographic, and clinical characteristics were not significantly different. In conclusion, qEEG measures of BRF, and relative power in θ band, are potential predictive biomarkers for cognitive impairment in patients with cerebral infarcts. These biomarkers might be valuable in early prediction of cognitive impairment in patients with cerebral infarcts.

  13. Fear of injury predicts self-reported and behavioral impairment in patients with chronic low back pain.

    PubMed

    Thibodeau, Michel A; Fetzner, Mathew G; Carleton, R Nicholas; Kachur, Shane S; Asmundson, Gordon J G

    2013-02-01

    Fear of injury has been posited as crucial in pain-related anxiety and in the development of chronic pain; however, research has only measured fear of injury indirectly through other constructs (eg, fear of illness and fear of movement). The current study tested fear of injury as an independent contributor to pain-related anxiety and impairment. Patients (n = 78; 37% women) in a work-hardening treatment program for chronic low back pain completed self-report measures of pain-related anxiety, anxiety sensitivity, fear of injury, current pain, and impairment. Behavioral measures of impairment included lifting capacity, treatment outcomes, and days absent from treatment. Structural equation modeling tested the role of fear of injury within contemporary theory. Fit for the theoretical model was excellent and superior to an alternative model. Variance accounted for in pain-related anxiety by fear of injury, anxiety sensitivity, and current pain was 64%, while pain-related anxiety and current pain predicted 49% of variance in latent impairment. Fear of injury directly predicted pain-related anxiety (β = .42) and indirectly predicted impairment through pain-related anxiety (β = .19). Fear of injury may warrant theoretical and clinical consideration as an important contributor to pain-related anxiety and impairment; however, research is needed to explore how it may be causally related with other constructs. Fear of injury directly predicts pain-related anxiety and indirectly predicts self-reported and behavioral impairment. Fear of injury may warrant inclusion in contemporary theories of chronic pain. Clinicians may benefit from considering the construct in interventions for chronic pain. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

  14. Early insulin resistance predicts weight gain and waist circumference increase in first-episode psychosis--A one year follow-up study.

    PubMed

    Keinänen, Jaakko; Mantere, Outi; Kieseppä, Tuula; Mäntylä, Teemu; Torniainen, Minna; Lindgren, Maija; Sundvall, Jouko; Suvisaari, Jaana

    2015-12-01

    First-episode psychosis (FEP) is associated with weight gain during the first year of treatment, and risk of abdominal obesity is particularly increased. To identify early risk markers of weight gain and abdominal obesity, we investigated baseline metabolic differences in 60 FEP patients and 27 controls, and longitudinal changes during the first year of treatment in patients. Compared to controls at baseline, patients had higher low-density lipoprotein, triglyceride and apolipoprotein B levels, and lower levels of high-density lipoprotein and apolipoprotein A-I but no difference in body mass index or waist circumference. At 12-month follow-up, 60.6% of patients were overweight or obese and 58.8% had abdominal obesity. No significant increase during follow-up was seen in markers of glucose and lipid metabolism or blood pressure, but increase in C-reactive protein between baseline and 12-month follow-up was statistically significant. Weight increase was predicted by baseline insulin resistance and olanzapine use, while increase in waist circumference was predicted by baseline insulin resistance only. In conclusion, insulin resistance may be an early marker of increased vulnerability to weight gain and abdominal obesity in young adults with FEP. Olanzapine should be avoided as a first-line treatment in FEP due to the substantial weight increase it causes. In addition, the increase in the prevalence of overweight and abdominal obesity was accompanied by the emergence of low-grade systemic inflammation. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. The relevance of cognitive, clinical and premorbid variables in predicting functional outcome for individuals with first-episode psychosis: a 3 year longitudinal study.

    PubMed

    Ayesa-Arriola, Rosa; Rodríguez-Sánchez, José Manuel; Pérez-Iglesias, Rocío; González-Blanch, César; Pardo-García, Gema; Tabares-Seisdedos, Rafael; Vázquez-Barquero, Jose L; Crespo-Facorro, Benedicto

    2013-10-30

    Real-world functional deficits are common and persistent in individuals with psychosis. Cognitive deficits have been shown to compromise functioning. We aimed to study the predictive values of premorbid, sociodemographic, and baseline clinical and neurocognitive factors on long-term functional outcome for individuals with first episode non-affective psychosis. We failed to demonstrate a significant relationship between cognitive deficits at baseline and functional disability at 3 year follow-up. Diagnosis of schizophrenia (OR=2.457, p=0.011), shorter education (OR=1.177, p=0.005) and poor premorbid social adjustment (OR=1.628, p=0.013) emerged as the strongest predictors for the 114 subjects (56%) that exhibited functional disability at 3-year follow-up. A considerable proportion of the variance in functioning (74% at 1 year and 77% at 3 year) remained unexplained by baseline variables. The set of variables that predicted functional outcome at medium- (1 year) and long-term (3 years) differed. In conclusion, the length of follow-up influenced the relationship between baseline variables and functional outcome. A substantial proportion of the variance in function was not explained by these variables and therefore the influence of other factors warrants further investigation. The data support the notion that premorbid social adjustment is an important aspect in functional outcome over the course of the illness. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  16. Linear combination of one-step predictive information with an external reward in an episodic policy gradient setting: a critical analysis

    PubMed Central

    Zahedi, Keyan; Martius, Georg; Ay, Nihat

    2013-01-01

    One of the main challenges in the field of embodied artificial intelligence is the open-ended autonomous learning of complex behaviors. Our approach is to use task-independent, information-driven intrinsic motivation(s) to support task-dependent learning. The work presented here is a preliminary step in which we investigate the predictive information (the mutual information of the past and future of the sensor stream) as an intrinsic drive, ideally supporting any kind of task acquisition. Previous experiments have shown that the predictive information (PI) is a good candidate to support autonomous, open-ended learning of complex behaviors, because a maximization of the PI corresponds to an exploration of morphology- and environment-dependent behavioral regularities. The idea is that these regularities can then be exploited in order to solve any given task. Three different experiments are presented and their results lead to the conclusion that the linear combination of the one-step PI with an external reward function is not generally recommended in an episodic policy gradient setting. Only for hard tasks a great speed-up can be achieved at the cost of an asymptotic performance lost. PMID:24204351

  17. Neuropsychological Testing Predicts Cerebrospinal Fluid Aβ in Mild Cognitive Impairment (MCI)

    PubMed Central

    Kandel, Benjamin M.; Avants, Brian B.; Gee, James C.; Arnold, Steven E.; Wolk, David A.

    2015-01-01

    Background Psychometric tests predict conversion of Mild Cognitive Impairment (MCI) to probable Alzheimer's Disease (AD). Because the definition of clinical AD relies on those same psychometric tests, the ability of these tests to identify underlying AD pathology remains unclear. Objective To determine the degree to which psychometric testing predicts molecular evidence of AD amyloid pathology, as indicated by CSF Aβ1–42, in patients with MCI, as compared to neuroimaging biomarkers. Methods We identified 408 MCI subjects with CSF Aβ levels, psychometric test data, FDG-PET scans, and acceptable volumetric MR scans from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). We used psychometric tests and imaging biomarkers in univariate and multivariate models to predict Aβ status. Results The 30-minute delayed recall score of the Rey Auditory Verbal Learning Test (AVLT) was the best predictor of Aβ status among the psychometric tests, achieving an AUC of 0.67±0.02 and odds ratio of 2.5±0.4. FDG-PET was the best imaging-based biomarker (AUC 0.67±0.03, OR 3.2±1.2), followed by hippocampal volume (AUC 0.64±0.02,,OR 2.4±0.3). A multivariate analysis based on the psychometric tests improved on the univariate predictors, achieving an AUC of 0.68±0.03 (OR 3.38±1.2). Adding imaging biomarkers to the multivariate analysis did not improve the AUC. Conclusion Psychometric tests perform as well as imaging biomarkers to predict presence of molecular markers of AD pathology in MCI patients and should be considered in the determination of the likelihood that MCI is due to AD. PMID:25881908

  18. Single episode of mild murine malaria induces neuroinflammation, alters microglial profile, impairs adult neurogenesis, and causes deficits in social and anxiety-like behavior.

    PubMed

    Guha, Suman K; Tillu, Rucha; Sood, Ankit; Patgaonkar, Mandar; Nanavaty, Ishira N; Sengupta, Arjun; Sharma, Shobhona; Vaidya, Vidita A; Pathak, Sulabha

    2014-11-01

    Cerebral malaria is associated with cerebrovascular damage and neurological sequelae. However, the neurological consequences of uncomplicated malaria, the most prevalent form of the disease, remain uninvestigated. Here, using a mild malaria model, we show that a single Plasmodium chabaudi adami infection in adult mice induces neuroinflammation, neurogenic, and behavioral changes in the absence of a blood-brain barrier breach. Using cytokine arrays we show that the infection induces differential serum and brain cytokine profiles, both at peak parasitemia and 15days post-parasite clearance. At the peak of infection, along with the serum, the brain also exhibited a definitive pro-inflammatory cytokine profile, and gene expression analysis revealed that pro-inflammatory cytokines were also produced locally in the hippocampus, an adult neurogenic niche. Hippocampal microglia numbers were enhanced, and we noted a shift to an activated profile at this time point, accompanied by a striking redistribution of the microglia to the subgranular zone adjacent to hippocampal neuronal progenitors. In the hippocampus, a distinct decline in progenitor turnover and survival was observed at peak parasitemia, accompanied by a shift from neuronal to glial fate specification. Studies in transgenic Nestin-GFP reporter mice demonstrated a decline in the Nestin-GFP(+)/GFAP(+) quiescent neural stem cell pool at peak parasitemia. Although these cellular changes reverted to normal 15days post-parasite clearance, specific brain cytokines continued to exhibit dysregulation. Behavioral analysis revealed selective deficits in social and anxiety-like behaviors, with no change observed in locomotor, cognitive, and depression-like behaviors, with a return to baseline at recovery. Collectively, these findings indicate that even a single episode of mild malaria results in alterations of the brain cytokine profile, causes specific behavioral dysfunction, is accompanied by hippocampal microglial

  19. Preliminary study of higher-order language and extralinguistic impairments in individuals with high clinical risk of psychosis and first episode of schizophrenia.

    PubMed

    Pawełczyk, Agnieszka; Kotlicka-Antczak, Magdalena; Łojek, Emila; Pawełczyk, Tomasz

    2017-08-31

    Higher-order language functions are associated with understanding indirect speech acts, lexical-semantic processes, the understanding and production of prosody, discourse production and comprehension. Only a few studies imply that language abnormalities may be present in individuals at ultra-high risk for psychosis (UHR) and first-episode of schizophrenia (FE). The purpose of this study was to test the presence of higher-order language dysfunctions in UHR and FE subjects using a standardized comprehensive test battery. Twenty patients experiencing FE schizophrenia, 33 UHR individuals and 20 healthy controls (HC) took part in the study. Higher-order language and extralinguistic abilities were evaluated using the Right Hemisphere Language Battery (RHLB-PL). The battery consisted of tests covering the comprehension of implicit information, lexico-semantic processing, understanding humour, making inappropriate remarks and comments, understanding and explaining metaphors, understanding prosody and appropriateness of behaviour in communication settings. The UHR patients scored lower than HC when comprehending implicit information, discourse and in areas associated with the effectiveness of interpersonal communication; however, they scored higher than the FE participants in explanation of metaphors and processing language information in the context of general knowledge. The FE participants scored lower than healthy controls in comprehension of implicit information, explanation of metaphors, discourse understanding, processing language information in the context of general knowledge and effectiveness of interpersonal communication. The higher-order language dysfunctions mediated by the right hemisphere appear to be present in subjects at UHR of schizophrenia and those experiencing their FE. The results may play a crucial role in diagnostic processes. © 2017 John Wiley & Sons Australia, Ltd.

  20. Prediction of regional functional impairment following experimental stroke via connectome analysis.

    PubMed

    Schmitt, O; Badurek, S; Liu, W; Wang, Y; Rabiller, G; Kanoke, A; Eipert, P; Liu, J

    2017-04-13

    Recent advances in functional connectivity suggest that shared neuronal activation patterns define brain networks linking anatomically separate brain regions. We sought to investigate how cortical stroke disrupts multiple brain regions in processing spatial information. We conducted a connectome investigation at the mesoscale-level using the neuroVIISAS-framework, enabling the analysis of directed and weighted connectivity in bilateral hemispheres of cortical and subcortical brain regions. We found that spatial-exploration induced brain activation mapped by Fos, a proxy of neuronal activity, was differentially affected by stroke in a region-specific manner. The extent of hypoactivation following spatial exploration is inversely correlated with the spatial distance between the region of interest and region damaged by stroke, in particular within the parietal association and the primary somatosensory cortex, suggesting that the closer a region is to a stroke lesion, the more it would be affected during functional activation. Connectome modelling with 43 network parameters failed to reliably predict regions of hypoactivation in stroke rats exploring a novel environment, despite a modest correlation found for the centrality and hubness parameters in the home-caged animals. Further investigation in the inhibitory versus excitatory neuronal networks and microcircuit connectivity is warranted to improve the accuracy of predictability in post-stroke functional impairment.

  1. Neuroimaging Biomarkers Predict Brain Structural Connectivity Change in a Mouse Model of Vascular Cognitive Impairment

    PubMed Central

    Boehm-Sturm, Philipp; Füchtemeier, Martina; Foddis, Marco; Mueller, Susanne; Trueman, Rebecca C.; Zille, Marietta; Rinnenthal, Jan Leo; Kypraios, Theodore; Shaw, Laurence; Dirnagl, Ulrich

    2017-01-01

    Background and Purpose— Chronic hypoperfusion in the mouse brain has been suggested to mimic aspects of vascular cognitive impairment, such as white matter damage. Although this model has attracted attention, our group has struggled to generate a reliable cognitive and pathological phenotype. This study aimed to identify neuroimaging biomarkers of brain pathology in aged, more severely hypoperfused mice. Methods— We used magnetic resonance imaging to characterize brain degeneration in mice hypoperfused by refining the surgical procedure to use the smallest reported diameter microcoils (160 μm). Results— Acute cerebral blood flow decreases were observed in the hypoperfused group that recovered over 1 month and coincided with arterial remodeling. Increasing hypoperfusion resulted in a reduction in spatial learning abilities in the water maze that has not been previously reported. We were unable to observe severe white matter damage with histology, but a novel approach to analyze diffusion tensor imaging data, graph theory, revealed substantial reorganization of the hypoperfused brain network. A logistic regression model from the data revealed that 3 network parameters were particularly efficient at predicting group membership (global and local efficiency and degrees), and clustering coefficient was correlated with performance in the water maze. Conclusions— Overall, these findings suggest that, despite the autoregulatory abilities of the mouse brain to compensate for a sudden decrease in blood flow, there is evidence of change in the brain networks that can be used as neuroimaging biomarkers to predict outcome. PMID:28070001

  2. Hyperbolic Space Sparse Coding with Its Application on Prediction of Alzheimer's Disease in Mild Cognitive Impairment.

    PubMed

    Zhang, Jie; Shi, Jie; Stonnington, Cynthia; Li, Qingyang; Gutman, Boris A; Chen, Kewei; Reiman, Eric M; Caselli, Richard J; Thompson, Paul M; Ye, Jieping; Wang, Yalin

    2016-10-01

    Mild Cognitive Impairment (MCI) is a transitional stage between normal age-related cognitive decline and Alzheimer's disease (AD). Here we introduce a hyperbolic space sparse coding method to predict impending decline of MCI patients to dementia using surface measures of ventricular enlargement. First, we compute diffeomorphic mappings between ventricular surfaces using a canonical hyperbolic parameter space with consistent boundary conditions and surface tensor-based morphometry is computed to measure local surface deformations. Second, ring-shaped patches of TBM features are selected according to the geometric structure of the hyperbolic parameter space to initialize a dictionary. Sparse coding is then applied on the patch features to learn sparse codes and update the dictionary. Finally, we adopt max-pooling to reduce the feature dimensions and apply Adaboost to predict AD in MCI patients (N = 133) from the Alzheimer's Disease Neuroimaging Initiative baseline dataset. Our work achieved an accuracy rate of 96.7% and outperformed some other morphometry measures. The hyperbolic space sparse coding method may offer a more sensitive tool to study AD and its early symptom.

  3. Neuroimaging Biomarkers Predict Brain Structural Connectivity Change in a Mouse Model of Vascular Cognitive Impairment.

    PubMed

    Boehm-Sturm, Philipp; Füchtemeier, Martina; Foddis, Marco; Mueller, Susanne; Trueman, Rebecca C; Zille, Marietta; Rinnenthal, Jan Leo; Kypraios, Theodore; Shaw, Laurence; Dirnagl, Ulrich; Farr, Tracy D

    2017-02-01

    Chronic hypoperfusion in the mouse brain has been suggested to mimic aspects of vascular cognitive impairment, such as white matter damage. Although this model has attracted attention, our group has struggled to generate a reliable cognitive and pathological phenotype. This study aimed to identify neuroimaging biomarkers of brain pathology in aged, more severely hypoperfused mice. We used magnetic resonance imaging to characterize brain degeneration in mice hypoperfused by refining the surgical procedure to use the smallest reported diameter microcoils (160 μm). Acute cerebral blood flow decreases were observed in the hypoperfused group that recovered over 1 month and coincided with arterial remodeling. Increasing hypoperfusion resulted in a reduction in spatial learning abilities in the water maze that has not been previously reported. We were unable to observe severe white matter damage with histology, but a novel approach to analyze diffusion tensor imaging data, graph theory, revealed substantial reorganization of the hypoperfused brain network. A logistic regression model from the data revealed that 3 network parameters were particularly efficient at predicting group membership (global and local efficiency and degrees), and clustering coefficient was correlated with performance in the water maze. Overall, these findings suggest that, despite the autoregulatory abilities of the mouse brain to compensate for a sudden decrease in blood flow, there is evidence of change in the brain networks that can be used as neuroimaging biomarkers to predict outcome. © 2017 The Authors.

  4. Predicting Alcohol-Impaired Driving among Spanish Youth with the Theory of Reasoned Action.

    PubMed

    Espada, José P; Griffin, Kenneth W; Gonzálvez, María T; Orgilés, Mireia

    2015-06-19

    Alcohol consumption is a risk factor for motor vehicle accidents in young drivers. Crashes associated with alcohol consumption typically have greater severity. This study examines the prevalence of driving under the influence among Spanish youth and tests the theory of reasoned action as a model for predicting driving under the influence. Participants included 478 Spanish university students aged 17-26 years. Findings indicated that alcohol was the substance most associated with impaired driving, and was involved in more traffic crashes. Men engage in higher levels of alcohol and other drug use, and perceived less risk in drunk driving (p < .01). The study confirms that alcohol use and driving under the influence of alcohol are highly prevalent in Spanish young people, and some gender differences exist in these behaviors (p < .01). Furthermore, the study confirms the validity of theory of reasoned action as a predictive model of driving under the influence of alcohol among youth in Spain (p < .001) and can help in the design of prevention programs.

  5. Machine learning to predict rapid progression of carotid atherosclerosis in patients with impaired glucose tolerance.

    PubMed

    Hu, Xia; Reaven, Peter D; Saremi, Aramesh; Liu, Ninghao; Abbasi, Mohammad Ali; Liu, Huan; Migrino, Raymond Q

    2016-12-01

    Prediabetes is a major epidemic and is associated with adverse cardio-cerebrovascular outcomes. Early identification of patients who will develop rapid progression of atherosclerosis could be beneficial for improved risk stratification. In this paper, we investigate important factors impacting the prediction, using several machine learning methods, of rapid progression of carotid intima-media thickness in impaired glucose tolerance (IGT) participants. In the Actos Now for Prevention of Diabetes (ACT NOW) study, 382 participants with IGT underwent carotid intima-media thickness (CIMT) ultrasound evaluation at baseline and at 15-18 months, and were divided into rapid progressors (RP, n = 39, 58 ± 17.5 μM change) and non-rapid progressors (NRP, n = 343, 5.8 ± 20 μM change, p < 0.001 versus RP). To deal with complex multi-modal data consisting of demographic, clinical, and laboratory variables, we propose a general data-driven framework to investigate the ACT NOW dataset. In particular, we first employed a Fisher Score-based feature selection method to identify the most effective variables and then proposed a probabilistic Bayes-based learning method for the prediction. Comparison of the methods and factors was conducted using area under the receiver operating characteristic curve (AUC) analyses and Brier score. The experimental results show that the proposed learning methods performed well in identifying or predicting RP. Among the methods, the performance of Naïve Bayes was the best (AUC 0.797, Brier score 0.085) compared to multilayer perceptron (0.729, 0.086) and random forest (0.642, 0.10). The results also show that feature selection has a significant positive impact on the data prediction performance. By dealing with multi-modal data, the proposed learning methods show effectiveness in predicting prediabetics at risk for rapid atherosclerosis progression. The proposed framework demonstrated utility in outcome prediction in a typical

  6. Changes in Tryptophan Catabolite (TRYCAT) Pathway Patterning Are Associated with Mild Impairments in Declarative Memory in Schizophrenia and Deficits in Semantic and Episodic Memory Coupled with Increased False-Memory Creation in Deficit Schizophrenia.

    PubMed

    Kanchanatawan, Buranee; Hemrungrojn, Solaphat; Thika, Supaksorn; Sirivichayakul, Sunee; Ruxrungtham, Kiat; Carvalho, André F; Geffard, Michel; Anderson, George; Maes, Michael

    2017-09-05

    Evidence indicates that schizophrenia and in particular negative symptoms and deficit schizophrenia are accompanied by neurocognitive impairments and changes in the patterning of the tryptophan catabolite (TRYCAT) pathway. This cross-sectional study was carried out to examine the associations between cognitive functions (as measured with Consortium to Establish a Registry for Alzheimer's disease (CERAD)) and TRYCAT pathway patterning in patients with (n = 40) and without (n = 40) deficit schizophrenia and normal controls (n = 40). Cognitive measures were assessed with the Verbal Fluency Test (VFT), Boston Naming Test (BNT), Mini-Mental State Examination (MMSE), Word List Memory (WLM), Constructional Praxis, Word List Recall (WLRecall), and Word List Recognition (WLRecognition), while TRYCAT measurements assessed the IgA/IgM responses to noxious TRYCATs, namely quinolinic acid (QA), 3-OH-kynurenine (3HK), picolinic acid (PA), and xanthurenic (XA) acid, and more protective (PRO) TRYCATs, including kynurenic acid (KA) and anthranilic acid (AA). IgA NOX/PRO, IgM KA/3HK, and IgA/IgM NOX/PRO ratios were computed. Schizophrenia was accompanied by lower VFT and WLM, while BNT (dysnomia) and MMSE are significantly lower in multiple- than first-episode schizophrenia. Deficit schizophrenia is strongly associated with worse outcomes on VFT, MMSE, WLM, WLRecall, WLRecognition, and delayed recall savings and increased false memories. Around 40-50% of the variance in negative symptoms' scores was explained by VFT, WLM, WLRecall, and MMSE. Increases in IgA NOX/PRO, IgM KA/3HK, and/or IgA/IgM NOX/PRO ratios were associated with impairments in VFT, BNT, MMSE, WLM, WLRecall, WLRecognition, and false-memory creation. In conclusion, nondeficit schizophrenia is accompanied by mild memory impairments, while disease progression is accompanied by broader cognitive impairments. Deficit schizophrenia and negative symptoms are strongly associated with deficits in working memory, delayed

  7. Prolonged impairment of deglutition in supratentorial ischaemic stroke: the predictive value of Parramatta Hospitals' Assessment of Dysphagia.

    PubMed

    Kägi, Georg; Leisi, Natascha; Galovic, Marian; Müller-Baumberger, Marlise; Krammer, Werner; Weder, Bruno

    Up to 50% of ischaemic stroke patients show initial dysphagia, which may persist for months. Guidelines recommend switching nasogastric (NG) to percutaneous endoscopic gastrostomy (PEG) tube feeding at the second week after the stroke if impaired deglutition is expected for another 4 weeks. Precise prognostic criteria are lacking. We hypothesised that the Parramatta Hospitals' Assessment of Dysphagia (PAHD) performed 8 to 10 days after the stroke predicts impaired deglutition for another 4 weeks. After a first dysphagia assessment (buccolingual motor function, liquid and semisolid swallow tests, "two-out-of-six" scale) within 48 hours of onset, patients with a first hemispheric stroke and risk of aspiration, defined as a two-out-of-six scale score of ≥2 (dysphonia, dysarthria, abnormal gag reflex, abnormal volitional cough, cough / voice change after swallowing) were included and were assessed by a blinded rater using the PHAD. The same dysphagia assessments were repeated 8 to 10 days after the stroke (second assessment) and patients remained in the study if the two-out-of-six scale score remained ≥2. At a final evaluation by telephone after 4 weeks, impaired deglutition was assessed with the Bogenhausen dysphagia score (BODS-2). Exclusion criteria were infratentorial or recurrent stroke and pre-existing dysphagia. The primary objective was to define a threshold score and value of the PHAD at second assessment that predicted impaired deglutition as assessed with the BODS-2 (score ≥4) at the final evaluation. The secondary objective was to explore the value of the PHAD assessed within 48 hours to predict impaired deglutition (BODS-2 ≥4) at final evaluation. To evaluate the predictive value of the PHAD score assessed 8 to 10 days after stroke onset for impaired deglutition for another 4 weeks, we determined the area under the receiver operating curve (ROC AUC). Over a 1-year period, 29 out of 252 assessed patients remained at risk of aspiration after the

  8. Parkinsonian motor impairment predicts personality domains related to genetic risk and treatment outcomes in schizophrenia.

    PubMed

    Molina, Juan L; Calvó, María; Padilla, Eduardo; Balda, Mara; Alemán, Gabriela González; Florenzano, Néstor V; Guerrero, Gonzalo; Kamis, Danielle; Rangeon, Beatriz Molina; Bourdieu, Mercedes; Strejilevich, Sergio A; Conesa, Horacio A; Escobar, Javier I; Zwir, Igor; Cloninger, C Robert; de Erausquin, Gabriel A

    2017-01-01

    Identifying endophenotypes of schizophrenia is of critical importance and has profound implications on clinical practice. Here we propose an innovative approach to clarify the mechanims through which temperament and character deviance relates to risk for schizophrenia and predict long-term treatment outcomes. We recruited 61 antipsychotic naïve subjects with chronic schizophrenia, 99 unaffected relatives, and 68 healthy controls from rural communities in the Central Andes. Diagnosis was ascertained with the Schedules of Clinical Assessment in Neuropsychiatry; parkinsonian motor impairment was measured with the Unified Parkinson's Disease Rating Scale; mesencephalic parenchyma was evaluated with transcranial ultrasound; and personality traits were assessed using the Temperament and Character Inventory. Ten-year outcome data was available for ~40% of the index cases. Patients with schizophrenia had higher harm avoidance and self-transcendence (ST), and lower reward dependence (RD), cooperativeness (CO), and self-directedness (SD). Unaffected relatives had higher ST and lower CO and SD. Parkinsonism reliably predicted RD, CO, and SD after correcting for age and sex. The average duration of untreated psychosis (DUP) was over 5 years. Further, SD was anticorrelated with DUP and antipsychotic dosing at follow-up. Baseline DUP was related to antipsychotic dose-years. Further, 'explosive/borderline', 'methodical/obsessive', and 'disorganized/schizotypal' personality profiles were associated with increased risk of schizophrenia. Parkinsonism predicts core personality features and treatment outcomes in schizophrenia. Our study suggests that RD, CO, and SD are endophenotypes of the disease that may, in part, be mediated by dopaminergic function. Further, SD is an important determinant of treatment course and outcome.

  9. Parkinsonian motor impairment predicts personality domains related to genetic risk and treatment outcomes in schizophrenia

    PubMed Central

    Molina, Juan L; Calvó, María; Padilla, Eduardo; Balda, Mara; Alemán, Gabriela González; Florenzano, Néstor V; Guerrero, Gonzalo; Kamis, Danielle; Rangeon, Beatriz Molina; Bourdieu, Mercedes; Strejilevich, Sergio A; Conesa, Horacio A; Escobar, Javier I; Zwir, Igor; Cloninger, C Robert; de Erausquin, Gabriel A

    2017-01-01

    Identifying endophenotypes of schizophrenia is of critical importance and has profound implications on clinical practice. Here we propose an innovative approach to clarify the mechanims through which temperament and character deviance relates to risk for schizophrenia and predict long-term treatment outcomes. We recruited 61 antipsychotic naïve subjects with chronic schizophrenia, 99 unaffected relatives, and 68 healthy controls from rural communities in the Central Andes. Diagnosis was ascertained with the Schedules of Clinical Assessment in Neuropsychiatry; parkinsonian motor impairment was measured with the Unified Parkinson’s Disease Rating Scale; mesencephalic parenchyma was evaluated with transcranial ultrasound; and personality traits were assessed using the Temperament and Character Inventory. Ten-year outcome data was available for ~40% of the index cases. Patients with schizophrenia had higher harm avoidance and self-transcendence (ST), and lower reward dependence (RD), cooperativeness (CO), and self-directedness (SD). Unaffected relatives had higher ST and lower CO and SD. Parkinsonism reliably predicted RD, CO, and SD after correcting for age and sex. The average duration of untreated psychosis (DUP) was over 5 years. Further, SD was anticorrelated with DUP and antipsychotic dosing at follow-up. Baseline DUP was related to antipsychotic dose-years. Further, ‘explosive/borderline’, ‘methodical/obsessive’, and ‘disorganized/schizotypal’ personality profiles were associated with increased risk of schizophrenia. Parkinsonism predicts core personality features and treatment outcomes in schizophrenia. Our study suggests that RD, CO, and SD are endophenotypes of the disease that may, in part, be mediated by dopaminergic function. Further, SD is an important determinant of treatment course and outcome. PMID:28127577

  10. Hippocampal volumes predict risk of dementia with Lewy bodies in mild cognitive impairment

    PubMed Central

    Lesnick, Timothy; Ferman, Tanis J.; Przybelski, Scott A.; Boeve, Bradley F.; Smith, Glenn E.; Kremers, Walter K.; Knopman, David S.; Jack, Clifford R.; Petersen, Ronald C.

    2016-01-01

    Objective: To predict the risk of probable dementia with Lewy bodies (DLB) competing with Alzheimer disease (AD) dementia by hippocampal volume (HV) in patients with mild cognitive impairment (MCI) with impairments in amnestic or nonamnestic cognitive domains. Methods: Patients with MCI (n = 160) from the Mayo Clinic Alzheimer's Disease Research Center, who participated in an MRI study at baseline from 2005 to 2014, were followed with approximately annual clinical evaluations. HVs were analyzed from 3T MRIs using FreeSurfer (5.3). Hippocampal atrophy was determined from the most normal 10th percentile of the measurement distributions in a separate cohort of clinically diagnosed patients with AD dementia. The subdistribution hazard ratios for progression to probable DLB and AD dementia were estimated by taking into account the competing risks. Results: During a median (range) follow-up of 2.0 (0.7–8.1) years, 20 (13%) patients with MCI progressed to probable DLB, and 61 (38%) progressed to AD dementia. The estimated subdistribution hazard ratio (95% confidence interval) for normal HV relative to hippocampal atrophy for progression to AD dementia was 0.56 (0.34–0.91; p = 0.02) after taking into account the competing risks. The estimated hazard ratio for normal HV relative to hippocampal atrophy for progression to probable DLB was 4.22 (1.42–12.6; p = 0.01) after adjusting for age and after including the MCI subtype in the model. Conclusions: Preserved hippocampal volumes are associated with increased risk of probable DLB competing with AD dementia in patients with MCI. Preservation of HV may support prodromal DLB over AD, particularly in patients with MCI with nonamnestic features. PMID:27807186

  11. Global Sensory Impairment Predicts Morbidity and Mortality in Older U.S. Adults.

    PubMed

    Pinto, Jayant M; Wroblewski, Kristen E; Huisingh-Scheetz, Megan; Correia, Camil; Lopez, Kevin J; Chen, Rachel C; Kern, David W; Schumm, Philip L; Dale, William; McClintock, Martha K

    2017-09-24

    To evaluate global sensory impairment (GSI, an integrated measure of sensory dysfunction) as a predictor of physical function, cognition, overall health, and mortality. Prospective study. The National Social Life, Health, and Aging Project. A national probability sample of 3,005 home-dwelling older U.S. adults assessed at baseline (2005-06) and 5-year follow-up (2010-11). Gait speed, activity, disability, cognition, overall health, 5-year mortality. At baseline, older adults with worse GSI were slower (Timed Up and Go times: odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.17-1.50) and had more activity of daily living deficits (≥2: OR = 1.26, 95% CI = 1.10-1.46). Five years later, they were still slower (timed walk: OR = 1.22, 95% CI = 1.05-1.42), had more disabilities (≥2 instrumental activities of daily living; OR = 1.45, 95% CI = 1.23-1.70), were less active (daytime activity according to accelerometry: β = -2.7, 95% CI = -5.2 to -0.2), had worse cognitive function (Montreal Cognitive Assessment; β = -0.64, 95% CI = -0.84 to -0.44), more likely to have poorer overall health (OR = 1.16, 95% CI = 1.03-1.31) and lose weight (>10%: OR = 1.31, 95% CI = 1.04-1.64), and have died (OR = 1.45, 95% CI = 1.19-1.76). All analyses were adjusted for relevant confounders at baseline, including age, sex, race and ethnicity, education, smoking, problem drinking, body mass index, comorbidities, and cognitive function. GSI predicts impaired physical function, cognitive dysfunction, significant weight loss, and mortality 5 years later in older U.S. adults. Multisensory evaluation may identify vulnerable individuals, offering the opportunity for early intervention to mitigate adverse outcomes. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

  12. Homocysteine predicts increased NT-pro-BNP through impaired fatty acid oxidation.

    PubMed

    Guéant Rodriguez, R M; Spada, R; Pooya, S; Jeannesson, E; Moreno Garcia, M A; Anello, G; Bosco, P; Elia, M; Romano, A; Alberto, J M; Juillière, Y; Guéant, J L

    2013-08-10

    The deficiency in methyl donors, folate and vitamin B12, increases homocysteine and produces myocardium hypertrophy with impaired mitochondrial fatty acid oxidation and increased BNP, through hypomethylation of peroxisome-proliferator-activated-receptor gamma co-activator-1α, in rat. This may help to understand better the elusive link previously reported between hyperhomocysteinemia and BNP, in human. We investigated therefore the influence of methyl donors on heart mitochondrial fatty acid oxidation and brain natriuretic peptide, in two contrasted populations. Biomarkers of heart disease, of one carbon metabolism and of mitochondrial fatty acid oxidation were assessed in 1020 subjects, including patients undergoing coronarography and ambulatory elderly subjects from OASI cohort. Folate deficit was more frequent in the coronarography population than in the elderly ambulatory volunteers and produced a higher concentration of homocysteine (19.3 ± 6.8 vs. 15.3 ± 5.6, P<0.001). Subjects with homocysteine in the upper quartile (≥ 18 μmol/L) had higher concentrations of NT-pro-BNP (or BNP in ambulatory subjects) and of short chain-, medium chain-, and long chain-acylcarnitines, compared to those in the lower quartile (≤ 12 μmol/L), in both populations (P<0.001). Homocysteine and NT-pro-BNP were positively correlated with short chain-, medium chain-, long chain-acylcarnitines and with acylcarnitine ratios indicative of decreased mitochondrial acyldehydrogenase activities (P<0.001). In multivariate analysis, homocysteine and long chain acylcarnitines were two interacting determinants of NT-pro-BNP, in addition to left ventricular ejection fraction, body mass index, creatinine and folate. This study showed that homocysteine predicts increased NT-pro-BNP (or BNP) through a link with impaired mitochondrial fatty oxidation, in two contrasted populations. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  13. Impaired Cross-Talk between Mesolimbic Food Reward Processing and Metabolic Signaling Predicts Body Mass Index

    PubMed Central

    Simon, Joe J.; Skunde, Mandy; Hamze Sinno, Maria; Brockmeyer, Timo; Herpertz, Sabine C.; Bendszus, Martin; Herzog, Wolfgang; Friederich, Hans-Christoph

    2014-01-01

    The anticipation of the pleasure derived from food intake drives the motivation to eat, and hence facilitate overconsumption of food, which ultimately results in obesity. Brain imaging studies provide evidence that mesolimbic brain regions underlie both general as well as food-related anticipatory reward processing. In light of this knowledge, the present study examined the neural responsiveness of the ventral striatum (VS) in participants with a broad BMI spectrum. The study differentiated between general (i.e., monetary) and food-related anticipatory reward processing. We recruited a sample of volunteers with greatly varying body weights, ranging from a low BMI (below 20 kg/m2) over a normal (20–25 kg/m2) and overweight (25–30 kg/m2) BMI, to class I (30–35 kg/m2) and class II (35–40 kg/m2) obesity. A total of 24 participants underwent functional magnetic resonance imaging while performing both a food and monetary incentive delay task, which allows to measure neural activation during the anticipation of rewards. After the presentation of a cue indicating the amount of food or money to be won, participants had to react correctly in order to earn “snack points” or “money coins,” which could then be exchanged for real food or money, respectively, at the end of the experiment. During the anticipation of both types of rewards, participants displayed activity in the VS, a region that plays a pivotal role in the anticipation of rewards. Additionally, we observed that specifically anticipatory food reward processing predicted the individual BMI (current and maximum lifetime). This relation was found to be mediated by impaired hormonal satiety signaling, i.e., increased leptin levels and insulin resistance. These findings suggest that heightened food reward motivation contributes to obesity through impaired metabolic signaling. PMID:25368558

  14. Curcumin improves episodic memory in cadmium induced memory impairment through inhibition of acetylcholinesterase and adenosine deaminase activities in a rat model.

    PubMed

    Akinyemi, Ayodele Jacob; Okonkwo, Princess Kamsy; Faboya, Opeyemi Ayodeji; Onikanni, Sunday Amos; Fadaka, Adewale; Olayide, Israel; Akinyemi, Elizabeth Olufisayo; Oboh, Ganiyu

    2017-02-01

    Curcumin, the main polyphenolic component of turmeric (Curcuma longa) rhizomes has been reported to exert cognitive enhancing potential with limited scientific basis. Hence, this study sought to evaluate the effect of curcumin on cerebral cortex acetylcholinesterase (AChE) and adenosine deaminase (ADA) activities in cadmium (Cd)-induced memory impairment in rats. Animals were divided into six groups (n = 6): saline/vehicle, saline/curcumin 12.5 mg/kg, saline/curcumin 25 mg/kg, Cd/vehicle, Cd/curcumin 12.5 mg/kg, and Cd/curcumin 25 mg/kg. Rats received Cd (2.5 mg/kg) and curcumin (12.5 and 25 mg/kg, respectively) by gavage for 7 days. The results of this study revealed that cerebral cortex AChE and ADA activities were increased in Cd-poisoned rats, and curcumin co-treatment reversed these activities to the control levels. Furthermore, Cd intoxication increased the level of lipid peroxidation in cerebral cortex with a concomitant decreased in functional sulfuhydryl (-SH) group and nitric oxide (NO), a potent neurotransmitter and neuromodulatory agent. However, the co-treatment with curcumin at 12.5 and 25 mg/kg, respectively increased the non-enzymatic antioxidant status and NO in cerebral cortex with a decreased in malondialdehyde (MDA) level. Therefore, inhibition of AChE and ADA activities as well as increased antioxidant status by curcumin in Cd-induced memory dysfunction could suggest some possible mechanism of action for their cognitive enhancing properties.

  15. Neural correlates of aberrant emotional salience predict psychotic symptoms and global functioning in high-risk and first-episode psychosis.

    PubMed

    Modinos, Gemma; Tseng, Huai-Hsuan; Falkenberg, Irina; Samson, Carly; McGuire, Philip; Allen, Paul

    2015-10-01

    Neurobiological and behavioral findings suggest that psychosis is associated with corticolimbic hyperactivity during the processing of emotional salience. This has not been widely studied in the early stages of psychosis, and the impact of these abnormalities on psychotic symptoms and global functioning is unknown. We sought to address this issue in 18 patients with first-episode psychosis (FEP), 18 individuals at ultra high risk of psychosis (UHR) and 22 healthy controls (HCs). Corticolimbic response and subjective ratings to emotional and neutral scenes were measured using functional magnetic resonance imaging. The clinical and functional impact of corticolimbic abnormalities was assessed with regression analyses. The FEP and UHR groups reported increased subjective emotional arousal to neutral scenes compared with HCs. Across groups, emotional vs neutral scenes elicited activation in the dorsomedial prefrontal cortex, inferior frontal gyrus/anterior insula and amygdala. Although FEP and UHR participants showed reduced activation in these regions when viewing emotional scenes compared with controls, this was driven by increased activation to neutral scenes. Corticolimbic hyperactivity to neutral scenes predicted higher levels of positive symptoms and poorer levels of functioning. These results indicate that disruption of emotional brain systems may represent an important biological substrate for the pathophysiology of early psychosis and UHR states. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  16. Neural correlates of aberrant emotional salience predict psychotic symptoms and global functioning in high-risk and first-episode psychosis

    PubMed Central

    Tseng, Huai-Hsuan; Falkenberg, Irina; Samson, Carly; McGuire, Philip; Allen, Paul

    2015-01-01

    Neurobiological and behavioral findings suggest that psychosis is associated with corticolimbic hyperactivity during the processing of emotional salience. This has not been widely studied in the early stages of psychosis, and the impact of these abnormalities on psychotic symptoms and global functioning is unknown. We sought to address this issue in 18 patients with first-episode psychosis (FEP), 18 individuals at ultra high risk of psychosis (UHR) and 22 healthy controls (HCs). Corticolimbic response and subjective ratings to emotional and neutral scenes were measured using functional magnetic resonance imaging. The clinical and functional impact of corticolimbic abnormalities was assessed with regression analyses. The FEP and UHR groups reported increased subjective emotional arousal to neutral scenes compared with HCs. Across groups, emotional vs neutral scenes elicited activation in the dorsomedial prefrontal cortex, inferior frontal gyrus/anterior insula and amygdala. Although FEP and UHR participants showed reduced activation in these regions when viewing emotional scenes compared with controls, this was driven by increased activation to neutral scenes. Corticolimbic hyperactivity to neutral scenes predicted higher levels of positive symptoms and poorer levels of functioning. These results indicate that disruption of emotional brain systems may represent an important biological substrate for the pathophysiology of early psychosis and UHR states. PMID:25809400

  17. Naming Speed as a Clinical Marker in Predicting Basic Calculation Skills in Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Kleemans, Tijs; Segers, Eliane; Verhoeven, Ludo

    2012-01-01

    The present study investigated the role of naming speed in predicting the basic calculation skills (i.e., addition and subtraction) of kindergartners with Specific Language Impairment (SLI), when compared to a group of Normal Language Achieving (NLA) children. Fifty-three kindergartners with SLI and 107 kindergartners with NLA were tested on…

  18. Naming Speed as a Clinical Marker in Predicting Basic Calculation Skills in Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Kleemans, Tijs; Segers, Eliane; Verhoeven, Ludo

    2012-01-01

    The present study investigated the role of naming speed in predicting the basic calculation skills (i.e., addition and subtraction) of kindergartners with Specific Language Impairment (SLI), when compared to a group of Normal Language Achieving (NLA) children. Fifty-three kindergartners with SLI and 107 kindergartners with NLA were tested on…

  19. Repeated social stress increases reward salience and impairs encoding of prediction by rat locus coeruleus neurons.

    PubMed

    Chaijale, Nayla N; Snyder, Kevin; Arner, Jay; Curtis, Andre L; Valentino, Rita J

    2015-01-01

    Stress is implicated in psychopathology characterized by cognitive dysfunction. Cognitive responses to stress are regulated by the locus coeruleus-norepinephrine (LC-NE) system. As social stress is a prevalent human stressor, this study determined the impact of repeated social stress on the relationship between LC neuronal activity and behavior during the performance of cognitive tasks. Social stress-exposed rats performed better at intradimensional set shifting (IDS) and made fewer perseverative errors during reversal learning (REV). LC neurons of control rats were task responsive, being activated after the choice and before reward. Social stress shifted LC neuronal activity from being task responsive to being reward responsive during IDS and REV. LC neurons of stressed rats were activated by reward and tonically inhibited by reward omission with incorrect choices. In contrast, LC neurons of stress-naive rats were only tonically inhibited by reward omission. Reward-related LC activation in stressed rats was unrelated to predictability because it did not habituate as learning progressed. The findings suggest that social stress history increases reward salience and impairs processes that compute predictability for LC neurons. These effects of social stress on LC neuronal activity could facilitate learning as indicated by improved performance in stressed rats. However, the ability of social stress history to enhance responses to behavioral outcomes may have a role in the association between stress and addictive behaviors. In addition, magnified fluctuations in LC activity in response to opposing behavioral consequences may underlie volatile changes in emotional arousal that characterize post-traumatic stress disorder.

  20. CSF biomarkers in prediction of cerebral and clinical change in mild cognitive impairment and Alzheimer's disease.

    PubMed

    Fjell, Anders M; Walhovd, Kristine B; Fennema-Notestine, Christine; McEvoy, Linda K; Hagler, Donald J; Holland, Dominic; Brewer, James B; Dale, Anders M

    2010-02-10

    Brain atrophy and altered CSF levels of amyloid beta (Abeta(42)) and the microtubule-associated protein tau are potent biomarkers of Alzheimer's disease (AD)-related pathology. However, the relationship between CSF biomarkers and brain morphometry is poorly understood. Thus, we addressed the following questions. (1) Can CSF biomarker levels explain the morphometric differences between normal controls (NC) and patients with mild cognitive impairment (MCI) or AD? (2) How are CSF biomarkers related to atrophy across the brain? (3) How closely are CSF biomarkers and morphometry related to clinical change [clinical dementia rating sum of boxes (CDR-sb)]? Three hundred seventy participants (105 NC, 175 MCI, 90 AD) from the Alzheimer's Disease Neuroimaging Initiative were studied, of whom 309 were followed for 1 year and 176 for 2 years. Analyses were performed across the entire cortical surface, as well as for 30 cortical and subcortical regions of interest. Results showed that CSF biomarker levels could not account for group differences in brain morphometry at baseline but that CSF biomarker levels showed moderate relationships to longitudinal atrophy rates in numerous brain areas, not restricted to medial temporal structures. Baseline morphometry was at least as predictive of atrophy as were CSF biomarkers. Even MCI patients with levels of Abeta(42) comparable with controls and of p-tau lower than controls showed more atrophy than the controls. Morphometry predicted change in CDR-sb better than did CSF biomarkers. These results indicate that morphometric changes in MCI and AD are not secondary to CSF biomarker changes and that the two types of biomarkers yield complementary information.

  1. Repeated Social Stress Increases Reward Salience and Impairs Encoding of Prediction by Rat Locus Coeruleus Neurons

    PubMed Central

    Chaijale, Nayla N; Snyder, Kevin; Arner, Jay; Curtis, Andre L; Valentino, Rita J

    2015-01-01

    Stress is implicated in psychopathology characterized by cognitive dysfunction. Cognitive responses to stress are regulated by the locus coeruleus–norepinephrine (LC–NE) system. As social stress is a prevalent human stressor, this study determined the impact of repeated social stress on the relationship between LC neuronal activity and behavior during the performance of cognitive tasks. Social stress-exposed rats performed better at intradimensional set shifting (IDS) and made fewer perseverative errors during reversal learning (REV). LC neurons of control rats were task responsive, being activated after the choice and before reward. Social stress shifted LC neuronal activity from being task responsive to being reward responsive during IDS and REV. LC neurons of stressed rats were activated by reward and tonically inhibited by reward omission with incorrect choices. In contrast, LC neurons of stress-naive rats were only tonically inhibited by reward omission. Reward-related LC activation in stressed rats was unrelated to predictability because it did not habituate as learning progressed. The findings suggest that social stress history increases reward salience and impairs processes that compute predictability for LC neurons. These effects of social stress on LC neuronal activity could facilitate learning as indicated by improved performance in stressed rats. However, the ability of social stress history to enhance responses to behavioral outcomes may have a role in the association between stress and addictive behaviors. In addition, magnified fluctuations in LC activity in response to opposing behavioral consequences may underlie volatile changes in emotional arousal that characterize post-traumatic stress disorder. PMID:25109891

  2. Mild cognitive impairment: baseline and longitudinal structural MR imaging measures improve predictive prognosis.

    PubMed

    McEvoy, Linda K; Holland, Dominic; Hagler, Donald J; Fennema-Notestine, Christine; Brewer, James B; Dale, Anders M

    2011-06-01

    To assess whether single-time-point and longitudinal volumetric magnetic resonance (MR) imaging measures provide predictive prognostic information in patients with amnestic mild cognitive impairment (MCI). This study was conducted with institutional review board approval and in compliance with HIPAA regulations. Written informed consent was obtained from all participants or the participants' legal guardians. Cross-validated discriminant analyses of MR imaging measures were performed to differentiate 164 Alzheimer disease (AD) cases from 203 healthy control cases. Separate analyses were performed by using data from MR images obtained at one time point or by combining single-time-point measures with 1-year change measures. Resulting discriminant functions were applied to 317 MCI cases to derive individual patient risk scores. Risk of conversion to AD was estimated as a continuous function of risk score percentile. Kaplan-Meier survival curves were computed for risk score quartiles. Odds ratios (ORs) for the conversion to AD were computed between the highest and lowest quartile scores. Individualized risk estimates from baseline MR examinations indicated that the 1-year risk of conversion to AD ranged from 3% to 40% (average group risk, 17%; OR, 7.2 for highest vs lowest score quartiles). Including measures of 1-year change in global and regional volumes significantly improved risk estimates (P = 001), with the risk of conversion to AD in the subsequent year ranging from 3% to 69% (average group risk, 27%; OR, 12.0 for highest vs lowest score quartiles). Relative to the risk of conversion to AD conferred by the clinical diagnosis of MCI alone, MR imaging measures yield substantially more informative patient-specific risk estimates. Such predictive prognostic information will be critical if disease-modifying therapies become available. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11101975/-/DC1. RSNA, 2011

  3. 25-Hydroxyvitamin D3 Deficiency Independently Predicts Cognitive Impairment in Patients with Systemic Lupus Erythematosus

    PubMed Central

    Tay, Sen Hee; Ho, Chung Shun; Ho, Roger Chun-Man; Mak, Anselm

    2015-01-01

    Objectives Cognitive dysfunction has been reported in 20–80% of SLE patients. Converging evidence has indicated the importance of vitamin D as a neuroimmunomodulator for cognitive function. In this study, we evaluated the relationship between vitamin D and cognitive dysfunction. Methods Consecutive age- and gender-matched SLE patients and healthy controls (HCs) were administered Automated Neuropsychological Assessment Metrics in this cross-sectional study. The primary outcome was the total throughput score (TTS). Anxiety and depression were measured using the Hospital Anxiety and Depression Scale (HADS). Levels of 25-hydroxyvitamin D [25(OH)D3 and total 25(OH)D] were measured using Liquid Chromatography-Tandem Mass Spectrometry. Results In total, 61 SLE patients and 61 HCs were studied. SLE patients scored significantly lower than HCs in the TTS (p = 0.004). There were no statistically significant differences in 25(OH)D3 levels, total 25(OH)D levels and total 25(OH)D deficiency between SLE patients and HCs. However, more SLE patients had 25(OH)D3 deficiency compared to HCs [12 (19.7%) versus 2 (3.3%), p = 0.003]. Deficiency of 25(OH)D3 (β = -63.667, SE = 27.456, p = 0.025), but not other vitamin D variables, independently predicted worse TTS after adjusting for age, education, gender, ethnicity, HADS-Total, duration of SLE, SELENA-SLEDAI, SLICC/ACR Damage Index and cumulative steroid dose in SLE patients. Age (β = -4.261, SE = 0.866, p < 0.001) was the only predictor of TTS after adjusting for education, gender, ethnicity, HADS-Total, vitamin D levels or status in HCs. Conclusions Deficiency of 25(OH)D3, a potentially modifiable risk factor, independently predicted cognitive impairment in SLE patients. PMID:26636681

  4. Do Alzheimer-specific microstructural changes in mild cognitive impairment predict conversion?

    PubMed

    van Bruggen, Thomas; Stieltjes, Bram; Thomann, Philipp A; Parzer, Peter; Meinzer, Hans-Peter; Fritzsche, Klaus H

    2012-01-01

    Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique that provides information on the fiber architecture of the brain by measuring water diffusion. Prior work has shown that neuronal degeneration in Alzheimer's disease (AD) and mild cognitive impairment (MCI) alters this architecture. Since the conversion rate to AD is much higher for MCI patients than for normal healthy people, it is important to identify biomarkers with a predictive value on this conversion. In this study, we applied tract-based spatial statistics (TBSS) on datasets of 15 healthy controls, 15 AD patients, and 17 MCI patients. Of these MCI patients eight remained stable, whereas nine developed AD within the first 12-18 months of follow-up investigations. Analysis using TBSS combined with a maximum likelihood regression with random effects of the fornix, the corpus callosum, and the cingulum identified significant differences between these two types of MCI patients in fractional anisotropy (FA) and radial diffusivity (DR). Thus, DTI reveals Alzheimer-specific changes in those MCI subjects that later convert, although they were clinically identical to the other MCI-patients at the time the data were acquired. This finding could lead to early identification of AD and thereby aid early clinical intervention.

  5. Sleepiness and prediction of driver impairment in simulator studies using a Cox proportional hazard approach.

    PubMed

    Vadeby, Anna; Forsman, Asa; Kecklund, Göran; Akerstedt, Torbjörn; Sandberg, David; Anund, Anna

    2010-05-01

    Cox proportional hazard models were used to study relationships between the event that a driver is leaving the lane caused by sleepiness and different indicators of sleepiness. In order to elucidate different indicators' performance, five different models developed by Cox proportional hazard on a data set from a simulator study were used. The models consisted of physiological indicators and indicators from driving data both as stand alone and in combination. The different models were compared on two different data sets by means of sensitivity and specificity and the models' ability to predict lane departure was studied. In conclusion, a combination of blink indicators based on the ratio between blink amplitude and peak closing velocity of eyelid (A/PCV) (or blink amplitude and peak opening velocity of eyelid (A/POV)), standard deviation of lateral position and standard deviation of lateral acceleration relative road (ddy) was the most sensitive approach with sensitivity 0.80. This is also supported by the fact that driving data only shows the impairment of driving performance while blink data have a closer relation to sleepiness. Thus, an effective sleepiness warning system may be based on a combination of lane variability measures and variables related to eye movements (particularly slow eye closure) in order to have both high sensitivity (many correct warnings) and acceptable specificity (few false alarms). Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  6. Peripubertal anxiety profile can predict predisposition to spatial memory impairments following chronic stress.

    PubMed

    Bellani, Rudy; Luecken, Linda J; Conrad, Cheryl D

    2006-01-30

    We tested the hypothesis that peripubertal anxiety levels are predictive of the detrimental effects of chronic stress on hippocampal-dependent spatial memory. The anxiety levels of peripubertal male Sprague-Dawley rats (43 days old) were characterized using open field and elevated plus mazes, followed by chronic restraint stress for 6 h/day/21 days beginning in young adulthood (75 days). Following chronic stress treatment, rats were tested on the spatial Y-maze using two inter-trial interval levels of difficulty (4 h: 1 day post-chronic stress; 1 min: 2 days post-chronic stress). As expected, all groups displayed intact spatial memory in the less difficult 1 min version of the Y-maze. However, in the 4 h version of the Y-maze, chronically stressed high anxiety rats showed impaired spatial memory, while chronically stressed low anxiety and control (low and high anxiety) rats displayed intact spatial memory. Moreover, a month after chronic stress ended, high anxiety rats had significantly higher basal corticosterone levels than low anxiety rats (control and stress). These results indicate that peripubertal anxiety and chronic stress interact to influence hippocampal-dependent spatial memory in adulthood.

  7. [A new assessment for episodic memory. Episodic memory test and caregiver's episodic memory test].

    PubMed

    Ojea Ortega, T; González Álvarez de Sotomayor, M M; Pérez González, O; Fernández Fernández, O

    2013-10-01

    The purpose of the episodic memory test and the caregiver's episodic memory test is to evaluate episodic memory according to its definition in a way that is feasible for families and achieves high degrees of sensitivity and specificity. We administered a test consisting of 10 questions about episodic events to 332 subjects, of whom 65 had Alzheimer's disease (AD), 115 had amnestic MCI (aMCI) and 152 showed no cognitive impairment according to Reisberg's global deterioration scale (GDS). We calculated the test's sensitivity and specificity to distinguish AD from episodic aMCI and from normal ageing. The area under the ROC curve for the diagnosis of aMCI was 0.94 and the best cut-off value was 20; for that value, sensitivity was 89% and specificity was 82%. For a diagnosis of AD, the area under the ROC curve was 0.99 and the best cut-off point was 17, with a sensitivity of 98% and a specificity of 91%. A subsequent study using similar methodology yielded similar results when the test was administered directly by the caregiver. The episodic memory test and the caregiver's episodic memory test are useful as brief screening tools for identifying patients with early-stage AD. It is suitable for use by primary care medical staff and in the home, since it can be administered by a caregiver. The test's limitations are that it must be administered by a reliable caregiver and the fact that it measures episodic memory only. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  8. The roles of cognitive and language abilities in predicting decoding and reading comprehension: comparisons of dyslexia and specific language impairment.

    PubMed

    Lauterbach, Alexandra A; Park, Yujeong; Lombardino, Linda J

    2016-11-15

    This study aimed to (a) explore the roles of cognitive and language variables in predicting reading abilities of two groups of individuals with reading disabilities (i.e., dyslexia and specific language impairment) and (b) examine which variable(s) is the most predictive in differentiating two groups. Inclusion/exclusion criteria applied to categorize the two groups yielded a total of 63 participants (n = 44 for the dyslexia; n = 19 for the specific language impairment). A stepwise multiple regression approach was conducted to examine which cognitive and/or language variables made the largest contribution to reading abilities (i.e., Phonetic Decoding Efficiency, Word Attack, Sight Word Efficiency, and Passage Comprehension). Results revealed that there were significant differences in which measures of cognitive and language ability predicted individuals with dyslexia and speech and language impairments reading ability, showing that the cognitive and language variables underlying their difficulty with reading abilities were not the same across the two groups. A discriminant function analysis showed that a measure of Verbal Comprehension, Phonological Awareness, and Phonetic Decoding Efficiency can be used to differentiate the two groups. These findings support the tenet that dyslexia and specific language impairment are two subgroups of reading disabilities and that thorough diagnostic evaluations are needed to differentiate between these two subgroups. Distinctions of this nature are central to determining the type and intensity of language-based interventions.

  9. Promising Role of Neuromodulation in Predicting the Progression of Mild Cognitive Impairment to Dementia.

    PubMed

    Naro, Antonino; Corallo, Francesco; De Salvo, Simona; Marra, Angela; Di Lorenzo, Giuseppe; Muscarà, Nunzio; Russo, Margherita; Marino, Silvia; De Luca, Rosaria; Bramanti, Placido; Calabrò, Rocco Salvatore

    2016-07-01

    The differential diagnosis of mild cognitive impairment (MCI) and Alzheimer's disease (AD) is not always straightforward, and the rate of progression of MCI to dementia is not negligible. Thus, there is a need for para-clinical approaches that can improve the differential diagnosis and identify patients that are at risk of progression. There is a growing interest, at present, in the role of the deterioration of brain oscillations as a predictor of MCI-to-AD conversion. For this reason, we experimentally modulated γ-band oscillations (GBO) in a sample of MCI and AD patients and an age-matched healthy elderly group, using a transcranial alternating current stimulation (tACS) protocol that was applied to different cortical sites. We correlated the after-effects of tACS on the GBO and the neuropsychological data, in an attempt to differentiate MCI from AD patients and identify, among the MCI patients, those that could be at potential risk of MCI-to-dementia conversion. MCI patients showed a partial GBO increase and improvement in some neuropsychological tests whereas AD individuals did not show significant tACS after-effects. Notably, some MCI subjects lacked significant neuropsychological and electrophysiological after-effects, similar to AD individuals. In a two-year follow-up, such MCI individuals had converted into AD. Therefore, our data suggest that tACS may support the clinical differential diagnosis of MCI and AD and identify MCI patients who could be at risk of developing dementia. This prediction index may help the clinician to adopt a better prevention/follow-up strategy in such a disabling neurodegenerative disease.

  10. Can Impaired Elasticity of Aorta Predict the Success of Vardenafil Treatment in Patients with Erectile Dysfunction?

    PubMed Central

    Ede, Hüseyin; Tanik, Serhat; Yaylak, Barış; Zengın, Kürşad; Albayrak, Sebahattin; Akkaya, Suleyman; Polat, Cegergun; Turan, Yaşar; Erbay, Alirıza

    2016-01-01

    Objective. Vardenafil is used in treatment of erectile dysfunction (ED) but reveals variable clinical outcomes. Here, we aimed to evaluate the role of aortic elasticity in predicting vardenafil success among patients with ED. Methods. Sixty-one consecutive male subjects with primary ED and indication for vardenafil treatment were included. All subjects fulfilled 5-item version of the International Index of Erectile Function (IIEF-5) before the vardenafil treatment. Pretreatment aortic stiffness index (ASI) and aortic distensibility (AD) were obtained echocardiographically. Following two-month vardenafil treatment, the patients were reevaluated with IIEF-5. Pretreatment, posttreatment, and ΔIIEF-5 scores and ASI values were compared. Results. Average age was 54 ± 8 years. Pretreatment and posttreatment IIEF-5 and ΔIIEF-5 scores were 9.1 ± 2.5; 18.5 ± 2.3; and 9.4 ± 3, respectively. Mean ASI and AD values were 3.10 ± 0.54 and 4.13 ± 2.55 1/(103  ×  mmHg) accordingly. ASI value of severe pretreatment ED (n = 15) was significantly higher than that of mild-moderate pretreatment ED (n = 12) (p < 0.001). All pretreatment IIEF-5 scores increased significantly compared to posttreatment IIEF-5 scores (p < 0.001). ASI values were significantly correlated to pretreatment IIEF-5 scores (p < 0.001) and ΔIIEF-5 value (p < 0.001) but not to posttreatment IIEF-5 score. Conclusion. Aortic elasticity was impaired in accordance with degree of ED. The subjects with higher ASI values obtained more benefits from vardenafil. PMID:27200210

  11. Body Mass Index Predicts Progression of Mild Cognitive Impairment to Dementia.

    PubMed

    Cova, Ilaria; Clerici, Francesca; Maggiore, Laura; Pomati, Simone; Cucumo, Valentina; Ghiretti, Roberta; Galimberti, Daniela; Scarpini, Elio; Mariani, Claudio; Caracciolo, Barbara

    2016-01-01

    To examine the relationship between body mass index (BMI) and progression to dementia and Alzheimer's disease (AD) in mild cognitive impairment (MCI). Two hundred and twenty-eight MCI subjects (mean age 74.04 ± 6.94 years; 57% female) from a memory clinic were followed for 2.40 ± 1.58 years. Baseline height and weight were used to calculate the BMI. The main outcome was progression to dementia (DSM-IV criteria) and AD (NINCDS-ADRDA criteria). Cox proportional hazard models were used to assess the longitudinal association of BMI with dementia and AD, adjusting for a comprehensive set of covariates, including vascular risk factors/diseases and neuroimaging profiles. Out of 228 subjects with MCI, 117 (51.3%) progressed to dementia. Eighty-nine (76%) of the incident dementia cases had AD. In both unadjusted and multi-adjusted models, a higher BMI was associated with a reduced risk of dementia (multi-adjusted HR 0.9; 95% CI 0.8-0.9) and AD (multi-adjusted HR 0.9; 95% CI 0.8-0.9). Being underweight increased the risk of all types of dementia (multi-adjusted HR 2.5; 95% CI 1.2-5.1) but was not specifically associated with AD (multi-adjusted HR 2.2; 95% CI 0.9-5.3). BMI predicted progression of MCI to dementia and AD. In particular, a higher BMI was associated with a lower risk of dementia and AD, and underweight was associated with a higher risk of dementia. BMI assessment may improve the prognostic accuracy of MCI in clinical practice. © 2016 S. Karger AG, Basel.

  12. Predicting the risk of mild cognitive impairment in the Mayo Clinic Study of Aging

    PubMed Central

    Pankratz, V. Shane; Roberts, Rosebud O.; Mielke, Michelle M.; Knopman, David S.; Jack, Clifford R.; Geda, Yonas E.; Rocca, Walter A.

    2015-01-01

    Objective: We sought to develop risk scores for the progression from cognitively normal (CN) to mild cognitive impairment (MCI). Methods: We recruited into a longitudinal cohort study a randomly selected, population-based sample of Olmsted County, MN, residents, aged 70 to 89 years on October 1, 2004. At baseline and subsequent visits, participants were evaluated for demographic, clinical, and neuropsychological measures, and were classified as CN, MCI, or dementia. Using baseline demographic and clinical variables in proportional hazards models, we derived scores that predicted the risk of progressing from CN to MCI. We evaluated the ability of these risk scores to classify participants for MCI risk. Results: Of 1,449 CN participants, 401 (27.7%) developed MCI. A basic model had a C statistic of 0.60 (0.58 for women, 0.62 for men); an augmented model resulted in a C statistic of 0.70 (0.69 for women, 0.71 for men). Both men and women in the highest vs lowest sex-specific quartiles of the augmented model's risk scores had an approximately 7-fold higher risk of developing MCI. Adding APOE ε4 carrier status improved the model (p = 0.002). Conclusions: We have developed MCI risk scores using variables easily assessable in the clinical setting and that may be useful in routine patient care. Because of variability among populations, validation in independent samples is required. These models may be useful in identifying patients who might benefit from more expensive or invasive diagnostic testing, and can inform clinical trial design. Inclusion of biomarkers or other risk factors may further enhance the models. PMID:25788555

  13. Prediction of Incipient Alzheimer's Disease Dementia in Patients with Mild Cognitive Impairment.

    PubMed

    Ardekani, Babak A; Bermudez, Elaine; Mubeen, Asim M; Bachman, Alvin H

    2017-01-01

    Mild cognitive impairment (MCI) is a transitional stage from normal aging to Alzheimer's disease (AD) dementia. It is extremely important to develop criteria that can be used to separate the MCI subjects at imminent risk of conversion to Alzheimer-type dementia from those who would remain stable. We have developed an automatic algorithm for computing a novel measure of hippocampal volumetric integrity (HVI) from structural MRI scans that may be useful for this purpose. To determine the utility of HVI in classification between stable and progressive MCI patients using the Random Forest classification algorithm. We used a 16-dimensional feature space including bilateral HVI obtained from baseline and one-year follow-up structural MRI, cognitive tests, and genetic and demographic information to train a Random Forest classifier in a sample of 164 MCI subjects categorized into two groups [progressive (n = 86) or stable (n = 78)] based on future conversion (or lack thereof) of their diagnosis to probable AD. The overall accuracy of classification was estimated to be 82.3% (86.0% sensitivity, 78.2% specificity). The accuracy in women (89.1%) was considerably higher than that in men (78.9%). The prediction accuracy achieved in women is the highest reported in any previous application of machine learning to AD diagnosis in MCI. The method presented in this paper can be used to separate stable MCI patients from those who are at early stages of AD dementia with high accuracy. There may be stronger indicators of imminent AD dementia in women with MCI as compared to men.

  14. Effects of cognitive impairment on substance abuse treatment attendance: predictive validation of a brief cognitive screening measure.

    PubMed

    Copersino, Marc L; Schretlen, David J; Fitzmaurice, Garrett M; Lukas, Scott E; Faberman, Judith; Sokoloff, Jody; Weiss, Roger D

    2012-05-01

    Neuropsychological impairment among patients with substance use disorders (SUDs) contributes to poorer treatment processes and outcomes. However, neuropsychological assessment is typically not an aspect of patient evaluation in SUD treatment programs because it is prohibitively time and resource consuming. In a previous study, we examined the concurrent validity, classification accuracy, and clinical utility of a brief screening measure, the Montreal Cognitive Assessment (MoCA), in identifying cognitive impairment among SUD patients. To provide further evidence of criterion-related validity, MoCA classification should optimally predict a clinically relevant behavior or outcome among SUD patients. The purpose of this study was to examine the validity of the MoCA in predicting treatment attendance. We compared previously collected clinical assessment data on 60 SUD patients receiving treatment in a program of short duration and high intensity to attendance data obtained via medical chart review. Though the proportion of therapy sessions attended did not differ between groups, cognitively impaired subjects were significantly less likely than unimpaired subjects to attend all of their group therapy sessions. These results complement our previous findings by providing further evidence of criterion-related validity of the MoCA in predicting a clinically relevant behavior (i.e., perfect attendance) among SUD patients. The capacity of the MoCA to predict a clinically relevant behavior provides support for its validity as a brief cognitive screening measure.

  15. The predictive value of arterial stiffness on major adverse cardiovascular events in individuals with mildly impaired renal function

    PubMed Central

    Han, Jie; Wang, Xiaona; Ye, Ping; Cao, Ruihua; Yang, Xu; Xiao, Wenkai; Zhang, Yun; Bai, Yongyi; Wu, Hongmei

    2016-01-01

    Objectives Despite growing evidence that arterial stiffness has important predictive value for cardiovascular disease in patients with advanced stages of chronic kidney disease, the predictive significance of arterial stiffness in individuals with mildly impaired renal function has not been established. The aim of this study was to evaluate the predictive value of arterial stiffness on cardiovascular disease in this specific population. Materials and methods We analyzed measurements of arterial stiffness (carotid–femoral pulse-wave velocity [cf-PWV]) and the incidence of major adverse cardiovascular events (MACEs) in 1,499 subjects from a 4.8-year longitudinal study. Results A multivariate Cox proportional-hazard regression analysis showed that in individuals with normal renal function (estimated glomerular filtration rate [eGFR] ≥90 mL/min/1.73 m2), the baseline cf-PWV was not associated with occurrence of MACEs (hazard ratio 1.398, 95% confidence interval 0.748–2.613; P=0.293). In individuals with mildly impaired renal function (eGFR <90 mL/min/1.73 m2), a higher baseline cf-PWV level was associated with a higher risk of MACEs (hazard ratio 2.334, 95% confidence interval 1.082–5.036; P=0.031). Conclusion Arterial stiffness is a moderate and independent predictive factor for MACEs in individuals with mildly impaired renal function (eGFR <90 mL/min/1.73 m2). PMID:27621605

  16. Amyloid-independent atrophy patterns predict time to progression to dementia in mild cognitive impairment.

    PubMed

    Ten Kate, Mara; Barkhof, Frederik; Visser, Pieter Jelle; Teunissen, Charlotte E; Scheltens, Philip; van der Flier, Wiesje M; Tijms, Betty M

    2017-09-12

    Amyloid pathology in subjects with mild cognitive impairment (MCI) is an important risk factor for progression to dementia due to Alzheimer's disease. Predicting the onset of dementia is challenging even in the presence of amyloid, as time to progression varies considerably among patients and depends on the onset of neurodegeneration. Survival analysis can account for variability in time to event, but has not often been applied to MRI measurements beyond singular predefined brain regions such as the hippocampus. Here we used a voxel-wise survival analysis to identify in an unbiased fashion brain regions where decreased gray matter volume is associated with time to dementia, and assessed the effects of amyloid on these associations. We included 276 subjects with MCI (mean age 67 ± 8, 41% female, mean Mini-Mental State Examination 26.6 ± 2.4), baseline 3D T1-weighted structural MRI, baseline cerebrospinal fluid (CSF) biomarkers, and prospective clinical follow-up. We fitted for each voxel a proportional Cox hazards regression model to study whether decreased gray matter volume predicted progression to dementia in the total sample, and stratified for baseline amyloid status. Dementia at follow-up occurred in 122 (44%) subjects over an average follow-up period of 2.5 ± 1.5 years. Baseline amyloid positivity was associated with progression to dementia (hazard ratio 2.4, p < 0.001). Within amyloid-positive subjects, decreased gray matter volume in the hippocampal, temporal, parietal, and frontal regions was associated with more rapid progression to dementia (median (interquartile range) hazard ratio across significant voxels 1.35 (1.32-1.40)). Repeating the analysis in amyloid-negative subjects revealed similar patterns (median (interquartile range) hazard ratio 1.76 (1.66-1.91)). In subjects with MCI, both abnormal amyloid CSF and decreased gray matter volume were associated with future progression to dementia. The spatial pattern of decreased gray

  17. Service engagement in first episode psychosis: clinical and premorbid correlates.

    PubMed

    Macbeth, Angus; Gumley, Andrew; Schwannauer, Matthias; Fisher, Rebecca

    2013-05-01

    Engagement can be understood as a multifactorial process, incorporating acceptance of treatment, therapeutic rapport, and collaboration in a shared goal of clinical and functional recovery. Difficulties in engagement with clinical services represent a risk factor for treatment discontinuation in first episode psychosis. The current study explored the associations between engagement, clinical, and preonset variables. We report the cross-sectional data on a Scottish sample with first episode psychosis, characterized in terms of psychotic symptoms, premorbid adjustment, duration of untreated psychosis, and clinician-rated engagement. Poorer clinician-rated engagement was associated with greater positive and negative symptoms, greater general psychopathology, and poorer premorbid social adjustment. In a regression analysis, only severity of negative symptoms predicted engagement. The study highlights the role of negative symptoms and impairments in social functioning as factors associated with poorer engagement with clinical services. The value of detailed assessment of social and premorbid functioning is highlighted.

  18. Auditory-nerve responses predict pitch attributes related to musical consonance-dissonance for normal and impaired hearinga

    PubMed Central

    Bidelman, Gavin M.; Heinz, Michael G.

    2011-01-01

    Human listeners prefer consonant over dissonant musical intervals and the perceived contrast between these classes is reduced with cochlear hearing loss. Population-level activity of normal and impaired model auditory-nerve (AN) fibers was examined to determine (1) if peripheral auditory neurons exhibit correlates of consonance and dissonance and (2) if the reduced perceptual difference between these qualities observed for hearing-impaired listeners can be explained by impaired AN responses. In addition, acoustical correlates of consonance-dissonance were also explored including periodicity and roughness. Among the chromatic pitch combinations of music, consonant intervals∕chords yielded more robust neural pitch-salience magnitudes (determined by harmonicity∕periodicity) than dissonant intervals∕chords. In addition, AN pitch-salience magnitudes correctly predicted the ordering of hierarchical pitch and chordal sonorities described by Western music theory. Cochlear hearing impairment compressed pitch salience estimates between consonant and dissonant pitch relationships. The reduction in contrast of neural responses following cochlear hearing loss may explain the inability of hearing-impaired listeners to distinguish musical qualia as clearly as normal-hearing individuals. Of the neural and acoustic correlates explored, AN pitch salience was the best predictor of behavioral data. Results ultimately show that basic pitch relationships governing music are already present in initial stages of neural processing at the AN level. PMID:21895089

  19. Impairment in Occupational Functioning and Adult ADHD: The Predictive Utility of Executive Function (EF) Ratings Versus EF Tests

    PubMed Central

    Barkley, Russell A.; Murphy, Kevin R.

    2010-01-01

    Attention deficit hyperactivity disorder (ADHD) is associated with deficits in executive functioning (EF). ADHD in adults is also associated with impairments in major life activities, particularly occupational functioning. We investigated the extent to which EF deficits assessed by both tests and self-ratings contributed to the degree of impairment in 11 measures involving self-reported occupational problems, employer reported workplace adjustment, and clinician rated occupational adjustment. Three groups of adults were recruited as a function of their severity of ADHD: ADHD diagnosis (n = 146), clinical controls self-referring for ADHD but not diagnosed with it (n = 97), and community controls (n = 109). Groups were combined and regression analyses revealed that self-ratings of EF were significantly predictive of impairments in all 11 measures of occupational adjustment. Although several tests of EF also did so, they contributed substantially less than did the EF ratings, particularly when analyzed jointly with the ratings. We conclude that EF deficits contribute to the impairments in occupational functioning that occur in conjunction with adult ADHD. Ratings of EF in daily life contribute more to such impairments than do EF tests, perhaps because, as we hypothesize, each assesses a different level in the hierarchical organization of EF as a meta-construct. PMID:20197297

  20. Auditory-nerve responses predict pitch attributes related to musical consonance-dissonance for normal and impaired hearing.

    PubMed

    Bidelman, Gavin M; Heinz, Michael G

    2011-09-01

    Human listeners prefer consonant over dissonant musical intervals and the perceived contrast between these classes is reduced with cochlear hearing loss. Population-level activity of normal and impaired model auditory-nerve (AN) fibers was examined to determine (1) if peripheral auditory neurons exhibit correlates of consonance and dissonance and (2) if the reduced perceptual difference between these qualities observed for hearing-impaired listeners can be explained by impaired AN responses. In addition, acoustical correlates of consonance-dissonance were also explored including periodicity and roughness. Among the chromatic pitch combinations of music, consonant intervals/chords yielded more robust neural pitch-salience magnitudes (determined by harmonicity/periodicity) than dissonant intervals/chords. In addition, AN pitch-salience magnitudes correctly predicted the ordering of hierarchical pitch and chordal sonorities described by Western music theory. Cochlear hearing impairment compressed pitch salience estimates between consonant and dissonant pitch relationships. The reduction in contrast of neural responses following cochlear hearing loss may explain the inability of hearing-impaired listeners to distinguish musical qualia as clearly as normal-hearing individuals. Of the neural and acoustic correlates explored, AN pitch salience was the best predictor of behavioral data. Results ultimately show that basic pitch relationships governing music are already present in initial stages of neural processing at the AN level.

  1. Folate and MMA predict cognitive impairment in elderly stroke survivors: A cross sectional study.

    PubMed

    Pascoe, Michaela C; Linden, Thomas

    2016-09-30

    Elderly stroke survivors are at risk of malnutrition and long-term cognitive impairment. Vitamin B-related metabolites, folate and methylmalonic acid, have been implicated in cognitive function. We conducted a study exploring the relationship between blood folate, methylmalonic acid and post-stroke cognitive impairment. This is a cross sectional study of elderly Swedish patients (n=149) 20 months post-stroke, assessed using the Mini Mental State Examination, serum blood levels of methylmalonic acid and red blood cell levels of folate. Linear modeling indicated that low levels of blood folate and elevated methylmalonic acid significantly contributed to cognitive impairment in stroke survivors. Half of the stroke survivors were shown to have folate deficiency at 20 months after stroke. Folate deficiency is common long term after stroke and both low folate and elevated methylmalonic acid appear to be associated with long term cognitive impairment, in elderly Swedish stroke survivors.

  2. Contrast-Enhanced Ultrasound for Assessing Renal Perfusion Impairment and Predicting Acute Kidney Injury to Chronic Kidney Disease Progression.

    PubMed

    Cao, Wei; Cui, Shuang; Yang, Li; Wu, Chunyi; Liu, Jian; Yang, Fang; Liu, Youhua; Bin, Jianping; Hou, Fan Fan

    2017-08-22

    Acute kidney injury (AKI) is increasingly recognized as a major risk factor leading to progression to chronic kidney disease (CKD). However, the diagnostic tools for predicting AKI to CKD progression are particularly lacking. Here, we tested the utility of contrast-enhanced ultrasound (CEUS) for predicting progression to CKD after AKI by using both mild (20-min) and severe (45-min) bilateral renal ischemia-reperfusion injury mice. Renal perfusion measured by CEUS reduced to 25% ± 7% and 14% ± 6% of the pre-ischemic levels in mild and severe AKI 1 h after ischemia (p < 0.05). Renal perfusion returned to pre-ischemic levels 1 day after mild AKI followed by restoration of kidney function. However, severe AKI caused persistent renal perfusion impairment (60% ± 9% of baseline levels) accompanied by progressive renal fibrosis and sustained decrease in renal function. Renal perfusion at days 1-21 significantly correlated with tubulointerstitial fibrosis 42 days after AKI. For predicting renal fibrosis at day 42, the area under the receiver operating characteristics curve of renal perfusion impairment at day 1 was 0.84. Similar changes in the renal image of CEUS were observed in patients with AKI-CKD progression. This study demonstrates that CEUS enables dynamic and noninvasive detection of renal perfusion impairment after ischemic AKI and the perfusion abnormalities shown by CEUS can early predict the progression to CKD after AKI. These results indicate that CEUS enables the evaluation of renal perfusion impairment associated with CKD after ischemic AKI and may serve as a noninvasive technique for assessing AKI-CKD progression. Antioxid. Redox Signal. 00, 000-000.

  3. Alcohol use longitudinally predicts adjustment and impairment in college students with ADHD: The role of executive functions.

    PubMed

    Langberg, Joshua M; Dvorsky, Melissa R; Kipperman, Kristen L; Molitor, Stephen J; Eddy, Laura D

    2015-06-01

    The primary aim of this study was to evaluate whether alcohol consumption longitudinally predicts the adjustment, overall functioning, and grade point average (GPA) of college students with ADHD and to determine whether self-report of executive functioning (EF) mediates these relationships. Sixty-two college students comprehensively diagnosed with ADHD completed ratings at the beginning and end of the school year. Regression analyses revealed that alcohol consumption rated at the beginning of the year significantly predicted self-report of adjustment and overall impairment at the end of the year, above and beyond ADHD symptoms and baseline levels of adjustment/impairment but did not predict GPA. Exploratory multiple mediator analyses suggest that alcohol use impacts impairment primarily through EF deficits in self-motivation. EF deficits in the motivation to refrain from pursuing immediately rewarding behaviors in order to work toward long-term goals appear to be particularly important in understanding why college students with ADHD who consume alcohol have a higher likelihood of experiencing significant negative outcomes. The implications of these findings for the prevention of the negative functional outcomes often experienced by college students with ADHD are discussed. (PsycINFO Database Record

  4. Clinical variables and biomarkers in prediction of cognitive impairment in patients with newly diagnosed Parkinson's disease: a cohort study.

    PubMed

    Schrag, Anette; Siddiqui, Uzma Faisal; Anastasiou, Zacharias; Weintraub, Daniel; Schott, Jonathan M

    2017-01-01

    Parkinson's disease is associated with an increased incidence of cognitive impairment and dementia. Predicting who is at risk of cognitive decline early in the disease course has implications for clinical prognosis and for stratification of participants in clinical trials. We assessed the use of clinical information and biomarkers as predictive factors for cognitive decline in patients with newly diagnosed Parkinson's disease. The Parkinson's Progression Markers Initiative (PPMI) study is a cohort study in patients with newly diagnosed Parkinson's disease. We evaluated cognitive performance (Montreal Cognitive Assessment [MoCA] scores), demographic and clinical data, APOE status, and biomarkers (CSF and dopamine transporter [DAT] imaging results). Using change in MoCA scores over 2 years, MoCA scores at 2 years' follow-up, and a diagnosis of cognitive impairment (combined mild cognitive impairment or dementia) at 2 years as outcome measures, we assessed the predictive values of baseline clinical variables and separate or combined additions of APOE status, DAT imaging, and CSF biomarkers. We did univariate and multivariate linear analyses with MoCA change scores between baseline and 2 years, and with MoCA scores at 2 years as dependent variables, using backwards linear regression analysis. Additionally, we constructed a prediction model for diagnosis of cognitive impairment using logistic regression analysis. 390 patients with Parkinson's disease recruited between July 1, 2010, and May 31, 2013, and for whom data on MoCA scores at baseline and 2 years were available. In multivariate analyses, baseline age, University of Pennsylvania Smell Inventory Test (UPSIT) scores, CSF amyloid - (Aβ42) to t-tau ratio, and APOE status were associated with change in MoCA scores over time. Baseline age, MoCA and UPSIT scores, and CSF Aβ42 to t-tau ratio were associated with MoCA score at 2 years (using a backwards p-removal threshold of 0·1). Accuracy of prediction of cognitive

  5. Impaired Control and Undergraduate Problem Drinking

    PubMed Central

    Leeman, Robert F.; Fenton, Miriam; Volpicelli, Joseph R.

    2008-01-01

    Aims Impaired control, one of the hallmarks of addiction, is also one of the earliest dependence symptoms to develop. Thus impaired control is particularly relevant to undergraduates and other young adults with relatively brief drinking histories. The main goal of this study was to determine whether impaired control predicted heavy episodic drinking and alcohol-related problems cross-sectionally in an undergraduate sample after controlling for gender, family history of alcohol and drug problems and several other established predictor variables from the undergraduate alcohol literature. Methods A sample of first-year undergraduates (N = 312) completed Part 2 of the Impaired Control Scale (ICS; Heather et al., 1993) and other measures related to alcohol use as part of a larger study on problem drinking in undergraduates. Results Scores on Part 2 of the ICS predicted heavy episodic drinking and alcohol-related problems cross-sectionally even after controlling for all other predictor variables. Notably, impaired control was a stronger predictor of alcohol-related problems than overall weekly alcohol consumption. Part 2 of the ICS was found to be a reliable and valid measure for use with undergraduates. Conclusions These findings support the notion that impaired control is one of the earliest dependence symptoms to develop. The ICS is an effective tool for identifying young adults at risk for problem drinking. PMID:17142826

  6. FDG-PET and CSF phospho-tau for prediction of cognitive decline in mild cognitive impairment.

    PubMed

    Fellgiebel, Andreas; Scheurich, Armin; Bartenstein, Peter; Müller, Matthias J

    2007-07-15

    Specific patterns of cortical glucose metabolism disturbances and increased CSF phospho-tau (p-tau(181)) concentrations could be demonstrated to predict cognitive decline and shift to dementia in amnestic mild cognitive impairment (MCI). But comparisons of both diagnostic tools have not been undertaken so far. The aim of the study was to compare (18)F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) findings and CSF phospho-tau (p-tau(181)) measurements in the prediction of cognitive deterioration and conversion to dementia in MCI. During follow-up (mean 19 months) eight of 16 patients (50%) showed progressive cognitive decline, and four patients shifted to dementia. Pathological FDG-PET and elevated p-tau(181) levels both predicted deterioration. While p-tau(181) was highly sensitive for cognitive decline, FDG-PET was superior in predicting conversion to clinical dementia in MCI patients.

  7. Association between impaired brain activity and volume at the sub-region of Broca's area in ultra-high risk and first-episode schizophrenia: A multi-modal neuroimaging study.

    PubMed

    Iwashiro, Norichika; Koike, Shinsuke; Satomura, Yoshihiro; Suga, Motomu; Nagai, Tatsuya; Natsubori, Tatsunobu; Tada, Mariko; Gonoi, Wataru; Takizawa, Ryu; Kunimatsu, Akira; Yamasue, Hidenori; Kasai, Kiyoto

    2016-04-01

    Recent studies have suggested that functional abnormalities in Broca's area, which is important in language production (speech and thoughts before speech), play an important role in the pathophysiology of schizophrenia. While multi-modal approaches have proved useful in revealing the specific pathophysiology of psychosis, the association of functional abnormalities with gray matter volume (GMV) here in subjects with an ultra-high risk (UHR) of schizophrenia, those with first-episode schizophrenia (FES), and healthy controls has yet to be clarified. Therefore, the relationship between cortical activity measured using functional near-infrared spectroscopy (fNIRS) during a verbal fluency task, and GMV in the Broca's area assessed using a manual tracing in magnetic resonance imaging (MRI), which considers individual structural variation, was examined for 57 subjects (23 UHR/18 FES/16 controls). The UHR and FES group showed significantly reduced brain activity compared to control group in the left pars triangularis (PT) (P=.036, .003, respectively). Furthermore in the FES group, the reduced brain activity significantly positively correlated with the volume in the left PT (B=0.29, P=.027), while significant negative association was evident for all subjects (B=-0.18, P=.010). This correlation remained significant after adjusting for antipsychotics dosage, and voxel-wise analysis could not detect any significant correlation between impaired cortical activity and volume. The significant relationship between neural activity and GMV in the left PT may reflect a specific pathophysiology related to the onset of schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Methamphetamine use parameters do not predict neuropsychological impairment in currently abstinent dependent adults.

    PubMed

    Cherner, Mariana; Suarez, Paola; Casey, Corinna; Deiss, Robert; Letendre, Scott; Marcotte, Thomas; Vaida, Florin; Atkinson, J Hampton; Grant, Igor; Heaton, Robert K

    2010-01-15

    Methamphetamine (meth) abuse is increasingly of public health concern and has been associated with neurocognitive dysfunction. Some previous studies have been hampered by background differences between meth users and comparison subjects, as well as unknown HIV and hepatitis C (HCV) status, which can also affect brain functioning. We compared the neurocognitive functioning of 54 meth dependent (METH+) study participants who had been abstinent for an average of 129 days, to that of 46 demographically comparable control subjects (METH-) with similar level of education and reading ability. All participants were free of HIV and HCV infection. The METH+ group exhibited higher rates of neuropsychological impairment in most areas tested. Among meth users, neuropsychologically normal (n=32) and impaired (n=22) subjects did not differ with respect to self-reported age at first use, total years of use, route of consumption, or length of abstinence. Those with motor impairment had significantly greater meth use in the past year, but impairment in cognitive domains was unrelated to meth exposure. The apparent lack of correspondence between substance use parameters and cognitive impairment suggests the need for further study of individual differences in vulnerability to the neurotoxic effects of methamphetamine.

  9. Alzheimer Disease Cerebrospinal Fluid Biomarkers Moderate Baseline Differences and Predict Longitudinal Change in Attentional Control and Episodic Memory Composites in the Adult Children Study.

    PubMed

    Aschenbrenner, Andrew J; Balota, David A; Fagan, Anne M; Duchek, Janet M; Benzinger, Tammie L S; Morris, John C

    2015-09-01

    Cognitive measures that are sensitive to biological markers of Alzheimer disease (AD) pathology are needed to (a) facilitate preclinical staging, (b) identify individuals who are at the highest risk for developing clinical symptoms, and (c) serve as endpoints for evaluating the efficacy of interventions. The present study assesses the utility of two cognitive composite scores of attentional control and episodic memory as markers for preclinical AD pathology in a group of cognitively normal older adults (N = 238), as part of the Adult Children Study. All participants were given a baseline cognitive assessment and follow-up assessments every 3 years over an 8-year period, as well as a lumbar puncture within 2 years of the initial assessment to collect cerebrospinal fluid (CSF) and amyloid tracer Pittsburgh compound-B scan for amyloid imaging. Results indicated that attentional control was correlated with levels of Aβ42 at the initial assessment whereas episodic memory was not. Longitudinally, individuals with high CSF tau exhibited a decline in both attention and episodic memory over the course of the study. These results indicate that measures of attentional control and episodic memory can be used to evaluate cognitive decline in preclinical AD and provide support that CSF tau may be a key mechanism driving longitudinal cognitive change.

  10. Alzheimer Disease Cerebrospinal Fluid Biomarkers Moderate Baseline Differences and Predict Longitudinal Change in Attentional Control and Episodic Memory Composites in the Adult Children Study

    PubMed Central

    Aschenbrenner, Andrew J.; Balota, David A.; Fagan, Anne M.; Duchek, Janet M.; Benzinger, Tammie L.S.; Morris, John C.

    2015-01-01

    Objective Cognitive measures that are sensitive to biological markers of Alzheimer disease (AD) pathology are needed in order to (a) facilitate preclinical staging, (b) identify individuals who are at the highest risk for developing clinical symptoms and (c) serve as endpoints for evaluating the efficacy of interventions. The present study assesses the utility of two cognitive composite scores of attentional control and episodic memory as markers for preclinical AD pathology in a group of cognitively normal older adults (N = 238), as part of the Adult Children Study. Method All participants were given a baseline cognitive assessment and follow-up assessments every 3 years over an 8-year period, as well as a lumbar puncture within two years of the initial assessment to collect cerebrospinal fluid (CSF) and a PET-PIB scan for amyloid imaging. Results Results indicated that attentional control was correlated with levels of Aβ42 at the initial assessment whereas episodic memory was not. Longitudinally, individuals with high CSF tau exhibited a decline in both attention and episodic memory over the course of the study. Conclusion These results indicate that measures of attentional control and episodic memory can be utilized to evaluate cognitive decline in preclinical AD and provide support that CSF tau may be a key mechanism driving longitudinal cognitive change. PMID:26416094

  11. Report of stroke-like symptoms predicts incident cognitive impairment in a stroke-free cohort.

    PubMed

    Kelley, Brendan J; McClure, Leslie A; Letter, Abraham J; Wadley, Virginia G; Unverzagt, Frederick W; Kissela, Brett M; Kleindorfer, Dawn; Howard, George

    2013-07-09

    The present study characterizes the relationship between report of stroke symptoms (SS) or TIA and incident cognitive impairment in the large biracial cohort of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study. The REGARDS Study is a population-based, biracial, longitudinal cohort study that has enrolled 30,239 participants from the United States. Exclusion of those with baseline cognitive impairment, stroke before enrollment, or incomplete data resulted in a sample size of 23,830. Participants reported SS/TIA on the Questionnaire for Verifying Stroke-free Status at baseline and every 6 months during follow-up. Incident cognitive impairment was detected using the Six-item Screener, which was administered annually. Logistic regression found significant association between report of SS/TIA and subsequent incident cognitive impairment. Among white participants, the odds ratio for incident cognitive impairment was 2.08 (95% confidence interval: 1.81, 2.39) for those reporting at least one SS/TIA compared with those reporting no SS/TIA. Among black participants, the odds ratio was 1.66 (95% confidence interval: 1.45, 1.89) using the same modeling. The magnitude of impact was largest among those with fewer traditional stroke risk factors, particularly among white participants. Report of SS/TIA showed a strong association with incident cognitive impairment and supports the use of the Questionnaire for Verifying Stroke-free Status as a quick, low-cost instrument to screen for people at increased risk of cognitive decline.

  12. Prefrontal recruitment during social rejection predicts greater subsequent self-regulatory imbalance and impairment: neural and longitudinal evidence.

    PubMed

    Chester, David S; DeWall, C Nathan

    2014-11-01

    Social rejection impairs self-regulation, yet the neural mechanisms underlying this relationship remain unknown. The right ventrolateral prefrontal cortex (rVLPFC) facilitates self-regulation and plays a robust role in regulating the distress of social rejection. However, recruiting this region's inhibitory function during social rejection may come at a self-regulatory cost. As supported by prominent theories of self-regulation, we hypothesized that greater rVLPFC recruitment during rejection would predict a subsequent self-regulatory imbalance that favored reflexive impulses (i.e., cravings), which would then impair self-regulation. Supporting our hypotheses, rVLPFC activation during social rejection was associated with greater subsequent nucleus accumbens (NAcc) activation and lesser functional connectivity between the NAcc and rVLPFC to appetitive cues. Over seven days, the effect of daily felt rejection on daily self-regulatory impairment was exacerbated among participants who showed a stronger rVLPFC response to social rejection. This interactive effect was mirrored in the effect of daily felt rejection on heightened daily alcohol cravings. Our findings suggest that social rejection likely impairs self-regulation by recruiting the rVLPFC, which then tips the regulatory balance towards reward-based impulses. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Self-Criticism versus Neuroticism in Predicting Depression and Psychosocial Impairment over Four Years in a Clinical Sample

    PubMed Central

    Dunkley, David M.; Sanislow, Charles A.; Grilo, Carlos M.; McGlashan, Thomas H.

    2009-01-01

    The present study extended previous findings demonstrating self-criticism, assessed by the Dysfunctional Attitude Scale (DAS; 1), as a potentially important prospective predictor of depressive symptomatology and psychosocial functional impairment over time. Using data from a prospective, 4-year study of a clinical sample, DAS self-criticism and neuroticism were associated with self-report depressive symptoms, interviewer-rated major depression, and global domains of psychosocial functional impairment four years later. Hierarchical multiple regression results indicated that self-criticism uniquely predicted depressive symptoms, major depression, and global psychosocial impairment 4 years later over and above the Time 1 assessments of these outcomes and neuroticism. In contrast, neuroticism was a unique predictor of self-report depressive symptoms only 4 years later. Path analyses were used to test a preliminary three-wave mediational model and demonstrated that negative perceptions of social support at three years mediated the relation between self-criticism and depression/global psychosocial impairment over four years. PMID:19486732

  14. Memory assessment in patients with temporal lobe epilepsy to predict memory impairment after surgery: A systematic review.

    PubMed

    Parra-Díaz, P; García-Casares, N

    2017-04-19

    Given that surgical treatment of refractory mesial temporal lobe epilepsy may cause memory impairment, determining which patients are eligible for surgery is essential. However, there is little agreement on which presurgical memory assessment methods are best able to predict memory outcome after surgery and identify those patients with a greater risk of surgery-induced memory decline. We conducted a systematic literature review to determine which presurgical memory assessment methods best predict memory outcome. The literature search of PubMed gathered articles published between January 2005 and December 2015 addressing pre- and postsurgical memory assessment in mesial temporal lobe epilepsy patients by means of neuropsychological testing, functional MRI, and other neuroimaging techniques. We obtained 178 articles, 31 of which were included in our review. Most of the studies used neuropsychological tests and fMRI; these methods are considered to have the greatest predictive ability for memory impairment. Other less frequently used techniques included the Wada test and FDG-PET. Current evidence supports performing a presurgical assessment of memory function using both neuropsychological tests and functional MRI to predict memory outcome after surgery. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Prediction of speech intelligibility in spatial noise and reverberation for normal-hearing and hearing-impaired listeners.

    PubMed

    Beutelmann, Rainer; Brand, Thomas

    2006-07-01

    Binaural speech intelligibility of individual listeners under realistic conditions was predicted using a model consisting of a gammatone filter bank, an independent equalization-cancellation (EC) process in each frequency band, a gammatone resynthesis, and the speech intelligibility index (SII). Hearing loss was simulated by adding uncorrelated masking noises (according to the pure-tone audiogram) to the ear channels. Speech intelligibility measurements were carried out with 8 normal-hearing and 15 hearing-impaired listeners, collecting speech reception threshold (SRT) data for three different room acoustic conditions (anechoic, office room, cafeteria hall) and eight directions of a single noise source (speech in front). Artificial EC processing errors derived from binaural masking level difference data using pure tones were incorporated into the model. Except for an adjustment of the SII-to-intelligibility mapping function, no model parameter was fitted to the SRT data of this study. The overall correlation coefficient between predicted and observed SRTs was 0.95. The dependence of the SRT of an individual listener on the noise direction and on room acoustics was predicted with a median correlation coefficient of 0.91. The effect of individual hearing impairment was predicted with a median correlation coefficient of 0.95. However, for mild hearing losses the release from masking was overestimated.

  16. Developmental ethanol exposure-induced sleep fragmentation predicts adult cognitive impairment.

    PubMed

    Wilson, D A; Masiello, K; Lewin, M P; Hui, M; Smiley, J F; Saito, M

    2016-05-13

    Developmental ethanol (EtOH) exposure can lead to long-lasting cognitive impairment, hyperactivity, and emotional dysregulation among other problems. In healthy adults, sleep plays an important role in each of these behavioral manifestations. Here we explored circadian rhythms (activity, temperature) and slow-wave sleep (SWS) in adult mice that had received a single day of EtOH exposure on postnatal day 7 and saline littermate controls. We tested for correlations between slow-wave activity and both contextual fear conditioning and hyperactivity. Developmental EtOH resulted in adult hyperactivity within the home cage compared to controls but did not significantly modify circadian cycles in activity or temperature. It also resulted in reduced and fragmented SWS, including reduced slow-wave bout duration and increased slow-wave/fast-wave transitions over 24-h periods. In the same animals, developmental EtOH exposure also resulted in impaired contextual fear conditioning memory. The impairment in memory was significantly correlated with SWS fragmentation. Furthermore, EtOH-treated animals did not display a post-training modification in SWS which occurred in controls. In contrast to the memory impairment, sleep fragmentation was not correlated with the developmental EtOH-induced hyperactivity. Together these results suggest that disruption of SWS and its plasticity are a secondary contributor to a subset of developmental EtOH exposure's long-lasting consequences.

  17. Prefrontal cortex activity during response selection predicts processing speed impairment in schizophrenia

    PubMed Central

    Woodward, Neil D.; Duffy-Alberto, Brittney; Karbasforoushan, Haleh

    2014-01-01

    Processing speed is the most impaired neuropsychological domain in schizophrenia and a robust predictor of functional outcome. Determining the specific cognitive operations underlying processing speed dysfunction and indentifying their neural correlates may assist in developing pro-cognitive interventions. Response selection, the process of mapping stimuli onto motor responses, correlates with neuropsychological tests of processing speed and may contribute to processing speed impairment in schizophrenia. This study investigated the relationship between behavioral and neural measures of response selection, and a neuropsychological index of processing speed in schizophrenia. 26 patients with schizophrenia and 21 healthy subjects underwent fMRI scanning during performance of 2 and 4-choice-reaction time (RT) tasks and completed the Wechsler Adult Intelligence Scale-III (WAIS) Processing Speed Index (PSI). Response selection, defined as RT slowing between 2 and 4-choice RT, was impaired in schizophrenia and correlated with psychometric processing speed. Greater activation of the dorsolateral prefrontal cortex (PFC) was observed in schizophrenia and correlated with poorer WAIS PSI scores. Deficient response selection and abnormal recruitment of the dorsolateral PFC during response selection contribute to processing speed impairment in schizophrenia. Interventions that improve response selection and normalize dorsolateral PFC function may improve processing speed in schizophrenia. PMID:23816240

  18. Avoidance of Emotionally Arousing Stimuli Predicts Social-Perceptual Impairment in Asperger's Syndrome

    ERIC Educational Resources Information Center

    Corden, Ben; Chilvers, Rebecca; Skuse, David

    2008-01-01

    We combined eye-tracking technology with a test of facial affect recognition and a measure of self-reported social anxiety in order to explore the aetiology of social-perceptual deficits in Asperger's syndrome (AS). Compared to controls matched for age, IQ and visual-perceptual ability, we found a group of AS adults was impaired in their…

  19. Individual Differences in Anatomy Predict Reading and Oral Language Impairments in Children

    ERIC Educational Resources Information Center

    Leonard, Christiana; Eckert, Mark; Given, Barbara; Virginia, Berninger; Eden, Guinevere

    2006-01-01

    Developmental dyslexia (DD) and specific language impairment (SLI) are disorders of language that differ in diagnostic criteria and outcome. DD is defined by isolated reading deficits. SLI is defined by poor receptive and expressive oral language skills. Reading deficits, although prevalent, are not necessary for the diagnosis of SLI. An enduring…

  20. Predicting Early Spelling Difficulties in Children with Specific Language Impairment: A Clinical Perspective

    ERIC Educational Resources Information Center

    Cordewener, Kim A. H.; Bosman, Anna M. T.; Verhoeven, Ludo

    2012-01-01

    This study focused on the precursors of spelling difficulties in first grade for children with specific language impairment (SLI). A sample of 58 second-year kindergartners in the Netherlands was followed until the end of first grade. Linguistic, phonological, orthographic, letter knowledge, memory, and nonverbal-reasoning skills were considered…

  1. Neonatal White Matter Abnormality Predicts Childhood Motor Impairment in Very Preterm Children

    ERIC Educational Resources Information Center

    Spittle, Alicia J.; Cheong, Jeanie; Doyle, Lex W.; Roberts, Gehan; Lee, Katherine J.; Lim, Jeremy; Hunt, Rod W.; Inder, Terrie E.; Anderson, Peter J.

    2011-01-01

    Aim: Children born very preterm are at risk for impaired motor performance ranging from cerebral palsy (CP) to milder abnormalities, such as developmental coordination disorder. White matter abnormalities (WMA) at term have been associated with CP in very preterm children; however, little is known about the impact of WMA on the range of motor…

  2. Impaired Contingent Attentional Capture Predicts Reduced Working Memory Capacity in Schizophrenia

    PubMed Central

    Mayer, Jutta S.; Fukuda, Keisuke; Vogel, Edward K.; Park, Sohee

    2012-01-01

    Although impairments in working memory (WM) are well documented in schizophrenia, the specific factors that cause these deficits are poorly understood. In this study, we hypothesized that a heightened susceptibility to attentional capture at an early stage of visual processing would result in working memory encoding problems. 30 patients with schizophrenia and 28 demographically matched healthy participants were presented with a search array and asked to report the orientation of the target stimulus. In some of the trials, a flanker stimulus preceded the search array that either matched the color of the target (relevant-flanker capture) or appeared in a different color (irrelevant-flanker capture). Working memory capacity was determined in each individual using the visual change detection paradigm. Patients needed considerably more time to find the target in the no-flanker condition. After adjusting the individual exposure time, both groups showed equivalent capture costs in the irrelevant-flanker condition. However, in the relevant-flanker condition, capture costs were increased in patients compared to controls when the stimulus onset asynchrony between the flanker and the search array was high. Moreover, the increase in relevant capture costs correlated negatively with working memory capacity. This study demonstrates preserved stimulus-driven attentional capture but impaired contingent attentional capture associated with low working memory capacity in schizophrenia. These findings suggest a selective impairment of top-down attentional control in schizophrenia, which may impair working memory encoding. PMID:23152783

  3. Interhemispheric Temporal Lobe Connectivity Predicts Language Impairment in Adolescents Born Preterm

    ERIC Educational Resources Information Center

    Northam, Gemma B.; Liegeois, Frederique; Tournier, Jacques-Donald; Croft, Louise J.; Johns, Paul N.; Chong, Wui K.; Wyatt, John S.; Baldeweg, Torsten

    2012-01-01

    Although language difficulties are common in children born prematurely, robust neuroanatomical correlates of these impairments remain to be established. This study investigated whether the greater prevalence of language problems in preterm (versus term-born) children might reflect injury to major intra- or interhemispheric white matter pathways…

  4. Preschool Impairments in Auditory Processing and Speech Perception Uniquely Predict Future Reading Problems

    ERIC Educational Resources Information Center

    Boets, Bart; Vandermosten, Maaike; Poelmans, Hanne; Luts, Heleen; Wouters, Jan; Ghesquiere, Pol

    2011-01-01

    Developmental dyslexia is characterized by severe reading and spelling difficulties that are persistent and resistant to the usual didactic measures and remedial efforts. It is well established that a major cause of these problems lies in poorly specified phonological representations. Many individuals with dyslexia also present impairments in…

  5. Neonatal White Matter Abnormality Predicts Childhood Motor Impairment in Very Preterm Children

    ERIC Educational Resources Information Center

    Spittle, Alicia J.; Cheong, Jeanie; Doyle, Lex W.; Roberts, Gehan; Lee, Katherine J.; Lim, Jeremy; Hunt, Rod W.; Inder, Terrie E.; Anderson, Peter J.

    2011-01-01

    Aim: Children born very preterm are at risk for impaired motor performance ranging from cerebral palsy (CP) to milder abnormalities, such as developmental coordination disorder. White matter abnormalities (WMA) at term have been associated with CP in very preterm children; however, little is known about the impact of WMA on the range of motor…

  6. Interhemispheric Temporal Lobe Connectivity Predicts Language Impairment in Adolescents Born Preterm

    ERIC Educational Resources Information Center

    Northam, Gemma B.; Liegeois, Frederique; Tournier, Jacques-Donald; Croft, Louise J.; Johns, Paul N.; Chong, Wui K.; Wyatt, John S.; Baldeweg, Torsten

    2012-01-01

    Although language difficulties are common in children born prematurely, robust neuroanatomical correlates of these impairments remain to be established. This study investigated whether the greater prevalence of language problems in preterm (versus term-born) children might reflect injury to major intra- or interhemispheric white matter pathways…

  7. Accurately Predicting Future Reading Difficulty for Bilingual Latino Children at Risk for Language Impairment

    ERIC Educational Resources Information Center

    Petersen, Douglas B.; Gillam, Ronald B.

    2013-01-01

    Sixty-three bilingual Latino children who were at risk for language impairment were administered reading-related measures in English and Spanish (letter identification, phonological awareness, rapid automatized naming, and sentence repetition) and descriptive measures including English language proficiency (ELP), language ability (LA),…

  8. Social knowledge in children with language impairments: examination of strategies, predicted consequences, and goals in peer conflict situations.

    PubMed

    Timler, Geralyn R

    2008-09-01

    This study investigated social knowledge in school-age children, aged 8-12 years, with and without language impairment (LI and TD groups). A hypothetical peer conflict task was administered to examine the relationship among prosocial responses and parent/teacher ratings of children's social behaviours. Stimuli included 12 hypothetical peer conflict vignettes presented in an open-ended and forced choice condition. The LI group generated (open-ended) and selected (forced choice) fewer prosocial strategies. When asked to predict a friend's reaction to a selected conflict resolution strategy, the LI group predicted fewer positive consequences; however, the proportion of prosocial strategies followed by prediction of a positive peer consequence was similar across groups. Both groups identified more self-interest than relationship goals as the rationale for selected strategies. In the LI group, teacher ratings of children's social skills and problems in peer provocation situations were associated with selection of prosocial strategies. Implications for clinical service providers are discussed.

  9. Artificial neural networks identify the predictive values of risk factors on the conversion of amnestic mild cognitive impairment.

    PubMed

    Tabaton, Massimo; Odetti, Patrizio; Cammarata, Sergio; Borghi, Roberta; Monacelli, Fiammetta; Caltagirone, Carlo; Bossù, Paola; Buscema, Massimo; Grossi, Enzo

    2010-01-01

    The search for markers that are able to predict the conversion of amnestic mild cognitive impairment (aMCI) to Alzheimer's disease (AD) is crucial for early mechanistic therapies. Using artificial neural networks (ANNs), 22 variables that are known risk factors of AD were analyzed in 80 patients with aMCI, for a period spanning at least 2 years. The cases were chosen from 195 aMCI subjects recruited by four Italian Alzheimer's disease units. The parameters of glucose metabolism disorder, female gender, and apolipoprotein E epsilon3/epsilon4 genotype were found to be the biological variables with high relevance for predicting the conversion of aMCI. The scores of attention and short term memory tests also were predictors. Surprisingly, the plasma concentration of amyloid-beta (42) had a low predictive value. The results support the utility of ANN analysis as a new tool in the interpretation of data from heterogeneous and distinct sources.

  10. Swallowing impairment is a significant factor for predicting life prognosis of elderly at the end of life.

    PubMed

    Naruishi, Koji; Nishikawa, Yasufumi

    2017-04-08

    In end-of-life care of elderly, the decision of care plan including gastrostomy is difficult frequently because of insufficient knowledge relating the life prognosis of elderly. It is important the families to decide correctly the life prognosis of elderly with geriatric diseases. Our purpose is to examine the significant factors for predicting life prognosis of elderly in end-of-life care. A total of 320 elderly patients was enrolled (male/female 151/169; averaged age: male 84.7 ± 5.9 year, female 86.8 ± 6.3 year) and retrospective analyses were performed. The elderly patients were classified as either: (1) with or without past illness of aspiration pneumonia; (2) with or without incidence of cerebrovascular disorder; (3) impaired or normal cognitive function; (4) impaired or normal swallowing function, and performed Kaplan-Meier survival analysis. Swallowing function was examined using video endoscopic (VE) evaluation method. The Kaplan-Meier analysis of the number of days from implementation of VE test (day 0) to death was evaluated with the log-rank Mantel-Cox test. The maximum follow-up time recorded was 180 days. There were no significant differences in number of days when divided with or without past illness of aspiration pneumonia, cerebrovascular disorder and impaired cognitive function. The survival probabilities of elderly with impaired swallowing function were significant lower than in elderly with the normal function. For judgement of life prognosis, the condition of being frail such as impaired swallowing function might be a useful factor, and the viewpoint would contribute to decide the treatment plan for the good end-of-life care of elderly.

  11. Anemia and Red Blood Cell Indices Predict HIV-Associated Neurocognitive Impairment in the Highly Active Antiretroviral Therapy Era

    PubMed Central

    Kallianpur, Asha R.; Wang, Quan; Jia, Peilin; Hulgan, Todd; Zhao, Zhongming; Letendre, Scott L.; Ellis, Ronald J.; Heaton, Robert K.; Franklin, Donald R.; Barnholtz-Sloan, Jill; Collier, Ann C.; Marra, Christina M.; Clifford, David B.; Gelman, Benjamin B.; McArthur, Justin C.; Morgello, Susan; Simpson, David M.; McCutchan, J. A.; Grant, Igor

    2016-01-01

    Background. Anemia has been linked to adverse human immunodeficiency virus (HIV) outcomes, including dementia, in the era before highly active antiretroviral therapy (HAART). Milder forms of HIV-associated neurocognitive disorder (HAND) remain common in HIV-infected persons, despite HAART, but whether anemia predicts HAND in the HAART era is unknown. Methods. We evaluated time-dependent associations of anemia and cross-sectional associations of red blood cell indices with neurocognitive impairment in a multicenter, HAART-era HIV cohort study (N = 1261), adjusting for potential confounders, including age, nadir CD4+ T-cell count, zidovudine use, and comorbid conditions. Subjects underwent comprehensive neuropsychiatric and neuromedical assessments. Results. HAND, defined according to standardized criteria, occurred in 595 subjects (47%) at entry. Mean corpuscular volume and mean corpuscular hemoglobin were positively associated with the global deficit score, a continuous measure of neurocognitive impairment (both P < .01), as well as with all HAND, milder forms of HAND, and HIV-associated dementia in multivariable analyses (all P < .05). Anemia independently predicted development of HAND during a median follow-up of 72 months (adjusted hazard ratio, 1.55; P < .01). Conclusions. Anemia and red blood cell indices predict HAND in the HAART era and may contribute to risk assessment. Future studies should address whether treating anemia may help to prevent HAND or improve cognitive function in HIV-infected persons. PMID:26690344

  12. Prediction of consonant recognition in quiet for listeners with normal and impaired hearing using an auditory model.

    PubMed

    Jürgens, Tim; Ewert, Stephan D; Kollmeier, Birger; Brand, Thomas

    2014-03-01

    Consonant recognition was assessed in normal-hearing (NH) and hearing-impaired (HI) listeners in quiet as a function of speech level using a nonsense logatome test. Average recognition scores were analyzed and compared to recognition scores of a speech recognition model. In contrast to commonly used spectral speech recognition models operating on long-term spectra, a "microscopic" model operating in the time domain was used. Variations of the model (accounting for hearing impairment) and different model parameters (reflecting cochlear compression) were tested. Using these model variations this study examined whether speech recognition performance in quiet is affected by changes in cochlear compression, namely, a linearization, which is often observed in HI listeners. Consonant recognition scores for HI listeners were poorer than for NH listeners. The model accurately predicted the speech reception thresholds of the NH and most HI listeners. A partial linearization of the cochlear compression in the auditory model, while keeping audibility constant, produced higher recognition scores and improved the prediction accuracy. However, including listener-specific information about the exact form of the cochlear compression did not improve the prediction further.

  13. Major depressive episodes over the course of 7 years and hippocampal subfield volumes at 7 tesla MRI: the PREDICT-MR study.

    PubMed

    Wisse, L E M; Biessels, G J; Stegenga, B T; Kooistra, M; van der Veen, P H; Zwanenburg, J J M; van der Graaf, Y; Geerlings, M I

    2015-04-01

    Smaller hippocampal volumes have been associated with major depressive disorder (MDD). The hippocampus consists of several subfields that may be differentially related to MDD. We investigated the association of occurrence of major depressive episodes (MDEs), assessed five times over seven years, with hippocampal subfield and entorhinal cortex volumes at 7 tesla MRI. In this prospective study of randomly selected general practice attendees, MDEs according to DSM-IV-R criteria were assessed at baseline and after 6, 12, 39 and 84 months follow-up. At the last follow-up, a T2 (0.7 mm(3)) 7 tesla MRI scan was obtained in 47 participants (60±10 years). The subiculum, cornu ammonis (CA) 1 to 3, dentate gyrus&CA4 and entorhinal cortex volumes were manually segmented according a published protocol. Of the 47 participants, 13 had one MDE and 5 had multiple MDEs. ANCOVAs, adjusted for age, sex, education and intracranial volume, revealed no significant differences in hippocampal subfield or entorhinal cortex volumes between participants with and without an MDE in the preceding 84 months. Multiple episodes were associated with smaller subiculum volumes (B=-0.03 mL/episode; 95% CI -0.06; -0.003), but not with the other hippocampal subfield volumes, entorhinal cortex, or total hippocampal volume. A limitation of this study is the small sample size which makes replication necessary. In this exploratory study, we found that an increasing number of major depressive episodes was associated with smaller subiculum volumes in middle-aged and older persons, but not with smaller volumes in other hippocampal subfields or the entorhinal cortex. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Interhemispheric temporal lobe connectivity predicts language impairment in adolescents born preterm

    PubMed Central

    Northam, Gemma B.; Liégeois, Frédérique; Tournier, Jacques-Donald; Croft, Louise J.; Johns, Paul N.; Chong, Wui K.; Wyatt, John S.

    2012-01-01

    Although language difficulties are common in children born prematurely, robust neuroanatomical correlates of these impairments remain to be established. This study investigated whether the greater prevalence of language problems in preterm (versus term-born) children might reflect injury to major intra- or interhemispheric white matter pathways connecting frontal and temporal language regions. To investigate this, we performed a comprehensive assessment of language and academic abilities in a group of adolescents born prematurely, some of whom had evidence of brain injury at birth (n = 50, mean age: 16 years, mean gestational age: 27 weeks) and compared them to a term-born control group (n = 30). Detailed structural magnetic resonance imaging and diffusion-tractography analyses of intrahemispheric and interhemispheric white matter bundles were performed. Analysis of intrahemispheric pathways included the arcuate fasciculus (dorsal language pathway) and uncinate fasciculus/extreme capsule (ventral language pathway). Analysis of interhemispheric pathways (in particular, connections between the temporal lobes) included the two major commissural bundles: the corpus callosum and anterior commissure. We found language impairment in 38% of adolescents born preterm. Language impairment was not related to abnormalities of the arcuate fasciculus (or its subsegments), but was associated with bilateral volume reductions in the ventral language pathway. However, the most significant volume reduction was detected in the posterior corpus callosum (splenium), which contains interhemispheric connections between the occipital, parietal and temporal lobes. Diffusion tractography showed that of the three groups of interhemispheric fibres within the splenium, only those connecting the temporal lobes were reduced. Crucially, we found that language impairment was only detectable if the anterior commissure (a second temporal lobe commissural pathway) was also small. Regression analyses

  15. Predicting Progression from Mild Cognitive Impairment to Alzheimer's Dementia Using Clinical, MRI, and Plasma Biomarkers via Probabilistic Pattern Classification

    PubMed Central

    Korolev, Igor O.; Symonds, Laura L.; Bozoki, Andrea C.

    2016-01-01

    Background Individuals with mild cognitive impairment (MCI) have a substantially increased risk of developing dementia due to Alzheimer's disease (AD). In this study, we developed a multivariate prognostic model for predicting MCI-to-dementia progression at the individual patient level. Methods Using baseline data from 259 MCI patients and a probabilistic, kernel-based pattern classification approach, we trained a classifier to distinguish between patients who progressed to AD-type dementia (n = 139) and those who did not (n = 120) during a three-year follow-up period. More than 750 variables across four data sources were considered as potential predictors of progression. These data sources included risk factors, cognitive and functional assessments, structural magnetic resonance imaging (MRI) data, and plasma proteomic data. Predictive utility was assessed using a rigorous cross-validation framework. Results Cognitive and functional markers were most predictive of progression, while plasma proteomic markers had limited predictive utility. The best performing model incorporated a combination of cognitive/functional markers and morphometric MRI measures and predicted progression with 80% accuracy (83% sensitivity, 76% specificity, AUC = 0.87). Predictors of progression included scores on the Alzheimer's Disease Assessment Scale, Rey Auditory Verbal Learning Test, and Functional Activities Questionnaire, as well as volume/cortical thickness of three brain regions (left hippocampus, middle temporal gyrus, and inferior parietal cortex). Calibration analysis revealed that the model is capable of generating probabilistic predictions that reliably reflect the actual risk of progression. Finally, we found that the predictive accuracy of the model varied with patient demographic, genetic, and clinical characteristics and could be further improved by taking into account the confidence of the predictions. Conclusions We developed an accurate prognostic model for predicting

  16. Concordant parent-child reports of anxiety predict impairment in youth with functional abdominal pain.

    PubMed

    Cunningham, Natoshia R; Cohen, Mitchell B; Farrell, Michael K; Mezoff, Adam G; Lynch-Jordan, Anne; Kashikar-Zuck, Susmita

    2015-03-01

    Functional abdominal pain (FAP) is associated with significant anxiety and impairment. Prior investigations of child anxiety in youth with FAP are generally limited by small sample sizes, based on child report, and use lengthy diagnostic tools. It is unknown whether a brief anxiety-screening tool is feasible, whether parent and child reports of anxiety are congruent, and whether parent and child agreement of child anxiety corresponds to increased impairment. The purpose of this investigation was to examine anxiety characteristics in youth with FAP using parent and child reports. Parent-child agreement of child anxiety symptoms was examined in relation to pain and disability. One hundred patients with FAP (8-18 years of age) recruited from pediatric gastroenterology clinics completed measures of pain intensity (Numeric Rating Scale) and disability (Functional Disability Inventory). Patients and caregivers both completed a measure of child anxiety characteristics (Screen for Child Anxiety and Related Disorders). Clinically significant anxiety symptoms were more commonly reported by youth (54%) than their parents (30%). Panic/somatic symptoms, generalized anxiety, and separation anxiety were most commonly endorsed by patients, whereas generalized anxiety, separation anxiety, and school avoidance were most commonly reported by parents. The majority (65%) of parents and children agreed on the presence (26%) or absence (39%) of clinically significant anxiety. Parent-child agreement of clinically significant anxiety was related to increased impairment. A brief screening instrument of parent and child reports of anxiety can provide clinically relevant information for comprehensive treatment planning in children with FAP.

  17. Intraindividual Stepping Reaction Time Variability Predicts Falls in Older Adults With Mild Cognitive Impairment.

    PubMed

    Bunce, David; Haynes, Becky I; Lord, Stephen R; Gschwind, Yves J; Kochan, Nicole A; Reppermund, Simone; Brodaty, Henry; Sachdev, Perminder S; Delbaere, Kim

    2017-06-01

    Reaction time measures have considerable potential to aid neuropsychological assessment in a variety of health care settings. One such measure, the intraindividual reaction time variability (IIV), is of particular interest as it is thought to reflect neurobiological disturbance. IIV is associated with a variety of age-related neurological disorders, as well as gait impairment and future falls in older adults. However, although persons diagnosed with Mild Cognitive Impairment (MCI) are at high risk of falling, the association between IIV and prospective falls is unknown. We conducted a longitudinal cohort study in cognitively intact (n = 271) and MCI (n = 154) community-dwelling adults aged 70-90 years. IIV was assessed through a variety of measures including simple and choice hand reaction time and choice stepping reaction time tasks (CSRT), the latter administered as a single task and also with a secondary working memory task. Logistic regression did not show an association between IIV on the hand-held tasks and falls. Greater IIV in both CSRT tasks, however, did significantly increase the risk of future falls. This effect was specific to the MCI group, with a stronger effect in persons exhibiting gait, posture, or physiological impairment. The findings suggest that increased stepping IIV may indicate compromised neural circuitry involved in executive function, gait, and posture in persons with MCI increasing their risk of falling. IIV measures have potential to assess neurobiological disturbance underlying physical and cognitive dysfunction in old age, and aid fall risk assessment and routine care in community and health care settings.

  18. Frequent nocturia episodes, a suboptimal response to treatment, and small bladder capacity predict the need for persistent antimuscarinic therapy or re-treatment after discontinuation of antimuscarinics in female overactive bladder.

    PubMed

    Hsiao, Sheng-Mou; Chang, Ting-Chen; Chen, Chi-Hau; Wu, Wen-Yih; Lin, Ho-Hsiung

    2017-01-01

    The aim of the study was to investigate predictive factors of the need for persistent antimuscarinic therapy or re-treatment (PR) after discontinuation of antimuscarinic therapy for women with overactive bladder syndrome (OAB). All consecutive OAB women were enrolled in a prospective cohort study, and treated with solifenacin for 12 weeks in a University Hospital. Factors affecting PR were analyzed by Cox regression analysis. A total of 122 women were enrolled, and 107 women underwent 12-week solifenacin treatment. The dropout rate was 12.3%. The median follow-up period was 20.4 weeks (25-75 interquartile range: 16-102.3 wk). Twenty-seven (25%) women had PR. The median PR-free interval was 125.4 weeks (95% CI = 58.4 to - wk). Nocturia episodes (hazard ratio = 1.54), a suboptimal response (hazard ratio = 2.53), and the strong-desire volume (hazard ratio = 0.992) were independent predictors of PR by Cox backward stepwise regression analysis. The areas under the receiver-operating characteristic curves for nocturia episodes, a suboptimal response, and the strong-desire volume to predict PR were only 0.65, 0.63, and 0.59, respectively. In addition, normalized urinary nerve growth factor level was not significant (hazard ratio = 1.005, P = 0.68) for predicting PR. Furthermore, normalized urodynamic findings did not correlate with PR, a suboptimal response, or changes of Overactive Bladder Symptom Score and urinary nerve growth factor level. Frequent nocturia episodes, a suboptimal response, and small bladder capacity may predict PR after solifenacin treatment. These findings may serve as an initial guide in consultation regarding the treatment of OAB.

  19. Selective deficits in episodic feeling of knowing in ageing: a novel use of the general knowledge task.

    PubMed

    Morson, Suzannah M; Moulin, Chris J A; Souchay, Céline

    2015-05-01

    Failure to recall an item from memory can be accompanied by the subjective experience that the item is known but currently unavailable for report. The feeling of knowing (FOK) task allows measurement of the predictive accuracy of this reflective judgement. Young and older adults were asked to provide answers to general knowledge questions both prior to and after learning, thus measuring both semantic and episodic memory for the items. FOK judgements were made at each stage for all unrecalled responses, providing a measure of predictive accuracy for semantic and episodic knowledge. Results demonstrated a selective effect of age on episodic FOK resolution, with older adults found to have impaired episodic FOK accuracy while semantic FOK accuracy remained intact. Although recall and recognition measures of episodic memory are equivalent between the two age groups, older adults may have been unable to access contextual details on which to base their FOK judgements. The results suggest that older adults are not able to accurately predict future recognition of unrecalled episodic information, and consequently may have difficulties in monitoring recently encoded memories.

  20. FDG-PET measurement is more accurate than neuropsychological assessments to predict global cognitive deterioration in patients with mild cognitive impairment.

    PubMed

    Chételat, Gaël; Eustache, Francis; Viader, Fausto; De La Sayette, Vincent; Pélerin, Alice; Mézenge, Florence; Hannequin, Didier; Dupuy, Benoît; Baron, Jean-Claude; Desgranges, Béatrice

    2005-02-01

    The accurate prediction, at a pre-dementia stage of Alzheimer's disease (AD), of the subsequent clinical evolution of patients would be a major breakthrough from both therapeutic and research standpoints. Amnestic mild cognitive impairment (MCI) is presently the most common reference to address the pre-dementia stage of AD. However, previous longitudinal studies on patients with MCI assessing neuropsychological and PET markers of future conversion to AD are sparse and yield discrepant findings, while a comprehensive comparison of the relative accuracy of these two categories of measure is still lacking. In the present study, we assessed the global cognitive decline as measured by the Mattis scale in 18 patients with amnestic MCI over an 18-month follow-up period, studying which subtest of this scale showed significant deterioration over time. Using baseline measurements from neuropsychological evaluation of memory and PET, we then assessed significant markers of global cognitive change, that is, percent annual change in the Mattis scale total score, and searched for the best predictor of this global cognitive decline. Altogether, our results revealed significant decline over the 18-month follow-up period in the total score and the verbal initiation and memory-recall subscores of the Mattis scale. The percent annual change in the total Mattis score significantly correlated with age and baseline performances in delayed episodic memory recall as well as semantic autobiographical and category word fluencies. Regarding functional imaging, significant correlations were also found with baseline PET values in the right temporo-parietal and medial frontal areas. Age and right temporo-parietal PET values were the most significant predictors of subsequent global cognitive decline, and the only ones to survive stepwise regression analyses. Our findings are consistent with previous works showing predominant delayed recall and semantic memory impairment at a pre-dementia stage

  1. Neural Underpinnings of Impaired Predictive Motor Timing in Children with Developmental Coordination Disorder

    ERIC Educational Resources Information Center

    Debrabant, Julie; Gheysen, Freja; Caeyenberghs, Karen; Van Waelvelde, Hilde; Vingerhoets, Guy

    2013-01-01

    A dysfunction in predictive motor timing is put forward to underlie DCD-related motor problems. Predictive timing allows for the pre-selection of motor programmes (except "program" in computers) in order to decrease processing load and facilitate reactions. Using functional magnetic resonance imaging (fMRI), this study investigated the neural…

  2. Neural Underpinnings of Impaired Predictive Motor Timing in Children with Developmental Coordination Disorder

    ERIC Educational Resources Information Center

    Debrabant, Julie; Gheysen, Freja; Caeyenberghs, Karen; Van Waelvelde, Hilde; Vingerhoets, Guy

    2013-01-01

    A dysfunction in predictive motor timing is put forward to underlie DCD-related motor problems. Predictive timing allows for the pre-selection of motor programmes (except "program" in computers) in order to decrease processing load and facilitate reactions. Using functional magnetic resonance imaging (fMRI), this study investigated the neural…

  3. Can basic auditory and cognitive measures predict hearing-impaired listeners' localization and spatial speech recognition abilities?

    PubMed

    Neher, Tobias; Laugesen, Søren; Jensen, Niels Søgaard; Kragelund, Louise

    2011-09-01

    This study aimed to clarify the basic auditory and cognitive processes that affect listeners' performance on two spatial listening tasks: sound localization and speech recognition in spatially complex, multi-talker situations. Twenty-three elderly listeners with mild-to-moderate sensorineural hearing impairments were tested on the two spatial listening tasks, a measure of monaural spectral ripple discrimination, a measure of binaural temporal fine structure (TFS) sensitivity, and two (visual) cognitive measures indexing working memory and attention. All auditory test stimuli were spectrally shaped to restore (partial) audibility for each listener on each listening task. Eight younger normal-hearing listeners served as a control group. Data analyses revealed that the chosen auditory and cognitive measures could predict neither sound localization accuracy nor speech recognition when the target and maskers were separated along the front-back dimension. When the competing talkers were separated along the left-right dimension, however, speech recognition performance was significantly correlated with the attentional measure. Furthermore, supplementary analyses indicated additional effects of binaural TFS sensitivity and average low-frequency hearing thresholds. Altogether, these results are in support of the notion that both bottom-up and top-down deficits are responsible for the impaired functioning of elderly hearing-impaired listeners in cocktail party-like situations. © 2011 Acoustical Society of America

  4. Hepatic fat and abdominal adiposity in early pregnancy together predict impaired glucose homeostasis in mid-pregnancy

    PubMed Central

    De Souza, L R; Berger, H; Retnakaran, R; Vlachou, P A; Maguire, J L; Nathens, A B; Connelly, P W; Ray, J G

    2016-01-01

    Hepatic fat and abdominal adiposity individually reflect insulin resistance, but their combined effect on glucose homeostasis in mid-pregnancy is unknown. A cohort of 476 pregnant women prospectively underwent sonographic assessment of hepatic fat and visceral (VAT) and total (TAT) adipose tissue at 11–14 weeks' gestation. Logistic regression was used to assess the relation between the presence of maternal hepatic fat and/or the upper quartile (Q) of either VAT or TAT and the odds of developing the composite outcome of impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or gestational diabetes mellitus at 24–28 weeks' gestation, based on a 75 g OGTT. Upon adjusting for maternal age, ethnicity, family history of DM and body mass index (BMI), the co-presence of hepatic fat and quartile 4 (Q4) of VAT (adjusted odds ratio (aOR) 6.5, 95% CI: 2.3–18.5) or hepatic fat and Q4 of TAT (aOR 7.8 95% CI 2.8–21.7) were each associated with the composite outcome, relative to women with neither sonographic feature. First-trimester sonographic evidence of maternal hepatic fat and abdominal adiposity may independently predict the development of impaired glucose homeostasis and GDM in mid-pregnancy. PMID:27643724

  5. Fear of falling, but not gait impairment, predicts subjective memory complaints in cognitively intact older adults.

    PubMed

    Sakurai, Ryota; Suzuki, Hiroyuki; Ogawa, Susumu; Kawai, Hisashi; Yoshida, Hideyo; Hirano, Hirohiko; Ihara, Kazushige; Obuchi, Shuichi; Fujiwara, Yoshinori

    2017-07-01

    Understanding the risk factors for developing subjective memory complaints (SMC) could help with early screening and treatment for cognitive impairment. The aim of the present study was to explore the risk factors for developing SMC, by focusing on gait-related variables. A total of 406 community-dwelling older adults aged 65-85 years without impending cognitive impairment participated in baseline and 1-year follow-up evaluations. A comprehensive evaluation was carried out, and included gait speed and fear of falling (FoF) assessments, and the Montreal Cognitive Assessment test. Logistic regression analyses were carried out to independently evaluate the risk factors at baseline and follow-up evaluations. At baseline, 45.1% of older adults had SMC. The presence of SMC at baseline was associated with being female, subjective hearing loss and FoF. Of 223 participants who did not report SMC at baseline, 48 had newly developed SMC at follow up (21.5%). The significant predictors for developing SMC were being female and FoF, but not gait speed, and were independent of depression symptoms. The Montreal Cognitive Assessment total score at baseline was a marginally significant predictor for developing SMC at follow up (P = 0.06), but a lower score in the language domain was a significant predictor in further analysis. FoF was a significant risk for future development of SMC, suggesting that FoF might reflect the risk of cognitive impairment at an earlier stage, or that FoF and SMC could share the same basis of anxiety for daily activities. The mechanisms and consequence of this longitudinal relationship require further study. Geriatr Gerontol Int 2017; 17: 1125-1131. © 2016 Japan Geriatrics Society.

  6. Recruitment of medial prefrontal cortex neurons during alcohol withdrawal predicts cognitive impairment and excessive alcohol drinking

    PubMed Central

    George, Olivier; Sanders, Chelsea; Freiling, John; Grigoryan, Edward; Vu, Shayla; Allen, Camryn D.; Crawford, Elena; Mandyam, Chitra D.; Koob, George F.

    2012-01-01

    Chronic intermittent access to alcohol leads to the escalation of alcohol intake, similar to binge drinking in humans. Converging lines of evidence suggest that impairment of medial prefrontal cortex (mPFC) cognitive function and overactivation of the central nucleus of the amygdala (CeA) are key factors that lead to excessive drinking in dependence. However, the role of the mPFC and CeA in the escalation of alcohol intake in rats with a history of binge drinking without dependence is currently unknown. To address this issue, we examined FBJ murine osteosarcoma viral oncogene homolog (Fos) expression in the mPFC, CeA, hippocampus, and nucleus accumbens and evaluated working memory and anxiety-like behavior in rats given continuous (24 h/d for 7 d/wk) or intermittent (3 d/wk) access to alcohol (20% vol/vol) using a two-bottle choice paradigm. The results showed that abstinence from alcohol in rats with a history of escalation of alcohol intake specifically recruited GABA and corticotropin-releasing factor (CRF) neurons in the mPFC and produced working memory impairments associated with excessive alcohol drinking during acute (24–72 h) but not protracted (16 –68 d) abstinence. Moreover, abstinence from alcohol was associated with a functional disconnection of the mPFC and CeA but not mPFC and nucleus accumbens. These results show that recruitment of a subset of GABA and CRF neurons in the mPFC during withdrawal and disconnection of the PFC–CeA pathway may be critical for impaired executive control over motivated behavior, suggesting that dysregulation of mPFC interneurons may be an early index of neuroadaptation in alcohol dependence. PMID:23071333

  7. Concordant parent-child reports of anxiety predict impairment in youth with functional abdominal pain

    PubMed Central

    Cunningham, Natoshia Raishevich; Cohen, Mitchell B.; Farrell, Michael K.; Mezoff, Adam G.; Lynch-Jordan, Anne; Kashikar-Zuck, Susmita

    2014-01-01

    Introduction Functional abdominal pain (FAP) is associated with significant anxiety and impairment. Prior investigations of child anxiety in youth with FAP are generally limited by small sample sizes, based on child report, and use lengthy diagnostic tools. It is unknown 1) if a brief anxiety screening tool is feasible, 2) whether parent and child reports of anxiety are congruent, and 3) whether parent and child agreement of child anxiety corresponds to increased impairment. The purpose of this investigation was to examine anxiety characteristics in youth with FAP using parent and child reports. Parent-child agreement of child anxiety symptoms was examined in relation to pain and disability. Materials and Methods One-hundred patients with FAP (8-18 years of age) recruited from pediatric gastroenterology clinics completed measures of pain intensity (Numeric Rating Scale), and disability (Functional Disability Inventory). Patients and caregivers both completed a measure of child anxiety characteristics (Screen for Child Anxiety and Related Disorders). Results Clinically significant anxiety symptoms were more commonly reported by youth (54%) than their parents (30%). Panic/somatic symptoms, generalized anxiety, and separation anxiety were most commonly endorsed by patients whereas generalized anxiety, separation anxiety, and school avoidance were most commonly reported by parents. The majority (65%) of parents and children agreed on presence (26%) or absence (39%) of clinically significant anxiety. Parent-child agreement of clinically significant anxiety was related to increased impairment. Discussion A brief screening instrument of parent and child reports of anxiety can provide clinically relevant information for comprehensive treatment planning in children with FAP. PMID:25714575

  8. Impaired wound healing: facts and hypotheses for multi-professional considerations in predictive, preventive and personalised medicine.

    PubMed

    Avishai, Eden; Yeghiazaryan, Kristina; Golubnitschaja, Olga

    2017-03-01

    Whereas the physiologic wound healing (WH) successfully proceeds through the clearly defined sequence of the individual phases of wound healing, chronic non-healing wounds/ulcers fail to complete the individual stages and the entire healing process. There are many risk factors both modifiable (such as stress, smoking, inappropriate alcohol consumption, malnutrition, obesity, diabetes, cardio-vascular disease, etc.) and non-modifiable (such as genetic diseases and ageing) strongly contributing to the impaired WH. Current statistics demonstrate that both categories are increasingly presented in the populations, which causes dramatic socio-economic burden to the healthcare sector and society at large. Consequently, innovative concepts by predictive, preventive and personalised medicine are crucial to be implemented in the area. Individual risk factors, causality, functional interrelationships, molecular signature, predictive diagnosis, and primary and secondary prevention are thoroughly analysed followed by the expert recommendations in this paper.

  9. Impaired Spatio-Temporal Predictive Motor Timing Associated with Spinocerebellar Ataxia Type 6

    PubMed Central

    Onuki, Yoshiyuki; Abdelgabar, Abdel R.; Owens, Cullen B.; Picard, Samuel; Willems, Jessica; Boele, Henk-Jan; Gazzola, Valeria; Van der Werf, Ysbrand D.; De Zeeuw, Chris I.

    2016-01-01

    Many daily life activities demand precise integration of spatial and temporal information of sensory inputs followed by appropriate motor actions. This type of integration is carried out in part by the cerebellum, which has been postulated to play a central role in learning and timing of movements. Cerebellar damage due to atrophy or lesions may compromise forward-model processing, in which both spatial and temporal cues are used to achieve prediction for future motor states. In the present study we sought to further investigate the cerebellar contribution to predictive and reactive motor timing, as well as to learning of sequential order and temporal intervals in these tasks. We tested patients with spinocerebellar ataxia type 6 (SCA6) and healthy controls for two related motor tasks; one requiring spatio-temporal prediction of dynamic visual stimuli and another one requiring reactive timing only. We found that healthy controls established spatio-temporal prediction in their responses with high temporal precision, which was absent in the cerebellar patients. SCA6 patients showed lower predictive motor timing, coinciding with a reduced number of correct responses during the ‘anticipatory’ period on the task. Moreover, on the task utilizing reactive motor timing functions, control participants showed both sequence order and temporal interval learning, whereas patients only showed sequence order learning. These results suggest that SCA6 affects predictive motor timing and temporal interval learning. Our results support and highlight cerebellar contribution to timing and argue for cerebellar engagement during spatio-temporal prediction of upcoming events. PMID:27571363

  10. Validation of the R2CHADS2 and CHADS2 Scores for Predicting Post-stroke Cognitive Impairment.

    PubMed

    Washida, Kazuo; Kowa, Hisatomo; Hamaguchi, Hirotoshi; Kanda, Fumio; Toda, Tatsushi

    2017-09-15

    Objective Post-stroke cognitive impairment often afflicts stroke survivors and is a major obstacle both for cognitive and physical rehabilitation. Stroke risk scores ["Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, Stroke" (CHADS2) and "CHADS2 + creatinine clearance <60 mL/min" (R2CHADS2)] are used to assess the future risk of cardioembolic stroke in patients with atrial fibrillation (AF). However, congestive heart failure, hypertension, aging, diabetes mellitus, stroke, and renal dysfunction are also risk factors for cognitive impairment. Methods Sixty-two patients with nonvalvular AF-induced cardioembolic stroke underwent cognitive testing, including the Japanese version of the Montreal Cognitive Assessment (MoCA-J), Mini-Mental State Examination (MMSE), and Apathy Scale. The correlations between the MoCA-J/MMSE/Apathy Scale scores and stroke risk scores were examined. Results The average CHADS2 and R2CHADS2 scores were 4.1±1.0 and 5.6±1.6, respectively. The average MoCA-J, MMSE, and Apathy Scale scores were 17.4±6.2, 22.0±5.3, and 20.0±8.9, respectively. The CHADS2 and R2CHADS2 scores were negatively correlated with the MoCA-J/MMSE and positively correlated with the Apathy Scale. The R2CHADS2 score was more sensitive to poststroke cognitive impairment than the CHADS2 score. This correlation was stronger for MoCA-J than for MMSE, as the MMSE scores were skewed toward the higher end of the range. The results for individual MoCA-J and MMSE subtests indicated that the visuoexecutive, calculation, abstraction, and remote recall functions were significantly decreased after cardioembolic stroke. Conclusion These results suggest that the R2CHADS2 and CHADS2 scores are useful for predicting post-stroke cognitive impairment.

  11. [Episodic memory: from mind to brain].

    PubMed

    Tulving, E

    2004-04-01

    Episodic memory is a neurocognitive (brain/mind) system, uniquely different from other memory systems, that enables human beings to remember past experiences. The notion of episodic memory was first proposed some 30 Years ago. At that time it was defined in terms of materials and tasks. It was subsequently refined and elaborated in terms of ideas such as self, subjective time, and autonoetic consciousness. This chapter provides a brief history of the concept of episodic memory, describes how it has changed (indeed greatly changed) since its inception, considers criticisms of it, and then discusses supporting evidence provided by (a) neuropsychological studies of patterns of memory impairment caused by brain damage, and (b) functional neuroimaging studies of patterns of brain activity of normal subjects engaged in various memory tasks. I also suggest that episodic memory is a true, even if as yet generally unappreciated, marvel of nature.

  12. Episodic memory: from mind to brain.

    PubMed

    Tulving, Endel

    2002-01-01

    Episodic memory is a neurocognitive (brain/mind) system, uniquely different from other memory systems, that enables human beings to remember past experiences. The notion of episodic memory was first proposed some 30 years ago. At that time it was defined in terms of materials and tasks. It was subsequently refined and elaborated in terms of ideas such as self, subjective time, and autonoetic consciousness. This chapter provides a brief history of the concept of episodic memory, describes how it has changed (indeed greatly changed) since its inception, considers criticisms of it, and then discusses supporting evidence provided by (a) neuropsychological studies of patterns of memory impairment caused by brain damage, and (b) functional neuroimaging studies of patterns of brain activity of normal subjects engaged in various memory tasks. I also suggest that episodic memory is a true, even if as yet generally unappreciated, marvel of nature.

  13. Dynamic testing of learning potential in adults with cognitive impairments: A systematic review of methodology and predictive value.

    PubMed

    Boosman, Hileen; Bovend'Eerdt, Thamar J H; Visser-Meily, Johanna M A; Nijboer, Tanja C W; van Heugten, Caroline M

    2016-09-01

    Dynamic testing includes procedures that examine the effects of brief training on test performance where pre- to post-training change reflects patients' learning potential. The objective of this systematic review was to provide clinicians and researchers insight into the concept and methodology of dynamic testing and to explore its predictive validity in adult patients with cognitive impairments. The following electronic databases were searched: PubMed, PsychINFO, and Embase/Medline. Of 1141 potentially relevant articles, 24 studies met the inclusion criteria. The mean methodological quality score was 4.6 of 8. Eleven different dynamic tests were used. The majority of studies used dynamic versions of the Wisconsin Card Sorting Test. The training mostly consisted of a combination of performance feedback, reinforcement, expanded instruction, or strategy training. Learning potential was quantified using numerical (post-test score, difference score, gain score, regression residuals) and categorical (groups) indices. In five of six longitudinal studies, learning potential significantly predicted rehabilitation outcome. Three of four studies supported the added value of dynamic testing over conventional testing in predicting rehabilitation outcome. This review provides preliminary support that dynamic tests can provide a valuable addition to conventional tests to assess patients' abilities. Although promising, there was a large variability in methods used for dynamic testing and, therefore, it remains unclear which dynamic testing methods are most appropriate for patients with cognitive impairments. More research is warranted to further evaluate and refine dynamic testing methodology and to further elucidate its predictive validity concerning rehabilitation outcomes relative to other cognitive and functional status indices.

  14. DWI and complex brain network analysis predicts vascular cognitive impairment in spontaneous hypertensive rats undergoing executive function tests

    PubMed Central

    López-Gil, Xavier; Amat-Roldan, Iván; Tudela, Raúl; Castañé, Anna; Prats-Galino, Alberto; Planas, Anna M.; Farr, Tracy D.; Soria, Guadalupe

    2014-01-01

    The identification of biomarkers of vascular cognitive impairment is urgent for its early diagnosis. The aim of this study was to detect and monitor changes in brain structure and connectivity, and to correlate them with the decline in executive function. We examined the feasibility of early diagnostic magnetic resonance imaging (MRI) to predict cognitive impairment before onset in an animal model of chronic hypertension: Spontaneously Hypertensive Rats. Cognitive performance was tested in an operant conditioning paradigm that evaluated learning, memory, and behavioral flexibility skills. Behavioral tests were coupled with longitudinal diffusion weighted imaging acquired with 126 diffusion gradient directions and 0.3 mm3 isometric resolution at 10, 14, 18, 22, 26, and 40 weeks after birth. Diffusion weighted imaging was analyzed in two different ways, by regional characterization of diffusion tensor imaging (DTI) indices, and by assessing changes in structural brain network organization based on Q-Ball tractography. Already at the first evaluated times, DTI scalar maps revealed significant differences in many regions, suggesting loss of integrity in white and gray matter of spontaneously hypertensive rats when compared to normotensive control rats. In addition, graph theory analysis of the structural brain network demonstrated a significant decrease of hierarchical modularity, global and local efficacy, with predictive value as shown by regional three-fold cross validation study. Moreover, these decreases were significantly correlated with the behavioral performance deficits observed at subsequent time points, suggesting that the diffusion weighted imaging and connectivity studies can unravel neuroimaging alterations even overt signs of cognitive impairment become apparent. PMID:25100993

  15. White matter diffusivity predicts memory in patients with subjective and mild cognitive impairment and normal CSF total tau levels.

    PubMed

    Grambaite, Ramune; Stenset, Vidar; Reinvang, Ivar; Walhovd, Kristine B; Fjell, Anders M; Fladby, Tormod

    2010-01-01

    Subjective and mild cognitive impairment (SCI and MCI) are etiologically heterogeneous conditions. This poses problems for assessment of pathophysiological mechanisms and risk of conversion to dementia. Neuropsychological, imaging, and cerebrospinal fluid (CSF) findings serve to distinguish Alzheimer's disease (AD) and other etiological subgroups. Tau-molecules stabilize axonal microtubuli; high CSF total tau (T-tau) reflects ongoing axonal damage consistent with AD. Here, we stratify patients by CSF T-tau pathology to determine if memory network diffusion tensor imaging (DTI) predicts memory performance in the absence of elevated T-tau. We analyzed neuropsychological test results, hippocampus volume (HcV) and white matter diffusivity in 45 patients (35 with normal T-tau). The T-tau pathology group showed more hippocampus atrophy and memory impairment than the normal T-tau group. In the T-tau normal group: (1) memory was related with white matter diffusivity [fractional anisotropy (FA) and radial diffusivity (DR)], and (2) FA of the genu corpus callosum was a unique predictor of variance for verbal learning, and HcV did not contribute to this prediction. The smaller sample size in the T-tau pathology group precludes firm conclusions. In the normal T-tau group, white matter tract and memory changes may be associated with normal aging, or with non-tau related pathological mechanisms.

  16. Weight Loss Predicts Progression of Mild Cognitive Impairment to Alzheimer's Disease.

    PubMed

    Cova, Ilaria; Clerici, Francesca; Rossi, Annalia; Cucumo, Valentina; Ghiretti, Roberta; Maggiore, Laura; Pomati, Simone; Galimberti, Daniela; Scarpini, Elio; Mariani, Claudio; Caracciolo, Barbara

    2016-01-01

    Weight loss is common in people with Alzheimer's disease (AD) and it could be a marker of impending AD in Mild Cognitive Impairment (MCI) and improve prognostic accuracy, if accelerated progression to AD would be shown. To assess weight loss as a predictor of dementia and AD in MCI. One hundred twenty-five subjects with MCI (age 73.8 ± 7.1 years) were followed for an average of 4 years. Two weight measurements were carried out at a minimum time interval of one year. Dementia was defined according to DSM-IV criteria and AD according to NINCDS-ADRDA criteria. Weight loss was defined as a ≥4% decrease in baseline weight. Fifty-three (42.4%) MCI progressed to dementia, which was of the AD-type in half of the cases. Weight loss was associated with a 3.4-fold increased risk of dementia (95% CI = 1.5-6.9) and a 3.2-fold increased risk of AD (95% CI = 1.4-8.3). In terms of years lived without disease, weight loss was associated to a 2.3 and 2.5 years earlier onset of dementia and AD. Accelerated progression towards dementia and AD is expected when weight loss is observed in MCI patients. Weight should be closely monitored in elderly with mild cognitive impairment.

  17. Weight Loss Predicts Progression of Mild Cognitive Impairment to Alzheimer’s Disease

    PubMed Central

    Cova, Ilaria; Rossi, Annalia; Cucumo, Valentina; Ghiretti, Roberta; Maggiore, Laura; Pomati, Simone; Galimberti, Daniela; Scarpini, Elio; Mariani, Claudio; Caracciolo, Barbara

    2016-01-01

    Background Weight loss is common in people with Alzheimer’s disease (AD) and it could be a marker of impending AD in Mild Cognitive Impairment (MCI) and improve prognostic accuracy, if accelerated progression to AD would be shown. Aims To assess weight loss as a predictor of dementia and AD in MCI. Methods One hundred twenty-five subjects with MCI (age 73.8 ± 7.1 years) were followed for an average of 4 years. Two weight measurements were carried out at a minimum time interval of one year. Dementia was defined according to DSM-IV criteria and AD according to NINCDS-ADRDA criteria. Weight loss was defined as a ≥4% decrease in baseline weight. Results Fifty-three (42.4%) MCI progressed to dementia, which was of the AD-type in half of the cases. Weight loss was associated with a 3.4-fold increased risk of dementia (95% CI = 1.5–6.9) and a 3.2-fold increased risk of AD (95% CI = 1.4–8.3). In terms of years lived without disease, weight loss was associated to a 2.3 and 2.5 years earlier onset of dementia and AD. Conclusions Accelerated progression towards dementia and AD is expected when weight loss is observed in MCI patients. Weight should be closely monitored in elderly with mild cognitive impairment. PMID:26990757

  18. Increased hippocampal accumulation of autophagosomes predicts short-term recognition memory impairment in aged mice.

    PubMed

    Soontornniyomkij, Virawudh; Risbrough, Victoria B; Young, Jared W; Soontornniyomkij, Benchawanna; Jeste, Dilip V; Achim, Cristian L

    2012-04-01

    Constitutive macroautophagy involved in the turnover of defective long-lived proteins and organelles is crucial for neuronal homeostasis. We hypothesized that macroautophagic dysregulation in selective brain regions was associated with memory impairment in aged mice. We used the single-trial object recognition test to measure short-term memory in 18 aged mice compared to 22 young mice and employed immunohistochemistry to assess cellular distribution of proteins involved in the selective degradation of ubiquitinated proteins via macroautophagy. Values of the discrimination ratio (DR, a measure of short-term recognition memory performance) in aged mice were significantly lower than those in young mice (median, 0.54 vs. 0.67; p = 0.005, U test). Almost exclusively in aged mice, there were clusters of puncta immunoreactive for microtubule-associated protein 1 light chain 3 (LC3), ubiquitin- and LC3-binding protein p62, and ubiquitin in neuronal processes predominantly in the hippocampal formation, olfactory bulb/tubercle, and cerebellar cortex. The hippocampal burden of clustered puncta immunoreactive for LC3 and p62 exhibited inverse linear correlations with DR in aged mice (ρ = -0.48 and -0.55, p = 0.044 and 0.018, respectively, Spearman's rank correlation). These findings suggest that increased accumulation of autophagosomes within neuronal processes in selective brain regions is characteristic of aging. The dysregulation of macroautophagy can adversely affect the turnover of aggregate-prone proteins and defective organelles, which may contribute to memory impairment in aged mice.

  19. An evaluation of volume-based morphometry for prediction of mild cognitive impairment and Alzheimer's disease

    PubMed Central

    Schmitter, Daniel; Roche, Alexis; Maréchal, Bénédicte; Ribes, Delphine; Abdulkadir, Ahmed; Bach-Cuadra, Meritxell; Daducci, Alessandro; Granziera, Cristina; Klöppel, Stefan; Maeder, Philippe; Meuli, Reto; Krueger, Gunnar

    2014-01-01

    Voxel-based morphometry from conventional T1-weighted images has proved effective to quantify Alzheimer's disease (AD) related brain atrophy and to enable fairly accurate automated classification of AD patients, mild cognitive impaired patients (MCI) and elderly controls. Little is known, however, about the classification power of volume-based morphometry, where features of interest consist of a few brain structure volumes (e.g. hippocampi, lobes, ventricles) as opposed to hundreds of thousands of voxel-wise gray matter concentrations. In this work, we experimentally evaluate two distinct volume-based morphometry algorithms (FreeSurfer and an in-house algorithm called MorphoBox) for automatic disease classification on a standardized data set from the Alzheimer's Disease Neuroimaging Initiative. Results indicate that both algorithms achieve classification accuracy comparable to the conventional whole-brain voxel-based morphometry pipeline using SPM for AD vs elderly controls and MCI vs controls, and higher accuracy for classification of AD vs MCI and early vs late AD converters, thereby demonstrating the potential of volume-based morphometry to assist diagnosis of mild cognitive impairment and Alzheimer's disease. PMID:25429357

  20. [Bipolar disorder: inter-episode symptoms].

    PubMed

    Azorin, J-M

    2012-12-01

    The importance of inter-episode symptoms in bipolar disorder can be traced back to the middle of the 19th century, at a time when the two fathers of the concept in France, Falret and Baillarger were opposed on the issue as to whether the presence of free intervals between the episodes had to be part or not of the disease's definition. Modern studies have reported rates between 50 and 68% for those symptoms which refer to subsyndromal manifestations present between affective episodes but that do not meet the required criteria for episodes definition. These manifestations comprise residual symptoms, prodromes, axis I comorbid psychiatric disorders, side effects of treatment, temperamental features, and comorbidity with personality disorders. Inter- episodes symptoms represent a risk factor for the occurrence of relapses and recurrences and are usually associated with impairments in functioning in almost all domains of psychosocial and family life. As they are easy to miss, it is important in clinical practice, to draw the attention of clinicians, patients and relatives to the role they have in the course of the illness. As far as their management, it may be crucial to achieve a full remission of the episodes, using adequate dosages of psychotropic drugs. Residual symptoms, prodromes as well as other inter-episode symptoms may respond to strategies based on cognitive-behaviour therapy, and/or psychoeducation.

  1. Does chronic idiopathic dizziness reflect an impairment of sensory predictions of self-motion?

    PubMed

    Pomper, Jörn K; Gebert, Lena; Fischer, Matthias; Bunjes, Friedemann; Thier, Peter

    2013-01-01

    Most patients suffering from chronic idiopathic dizziness do not present signs of vestibular dysfunction or organic failures of other kinds. Hence, this kind of dizziness is commonly seen as psychogenic in nature, sharing commonalities with specific phobias, panic disorder, and generalized anxiety. A more specific concept put forward by Brandt and Dieterich (1) states that these patients suffer from dizziness because of an inadequate compensation of self-induced sensory stimulation. According to this hypothesis self-motion-induced reafferent visual stimulation is interpreted as motion in the world since a predictive signal reflecting the consequences of self-motion, needed to compensate the reafferent stimulus, is inadequate. While conceptually intriguing, experimental evidence supporting the idea of an inadequate prediction of the sensory consequences of own movements has as yet been lacking. Here we tested this hypothesis by applying it to the perception of background motion induced by smooth pursuit eye movements. As a matter of fact, we found the same mildly undercompensating prediction, responsible for the perception of slight illusory world motion ("Filehne illusion") in the 15 patients tested and their age-matched controls. Likewise, the ability to adapt this prediction to the needs of the visual context was not deteriorated in patients. Finally, we could not find any correlation between measures of the individual severity of dizziness and the ability to predict. In sum, our results do not support the concept of a deviant prediction of self-induced sensory stimulation as cause of chronic idiopathic dizziness.

  2. Alcohol-Induced Disinhibition Expectancies and Impaired Control as Prospective Predictors of Problem Drinking in Undergraduates

    PubMed Central

    Leeman, Robert F.; Toll, Benjamin A.; Taylor, Laura A.; Volpicelli, Joseph R.

    2009-01-01

    Trait disinhibition is associated with problem drinking and alcohol drinking itself can bring about a state of disinhibition. It is unclear however, if expectancies of alcohol-induced disinhibition are unique predictors of problem drinking. Impaired control (i.e., difficulty in limiting alcohol consumption) may be related to disinhibition expectancies in that both involve issues of control related to alcohol use. Data from a prospective survey of undergraduates assessed during freshman (N = 337) and senior year (N = 201) were analyzed to determine whether subscales of the Drinking-Induced Disinhibition Scale and the Impaired Control Scale predicted unique variance in heavy episodic drinking and alcohol-related problems. In Time 1 cross-sectional models, dysphoric disinhibition expectancies predicted alcohol-related problems and impaired control predicted both alcohol-related problems and heavy episodic drinking. In prospective models, Time 1 impaired control predicted Time 2 alcohol-related problems and Time 1 euphoric/social disinhibition expectancies predicted Time 2 heavy episodic drinking. These findings suggest that expectancies of alcohol-induced disinhibition and impaired control predict unique variance in problem drinking cross-sectionally and prospectively and that these phenomena should be targeted in early intervention efforts. PMID:20025361

  3. Alcohol-induced disinhibition expectancies and impaired control as prospective predictors of problem drinking in undergraduates.

    PubMed

    Leeman, Robert F; Toll, Benjamin A; Taylor, Laura A; Volpicelli, Joseph R

    2009-12-01

    Trait disinhibition is associated with problem drinking and alcohol drinking can bring about a state of disinhibition. It is unclear however, if expectancies of alcohol-induced disinhibition are unique predictors of problem drinking. Impaired control (i.e., difficulty in limiting alcohol consumption) may be related to disinhibition expectancies in that both involve issues of control related to alcohol use. Data from a prospective survey of undergraduates assessed during freshman (N = 337) and senior year (N = 201) were analyzed to determine whether subscales of the Drinking-Induced Disinhibition Scale (Leeman, Toll, & Volpicelli, 2007) and the Impaired Control Scale (Heather et al., 1993) predicted unique variance in heavy episodic drinking and alcohol-related problems. In Time 1 cross-sectional models, Dysphoric disinhibition expectancies predicted alcohol-related problems and impaired control predicted both alcohol-related problems and heavy episodic drinking. In prospective models, Time 1 impaired control predicted Time 2 alcohol-related problems and Time 1 Euphoric/social Disinhibition expectancies predicted Time 2 heavy episodic drinking. These findings suggest that expectancies of alcohol-induced disinhibition and impaired control predict unique variance in problem drinking cross-sectionally and prospectively, and that these phenomena should be targeted in early intervention efforts. Copyright 2009 APA

  4. Sequential Prediction of Literacy Achievement for Specific Learning Disabilities Contrasting in Impaired Levels of Language in Grades 4 to 9.

    PubMed

    Sanders, Elizabeth A; Berninger, Virginia W; Abbott, Robert D

    2017-02-01

    Sequential regression was used to evaluate whether language-related working memory components uniquely predict reading and writing achievement beyond cognitive-linguistic translation for students in Grades 4 through 9 ( N = 103) with specific learning disabilities (SLDs) in subword handwriting (dysgraphia, n = 25), word reading and spelling (dyslexia, n = 60), or oral and written language (oral and written language learning disabilities, n = 18). That is, SLDs are defined on the basis of cascading level of language impairment (subword, word, and syntax/text). A five-block regression model sequentially predicted literacy achievement from cognitive-linguistic translation (Block 1); working memory components for word-form coding (Block 2), phonological and orthographic loops (Block 3), and supervisory focused or switching attention (Block 4); and SLD groups (Block 5). Results showed that cognitive-linguistic translation explained an average of 27% and 15% of the variance in reading and writing achievement, respectively, but working memory components explained an additional 39% and 27% of variance. Orthographic word-form coding uniquely predicted nearly every measure, whereas attention switching uniquely predicted only reading. Finally, differences in reading and writing persisted between dyslexia and dysgraphia, with dysgraphia higher, even after controlling for Block 1 to 4 predictors. Differences in literacy achievement between students with dyslexia and oral and written language learning disabilities were largely explained by the Block 1 predictors. Applications to identifying and teaching students with these SLDs are discussed.

  5. Prediction of pre-exam state anxiety from ruminative disposition: The mediating role of impaired attentional disengagement from negative information.

    PubMed

    Vălenaş, Sergiu P; Szentágotai-Tătar, Aurora; Grafton, Ben; Notebaert, Lies; Miu, Andrei C; MacLeod, Colin

    2017-04-01

    Rumination is a maladaptive form of repetitive thinking that enhances stress responses, and heightened disposition to engage in rumination may contribute to the onset and persistence of stress-related symptoms. However, the cognitive mechanisms through which ruminative disposition influences stress reactivity are not yet fully understood. This study investigated the hypothesis that the impact of ruminative disposition on stress reactivity is carried by an attentional bias reflecting impaired attentional disengagement from negative information. We examined the capacity of a measure of ruminative disposition to predict both attentional biases to negative exam-related information, and state anxiety, in students approaching a mid-term exam. As expected, ruminative disposition predicted state anxiety, over and above the level predicted by trait anxiety. Ruminative disposition also predicted biased attentional disengagement from, but not biased attentional engagement with, negative information. Importantly, biased attentional disengagement from negative information mediated the relation between ruminative disposition and state anxiety. These findings confirm that dispositional rumination is associated with difficulty disengaging attention from negative information, and suggest that this attentional bias may be one of the mechanisms through which ruminative disposition influences stress reactivity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Predicting early spelling difficulties in children with specific language impairment: a clinical perspective.

    PubMed

    Cordewener, Kim A H; Bosman, Anna M T; Verhoeven, Ludo

    2012-01-01

    This study focused on the precursors of spelling difficulties in first grade for children with specific language impairment (SLI). A sample of 58 second-year kindergartners in The Netherlands was followed until the end of first grade. Linguistic, phonological, orthographic, letter knowledge, memory, and nonverbal-reasoning skills were considered as precursors, as was spelling level at an earlier point in time. Spelling difficulties at the end of first grade were most accurately identified by letter knowledge at the beginning of first grade and word spelling at the middle of first grade. It is concluded that spelling development in children with SLI can be seen as an autocatalytic process in which, without intervention, poor spellers generally remain poor spellers, and good spellers remain good spellers. A focus on early spelling intervention is thus emphasized. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Predicting angiography-induced acute renal function impairment: clinical risk model

    SciTech Connect

    Cochran, S.T.; Wong, W.S.; Roe, D.J.

    1983-11-01

    Two hundred sixty-six patients were evaluated for development of acute renal function impairment after renal angiography. Forty-five (16.9%) had a significant increase in serum level of creatinine (sCr), six developed oliguria or anuria, and one required permanent dialysis. Age, proteinuria, abnormal baseline sCr, use of Renografin 76, and preexisting renal disease were the five independent risk factors in the series. An odds-ratio analysis establishes the relative risk (i.e., likelihood) of developing acute renal insufficientcy after renal angiography on the basis of the number of risk factors present. An increasing relation was demonstrated; the more factors present, the more likely it becomes that a patient will develop acute renal insufficiency.

  8. Pituitary Macroadenoma and Visual Impairment: Postoperative Outcome Prediction with Contrast-Enhanced FIESTA.

    PubMed

    Hisanaga, S; Kakeda, S; Yamamoto, J; Watanabe, K; Moriya, J; Nagata, T; Fujino, Y; Kondo, H; Nishizawa, S; Korogi, Y

    2017-09-14

    Contrast-enhanced FIESTA can depict anterior optic pathways in patients with large suprasellar tumors. We assessed whether the degree of kink in the optic nerve at the optic canal orifice on contrast-enhanced FIESTA correlates with the postoperative improvement of visual impairment in patients with pituitary macroadenoma. Thirty-one patients with pituitary macroadenoma who underwent preoperative MR imaging and an operation were evaluated. We measured the optic nerve kinking angle on sagittal oblique contrast-enhanced FIESTA parallel to the optic nerve; the optic nerve kinking angle was defined as the angle between a line parallel to the planum sphenoidale and a line parallel to the intracranial optic nerve at the optic canal orifice. We used logistic regression analyses to determine whether the clinical (sex, age, and duration of symptoms) and imaging (tumor height, chiasmal compression severity, hyperintense optic nerve on T2WI, and optic nerve kinking angle) characteristics were associated with the postoperative improvement (good-versus-little improvement) of visual acuity disturbance and visual field defect. There were 53 impaired sides before the operation: 2 sides with visual acuity disturbance alone, 25 with visual field defect alone, and 26 with both. After the operation, good improvement was found in 17 of the 28 sides with visual acuity disturbance and in 32 of the 51 sides with visual field defects. Only the optic nerve kinking angle was significantly associated with good improvement of the visual acuity disturbance (P = .011) and visual field defect (P = .002). The degree of the optic nerve kinking angle was an independent predictor of postoperative improvement, indicating that irreversible damage to the optic nerve may be associated with its kinking at the optic canal orifice. © 2017 American Society of Neuroradiology.

  9. Early postnatal Illness severity scores predict neurodevelopmental impairments at 10 years of age in children born extremely preterm

    PubMed Central

    Logan, J. Wells; Dammann, Olaf; Allred, Elizabeth N.; Dammann, Christiane; Beam, Kristyn; Joseph, Robert M.; O'Shea, T. Michael; Leviton, Alan; Kuban, Karl C. K.

    2016-01-01

    Introduction A neonatal illness severity score, The Score for Neonatal Acute Physiology-II (SNAP-II), predicts neurodevelopmental impairments at two years of age among children born extremely preterm. We sought to evaluate to what extent SNAP-II is predictive of cognitive and other neurodevelopmental impairments at 10 years of age. Methods In a cohort of 874 children born before 28 weeks of gestation, we prospectively collected clinical, physiologic and laboratory data to calculate SNAP-II for each infant. When the children were 10 years old, examiners who were unaware of the child's medical history assessed neurodevelopmental outcomes, including neurocognitive, gross motor, social, and communication functions, diagnosis and treatment of seizures or attention deficit hyperactivity disorder (ADHD), academic achievement, and quality of life. We used logistic regression to adjust for potential confounders. Results An undesirably high SNAP-II (≥ 30), present in 23% of participants, was associated with an increased risk of cognitive impairment (IQ, executive function, language ability), adverse neurological outcomes (epilepsy, impaired gross motor function), behavioral abnormalities (attention deficit disorder and hyperactivity), social dysfunction (autistic spectrum disorder) and education-related adversities (school achievement and need for educational supports. In analyses that adjusted for potential confounders, Z-scores ≤ -1 on 11 of 18 cognitive outcomes were associated with SNAP-II in the highest category and 6 of 18 were associated with SNAP-II in the intermediate category. Odds ratios and 95% confidence intervals ranged from 1.4 (1.01, 2.1) to 2.1 (1.4, 3.1). Similarly, 2 of the 8 social dysfunctions were associated with SNAP-II in the highest category, and 3 of 8 were associated with SNAP-II in the intermediate category. Odds ratios and 95% confidence intervals were slightly higher for these assessments, ranging from 1.6 (1.1, 2.4) to 2.3 (1.2, 4

  10. Early postnatal illness severity scores predict neurodevelopmental impairments at 10 years of age in children born extremely preterm.

    PubMed

    Logan, J W; Dammann, O; Allred, E N; Dammann, C; Beam, K; Joseph, R M; O'Shea, T M; Leviton, A; Kuban, K C K

    2017-05-01

    A neonatal illness severity score, The Score for Neonatal Acute Physiology-II (SNAP-II), predicts neurodevelopmental impairments at two years of age among children born extremely preterm. We sought to evaluate to what extent SNAP-II is predictive of cognitive and other neurodevelopmental impairments at 10 years of age. In a cohort of 874 children born before 28 weeks of gestation, we prospectively collected clinical, physiologic and laboratory data to calculate SNAP-II for each infant. When the children were 10 years old, examiners who were unaware of the child's medical history assessed neurodevelopmental outcomes, including neurocognitive, gross motor, social and communication functions, diagnosis and treatment of seizures or attention deficit hyperactivity disorder (ADHD), academic achievement, and quality of life. We used logistic regression to adjust for potential confounders. An undesirably high SNAP-II (⩾30), present in 23% of participants, was associated with an increased risk of cognitive impairment (IQ, executive function, language ability), adverse neurological outcomes (epilepsy, impaired gross motor function), behavioral abnormalities (attention deficit disorder and hyperactivity), social dysfunction (autistic spectrum disorder) and education-related adversities (school achievement and need for educational supports. In analyses that adjusted for potential confounders, Z-scores ⩽-1 on 11 of 18 cognitive outcomes were associated with SNAP-II in the highest category, and 6 of 18 were associated with SNAP-II in the intermediate category. Odds ratios and 95% confidence intervals ranged from 1.4 (1.01, 2.1) to 2.1 (1.4, 3.1). Similarly, 2 of the 8 social dysfunctions were associated with SNAP-II in the highest category, and 3 of 8 were associated with SNAP-II in the intermediate category. Odds ratios and 95% confidence intervals were slightly higher for these assessments, ranging from 1.6 (1.1, 2.4) to 2.3 (1.2, 4.6). Among very preterm newborns

  11. Anemia and Red Blood Cell Indices Predict HIV-Associated Neurocognitive Impairment in the Highly Active Antiretroviral Therapy Era.

    PubMed

    Kallianpur, Asha R; Wang, Quan; Jia, Peilin; Hulgan, Todd; Zhao, Zhongming; Letendre, Scott L; Ellis, Ronald J; Heaton, Robert K; Franklin, Donald R; Barnholtz-Sloan, Jill; Collier, Ann C; Marra, Christina M; Clifford, David B; Gelman, Benjamin B; McArthur, Justin C; Morgello, Susan; Simpson, David M; McCutchan, J A; Grant, Igor

    2016-04-01

    Anemia has been linked to adverse human immunodeficiency virus (HIV) outcomes, including dementia, in the era before highly active antiretroviral therapy (HAART). Milder forms of HIV-associated neurocognitive disorder (HAND) remain common in HIV-infected persons, despite HAART, but whether anemia predicts HAND in the HAART era is unknown. We evaluated time-dependent associations of anemia and cross-sectional associations of red blood cell indices with neurocognitive impairment in a multicenter, HAART-era HIV cohort study (N = 1261), adjusting for potential confounders, including age, nadir CD4(+) T-cell count, zidovudine use, and comorbid conditions. Subjects underwent comprehensive neuropsychiatric and neuromedical assessments. HAND, defined according to standardized criteria, occurred in 595 subjects (47%) at entry. Mean corpuscular volume and mean corpuscular hemoglobin were positively associated with the global deficit score, a continuous measure of neurocognitive impairment (both P < .01), as well as with all HAND, milder forms of HAND, and HIV-associated dementia in multivariable analyses (all P < .05). Anemia independently predicted development of HAND during a median follow-up of 72 months (adjusted hazard ratio, 1.55; P < .01). Anemia and red blood cell indices predict HAND in the HAART era and may contribute to risk assessment. Future studies should address whether treating anemia may help to prevent HAND or improve cognitive function in HIV-infected persons. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  12. Use of the Cognitive Performance Scale (CPS) to detect cognitive impairment in the acute care setting: concurrent and predictive validity.

    PubMed

    Büla, Christophe J; Wietlisbach, Vincent

    2009-10-28

    The Cognitive Performance Scale (CPS) was initially designed to assess cognition in long term care residents. Subsequently, the CPS has also been used among in-home, post-acute, and acute care populations even though CPS' clinimetric performance has not been studied in these settings. This study aimed to determine CPS agreement with the Mini Mental Status Exam (MMSE) and its predictive validity for institutionalization and death in a cohort (N=401) of elderly medical inpatients aged 75 years and over. Medical, physical and mental status were assessed upon admission. The same day, the patient's nurse completed the CPS by interview. Follow-up data were gathered from the central billing system (nursing home stay) and proxies (death). Cognitive impairment was present in 92 (23%) patients according to CPS (score >or= 2). Agreement with MMSE was moderate (kappa 0.52, P<.001). Analysis of discordant results suggested that cognitive impairment was overestimated by the CPS in dependent patients with comorbidities and depressive symptoms, and underestimated in older ones. During follow-up, subjects with abnormal CPS had increased risks of death (adjusted hazard ratio (adjHR) 1.7, 95% CI 1.0-2.8, P=.035) and institutionalization (adjHR 2.7, 95% CI 1.3-5.3, P=.006), independent of demographic, health and functional status. Interestingly, subjects with abnormal CPS were at increased risk of death only if they also had abnormal MMSE. The CPS predicted death and institutionalization during follow-up, but correlated moderately well with the MMSE. Combining CPS and MMSE provided additional predictive information, suggesting that domains other than cognition are assessed by professionals when using the CPS in elderly medical inpatients.

  13. Development and validation of clinical prediction models for mortality, functional outcome and cognitive impairment after stroke: a study protocol.

    PubMed

    Fahey, Marion; Rudd, Anthony; Béjot, Yannick; Wolfe, Charles; Douiri, Abdel

    2017-08-18

    Stroke is a leading cause of adult disability and death worldwide. The neurological impairments associated with stroke prevent patients from performing basic daily activities and have enormous impact on families and caregivers. Practical and accurate tools to assist in predicting outcome after stroke at patient level can provide significant aid for patient management. Furthermore, prediction models of this kind can be useful for clinical research, health economics, policymaking and clinical decision support. 2869 patients with first-ever stroke from South London Stroke Register (SLSR) (1995-2004) will be included in the development cohort. We will use information captured after baseline to construct multilevel models and a Cox proportional hazard model to predict cognitive impairment, functional outcome and mortality up to 5 years after stroke. Repeated random subsampling validation (Monte Carlo cross-validation) will be evaluated in model development. Data from participants recruited to the stroke register (2005-2014) will be used for temporal validation of the models. Data from participants recruited to the Dijon Stroke Register (1985-2015) will be used for external validation. Discrimination, calibration and clinical utility of the models will be presented. Patients, or for patients who cannot consent their relatives, gave written informed consent to participate in stroke-related studies within the SLSR. The SLSR design was approved by the ethics committees of Guy's and St Thomas' NHS Foundation Trust, Kings College Hospital, Queens Square and Westminster Hospitals (London). The Dijon Stroke Registry was approved by the Comité National des Registres and the InVS and has authorisation of the Commission Nationale de l'Informatique et des Libertés. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. Impairment in predictive processes during auditory mismatch negativity in ScZ: Evidence from event-related fields.

    PubMed

    Sauer, Andreas; Zeev-Wolf, Maor; Grent-'t-Jong, Tineke; Recasens, Marc; Wacongne, Catherine; Wibral, Michael; Helbling, Saskia; Peled, Abraham; Grinshpoon, Alexander; Singer, Wolf; Goldstein, Abraham; Uhlhaas, Peter J

    2017-10-01

    Patients with schizophrenia (ScZ) show pronounced dysfunctions in auditory perception but the underlying mechanisms as well as the localization of the deficit remain unclear. To examine these questions, the current study examined whether alterations in the neuromagnetic mismatch negativity (MMNm) in ScZ-patients could involve an impairment in sensory predictions in local sensory and higher auditory areas. Using a whole-head MEG-approach, we investigated the MMNm as well as P300m and N100m amplitudes during a hierarchical auditory novelty paradigm in 16 medicated ScZ-patients and 16 controls. In addition, responses to omitted sounds were investigated, allowing for a critical test of the predictive coding hypothesis. Source-localization was performed to identify the generators of the MMNm, omission responses as well as the P300m. Clinical symptoms were examined with the positive and negative syndrome scale. Event-related fields (ERFs) to standard sounds were intact in ScZ-patients. However, the ScZ-group showed a reduction in the amplitude of the MMNm during both local (within trials) and global (across trials) conditions as well as an absent P300m at the global level. Importantly, responses to sound omissions were reduced in ScZ-patients which overlapped both in latency and generators with the MMNm sources. Thus, our data suggest that auditory dysfunctions in ScZ involve impaired predictive processes that involve deficits in both automatic and conscious detection of auditory regularities. Hum Brain Mapp 38:5082-5093, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  15. Talking about Teaching Episodes

    ERIC Educational Resources Information Center

    Nemirovsky, Ricardo; DiMattia, Cara; Ribeiro, Branca; Lara-Meloy, Teresa

    2005-01-01

    This paper examines two types of discourse in which teachers engage when discussing case studies based on classroom episodes, and the ways in which the availability of video data of these episodes may motivate a shift in the mode of discourse used. We interviewed two pairs of secondary school mathematics teachers after they had read a case study…

  16. A six-month longitudinal evaluation significantly improves accuracy of predicting incipient Alzheimer's disease in mild cognitive impairment.

    PubMed

    Mubeen, Asim M; Asaei, Ali; Bachman, Alvin H; Sidtis, John J; Ardekani, Babak A

    2017-07-01

    Early prediction of incipient Alzheimer's disease (AD) dementia in individuals with mild cognitive impairment (MCI) is important for timely therapeutic intervention and identifying participants for clinical trials at greater risk of developing AD. Methods to predict incipient AD in MCI have mostly utilized cross-sectional data. Longitudinal data enables estimation of the rate of change of variables, which along with the variable levels have been shown to improve prediction power. While some efforts have already been made in this direction, all previous longitudinal studies have been based on observation periods longer than one year, hence limiting their practical utility. It remains to be seen if follow-up evaluations within shorter intervals can significantly improve the accuracy of prediction in this problem. Our aim was to determine the added value of incorporating 6-month longitudinal data for predicting progression from MCI to AD. Using 6-months longitudinal data from 247 participants with MCI, we trained two Random Forest classifiers to distinguish between progressive MCI (n=162) and stable MCI (n=85) cases. These models utilized structural MRI, neurocognitive assessments, and demographic information. The first model (cross-sectional) only used baseline data. The second model (longitudinal) used data from both baseline and a 6-month follow-up evaluation allowing the model to additionally incorporate biomarkers' rate of change. The longitudinal model (AUC=0.87; accuracy=80.2%) performed significantly better (P<0.05) than the cross-sectional model (AUC=0.82; accuracy=71.7%). Short-term longitudinal assessments significantly enhance the performance of AD prediction models. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  17. Disorganized symptoms and executive functioning predict impaired social functioning in subjects at risk for psychosis.

    PubMed

    Eslami, Ali; Jahshan, Carol; Cadenhead, Kristin S

    2011-01-01

    Predictors of social functioning deficits were assessed in 22 individuals "at risk" for psychosis. Disorganized symptoms and executive functioning predicted social functioning at follow-up. Early intervention efforts that focus on social and cognitive skills are indicated in this vulnerable population.

  18. The case for episodic memory in animals.

    PubMed

    Dere, E; Kart-Teke, E; Huston, J P; De Souza Silva, M A

    2006-01-01

    The conscious recollection of unique personal experiences in terms of their details (what), their locale (where) and temporal occurrence (when) is known as episodic memory and is thought to require a 'self-concept', autonoetic awareness/conciousness, and the ability to subjectively sense time. It has long been held that episodic memory is unique to humans, because it was accepted that animals lack a 'self-concept', 'autonoetic awareness', and the ability to 'subjectively sense time'. These assumptions are now being questioned by behavioral evidence showing that various animal species indeed show behavioral manifestations of different features of episodic memory such as, e.g. 'metacognition', 'conscious recollection' of past events, 'temporal order memory', 'mental time travel' and have the capacity to remember personal experiences in terms of what happened, where and when. The aim of this review is to provide a comprehensive overview on the current progress in attempts to model different prerequisites and features of human episodic memory in animals and to identify possible neural substrates of animal episodic memory. The literature covered includes behavioral and physiological studies performed with different animal species, such as non-human primates, rodents, dolphins and birds. The search for episodic memory in animals has forced researchers to define objective behavioral criteria by which different features of episodic memory can be operationalized experimentally and assessed in both animals and humans. This is especially important because the current definition of episodic memory in terms of mentalistic constructs such as 'self', 'autonoetic awareness/consciousness', and 'subjectively sensed time', not only hinders animal research on the neurobiology of episodic memory but also research with healthy human subjects as well as neuropsychiatric patients with impaired language or in children with less-developed verbal abilities.

  19. Episode-Based Payment for the Medicare Outpatient Therapy Benefit.

    PubMed

    Amico, Peter; Pope, Gregory C; Meadow, Ann; West, Pamela

    2016-08-01

    To conduct an analysis of Medicare outpatient therapy episodes of care and associated payment implications. Retrospective observational design using Medicare claims data. To descriptively analyze the composition of outpatient therapy episodes, both variable- and fixed-length episodes are explored. The variable-length episode definition organizes services into episodes based on the time pattern of therapy service utilization, using 60-day clean periods. Fixed-length episodes are also examined, beginning with the first therapy utilization in calendar year 2010 and extending 30, 60, and 90 days. The study is focused on community-dwelling users of outpatient therapy. The sample includes all Medicare patients who used outpatient therapy beginning at any point in 2010. Not applicable. Mean episode payments and episode lengths in calendar days. Variable-length outpatient therapy episodes have a mean payment of $881. On average, outpatient therapy episodes last 43 calendar days. Mean therapy durations for the 30-, 60-, and 90-day fixed-length episodes are 20, 31, and 38 calendar days, respectively. The 30-, 60-, and 90-day fixed-length initial episodes account for 40%, 55%, and 63%, respectively, of total Medicare payments. Simulations of episode-based payment illustrate the difficulty of avoiding a large number of substantial underpayments, because of the right-skewed distribution of total actual payments. A strength of episode payment is that it reduces cost and potentially wasteful variation within episodes. Given the substantial variation in therapy episode expenditures, absent improvements in available data and in predictive information, a pure lump sum episode payment would result in substantial revenue changes for many episodes. Additional data are needed to better explain the wide variation in episode expenditures. Copyright © 2016 American Congress of Rehabilitation Medicine. All rights reserved.

  20. A trade-off between feedback-based learning and episodic memory for feedback events: evidence from Parkinson's disease.

    PubMed

    Foerde, Karin; Braun, Erin Kendall; Shohamy, Daphna

    2013-01-01

    Parkinson's disease (PD) is characterized by a loss of dopaminergic projections to the striatum, leading to both motor and cognitive impairments. The cognitive impairments are relatively selective and include deficits in incremental learning from trial-by-trial feedback, while other forms of learning, such as hippocampal-dependent episodic memory, remain intact. Interestingly, it has been suggested that the striatum and the hippocampus compete during learning, leading to the intriguing prediction that the striatal disruption in PD could lead to enhanced performance on tasks that depend on the hippocampus. We tested this prediction by simultaneously assessing incremental learning and episodic memory for trial-unique feedback events, within a single task, in patients with PD. Further, in order to modulate the engagement of the striatum versus the hippocampus, we manipulated the timing of feedback during learning, building on prior results showing that delaying feedback by a few seconds shifts learning to depend on the hippocampus instead of the striatum. We found that Parkinson's patients were impaired at learning from immediate feedback, but had enhanced episodic memory for those immediate feedback events. Thus, our results provide evidence for concurrent impaired and enhanced learning and memory functions within the same group of patients from a single task. Copyright © 2012 S. Karger AG, Basel.

  1. Working memory in mild cognitive impairment and Alzheimer's disease: contribution of forgetting and predictive value of complex span tasks.

    PubMed

    Gagnon, Lyssa G; Belleville, Sylvie

    2011-03-01

    This study examines working memory (WM) in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Performances on sentence span and operation span were measured in individuals meeting criteria for MCI (n = 20) and AD (n = 16) as well as in healthy older adults (n = 20). In addition, the effect of retention interval was assessed by manipulating the length of first and last items of trials (long-short vs. short-long), as forgetting might contribute to impaired performance in AD and MCI. Results show a group effect (p < .001, η² = .47): In both conditions and for both material types, WM span is lower in AD than in MCI (p < .001), which in turn is lower than in healthy aging (p < .05). An effect of retention interval on complex span was found for all groups (p < .001, η² = .57), supporting a role for forgetting within WM. When computing a proportional interval effect (p < .05, η² = .12), it was found that persons with AD were more sensitive to retention interval than were healthy older adults (p < .05). Among persons with MCI, those who later showed significant clinical deterioration or progression to AD were more affected by retention interval (p < .05, η² = .28) than were those who remained stable. Furthermore, deficits in AD are associated with a higher proportion of intrusion errors, particularly those from the current trial (p < .05, η² = .15), which could reflect inhibitory processes. Overall, these results indicate impaired WM in age-related disorders with a gradient between MCI and AD. Retention interval increases deficit in persons with AD. It also shows potential in predicting a negative prognosis in those with MCI. (c) 2011 APA, all rights reserved

  2. The relationship of level of positive mental health with current mental disorders in predicting suicidal behavior and academic impairment in college students.

    PubMed

    Keyes, Corey L M; Eisenberg, Daniel; Perry, Geraldine S; Dube, Shanta R; Kroenke, Kurt; Dhingra, Satvinder S

    2012-01-01

    To investigate whether level of positive mental health complements mental illness in predicting students at risk for suicidal behavior and impaired academic performance. A sample of 5,689 college students participated in the 2007 Healthy Minds Study and completed an Internet survey that included the Mental Health Continuum-Short Form and the Patient Health Questionnaire screening scales for depression and anxiety disorders, questions about suicide ideation, plans, and attempts, and academic impairment. Just under half (49.3%) of students were flourishing and did not screen positive for a mental disorder. Among students who did, and those who did not, screen for a mental disorder, suicidal behavior and impaired academic performance were lowest in those with flourishing, higher among those with moderate, and highest in those with languishing mental health. Positive mental health complements mental disorder screening in mental health surveillance and prediction of suicidal behavior and impairment of academic performance.

  3. Prefrontal activation may predict working-memory training gain in normal aging and mild cognitive impairment.

    PubMed

    Vermeij, Anouk; Kessels, Roy P C; Heskamp, Linda; Simons, Esther M F; Dautzenberg, Paul L J; Claassen, Jurgen A H R

    2017-02-01

    Cognitive training has been shown to result in improved behavioral performance in normal aging and mild cognitive impairment (MCI), yet little is known about the neural correlates of cognitive plasticity, or about individual differences in responsiveness to cognitive training. In this study, 21 healthy older adults and 14 patients with MCI received five weeks of adaptive computerized working-memory (WM) training. Before and after training, functional Near-Infrared Spectroscopy (fNIRS) was used to assess the hemodynamic response in left and right prefrontal cortex during performance of a verbal n-back task with varying levels of WM load. After training, healthy older adults demonstrated decreased prefrontal activation at high WM load, which may indicate increased processing efficiency. Although MCI patients showed improved behavioral performance at low WM load after training, no evidence was found for training-related changes in prefrontal activation. Whole-group analyses showed that a relatively strong hemodynamic response at low WM load was related to worse behavioral performance, while a relatively strong hemodynamic response at high WM load was related to higher training gain. Therefore, a 'youth-like' prefrontal activation pattern at older age may be associated with better behavioral outcome and cognitive plasticity.

  4. Hippocampal damage and memory impairment in congenital cyanotic heart disease.

    PubMed

    Muñoz-López, Mónica; Hoskote, Aparna; Chadwick, Martin J; Dzieciol, Anna M; Gadian, David G; Chong, Kling; Banks, Tina; de Haan, Michelle; Baldeweg, Torsten; Mishkin, Mortimer; Vargha-Khadem, Faraneh

    2017-04-01

    Neonatal hypoxia can lead to hippocampal atrophy, which can lead, in turn, to memory impairment. To test the generalizability of this causal sequence, we examined a cohort of 41 children aged 8-16, who, having received the arterial switch operation to correct for transposition of the great arteries, had sustained significant neonatal cyanosis but were otherwise neurodevelopmentally normal. As predicted, the cohort had significant bilateral reduction of hippocampal volumes relative to the volumes of 64 normal controls. They also had significant, yet selective, impairment of episodic memory as measured by standard tests of memory, despite relatively normal levels of intelligence, academic attainment, and verbal fluency. Across the cohort, degree of memory impairment was correlated with degree of hippocampal atrophy suggesting that even as early as neonatal life no other structure can fully compensate for hippocampal injury and its special role in serving episodic long term memory. © 2017 Wiley Periodicals, Inc.

  5. Hippocampal damage and memory impairment in congenital cyanotic heart disease

    PubMed Central

    Hoskote, Aparna; Chadwick, Martin J.; Dzieciol, Anna M.; Gadian, David G.; Chong, Kling; Banks, Tina; de Haan, Michelle; Baldeweg, Torsten; Mishkin, Mortimer; Vargha‐Khadem, Faraneh

    2017-01-01

    ABSTRACT Neonatal hypoxia can lead to hippocampal atrophy, which can lead, in turn, to memory impairment. To test the generalizability of this causal sequence, we examined a cohort of 41 children aged 8‐16, who, having received the arterial switch operation to correct for transposition of the great arteries, had sustained significant neonatal cyanosis but were otherwise neurodevelopmentally normal. As predicted, the cohort had significant bilateral reduction of hippocampal volumes relative to the volumes of 64 normal controls. They also had significant, yet selective, impairment of episodic memory as measured by standard tests of memory, despite relatively normal levels of intelligence, academic attainment, and verbal fluency. Across the cohort, degree of memory impairment was correlated with degree of hippocampal atrophy suggesting that even as early as neonatal life no other structure can fully compensate for hippocampal injury and its special role in serving episodic long term memory. © 2017 Wiley Periodicals, Inc. PMID:28032672

  6. Magnetic resonance imaging volume of the angular gyri predicts financial skill deficits in people with amnestic mild cognitive impairment.

    PubMed

    Griffith, H Randall; Stewart, Christopher C; Stoeckel, Luke E; Okonkwo, Ozioma C; den Hollander, Jan A; Martin, Roy C; Belue, Katherine; Copeland, Jacquelynn N; Harrell, Lindy E; Brockington, John C; Clark, David G; Marson, Daniel C

    2010-02-01

    To better understand how brain atrophy in amnestic mild cognitive impairment (MCI) as measured using magnetic resonance imaging (MRI) volumetrics could affect instrumental activities of daily living (IADLs) such as financial abilities. Controlled, matched-sample, cross-sectional analysis regressing MRI volumetrics with financial performance measures. University medical and research center. Thirty-eight people with MCI and 28 older adult controls. MRI volumetric measurement of the hippocampi, angular gyri, precunei, and medial frontal lobes. Participants also completed neuropsychological tests and the Financial Capacity Instrument (FCI). Correlations were performed between FCI scores and MRI volumes in the group with MCI. People with MCI performed significantly below controls on the FCI and had significantly smaller hippocampi. Among people with MCI, performance on the FCI was moderately correlated with angular gyri and precunei volumes. Regression models demonstrated that angular gyrus volumes were predictive of FCI scores. Tests of mediation showed that measures of arithmetic and possibly attention partially mediated the relationship between angular gyrus volume and FCI score. Impaired financial abilities in amnestic MCI correspond with volume of the angular gyri as mediated by arithmetic knowledge. The findings suggest that early neuropathology within the lateral parietal region in MCI leads to a breakdown of cognitive abilities that affect everyday financial skills. The findings have implications for diagnosis and clinical care of people with MCI and AD.

  7. Representation of the vowel /epsilon/ in normal and impaired auditory nerve fibers: model predictions of responses in cats.

    PubMed

    Zilany, Muhammad S A; Bruce, Ian C

    2007-07-01

    The temporal response of auditory-nerve (AN) fibers to a steady-state vowel is investigated using a computational auditory-periphery model. The model predictions are validated against a wide range of physiological data for both normal and impaired fibers in cats. The model incorporates two parallel filter paths, component 1 (C1) and component 2 (C2), which correspond to the active and passive modes of basilar membrane vibration, respectively, in the cochlea. The outputs of the two filters are subsequently transduced by two separate functions, added together, and then low-pass filtered by the inner hair cell (IHC) membrane, which is followed by the IHC-AN synapse and discharge generator. The C1 response dominates at low and moderate levels and is responsible for synchrony capture and multiformant responses seen in the vowel responses. The C2 response dominates at high levels and contributes to the loss of synchrony capture observed in normal and impaired fibers. The interaction between C1 and C2 responses explains the behavior of AN fibers in the transition region, which is characterized by two important observations in the vowel responses: First, all components of the vowel undergo the C1/C2 transition simultaneously, and second, the responses to the nonformant components of the vowel become substantial.

  8. Self-rated social skills predict visual perception: impairments in object discrimination requiring transient attention associated with high autistic tendency.

    PubMed

    Laycock, Robin; Cross, Alana Jade; Dalle Nogare, Felicity; Crewther, Sheila Gillard

    2014-02-01

    Autism is usually defined by impairments in the social domain but has also been linked to deficient dorsal visual stream processing. However, inconsistent findings make the nature of this relationship unclear and thus, we examined the role of stimulus-driven transient attention, presumably activated by the dorsal stream in autistic tendency. Contrast thresholds for object discrimination were compared between groups with high and low self-rated autistic tendency utilizing the socially based Autism Spectrum Quotient (AQ). Visual stimuli were presented with either abrupt or with ramped contrast onsets/offsets in order to manipulate the demands of transient attention. Larger impairments in performance of abrupt compared with ramped object presentation were established in the high AQ group. Furthermore, self-reported social skills predicted abrupt task performance, suggesting an important visual perception deficiency in autism-related traits. Autism spectrum disorder may be associated with reduced utilization of the dorsal stream to rapidly activate attention prior to ventral stream processing when stimuli are transient.

  9. Naming speed as a clinical marker in predicting basic calculation skills in children with specific language impairment.

    PubMed

    Kleemans, Tijs; Segers, Eliane; Verhoeven, Ludo

    2012-01-01

    The present study investigated the role of naming speed in predicting the basic calculation skills (i.e., addition and subtraction) of kindergartners with Specific Language Impairment (SLI), when compared to a group of Normal Language Achieving (NLA) children. Fifty-three kindergartners with SLI and 107 kindergartners with NLA were tested on cognitive, linguistic and basic calculation skills. The results showed that phonological awareness, grammatical ability, general intelligence and working memory accounted for the variation in the basic calculation skills of both groups. However, an additional effect of naming speed on both addition and subtraction was found for the group of children with SLI, suggesting that naming speed may act as a clinical marker in identifying those children who are likely to develop problems in basic calculation skills.

  10. Predicting the outcome of specific language impairment at five years of age through early developmental assessment in preterm infants.

    PubMed

    Woods, Patricia L; Rieger, Ingrid; Wocadlo, Crista; Gordon, Adrienne

    2014-10-01

    Very preterm infants (<30 weeks of gestation) are at increased risk of specific language impairment and systematic developmental follow-up is essential for the provision of targeted early intervention. To define the predictive value of early language testing and stability of language development, and perinatal and demographic risk factors for the diagnosis of SLI at 5 years, in a cohort of preterm infants. We used a retrospective hospital based cohort study. Preterm infants <30 weeks of gestation, were cared for in NICU at RPAH, between 2004 and 2007, and prospectively enrolled in developmental follow-up. Standardised developmental assessment was done at 3 years utilising the Bayley Scales of Infant and Toddler Development-III and the Wechsler Preschool and Primary Scale of Intelligence-III was done at 5 years. Predictive value and stability of early language testing were assessed with respect to SLI at 5 years, using measures of diagnostic accuracy and kappa values. Multivariate logistic regression was performed during the distribution of perinatal and demographic risk factors for SLI. One-in-five met diagnostic criteria for SLI (19%, n=24). Limited diagnostic accuracy was found with early expressive language and the stability of language scores demonstrated only fair agreement (Cohen's κ .383). Multilingual status and extreme gestational age at 24-25 weeks were associated with a six-fold increased risk of SLI (OR 6.09, 95% CI 1.89-19.56; OR 6.09, 95% CI 1.28-29.0). We defined a high incidence of SLI among our cohort, but only a limited diagnostic accuracy of early language testing. Multilingual status and extreme prematurity were independent risk factors for SLI. It remains imperative to perform continued developmental assessments beyond pre-school age to identify language impairment with greater accuracy. Crown Copyright © 2014. Published by Elsevier Ireland Ltd. All rights reserved.

  11. Chronic kidney disease predicts impaired membrane microviscosity of red blood cells in hypertensive and normotensive subjects.

    PubMed

    Tsuda, Kazushi

    2013-01-01

    Current evidence indicates that abnormalities in physical properties of the cell membranes may be strongly linked to hypertension and other circulatory disorders. Recent studies have shown that chronic kidney disease (CKD) might be a risk factor for cardiovascular and cerebrovascular outcomes. The purpose of the present study was to examine the possible relationship between kidney function and membrane fluidity (a reciprocal value of membrane microviscosity) of red blood cells (RBCs) in hypertensive and normotensive subjects using an electron spin resonance (ESR) and spin-labeling method. The order parameter (S) for the ESR spin-label agent (5-nitroxide stearate) in RBC membranes was significantly higher in hypertensive subjects than in normotensive subjects, indicating that membrane fluidity was decreased in hypertension. The order parameter (S) of RBCs was inversely correlated with estimated glomerular filtration rate (eGFR), suggesting that a decreased eGFR value might be associated with reduced membrane fluidity of RBCs. Multivariate regression analysis also demonstrated that, after adjustment for general risk factors, eGFR might be a significant predictor of membrane fluidity of RBCs. The reduced levels of both membrane fluidity of RBCs and eGFR were associated with increased plasma 8-iso-prostaglandin F2α (an index of oxidative stress) and decreased plasma nitric oxide (NO)-metabolites, suggesting that kidney function could be a determinant of membrane microviscosity of RBCs, at least in part, via oxidative stress- and NO-dependent mechanisms. The ESR study suggests that CKD might have a close correlation with impaired rheologic behavior of RBCs and microcirculatory disorders in hypertensive subjects.

  12. Structural Integrity of the Contralesional Hemisphere Predicts Cognitive Impairment in Ischemic Stroke at Three Months

    PubMed Central

    Dacosta-Aguayo, Rosalia; Graña, Manuel; Fernández-Andújar, Marina; López-Cancio, Elena; Cáceres, Cynthia; Bargalló, Núria; Barrios, Maite; Clemente, Immaculada; Monserrat, Pere Toran; Sas, Maite Alzamora; Dávalos, Antoni

    2014-01-01

    After stroke, white matter integrity can be affected both locally and distally to the primary lesion location. It has been shown that tract disruption in mirror’s regions of the contralateral hemisphere is associated with degree of functional impairment. Fourteen patients suffering right hemispheric focal stroke (S) and eighteen healthy controls (HC) underwent Diffusion Weighted Imaging (DWI) and neuropsychological assessment. The stroke patient group was divided into poor (SP; n = 8) and good (SG; n = 6) cognitive recovery groups according to their cognitive improvement from the acute phase (72 hours after stroke) to the subacute phase (3 months post-stroke). Whole-brain DWI data analysis was performed by computing Diffusion Tensor Imaging (DTI) followed by Tract Based Spatial Statistics (TBSS). Assessment of effects was obtained computing the correlation of the projections on TBSS skeleton of Fractional Anisotropy (FA) and Radial Diffusivity (RD) with cognitive test results. Significant decrease of FA was found only in right brain anatomical areas for the S group when compared to the HC group. Analyzed separately, stroke patients with poor cognitive recovery showed additional significant FA decrease in several left hemisphere regions; whereas SG patients showed significant decrease only in the left genu of corpus callosum when compared to the HC. For the SG group, whole brain analysis revealed significant correlation between the performance in the Semantic Fluency test and the FA in the right hemisphere as well as between the performance in the Grooved Pegboard Test (GPT) and theTrail Making Test-part A and the FA in the left hemisphere. For the SP group, correlation analysis revealed significant correlation between the performance in the GPT and the FA in the right hemisphere. PMID:24475078

  13. Impairment of heart rate recovery after peak exercise predicts poor outcome after pediatric heart transplantation.

    PubMed

    Giardini, Alessandro; Fenton, Matthew; Derrick, Graham; Burch, Michael

    2013-09-10

    A blunted heart rate recovery (HRR) from peak exercise is associated with adverse outcome in adults with ischemic heart disease. We assessed HRR after pediatric heart transplantation (HTx) and its prognostic use. Between 2004 and 2010 we performed 360 maximal exercise tests (median, 2 tests/patient; range, 1-7) in 128 children (66 men; age at test, 14 ± 3 years) who received HTx (age, 8.5 ± 5.1 years) because of cardiomyopathy (66%) or congenital heart defects (34%). The change in heart rate from peak exercise to 1 minute of recovery was measured as HRR and was expressed as Z score calculated from reference data obtained in 160 healthy children. HRR was impaired soon after HTx (average in first 2 years Z=-1.9 ± 3.5) but improved afterward (Z=+0.52/y), such that HRR Z score normalized in most patients by 6 years after HTx (average, 0.6 ± 1.8). A subsequent decline in HRR Z score was noted from 6 years after HTx (rate of Z=-0.11/y). After 27 ± 15 months from the most recent exercise test, 19 patients died or were re-heart transplantation. For the follow-up after 6 years, HRR Z score was the only predictor of death/re-heart transplantation (P=0.003). Patients in the lowest quartile of HRR Z score had a much higher 5-year event rate (event-free rate, 29% versus 84%; hazard ratio, 7.0; P=0.0013). HRR is blunted soon after HTx but normalizes at ≈ 6 years, potentially as a result of parasympathetic reinnervation of the graft, but then declines. This late decline in HRR Z score is associated with worse outcome.

  14. Structural integrity of the contralesional hemisphere predicts cognitive impairment in ischemic stroke at three months.

    PubMed

    Dacosta-Aguayo, Rosalia; Graña, Manuel; Fernández-Andújar, Marina; López-Cancio, Elena; Cáceres, Cynthia; Bargalló, Núria; Barrios, Maite; Clemente, Immaculada; Monserrat, Pere Toran; Sas, Maite Alzamora; Dávalos, Antoni; Auer, Tibor; Mataró, Maria

    2014-01-01

    After stroke, white matter integrity can be affected both locally and distally to the primary lesion location. It has been shown that tract disruption in mirror's regions of the contralateral hemisphere is associated with degree of functional impairment. Fourteen patients suffering right hemispheric focal stroke (S) and eighteen healthy controls (HC) underwent Diffusion Weighted Imaging (DWI) and neuropsychological assessment. The stroke patient group was divided into poor (SP; n = 8) and good (SG; n = 6) cognitive recovery groups according to their cognitive improvement from the acute phase (72 hours after stroke) to the subacute phase (3 months post-stroke). Whole-brain DWI data analysis was performed by computing Diffusion Tensor Imaging (DTI) followed by Tract Based Spatial Statistics (TBSS). Assessment of effects was obtained computing the correlation of the projections on TBSS skeleton of Fractional Anisotropy (FA) and Radial Diffusivity (RD) with cognitive test results. Significant decrease of FA was found only in right brain anatomical areas for the S group when compared to the HC group. Analyzed separately, stroke patients with poor cognitive recovery showed additional significant FA decrease in several left hemisphere regions; whereas SG patients showed significant decrease only in the left genu of corpus callosum when compared to the HC. For the SG group, whole brain analysis revealed significant correlation between the performance in the Semantic Fluency test and the FA in the right hemisphere as well as between the performance in the Grooved Pegboard Test (GPT) and the Trail Making Test-part A and the FA in the left hemisphere. For the SP group, correlation analysis revealed significant correlation between the performance in the GPT and the FA in the right hemisphere.

  15. Can Neurological Biomarkers of Brain Impairment Be Used to Predict Poststroke Motor Recovery? A Systematic Review.

    PubMed

    Kim, Bokkyu; Winstein, Carolee

    2017-01-01

    Background There is growing interest to establish recovery biomarkers, especially neurological biomarkers, in order to develop new therapies and prediction models for the promotion of stroke rehabilitation and recovery. However, there is no consensus among the neurorehabilitation community about which biomarker(s) have the highest predictive value for motor recovery. Objective To review the evidence and determine which neurological biomarker(s) meet the high evidence quality criteria for use in predicting motor recovery. Methods We searched databases for prognostic neuroimaging/neurophysiological studies. Methodological quality of each study was assessed using a previously employed comprehensive 15-item rating system. Furthermore, we used the GRADE approach and ranked the overall evidence quality for each category of neurologic biomarker. Results Seventy-one articles met our inclusion criteria; 5 categories of neurologic biomarkers were identified: diffusion tensor imaging (DTI), transcranial magnetic stimulation (TMS), functional magnetic resonance imaging (fMRI), conventional structural MRI (sMRI), and a combination of these biomarkers. Most studies were conducted with individuals after ischemic stroke in the acute and/or subacute stage (~70%). Less than one-third of the studies (21/71) were assessed with satisfactory methodological quality (80% or more of total quality score). Conventional structural MRI and the combination biomarker categories ranked "high" in overall evidence quality. Conclusions There were 3 prevalent methodological limitations: (a) lack of cross-validation, (b) lack of minimal clinically important difference (MCID) for motor outcomes, and (c) small sample size. More high-quality studies are needed to establish which neurological biomarkers are the best predictors of motor recovery after stroke. Finally, the quarter-century old methodological quality tool used here should be updated by inclusion of more contemporary methods and statistical

  16. Lower than predicted resting metabolic rate is associated with severely impaired cardiorespiratory fitness in obese individuals.

    PubMed

    Miller, Wendy M; Spring, Thomas J; Zalesin, Kerstyn C; Kaeding, Kaylee R; Nori Janosz, Katherine E; McCullough, Peter A; Franklin, Barry A

    2012-03-01

    Obese individuals have reduced cardiorespiratory fitness as compared with leaner counterparts. Regular exercise maintains or increases fitness and lean body mass. Lean body mass, in turn, has a direct impact on resting metabolic rate (RMR). Given these relationships, we sought to evaluate the association between RMR and cardiorespiratory fitness in obese individuals. We evaluated 64 obese individuals (78% female) with direct assessment of RMR and cardiorespiratory fitness via breath-by-breath measurement of oxygen consumption and carbon dioxide production at rest and during exercise. The mean age and BMI were 47.4 ± 12.2 years and 47.2 ± 9.2 kg/m(2), respectively. The majority of subjects, 69%, had a measured RMR above that predicted by the Harris-Benedict equation. Compared with the higher RMR group, those with a lower than predicted RMR had increased BMI, with values of 52.9 vs. 44.7 kg/m(2), P = 0.001, respectively. Analysis of those demonstrating significant effort during cardiopulmonary exercise testing (peak respiratory exchange ratio ≥1.10) revealed a significantly higher peak oxygen uptake (VO(2) peak) in the higher RMR group (17.3 ± 3.5 ml/min/kg) compared with the lower RMR group (13.6 ± 1.9 ml/min/kg), P = 0.003. In summary, a lower than predicted RMR was associated with a severely reduced VO(2) peak and a higher BMI in this cohort. These data suggest that morbid obesity may be a vicious cycle of increasing BMI, reduced cardiorespiratory fitness, muscle deconditioning, and lower RMR. Collectively, these responses may, over time, exacerbate the imbalance between energy intake and expenditure, resulting in progressive increases in body weight and fat stores.

  17. Early impairment of intracranial conduction time predicts mortality in deeply sedated critically ill patients: a prospective observational pilot study.

    PubMed

    Azabou, Eric; Rohaut, Benjamin; Heming, Nicholas; Magalhaes, Eric; Morizot-Koutlidis, Régine; Kandelman, Stanislas; Allary, Jeremy; Moneger, Guy; Polito, Andrea; Maxime, Virginie; Annane, Djillali; Lofaso, Frederic; Chrétien, Fabrice; Mantz, Jean; Porcher, Raphael; Sharshar, Tarek

    2017-12-01

    Somatosensory (SSEP) and brainstem auditory (BAEP) evoked potentials are neurophysiological tools which, respectively, explore the intracranial conduction time (ICCT) and the intrapontine conduction time (IPCT). The prognostic values of prolonged cerebral conduction times in deeply sedated patients have never been assessed. Sedated patients are at risk of developing new neurological complications, undetected. In this prospective observational bi-center pilot study, we investigated whether early impairment of SSEP's ICCT and/or BAEP's IPCT could predict in-ICU mortality or altered mental status (AMS), in deeply sedated critically ill patients. SSEP by stimulation of the median nerve and BAEP were assessed in critically ill patients receiving deep sedation on day 3 following ICU admission. Deep sedation was defined by a Richmond Assessment sedation Scale (RASS) <-3. Mean left- and right-side ICCT and IPCT were measured for each patient. Primary and secondary outcomes were, respectively, in-ICU mortality and AMS defined as the occurrence of delirium and/or delayed awakening after discontinuation of sedation. Eighty-six patients were studied of which 49 (57%) were non-brain-injured and 37 (43%) were brain-injured. Impaired ICCT was a predictor of in-ICU mortality after adjustment on the global Sequential Organ Failure Assessment score (SOFA) [OR (95% CI) = 2.69 (1.05-6.85); p = 0.039] and on the non-neurological SOFA components [2.67 (1.05-6.81); p = 0.040]. IPCT was more frequently delayed in the subgroup of patients who developed post-sedation AMS (24%) compared those without AMS (0%). However, this difference did not reach statistical significance (p = 0.053). Impairment rates of ICCT and IPCT were not found to be significantly different between non-brain- and brain-injured subgroups of patients. In critically ill patients receiving deep sedation, early ICCT impairment was associated with mortality. Somatosensory and brainstem auditory evoked potentials may

  18. Executive function, episodic memory, and Medicare expenditures.

    PubMed

    Bender, Alex C; Austin, Andrea M; Grodstein, Francine; Bynum, Julie P W

    2017-07-01

    We examined the relationship between health care expenditures and cognition, focusing on differences across cognitive systems defined by global cognition, executive function, or episodic memory. We used linear regression models to compare annual health expenditures by cognitive status in 8125 Nurses' Health Study participants who completed a cognitive battery and were enrolled in Medicare parts A and B. Adjusting for demographics and comorbidity, executive impairment was associated with higher total annual expenditures of $1488 per person (P < .01) compared with those without impairment. No association for episodic memory impairment was found. Expenditures exhibited a linear relationship with executive function, but not episodic memory ($584 higher for every 1 standard deviation decrement in executive function; P < .01). Impairment in executive function is specifically and linearly associated with higher health care expenditures. Focusing on management strategies that address early losses in executive function may be effective in reducing costly services. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  19. The role of parental perceptions of tic frequency and intensity in predicting tic-related functional impairment in youth with chronic tic disorders.

    PubMed

    Espil, Flint M; Capriotti, Matthew R; Conelea, Christine A; Woods, Douglas W

    2014-12-01

    Tic severity is composed of several dimensions. Tic frequency and intensity are two such dimensions, but little empirical data exist regarding their relative contributions to functional impairment in those with chronic tic disorders (CTD). The present study examined the relative contributions of these dimensions in predicting tic-related impairment across several psychosocial domains. Using data collected from parents of youth with CTD, multivariate regression analyses revealed that both tic frequency and intensity predicted tic-related impairment in several areas; including family and peer relationships, school interference, and social endeavors, even when controlling for the presence of comorbid anxiety symptoms and Attention Deficit Hyperactivity Disorder diagnostic status. Results showed that tic intensity predicted more variance across more domains than tic frequency.

  20. The Role of Parental Perceptions of Tic Frequency and Intensity in Predicting Tic-Related Functional Impairment in Youth with Chronic Tic Disorders

    PubMed Central

    Espil, Flint M.; Capriotti, Matthew R.; Conelea, Christine A.; Woods, Douglas W.

    2014-01-01

    Tic severity is composed of several dimensions. Tic frequency and intensity are two such dimensions, but little empirical data exist regarding their relative contributions to functional impairment in those with Chronic Tic Disorders (CTD). The present study examined the relative contributions of these dimensions in predicting tic-related impairment across several psychosocial domains. Using data collected from parents of youth with CTD, multivariate regression analyses revealed that both tic frequency and intensity predicted tic-related impairment in several areas; including family and peer relationships, school interference, and social endeavors, even when controlling for the presence of comorbid anxiety symptoms and Attention Deficit Hyperactivity Disorder diagnostic status. Results showed that tic intensity predicted more variance across more domains than tic frequency. PMID:24395287

  1. Alzheimer Disease: Quantitative Structural Neuroimaging for Detection and Prediction of Clinical and Structural Changes in Mild Cognitive Impairment

    PubMed Central

    McEvoy, Linda K.; Fennema-Notestine, Christine; Roddey, J. Cooper; Hagler, Donald J.; Holland, Dominic; Karow, David S.; Pung, Christopher J.; Brewer, James B.; Dale, Anders M.

    2009-01-01

    Purpose: To use structural magnetic resonance (MR) images to identify a pattern of regional atrophy characteristic of mild Alzheimer disease (AD) and to investigate whether presence of this pattern prospectively can aid prediction of 1-year clinical decline and increased structural loss in mild cognitive impairment (MCI). Materials and Methods: The study was conducted with institutional review board approval and compliance with HIPAA regulations. Written informed consent was obtained from each participant. High-throughput volumetric segmentation and cortical surface reconstruction methods were applied to MR images from 84 subjects with mild AD, 175 with MCI, and 139 healthy control (HC) subjects. Stepwise linear discriminant analysis was used to identify regions that best can aid discrimination of HC subjects from subjects with AD. A classifier trained on data from HC subjects and those with AD was applied to data from subjects with MCI to determine whether presence of phenotypic AD atrophy at baseline was predictive of clinical decline and structural loss. Results: Atrophy in mesial and lateral temporal, isthmus cingulate, and orbitofrontal areas aided discrimination of HC subjects from subjects with AD, with fully cross-validated sensitivity of 83% and specificity of 93%. Subjects with MCI who had phenotypic AD atrophy showed significantly greater 1-year clinical decline and structural loss than those who did not and were more likely to have progression to probable AD (annual progression rate of 29% for subjects with MCI who had AD atrophy vs 8% for those who did not). Conclusion: Semiautomated, individually specific quantitative MR imaging methods can be used to identify a pattern of regional atrophy in MCI that is predictive of clinical decline. Such information may aid in prediction of patient prognosis and increase the efficiency of clinical trials. © RSNA, 2009 PMID:19201945

  2. Magnetic Resonance Imaging and the Prediction of Outcome in First-Episode Schizophrenia: A Review of Current Evidence and Directions for Future Research

    PubMed Central

    Dazzan, Paola; Arango, Celso; Fleischacker, Wolfgang; Galderisi, Silvana; Glenthøj, Birte; Leucht, Stephan; Meyer-Lindenberg, Andreas; Kahn, Rene; Rujescu, Dan; Sommer, Iris; Winter, Inge; McGuire, Philip

    2015-01-01

    Magnetic Resonance Imaging (MRI) measures are promising outcome markers for schizophrenia, since regional frontal and temporal grey matter volumes reductions, and enlargement of the ventricles, have been associated with outcome in this disorder. However, a number of methodological issues have limited the potential clinical utility of these findings. This article reviewed studies that examined brain structure at illness onset as a predictor of outcome, discusses the limitations of the findings, and highlights the challenges that would need to be addressed if structural data are to inform the management of an individual patient. Methods: Using a set of a priori criteria, we systematically searched Medline and EMBASE databases for articles evaluating brain structure at the time of the first psychotic episode and assessed response to treatment, symptomatic outcome, or functional outcome at any point in the first 12 months of illness. Results: The 11 studies identified suggest that alterations in medial temporal and prefrontal cortical areas, and in the networks that connect them with subcortical structures, are promising neuroanatomical markers of poor symptomatic and functional outcomes. Conclusion: Neuroimaging data, possibly in combination with other biomarkers of disease, could help stratifying patients with psychoses to generate patient clusters clinically meaningful, and useful to detect true therapeutic effects in clinical trials. Optimization of Treatment and Management of Schizophrenia in Europe (OPTiMiSE), a large multicenter study funded by the FP7 European Commission, could generate these much-needed findings. PMID:25800248

  3. Posttraumatic stress symptoms predict impaired neutrophil recovery in stem cell transplant recipients

    PubMed Central

    Hobfoll, Stevan E.; Gerhart, James I.; Zalta, Alyson K.; Wells, Kurrie; Maciejewski, John; Fung, Henry

    2015-01-01

    Objective Despite the potentially life-saving effects of stem cell transplant (SCT), many transplant patients experience traumatic stress reactions due to mortality threat, interpersonal isolation, financial and occupational loss, and invasive medical procedures. Emerging evidence suggests that traumarelated stress symptoms (TSS) predict significant health complications following SCT. The aim of the current prospective study was to examine TSS in the acute aftermath of SCT as a predictor of neutrophil recovery following SCT, a crucial component of immune defense against infection. Methods Fifty-one autologous SCT recipients were assessed for TSS 7 days after SCT. Patients’ absolute neutrophil counts were collected from medical charts for the first 30 days following SCT. Hierarchical linear growth modeling was used to test the hypothesis that TSS at day 7 would be associated with delayed recovery of neutrophil counts from days 9 to 30 post SCT, that is, when neutrophil counts began to recover. Results As hypothesized, TSS measured 7 days after SCT was significantly associated with slower neutrophil recovery even after pre-existing TSS, depression, distress related to physical symptoms, and potential medical confounds were statistically controlled. Exploratory analyses showed that of the TSS symptom clusters, re-experiencing symptoms and hyperarousal symptoms predicted neutrophil recovery, whereas avoidance symptoms did not. Conclusion Though traumatic stress symptoms may be a normative response to SCT, our findings suggest that TSS following SCT may interfere with neutrophil recovery and overall health. These results provide further insight as to potential mechanisms by which traumatic stress translates to poor medical outcomes for SCT patients. PMID:25628257

  4. Hippocampal place cells, context, and episodic memory.

    PubMed

    Smith, David M; Mizumori, Sheri J Y

    2006-01-01

    Although most observers agree that the hippocampus has a critical role in learning and memory, there remains considerable debate about the precise functional contribution of the hippocampus to these processes. Two of the most influential accounts hold that the primary function of the hippocampus is to generate cognitive maps and to mediate episodic memory processes. The well-documented spatial firing patterns (place fields) of hippocampal neurons in rodents, along with the spatial learning impairments observed with hippocampal damage support the cognitive mapping hypothesis. The amnesia for personally experienced events seen in humans with hippocampal damage and the data of animal models, which show severe memory deficits associated with hippocampal lesions, support the episodic memory account. Although an extensive literature supports each of these hypotheses, a specific contribution of place cells to episodic memory has not been clearly demonstrated. Recent data from our laboratory, together with previous findings, indicate that hippocampal place fields and neuronal responses to task-relevant stimuli are highly sensitive to the context, even when the contexts are defined by abstract task demands rather than the spatial geometry of the environment. On the basis of these findings, it is proposed that place fields reflect a more general context processing function of the hippocampus. Hippocampal context representations could serve to differentiate contexts and prime the relevant memories and behaviors. Since episodic memories, by definition, include information about the time and place where the episode occurred, contextual information is a necessary prerequisite for any episodic memory. Thus, place fields contribute importantly to episodic memory as part of the needed context representations. Additionally, recent findings indicate that hippocampal neurons differentiate contexts at progressively finer levels of detail, suggesting a hierarchical coding scheme which

  5. Hyperbolic Space Sparse Coding with Its Application on Prediction of Alzheimer’s Disease in Mild Cognitive Impairment

    PubMed Central

    Zhang, Jie; Shi, Jie; Stonnington, Cynthia; Li, Qingyang; Gutman, Boris A.; Chen, Kewei; Reiman, Eric M.; Caselli, Richard J.; Thompson, Paul M.; Ye, Jieping; Wang, Yalin

    2016-01-01

    Mild Cognitive Impairment (MCI) is a transitional stage between normal age-related cognitive decline and Alzheimer’s disease (AD). Here we introduce a hyperbolic space sparse coding method to predict impending decline of MCI patients to dementia using surface measures of ventricular enlargement. First, we compute diffeomorphic mappings between ventricular surfaces using a canonical hyperbolic parameter space with consistent boundary conditions and surface tensor-based morphometry is computed to measure local surface deformations. Second, ring-shaped patches of TBM features are selected according to the geometric structure of the hyperbolic parameter space to initialize a dictionary. Sparse coding is then applied on the patch features to learn sparse codes and update the dictionary. Finally, we adopt max-pooling to reduce the feature dimensions and apply Adaboost to predict AD in MCI patients (N = 133) from the Alzheimer’s Disease Neuroimaging Initiative baseline dataset. Our work achieved an accuracy rate of 96.7% and outperformed some other morphometry measures. The hyperbolic space sparse coding method may offer a more sensitive tool to study AD and its early symptom. PMID:28066843