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Fogelson N.,Joseph Sagol Neuroscience Center | Litvak V.,University College London | Peled A.,Institute for Psychiatric Studies | Peled A.,Technion - Israel Institute of Technology | And 2 more authors.
Schizophrenia Research | Year: 2014

This paper tests the hypothesis that patients with schizophrenia have a deficit in selectively attending to predictable events. We used dynamic causal modeling (DCM) of electrophysiological responses - to predictable and unpredictable visual targets - to quantify the effective connectivity within and between cortical sources in the visual hierarchy in 25 schizophrenia patients and 25 age-matched controls. We found evidence for marked differences between normal subjects and schizophrenia patients in the strength of extrinsic backward connections from higher hierarchical levels to lower levels within the visual system. In addition, we show that not only do schizophrenia subjects have abnormal connectivity but also that they fail to adjust or optimize this connectivity when events can be predicted. Thus, the differential intrinsic recurrent connectivity observed during processing of predictable versus unpredictable targets was markedly attenuated in schizophrenia patients compared with controls, suggesting a failure to modulate the sensitivity of neurons responsible for passing sensory information of prediction errors up the visual cortical hierarchy. The findings support the proposed role of abnormal connectivity in the neuropathology and pathophysiology of schizophrenia. © 2014 The Authors. Source

Oriel S.,Ben - Gurion University of the Negev | Dori A.,Joseph Sagol Neuroscience Center | Kofman O.,Ben - Gurion University of the Negev
Behavioural Pharmacology | Year: 2014

The long-term effects of postnatal exposure to an organophosphate substance diisopropylfluorophosphate (DFP) were examined on fear conditioning in adult mice. Immediate and long-term changes in the expression of synaptic acetylcholinesterase (AChE-S) and readthrough acetylcholinesterase (AChE-R) transcripts were explored, in view of reports relating expression of these splice variants to stress and anxiety. BALB/c and C57BL/6 mice were injected daily, on postnatal days 4-10, with 1mg/kg of DFP or saline and tested as adults for cued and contextual freezing and scanning. Real-time PCR was used to investigate expression of the rare AChE-R and AChE-S mRNA postnatally and in fear-conditioned adults. DFP-pretreated male mice showed increased conditioned cued scanning and both male and female DFP-treated mice showed enhanced contextual scanning. DFP abolished the stress-induced increase in AChE transcript expression in BALB/c but not in C57BL/6 mice. A significant correlation was found between expression of AChE-S and AChE-R transcripts in the hippocampus and scanning behavior, but this was apparently unrelated to DFP treatment. The enhanced conditioned scanning in adults, following postnatal exposure to DFP, suggests long-term effects on the risk for anxiety disorders. The altered expression of AChE splice variant transcripts in the two strains did not account for the behavioral deficits, which were observed in both BALB/c and C57BL/6 strains. © 2014 Wolters Kluwer Health. Source

Beeri M.S.,Mount Sinai School of Medicine | Beeri M.S.,Joseph Sagol Neuroscience Center | Sonnen J.,University of Utah
Neurology | Year: 2016

Despite great scientific efforts to find treatments for Alzheimer disease (AD), only 5 medications are marketed, with limited beneficial effects on symptoms, on a limited proportion of patients, without modification of the disease course. The prevalence of AD doubles every 5 years, reaching the alarming rate of 50% in those aged 85 years and older. In the context of the demographic trends of modern society, where the elderly are the fastest growing segment of the population, identification of new therapeutic targets that may prevent, delay, or cure AD is critically needed. © 2016 American Academy of Neurology. Source

Ravona-Springer R.,The Medical Memory | Beeri M.S.,Mount Sinai School of Medicine | Beeri M.S.,Joseph Sagol Neuroscience Center | Goldbourt U.,Tel Aviv University
Journal of Alzheimer's Disease | Year: 2013

The present study aimed to assess the relationship of midlife Motivation to Improve Status at work (MIS) with dementia more than three decades later. In 1963, 9,920 out of 10,059 male participants of the Israel Ischemic Heart disease (IIHD) study, aged 40-65 years, were questioned about their MIS as follows: 'Do you want to improve your status at work and do you believe it is possible?'. One of four answers was possible: trying to change status and believe it is possible (MIS1) (n = 3,060); trying but unsure of success (MIS2) (n = 2,618); not trying, unlikely to succeed (MIS3) (n = 2,020); not trying, satisfied (MIS4) (n = 2,222). Dementia was assessed over three decades later in 1,714 survivors of the original cohort, including 1,691 who responded in 1963 to the questionnaire regarding MIS. Controlling for age, the estimated odds for dementia relative to MIS1 were 1.45 (95% CI 1.06-2.01) in MIS2, 1.52 (95% CI 1.04-2.23) in MIS3, and 1.96 (95% CI 1.38-2.81) in MIS4. Further adjustment for age and socioeconomic status index resulted in adjusted estimated odds for dementia relative to MIS1 were 1.26 (95% CI 0.90-1.75) in MIS2, 1.10 (95% CI 0.74-1.64) in MIS3, and 1.78 (95% CI 1.23-2.56) in MIS4. These results were not attenuated when midlife diabetes, blood pressure values, serum-cholesterol levels, and coronary heart disease were controlled for in the analysis. Among tenured working men, lack of MIS together with satisfaction with current status was associated with higher risk for dementia among survivors several decades later. This association was partially attenuated by socioeconomic status. © 2013 - IOS Press and the authors. All rights reserved. Source

Ravona-Springer R.,The Medical Memory | Heymann A.,Tel Aviv University | Schmeidler J.,Mount Sinai School of Medicine | Guerrero-Berroa E.,Mount Sinai School of Medicine | And 8 more authors.
Diabetes Care | Year: 2013

OBJECTIVE Haptoglobin (Hp) genotype (Hp 1-1, 1-2, or 2-2) is associated with risk for type 2 diabetes complications, but its relationship with cognitive compromise, a growing concern in type 2 diabetes, has rarely been studied. This study investigated whether Hp genotype is associated with cognitive function in cognitively normal elderly diabetic subjects. RESEARCH DESIGN AND METHODSdRelationships of Hp genotype with episodic memory, semantic categorization, attention/working memory and executive function, and an overall cognitive score were examined in subjects from the Israel Diabetes and Cognitive Decline (IDCD) study. RESULTSdIn the present analysis, 812 subjects participated (84 with Hp 1-1, 335 with Hp 1-2, and 393 with Hp 2-2 genotypes). Average was 72.9 years of age (SD 4.7), and Mini-Mental State Exam (MMSE) was 28.0 (SD 1.8). Compared with subjects with Hp 1-2 genotype, Hp 1-1 subjects performed significantly worse in semantic categorization (F = 7.03; P = 0.008) and the overall cognitive score (F = 5.57; P = 0.02). A separate stepwise multiple regression analysis demonstrated that compared with subjects with Hp 2-2 genotype, Hp 1-1 subjects performed significantlyworse in semantic categorization (F = 4.18; P = 0.04) and the overall cognitive score (F = 4.70; P = 0.03). The contribution of cardiovascular risk factors to cognition was significantly higher in subjects with Hp 1-1 genotype compared with Hp 2 carriers (Hp 1-2 and Hp 2-2) in the semantic categorization (P = 0.009) and attention/working memory (P = 0.002) cognitive domains. CONCLUSIONSdCompared with Hp 2 carriers, those with Hp 1-1 genotype present lower cognitive performance. Stronger relationships between cardiovascular risk factors and cognition in the latter group may suggest an underlying vascular mechanism. © 2013 by the American Diabetes Association. Source

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