Hippocampal dysfunction and cognitive impairments provoked by chronic early-life stress involve excessive activation of CRH receptors

PubMed Central

Ivy, Autumn S.; Rex, Christopher S.; Chen, Yuncai; Dubé, Céline; Maras, Pamela M.; Grigoriadis, Dimitri E.; Gall, Christine M.; Lynch, Gary; Baram, Tallie Z.

2010-01-01

Chronic stress impairs learning and memory in humans and rodents and disrupts long-term potentiation (LTP) in animal models. These effects are associated with structural changes in hippocampal neurons, including reduced dendritic arborization. Unlike the generally reversible effects of chronic stress on adult rat hippocampus, we have previously found that the effects of early-life stress endure and worsen during adulthood, yet the mechanisms for these clinically important sequelae are poorly understood. Stress promotes secretion of the neuropeptide corticotropin-releasing hormone (CRH) from hippocampal interneurons, activating receptors (CRF1) located on pyramidal cell dendrites. Additionally, chronic CRF1 occupancy negatively affects dendritic arborization in mouse organotypic slice cultures, similar to the pattern observed in middle-aged, early-stressed (CES) rats. Here we found that CRH-expression is augmented in hippocampus of middle-aged CES rats, and then tested if the morphological defects and poor memory performance in these animals involve excessive activation of CRF1 receptors. Central or peripheral administration of a CRF1 blocker following the stress period improved memory performance of CES rats in novel object recognition tests and in the Morris water maze. Consonant with these effects, the antagonist also prevented dendritic atrophy and LTP attenuation in CA1 Schaffer collateral synapses. Together, these data suggest that persistently elevated hippocampal CRH-CRF1 interaction contributes importantly to the structural and cognitive impairments associated with early-life stress. Reducing CRF1 occupancy post-hoc normalized hippocampal function during middle-age, thus offering potential mechanism-based therapeutic interventions for children affected by chronic stress. PMID:20881118

Neurogenic function in rats with unilateral hippocampal sclerosis that experienced early-life status epilepticus

PubMed Central

Dunleavy, Mark; Schindler, Clara K; Shinoda, Sachiko; Crilly, Shane; Henshall, David C

2014-01-01

Status epilepticus in the adult brain invariably causes an increase in hippocampal neurogenesis and the appearance of ectopic cells and this has been implicated as a causal factor in epileptogenesis. The effect of status epilepticus on neurogenesis in the developing brain is less well characterized and models of early-life seizures typically do not reproduce the hippocampal damage common to human mesial temporal sclerosis. We recently reported that evoking status epilepticus by intra-amygdala microinjection of kainic acid in post-natal (P) day 10 rats caused substantial acute neuronal death within the ipsilateral hippocampus and rats later developed unilateral hippocampal sclerosis and spontaneous recurrent seizures. Here, we examined the expression of a selection of genes associated with neurogenesis and assessed neurogenic function in this model. Protein levels of several markers of neurogenesis including polysialic acid neural cell adhesion molecule, neuroD and doublecortin were reduced in the hippocampus three days after status epilepticus in P10 rats. In contrast, protein levels of neurogenesis markers were similar to control in rats at P55. Pulse-chase experiments using thymidine analogues suggested there was a reduction in new neurons at 72 h after status epilepticus in P10 rats, whereas numbers of new neurons labelled in epileptic rats at P55 with hippocampal sclerosis were similar to controls. The present study suggests that status epilepticus in the immature brain suppresses neurogenesis but the neurogenic potential is retained in animals that later develop hippocampal sclerosis. PMID:25755841

The Influence of DAT1, COMT, and BDNF Genetic Polymorphisms on Total and Subregional Hippocampal Volumes in Early Onset Heavy Cannabis Users.

PubMed

Batalla, Albert; Lorenzetti, Valentina; Chye, Yann; Yücel, Murat; Soriano-Mas, Carles; Bhattacharyya, Sagnik; Torrens, Marta; Crippa, José A S; Martín-Santos, Rocío

2018-01-01

Introduction: Hippocampal neuroanatomy is affected by genetic variations in dopaminergic candidate genes and environmental insults, such as early onset of chronic cannabis exposure. Here, we examine how hippocampal total and subregional volumes are affected by cannabis use and functional polymorphisms of dopamine-relevant genes, including the catechol-O-methyltransferase (COMT), dopamine transporter (DAT1), and the brain-derived neurotrophic factor (BDNF) genes. Material and Methods: We manually traced total hippocampal volumes and automatically segmented hippocampal subregions using high-resolution MRI images, and performed COMT, DAT1, and BDNF genotyping in 59 male Caucasian young adults aged 18-30 years. These included 30 chronic cannabis users with early-onset (regular use at <16 years) and 29 age-, education-, and intelligence-matched controls. Results: Cannabis use and dopaminergic gene polymorphism had both distinct and interactive effects on the hippocampus. We found emerging alterations of hippocampal total and specific subregional volumes in cannabis users relative to controls (i.e., CA1, CA2/3, and CA4), and associations between cannabis use levels and total and specific subregional volumes. Furthermore, total hippocampal volume and the fissure subregion were affected by cannabis×DAT1 polymorphism (i.e., 9/9R and in 10/10R alleles), reflecting high and low levels of dopamine availability. Conclusion: These findings suggest that cannabis exposure alters the normal relationship between DAT1 polymorphism and the anatomy of total and subregional hippocampal volumes, and that specific hippocampal subregions may be particularly affected.

The prevalence and quality of silent, socially silent, and disclosed autobiographical memories across adulthood.

PubMed

Alea, Nicole

2010-02-01

Two separate studies examined the prevalence and quality of silent (infrequently recalled), socially silent (i.e., recalled but not shared), and disclosed autobiographical memories. In Study 1 young and older men and women remembered positive events. Positive memories were more likely to be disclosed than to be kept socially silent or completely silent. However, socially silent and disclosed memories did not differ in memory quality: the memories were equally vivid, significant, and emotional. Silent memories were less qualitatively rich. This pattern of results was generally replicated in Study 2 with a lifespan sample for both positive and negative memories, and with additional qualitative variables. The exception was that negative memories were kept silent more often. Age differences were minimal. Women disclosed their autobiographical memories more, but men told a greater variety of people. Results are discussed in terms of the functions that memory telling and silences might serve for individuals.

The interplay of early-life stress, nutrition, and immune activation programs adult hippocampal structure and function

PubMed Central

Hoeijmakers, Lianne; Lucassen, Paul J.; Korosi, Aniko

2015-01-01

Early-life adversity increases the vulnerability to develop psychopathologies and cognitive decline later in life. This association is supported by clinical and preclinical studies. Remarkably, experiences of stress during this sensitive period, in the form of abuse or neglect but also early malnutrition or an early immune challenge elicit very similar long-term effects on brain structure and function. During early-life, both exogenous factors like nutrition and maternal care, as well as endogenous modulators, including stress hormones and mediator of immunological activity affect brain development. The interplay of these key elements and their underlying molecular mechanisms are not fully understood. We discuss here the hypothesis that exposure to early-life adversity (specifically stress, under/malnutrition and infection) leads to life-long alterations in hippocampal-related cognitive functions, at least partly via changes in hippocampal neurogenesis. We further discuss how these different key elements of the early-life environment interact and affect one another and suggest that it is a synergistic action of these elements that shapes cognition throughout life. Finally, we consider different intervention studies aiming to prevent these early-life adversity induced consequences. The emerging evidence for the intriguing interplay of stress, nutrition, and immune activity in the early-life programming calls for a more in depth understanding of the interaction of these elements and the underlying mechanisms. This knowledge will help to develop intervention strategies that will converge on a more complete set of changes induced by early-life adversity. PMID:25620909

The Influence of DAT1, COMT, and BDNF Genetic Polymorphisms on Total and Subregional Hippocampal Volumes in Early Onset Heavy Cannabis Users

PubMed Central

Batalla, Albert; Lorenzetti, Valentina; Chye, Yann; Yücel, Murat; Soriano-Mas, Carles; Bhattacharyya, Sagnik; Torrens, Marta; Crippa, José A.S.; Martín-Santos, Rocío

2018-01-01

Abstract Introduction: Hippocampal neuroanatomy is affected by genetic variations in dopaminergic candidate genes and environmental insults, such as early onset of chronic cannabis exposure. Here, we examine how hippocampal total and subregional volumes are affected by cannabis use and functional polymorphisms of dopamine-relevant genes, including the catechol-O-methyltransferase (COMT), dopamine transporter (DAT1), and the brain-derived neurotrophic factor (BDNF) genes. Material and Methods: We manually traced total hippocampal volumes and automatically segmented hippocampal subregions using high-resolution MRI images, and performed COMT, DAT1, and BDNF genotyping in 59 male Caucasian young adults aged 18–30 years. These included 30 chronic cannabis users with early-onset (regular use at <16 years) and 29 age-, education-, and intelligence-matched controls. Results: Cannabis use and dopaminergic gene polymorphism had both distinct and interactive effects on the hippocampus. We found emerging alterations of hippocampal total and specific subregional volumes in cannabis users relative to controls (i.e., CA1, CA2/3, and CA4), and associations between cannabis use levels and total and specific subregional volumes. Furthermore, total hippocampal volume and the fissure subregion were affected by cannabis×DAT1 polymorphism (i.e., 9/9R and in 10/10R alleles), reflecting high and low levels of dopamine availability. Conclusion: These findings suggest that cannabis exposure alters the normal relationship between DAT1 polymorphism and the anatomy of total and subregional hippocampal volumes, and that specific hippocampal subregions may be particularly affected. PMID:29404409

Perspectives on the "Silent Period" for Emergent Bilinguals in England

ERIC Educational Resources Information Center

Bligh, Caroline; Drury, Rose

2015-01-01

This article draws together the research findings from two ethnographic studies as a means to problematize the "silent period" as experienced by young bilingual learners in two English speaking early-years settings in England. Most teachers and senior early-years practitioners in England are monolingual English speakers. The children…

Polygenic Risk Score for Alzheimer's Disease: Implications for Memory Performance and Hippocampal Volumes in Early Life.

PubMed

Axelrud, Luiza K; Santoro, Marcos L; Pine, Daniel S; Talarico, Fernanda; Gadelha, Ary; Manfro, Gisele G; Pan, Pedro M; Jackowski, Andrea; Picon, Felipe; Brietzke, Elisa; Grassi-Oliveira, Rodrigo; Bressan, Rodrigo A; Miguel, Eurípedes C; Rohde, Luis A; Hakonarson, Hakon; Pausova, Zdenka; Belangero, Sintia; Paus, Tomas; Salum, Giovanni A

2018-06-01

Alzheimer's disease is a heritable neurodegenerative disorder in which early-life precursors may manifest in cognition and brain structure. The authors evaluate this possibility by examining, in youths, associations among polygenic risk score for Alzheimer's disease, cognitive abilities, and hippocampal volume. Participants were children 6-14 years of age in two Brazilian cities, constituting the discovery (N=364) and replication samples (N=352). As an additional replication, data from a Canadian sample (N=1,029), with distinct tasks, MRI protocol, and genetic risk, were included. Cognitive tests quantified memory and executive function. Reading and writing abilities were assessed by standardized tests. Hippocampal volumes were derived from the Multiple Automatically Generated Templates (MAGeT) multi-atlas segmentation brain algorithm. Genetic risk for Alzheimer's disease was quantified using summary statistics from the International Genomics of Alzheimer's Project. Analyses showed that for the Brazilian discovery sample, each one-unit increase in z-score for Alzheimer's polygenic risk score significantly predicted a 0.185 decrement in z-score for immediate recall and a 0.282 decrement for delayed recall. Findings were similar for the Brazilian replication sample (immediate and delayed recall, β=-0.259 and β=-0.232, both significant). Quantile regressions showed lower hippocampal volumes bilaterally for individuals with high polygenic risk scores. Associations fell short of significance for the Canadian sample. Genetic risk for Alzheimer's disease may affect early-life cognition and hippocampal volumes, as shown in two independent samples. These data support previous evidence that some forms of late-life dementia may represent developmental conditions with roots in childhood. This result may vary depending on a sample's genetic risk and may be specific to some types of memory tasks.

Hippocampal and Amygdalar Volumes in Dissociative Identity Disorder

PubMed Central

Vermetten, Eric; Schmahl, Christian; Lindner, Sanneke; Loewenstein, Richard J.; Bremner, J. Douglas

2011-01-01

Objective Smaller hippocampal volume has been reported in several stress-related psychiatric disorders, including posttraumatic stress disorder (PTSD), borderline personality disorder with early abuse, and depression with early abuse. Patients with borderline personality disorder and early abuse have also been found to have smaller amygdalar volume. The authors examined hippocampal and amygdalar volumes in patients with dissociative identity disorder, a disorder that has been associated with a history of severe childhood trauma. Method The authors used magnetic resonance imaging to measure the volumes of the hippocampus and amygdala in 15 female patients with dissociative identity disorder and 23 female subjects without dissociative identity disorder or any other psychiatric disorder. The volumetric measurements for the two groups were compared. Results Hippocampal volume was 19.2% smaller and amygdalar volume was 31.6% smaller in the patients with dissociative identity disorder, compared to the healthy subjects. The ratio of hippocampal volume to amygdalar volume was significantly different between groups. Conclusions The findings are consistent with the presence of smaller hippocampal and amygdalar volumes in patients with dissociative identity disorder, compared with healthy subjects. PMID:16585437

Hippocampal and amygdalar volumes in dissociative identity disorder.

PubMed

Vermetten, Eric; Schmahl, Christian; Lindner, Sanneke; Loewenstein, Richard J; Bremner, J Douglas

2006-04-01

Smaller hippocampal volume has been reported in several stress-related psychiatric disorders, including posttraumatic stress disorder (PTSD), borderline personality disorder with early abuse, and depression with early abuse. Patients with borderline personality disorder and early abuse have also been found to have smaller amygdalar volume. The authors examined hippocampal and amygdalar volumes in patients with dissociative identity disorder, a disorder that has been associated with a history of severe childhood trauma. The authors used magnetic resonance imaging to measure the volumes of the hippocampus and amygdala in 15 female patients with dissociative identity disorder and 23 female subjects without dissociative identity disorder or any other psychiatric disorder. The volumetric measurements for the two groups were compared. Hippocampal volume was 19.2% smaller and amygdalar volume was 31.6% smaller in the patients with dissociative identity disorder, compared to the healthy subjects. The ratio of hippocampal volume to amygdalar volume was significantly different between groups. The findings are consistent with the presence of smaller hippocampal and amygdalar volumes in patients with dissociative identity disorder, compared with healthy subjects.

The extended trajectory of hippocampal development: implications for early memory development and disorder

PubMed Central

Gómez, Rebecca L.; Edgin, Jamie O.

2015-01-01

Hippocampus has an extended developmental trajectory, with refinements occurring in the trisynaptic circuit until adolescence. While structural change should suggest a protracted course in behavior, some studies find evidence of precocious hippocampal development in the first postnatal year and continuity in memory processes beyond. However, a number of memory functions, including binding and relational inference, can be cortically supported. Evidence from the animal literature suggests that tasks often associated with hippocampus (Visual Paired Comparison, binding of a visuomotor response) can be mediated by structures external to hippocampus. Thus, a complete examination of memory development will have to rule out cortex as a source of early memory competency. We propose that early memory must show properties associated with full function of the trisynaptic circuit to reflect “adult-like” memory function, mainly 1) rapid encoding of contextual details of overlapping patterns, and 2) retention of these details over sleep-dependent delays. A wealth of evidence suggests that these functions are not apparent until 18–24 months, with behavioral discontinuities reflecting shifts in the neural structures subserving memory beginning approximately at this point in development. We discuss the implications of these observations for theories of memory and for identifying and measuring memory function in populations with typical and atypical hippocampal function. PMID:26437910

Memory-related hippocampal activation in the sleeping toddler.

PubMed

Prabhakar, Janani; Johnson, Elliott G; Nordahl, Christine Wu; Ghetti, Simona

2018-06-19

Nonhuman research has implicated developmental processes within the hippocampus in the emergence and early development of episodic memory, but methodological challenges have hindered assessments of this possibility in humans. Here, we delivered a previously learned song and a novel song to 2-year-old toddlers during natural nocturnal sleep and, using functional magnetic resonance imaging, found that hippocampal activation was stronger for the learned song compared with the novel song. This was true regardless of whether the song was presented intact or backwards. Toddlers who remembered where and in the presence of which toy character they heard the song exhibited stronger hippocampal activation for the song. The results establish that hippocampal activation in toddlers reflects past experiences, persists despite some alteration of the stimulus, and is associated with behavior. This research sheds light on early hippocampal and memory functioning and offers an approach to interrogate the neural substrates of early memory.

A Silent Safety Program

NASA Technical Reports Server (NTRS)

Goodin, James Ronald

2006-01-01

NASA's Columbia Accident Investigation Board (CAIB) referred 8 times to the NASA "Silent Safety Program." This term, "Silent Safety Program" was not an original observation but first appeared in the Rogers Commission's Investigation of the Challenger Mishap. The CAIB on page 183 of its report in the paragraph titled 'Encouraging Minority Opinion,' stated "The Naval Reactor Program encourages minority opinions and "bad news." Leaders continually emphasize that when no minority opinions are present, the responsibility for a thorough and critical examination falls to management. . . Board interviews revealed that it is difficult for minority and dissenting opinions to percolate up through the agency's hierarchy. . ." The first question and perhaps the only question is - what is a silent safety program? Well, a silent safety program may be the same as the dog that didn't bark in Sherlock Holmes' "Adventure of the Silver Blaze" because system safety should behave as a devil's advocate for the program barking on every occasion to insure a critical review inclusion. This paper evaluates the NASA safety program and provides suggestions to prevent the recurrence of the silent safety program alluded to in the Challenger Mishap Investigation. Specifically targeted in the CAM report, "The checks and balances the safety system was meant to provide were not working." A silent system safety program is not unique to NASA but could emerge in any and every organization. Principles developed by Irving Janis in his book, Groupthink, listed criteria used to evaluate an organization's cultural attributes that allows a silent safety program to evolve. If evidence validates Jams's criteria, then Jams's recommendations for preventing groupthink can also be used to improve a critical evaluation and thus prevent the development of a silent safety program.

The hippocampal physiology of approaching middle-age: early indicators of change.

PubMed

Huxter, John R; Miranda, Jason A; Dias, Rebecca

2012-09-01

Age-related cognitive decline presents serious lifestyle challenges, and anatomical changes to the hippocampus are often implicated in clinical conditions later in life. However, relatively little is known about how hippocampal physiology is altered in the transition to middle-age, when early detection may offer the best opportunity for successful treatment. High-yield extracellular recording is a powerful tool for understanding brain function in freely moving animals at single-cell resolution and with millisecond precision. We used this technique to characterize changes to hippocampal physiology associated with maturation in 35-week-old rats. Combining a series of behavioral tasks with recordings of large numbers of neurons, local field potentials (LFP), and network patterns of activation, we were able to generate a comprehensive picture based on more than 25 different assays for each subject. Notable changes associated with aging included increased firing rates in interneurons, reduced LFP power but increased frequency in the 4-12 Hz theta band, and impairment in hippocampal pattern-separation for different environments. General properties of pyramidal cell firing and spatial map integrity were preserved. There was no impairment in theta phase-precession, experience-dependent place field expansion, or sleep reactivation of waking network patterns. There were however changes in foraging strategy and behavioral responses to the introduction of a novel environment. Taken together the results reveal a diverse pattern of changes which are of increasing relevance in an aging population. They also highlight areas where high-yield electrophysiological assays can be used to provide the sensitivity and throughput required for pre-clinical drug-discovery programs. Copyright © 2012 Wiley Periodicals, Inc.

The silent patent ductus arteriosus.

PubMed

Chehab, Ghassan; Saliba, Zakhia; El-Rassi, Issam

2008-01-01

To describe the characteristics and outcome of children with an isolated silent patent ductus arteriosus (SPDA), with comparison to non-silent ducts. Between 1999 and 2004, all consecutive cases of isolated silent and non-silent-patent ductus were recorded at the National Register of Pediatric and Congenital Heart Disease, Lebanese Society of Cardiology. Patients with a SPDA were followed clinically and by Doppler echocardiography while all non-SPDA were percutaneously or surgically closed. Twenty-four cases of isolated SPDA and 50 cases of isolated non-SPDA ducts were recorded. Male sex was significantly predominant in the silent group (70%). First-cousin consanguinity rates were not different between both groups, with 20.4% for the silent group versus 22% for the non-silent group. Down's syndrome was associated in three cases of SPDA. No cases of endocarditis were noted during a mean follow-up of 33.3 months. Four patients with a SPDA experienced spontaneous closure at the age of 25, 30, 36 and 58 months. SPDA is a relatively benign disease. The risk of endocarditis cannot be totally ignored, but the systematic closure of the SPDA is not warranted. Larger series and longer follow-up are needed in order to draw conclusions. Spontaneous closure occurred in four patients with SPDA.

The extended trajectory of hippocampal development: Implications for early memory development and disorder.

PubMed

Gómez, Rebecca L; Edgin, Jamie O

2016-04-01

Hippocampus has an extended developmental trajectory, with refinements occurring in the trisynaptic circuit until adolescence. While structural change should suggest a protracted course in behavior, some studies find evidence of precocious hippocampal development in the first postnatal year and continuity in memory processes beyond. However, a number of memory functions, including binding and relational inference, can be cortically supported. Evidence from the animal literature suggests that tasks often associated with hippocampus (visual paired comparison, binding of a visuomotor response) can be mediated by structures external to hippocampus. Thus, a complete examination of memory development will have to rule out cortex as a source of early memory competency. We propose that early memory must show properties associated with full function of the trisynaptic circuit to reflect "adult-like" memory function, mainly (1) rapid encoding of contextual details of overlapping patterns, and (2) retention of these details over sleep-dependent delays. A wealth of evidence suggests that these functions are not apparent until 18-24 months, with behavioral discontinuities reflecting shifts in the neural structures subserving memory beginning approximately at this point in development. We discuss the implications of these observations for theories of memory and for identifying and measuring memory function in populations with typical and atypical hippocampal function. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

The threat of silent earthquakes

USGS Publications Warehouse

Cervelli, Peter

2004-01-01

Not all earthquakes shake the ground. The so-called silent types are forcing scientists to rethink their understanding of the way quake-prone faults behave. In rare instances, silent earthquakes that occur along the flakes of seaside volcanoes may cascade into monstrous landslides that crash into the sea and trigger towering tsunamis. Silent earthquakes that take place within fault zones created by one tectonic plate diving under another may increase the chance of ground-shaking shocks. In other locations, however, silent slip may decrease the likelihood of destructive quakes, because they release stress along faults that might otherwise seem ready to snap.

Features of owl wings that promote silent flight

PubMed Central

Weger, Matthias; Klaas, Michael; Schröder, Wolfgang

2017-01-01

Owls are an order of birds of prey that are known for the development of a silent flight. We review here the morphological adaptations of owls leading to silent flight and discuss also aerodynamic properties of owl wings. We start with early observations (until 2005), and then turn to recent advances. The large wings of these birds, resulting in low wing loading and a low aspect ratio, contribute to noise reduction by allowing slow flight. The serrations on the leading edge of the wing and the velvet-like surface have an effect on noise reduction and also lead to an improvement of aerodynamic performance. The fringes at the inner feather vanes reduce noise by gliding into the grooves at the lower wing surface that are formed by barb shafts. The fringed trailing edge of the wing has been shown to reduce trailing edge noise. These adaptations to silent flight have been an inspiration for biologists and engineers for the development of devices with reduced noise production. Today several biomimetic applications such as a serrated pantograph or a fringed ventilator are available. Finally, we discuss unresolved questions and possible future directions. PMID:28163870

Impairment on a self-ordered working memory task in patients with early-acquired hippocampal atrophy.

PubMed

Geva, Sharon; Cooper, Janine M; Gadian, David G; Mishkin, Mortimer; Vargha-Khadem, Faraneh

2016-08-01

One of the features of both adult-onset and developmental forms of amnesia resulting from bilateral medial temporal lobe damage, or even from relatively selective damage to the hippocampus, is the sparing of working memory. Recently, however, a number of studies have reported deficits on working memory tasks in patients with damage to the hippocampus and in macaque monkeys with neonatal hippocampal lesions. These studies suggest that successful performance on working memory tasks with high memory load require the contribution of the hippocampus. Here we compared performance on a working memory task (the Self-ordered Pointing Task), between patients with early onset hippocampal damage and a group of healthy controls. Consistent with the findings in the monkeys with neonatal lesions, we found that the patients were impaired on the task, but only on blocks of trials with intermediate memory load. Importantly, only intermediate to high memory load blocks yielded significant correlations between task performance and hippocampal volume. Additionally, we found no evidence of proactive interference in either group, and no evidence of an effect of time since injury on performance. We discuss the role of the hippocampus and its interactions with the prefrontal cortex in serving working memory. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Early effects of whole-body (56)Fe irradiation on hippocampal function in C57BL/6J mice.

PubMed

Haley, Gwendolen E; Yeiser, Lauren; Olsen, Reid H J; Davis, Matthew J; Johnson, Lance A; Raber, Jacob

2013-05-01

Relatively little is known about early irradiation effects on hippocampal function in wild-type mice. In this study, the effects of (56)Fe irradiation on hippocampal function were assessed starting 2 weeks after whole-body irradiation. Compared to sham irradiation, radiation impaired novel object recognition in female and male C57BL/6J wild-type mice. There were no effects of irradiation on contextual fear conditioning or spatial memory retention in the water maze. It is possible that oxidative damage might contribute to radiation-induced cognitive changes. Therefore, hippocampal and cortical levels of 3-nitrotyrosine (3NT) and lipid peroxidation, measures of oxidative damage were assessed. There were no effects of irradiation on these measures of oxidative damage. As (56)Fe irradiation can increase reactive oxygen species (ROS) levels, which may contribute to the impairments in novel object recognition, the effects of the antioxidant alpha-lipoic acid (ALA) on cognition following sham irradiation and irradiation were also assessed. ALA did not prevent radiation-induced impairments in novel object recognition and impaired spatial memory retention of sham-irradiated and irradiated mice in the probe trial after the first day of hidden platform training in the water maze. Thus, the novel object recognition test is particularly sensitive to detect early cognitive effects of (56)Fe irradiation through a mechanism unlikely involving ROS or oxidative damage.

Ablation of proliferating neural stem cells during early life is sufficient to reduce adult hippocampal neurogenesis.

PubMed

Youssef, Mary; Krish, Varsha S; Kirshenbaum, Greer S; Atsak, Piray; Lass, Tamara J; Lieberman, Sophie R; Leonardo, E David; Dranovsky, Alex

2018-05-09

Environmental exposures during early life, but not during adolescence or adulthood, lead to persistent reductions in neurogenesis in the adult hippocampal dentate gyrus (DG). The mechanisms by which early life exposures lead to long-term deficits in neurogenesis remain unclear. Here, we investigated whether targeted ablation of dividing neural stem cells during early life is sufficient to produce long-term decreases in DG neurogenesis. Having previously found that the stem cell lineage is resistant to long-term effects of transient ablation of dividing stem cells during adolescence or adulthood (Kirshenbaum et al., 2014), we used a similar pharmacogenetic approach to target dividing neural stem cells for elimination during early life periods sensitive to environmental insults. We then assessed the Nestin stem cell lineage in adulthood. We found that the adult neural stem cell reservoir was depleted following ablation during the first postnatal week, when stem cells were highly proliferative, but not during the third postnatal week, when stem cells were more quiescent. Remarkably, ablating proliferating stem cells during either the first or third postnatal week led to reduced adult neurogenesis out of proportion to the changes in the stem cell pool, indicating a disruption of the stem cell function or niche following stem cell ablation in early life. These results highlight the first three postnatal weeks as a series of sensitive periods during which elimination of dividing stem cells leads to lasting alterations in adult DG neurogenesis and stem cell function. These findings contribute to our understanding of the relationship between DG development and adult neurogenesis, as well as suggest a possible mechanism by which early life experiences may lead to lasting deficits in adult hippocampal neurogenesis. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Underlying skills of oral and silent reading.

PubMed

van den Boer, Madelon; van Bergen, Elsje; de Jong, Peter F

2014-12-01

Many studies have examined reading and reading development. The majority of these studies, however, focused on oral reading rather than on the more dominant silent reading mode. Similarly, it is common practice to assess oral reading abilities rather than silent reading abilities in schools and in diagnosis of reading impairments. More important, insights gained through examinations of oral reading tend to be generalized to silent reading. In the current study, we examined whether such generalizations are justified. We directly compared oral and silent reading fluency by examining whether these reading modes relate to the same underlying skills. In total, 132 fourth graders read words, sentences, and text orally, and 123 classmates read the same material silently. As underlying skills, we considered phonological awareness, rapid naming, and visual attention span. All skills correlated significantly with both reading modes. Phonological awareness contributed equally to oral and silent reading. Rapid naming, however, correlated more strongly with oral reading than with silent reading. Visual attention span correlated equally strongly with both reading modes but showed a significant unique contribution only to silent reading. In short, we showed that oral and silent reading indeed are fairly similar reading modes, based on the relations with reading-related cognitive skills. However, we also found differences that warrant caution in generalizing findings across reading modes. Copyright © 2014 Elsevier Inc. All rights reserved.

TH-E-BRF-03: A Multivariate Interaction Model for Assessment of Hippocampal Vascular Dose-Response and Early Prediction of Radiation-Induced Neurocognitive Dysfunction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farjam, R; Pramanik, P; Srinivasan, A

Purpose: Vascular injury could be a cause of hippocampal dysfunction leading to late neurocognitive decline in patients receiving brain radiotherapy (RT). Hence, our aim was to develop a multivariate interaction model for characterization of hippocampal vascular dose-response and early prediction of radiation-induced late neurocognitive impairments. Methods: 27 patients (17 males and 10 females, age 31–80 years) were enrolled in an IRB-approved prospective longitudinal study. All patients were diagnosed with a low-grade glioma or benign tumor and treated by 3-D conformal or intensity-modulated RT with a median dose of 54 Gy (50.4–59.4 Gy in 1.8− Gy fractions). Six DCE-MRI scans weremore » performed from pre-RT to 18 months post-RT. DCE data were fitted to the modified Toft model to obtain the transfer constant of gadolinium influx from the intravascular space into the extravascular extracellular space, Ktrans, and the fraction of blood plasma volume, Vp. The hippocampus vascular property alterations after starting RT were characterized by changes in the hippocampal mean values of, μh(Ktrans)τ and μh(Vp)τ. The dose-response, Δμh(Ktrans/Vp)pre->τ, was modeled using a multivariate linear regression considering integrations of doses with age, sex, hippocampal laterality and presence of tumor/edema near a hippocampus. Finally, the early vascular dose-response in hippocampus was correlated with neurocognitive decline 6 and 18 months post-RT. Results: The μh(Ktrans) increased significantly from pre-RT to 1 month post-RT (p<0.0004). The multivariate model showed that the dose effect on Δμh(Ktrans)pre->1M post-RT was interacted with sex (p<0.0007) and age (p<0.00004), with the dose-response more pronounced in older females. Also, the vascular dose-response in the left hippocampus of females was significantly correlated with memory function decline at 6 (r = − 0.95, p<0.0006) and 18 (r = −0.88, p<0.02) months post-RT. Conclusion: The hippocampal

Neonatal allopregnanolone or finasteride administration modifies hippocampal K(+) Cl(-) co-transporter expression during early development in male rats.

PubMed

Mòdol, Laura; Casas, Caty; Llidó, Anna; Navarro, Xavier; Pallarès, Marc; Darbra, Sònia

2014-09-01

The maintenance of levels of endogenous neurosteroids (NS) across early postnatal development of the brain, particularly to the hippocampus, is crucial for their maturation. Allopregnanolone (Allop) is a NS that exerts its effect mainly through the modulation of the GABAA receptor (GABAAR). During early development, GABA, acting through GABAAR, that predominantly produces depolarization shifts to hyperpolarization in mature neurons, around the second postnatal week in rats. Several factors contribute to this change including the progressive increase of the neuron-specific K(+)/Cl(-) co-transporter 2 (KCC2) (a chloride exporter) levels. Thus, we aimed to analyze whether a different profile of NS levels during development is critical and can alter this natural progression of KCC2 stages. We administrated sustained Allop (20mg/kg) or Finasteride (5α-reductase inhibitor, 50mg/kg) from the 5th postnatal day (PD5) to PD9 and assessed changes in the hippocampal expression of KCC2 at transcript and protein levels as well as its active phosphorylated state in male rats. Taken together data indicated that manipulation of NS levels during early development influence KCC2 levels and point out the importance of neonatal NS levels for the hippocampal development. Copyright © 2014 Elsevier Ltd. All rights reserved.

Regular theta-firing neurons in the nucleus incertus during sustained hippocampal activation.

PubMed

Martínez-Bellver, Sergio; Cervera-Ferri, Ana; Martínez-Ricós, Joana; Ruiz-Torner, Amparo; Luque-Garcia, Aina; Luque-Martinez, Aina; Blasco-Serra, Arantxa; Guerrero-Martínez, Juan; Bataller-Mompeán, Manuel; Teruel-Martí, Vicent

2015-04-01

This paper describes the existence of theta-coupled neuronal activity in the nucleus incertus (NI). Theta rhythm is relevant for cognitive processes such as spatial navigation and memory processing, and can be recorded in a number of structures related to the hippocampal activation including the NI. Strong evidence supports the role of this tegmental nucleus in neural circuits integrating behavioural activation with the hippocampal theta rhythm. Theta oscillations have been recorded in the local field potential of the NI, highly coupled to the hippocampal waves, although no rhythmical activity has been reported in neurons of this nucleus. The present work analyses the neuronal activity in the NI in conditions leading to sustained hippocampal theta in the urethane-anaesthetised rat, in order to test whether such activation elicits a differential firing pattern. Wavelet analysis has been used to better define the neuronal activity already described in the nucleus, i.e., non-rhythmical neurons firing at theta frequency (type I neurons) and fast-firing rhythmical neurons (type II). However, the most remarkable finding was that sustained stimulation activated regular-theta neurons (type III), which were almost silent in baseline conditions and have not previously been reported. Thus, we describe the electrophysiological properties of type III neurons, focusing on their coupling to the hippocampal theta. Their spike rate, regularity and phase locking to the oscillations increased at the beginning of the stimulation, suggesting a role in the activation or reset of the oscillation. Further research is needed to address the specific contribution of these neurons to the entire circuit. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Silent PPOs: the stealth discounting of provider reimbursement.

PubMed

Marks, James W

2005-01-01

Physicians are losing millions of dollars per year from payers engaging in abusive discounting practices. One of the worst of these practices is the silent PPO. This article explains what a silent PPO is and how it unlawfully reduces a provider's reimbursement. The article discusses how providers can recognize silent PPOs and how to protect their practices from this discounting. The article also reviews statutes that prohibit or regulate silent PPOs and recent court decisions finding in favor of providers and against silent PPOs.

Anti-Hebbian long-term potentiation in the hippocampal feedback inhibitory circuit.

PubMed

Lamsa, Karri P; Heeroma, Joost H; Somogyi, Peter; Rusakov, Dmitri A; Kullmann, Dimitri M

2007-03-02

Long-term potentiation (LTP), which approximates Hebb's postulate of associative learning, typically requires depolarization-dependent glutamate receptors of the NMDA (N-methyl-D-aspartate) subtype. However, in some neurons, LTP depends instead on calcium-permeable AMPA-type receptors. This is paradoxical because intracellular polyamines block such receptors during depolarization. We report that LTP at synapses on hippocampal interneurons mediating feedback inhibition is "anti-Hebbian":Itis induced by presynaptic activity but prevented by postsynaptic depolarization. Anti-Hebbian LTP may occur in interneurons that are silent during periods of intense pyramidal cell firing, such as sharp waves, and lead to their altered activation during theta activity.

Silent ischemia: silent after all?

PubMed

D'Antono, Bianca; Dupuis, Gilles; Arsenault, André; Burelle, Denis

2008-04-01

To examine the association of nonpain symptoms in men and women with exercise-related silent ischemia, as well as the independence of these findings from other clinical factors. A prospective study of 482 women and 425 men (mean age 58 years) undergoing exercise stress testing with myocardial perfusion imaging. Analyses were performed on 60 women and 155 men with no angina but medical perfusion imaging evidence of ischemia during exercise. The presence of various non-pain-related symptoms. Ischemia is indicated by myocardial perfusion defects on exercise stress testing with single photon emission computed tomography. Women reported more nonangina symptoms than men (P<0.05). They experienced fatigue, hot flushes, tense muscles, shortness of breath and headaches more frequently (P<0.05). Symptoms relating to muscle tension and diaphoresis were associated with ischemia after controlling for pertinent clinical covariates. However, the direction of association differed according to sex and history of coronary artery disease events or procedures. Sensitivity of the detection models showed modest improvements with the addition of these symptoms. While patients who experience silent ischemia experience a number of nonpain symptoms, those symptoms may not be sufficiently specific to ischemia, nor sensitive in detecting ischemia, to be of particular help to physicians in the absence of other clinical information.

Assessing reading fluency in Kenya: Oral or silent assessment?

NASA Astrophysics Data System (ADS)

Piper, Benjamin; Zuilkowski, Stephanie Simmons

2015-04-01

In recent years, the Education for All movement has focused more intensely on the quality of education, rather than simply provision. Many recent and current education quality interventions focus on literacy, which is the core skill required for further academic success. Despite this focus on the quality of literacy instruction in developing countries, little rigorous research has been conducted on critical issues of assessment. This analysis, which uses data from the Primary Math and Reading Initiative (PRIMR) in Kenya, aims to begin filling this gap by addressing a key assessment issue - should literacy assessments in Kenya be administered orally or silently? The authors compared second-grade students' scores on oral and silent reading tasks of the Early Grade Reading Assessment (EGRA) in Kiswahili and English, and found no statistically significant differences in either language. They did, however, find oral reading rates to be more strongly related to reading comprehension scores. Oral assessment has another benefit for programme evaluators - it allows for the collection of data on student errors, and therefore the calculation of words read correctly per minute, as opposed to simply words read per minute. The authors therefore recommend that, in Kenya and in similar contexts, student reading fluency be assessed via oral rather than silent assessment.

Severely impaired hippocampal neurogenesis associates with an early serotonergic deficit in a BAC α-synuclein transgenic rat model of Parkinson's disease

PubMed Central

Kohl, Zacharias; Abdallah, Nada Ben; Vogelgsang, Jonathan; Tischer, Lucas; Deusser, Janina; Amato, Davide; Anderson, Scott; Müller, Christian P.; Riess, Olaf; Masliah, Eliezer; Nuber, Silke; Winkler, Jürgen

2016-01-01

Parkinson's disease (PD) is a multisystem disorder, involving several monoaminergic neurotransmitter systems resulting in a broad range of motor and non-motor symptoms. Pathological hallmarks of PD are the loss of dopaminergic neurons and the accumulation of alpha-synuclein, however also being present in the serotonergic raphe nuclei early in the disease course. The dysfunction of the serotonergic system projecting to the hippocampus might contribute to early non-motor symptoms such as anxiety and depression. The adult hippocampal dentate gyrus (DG), a unique niche of the forebrain continuously generating new neurons, may particularly present enhanced susceptibility towards accumulating alpha-synuclein levels. The underlying molecular mechanisms in the context of neuronal maturation and survival of new-born neurons are yet not well understood. To characterize the effects of overexpression of human full-length alpha-synuclein on hippocampal cellular and synaptic plasticity, we used a recently generated BAC alpha-synuclein transgenic rat model showing important features of PD such as widespread and progressive alpha-synuclein aggregation pathology, dopamine loss and age-dependent motor decline. At the age of four months, thus prior to the occurrence of the motor phenotype, we observed a profoundly impaired dendritogenesis of neuroblasts in the hippocampal DG resulting in severely reduced survival of adult new-born neurons. Diminished neurogenesis concurred with a serotonergic deficit in the hippocampus as defined by reduced levels of serotonin (5-HT) 1B receptor, decreased 5-HT neurotransmitter levels, and a loss of serotonergic nerve terminals innervating the DG/CA3 subfield, while the number of serotonergic neurons in the raphe nuclei remained unchanged. Moreover, alpha-synuclein overexpression reduced proteins involved in vesicle release, in particular synapsin-1 and Rab3 interacting molecule (RIM3), in conjunction with an altered ultrastructural architecture of

Parafoveal Processing in Silent and Oral Reading: Reading Mode Influences the Relative Weighting of Phonological and Semantic Information in Chinese

ERIC Educational Resources Information Center

Pan, Jinger; Laubrock, Jochen; Yan, Ming

2016-01-01

We examined how reading mode (i.e., silent vs. oral reading) influences parafoveal semantic and phonological processing during the reading of Chinese sentences, using the gaze-contingent boundary paradigm. In silent reading, we found in 2 experiments that reading times on target words were shortened with semantic previews in early and late…

Early classification of Alzheimer's disease using hippocampal texture from structural MRI

NASA Astrophysics Data System (ADS)

Zhao, Kun; Ding, Yanhui; Wang, Pan; Dou, Xuejiao; Zhou, Bo; Yao, Hongxiang; An, Ningyu; Zhang, Yongxin; Zhang, Xi; Liu, Yong

2017-03-01

Convergent evidence has been collected to support that Alzheimer's disease (AD) is associated with reduction in hippocampal volume based on anatomical magnetic resonance imaging (MRI) and impaired functional connectivity based on functional MRI. Radiomics texture analysis has been previously successfully used to identify MRI biomarkers of several diseases, including AD, mild cognitive impairment and multiple sclerosis. In this study, our goal was to determine if MRI hippocampal textures, including the intensity, shape, texture and wavelet features, could be served as an MRI biomarker of AD. For this purpose, the texture marker was trained and evaluated from MRI data of 48 AD and 39 normal samples. The result highlights the presence of hippocampal texture abnormalities in AD, and the possibility that texture may serve as a neuroimaging biomarker for AD.

Monitoring Progress toward Independent Silent Reading.

ERIC Educational Resources Information Center

Franc, Lillian H.; Hildebrandt, Jeannette

1984-01-01

Concludes, among other things, that fluent oral reading is an important step toward reading for meaning and independent silent reading and that silent reading should be encouraged from the beginning of reading instruction. (FL)

Hippocampal atrophy and memory dysfunction associated with physical inactivity in community-dwelling elderly subjects: The Sefuri study.

PubMed

Hashimoto, Manabu; Araki, Yuko; Takashima, Yuki; Nogami, Kohjiro; Uchino, Akira; Yuzuriha, Takefumi; Yao, Hiroshi

2017-02-01

Physical inactivity is one of the modifiable risk factors for hippocampal atrophy and Alzheimer's disease. We investigated the relationship between physical activity, hippocampal atrophy, and memory using structural equation modeling (SEM). We examined 213 community-dwelling elderly subjects (99 men and 114 women with a mean age of 68.9 years) without dementia or clinically apparent depression. All participants underwent Mini-Mental State Examination (MMSE) and Rivermead Behavioral Memory Test (RBMT). Physical activities were assessed with a structured questionnaire. We evaluated the degree of hippocampal atrophy (z-score-referred to as ZAdvance hereafter), using a free software program-the voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) based on statistical parametric mapping 8 plus Diffeomorphic Anatomical Registration Through an Exponentiated Lie algebra. Routine magnetic resonance imaging findings were as follows: silent brain infarction, n  = 24 (11.3%); deep white matter lesions, n  = 72 (33.8%); periventricular hyperintensities, n  = 35 (16.4%); and cerebral microbleeds, n  = 14 (6.6%). Path analysis based on SEM indicated that the direct paths from leisure-time activity to hippocampal atrophy (β = -.18, p  < .01) and from hippocampal atrophy to memory dysfunction (RBMT) (β = -.20, p  < .01) were significant. Direct paths from "hippocampus" gray matter volume to RBMT and MMSE were highly significant, while direct paths from "whole brain" gray matter volume to RBMT and MMSE were not significant. The presented SEM model fit the data reasonably well. Based on the present SEM analysis, we found that hippocampal atrophy was associated with age and leisure-time physical inactivity, and hippocampal atrophy appeared to cause memory dysfunction, although we are unable to infer a causal or temporal association between hippocampal atrophy and memory dysfunction from the present observational study.

Hippocampal Contribution to Context Encoding across Development Is Disrupted following Early-Life Adversity.

PubMed

Lambert, Hilary K; Sheridan, Margaret A; Sambrook, Kelly A; Rosen, Maya L; Askren, Mary K; McLaughlin, Katie A

2017-02-15

Context can drastically influence responses to environmental stimuli. For example, a gunshot should provoke a different response at a public park than a shooting range. Little is known about how contextual processing and neural correlates change across human development or about individual differences related to early environmental experiences. Children ( N = 60; 8-19 years, 24 exposed to interpersonal violence) completed a context encoding task during fMRI scanning using a delayed match-to-sample design with neutral, happy, and angry facial cues embedded in realistic background scenes. Outside the scanner, participants completed a memory test for context-face pairings. Context memory and neural correlates of context encoding did not vary with age. Larger hippocampal volume was associated with better context memory. Posterior hippocampus was recruited during context encoding, and greater activation in this region predicted better memory for contexts paired with angry faces. Children exposed to violence had poor memory of contexts paired with angry faces, reduced hippocampal volume, and atypical neural recruitment on encoding trials with angry faces, including reduced hippocampal activation and greater functional connectivity between hippocampus and ventrolateral prefrontal cortex (vlPFC). Greater hippocampus-vlPFC connectivity was associated with worse memory for contexts paired with angry faces. Posterior hippocampus appears to support context encoding, a process that does not exhibit age-related variation from middle childhood to late adolescence. Exposure to dangerous environments in childhood is associated with poor context encoding in the presence of threat, likely due to greater vlPFC-dependent attentional narrowing on threat cues at the expense of hippocampus-dependent processing of the broader context. SIGNIFICANCE STATEMENT The ability to use context to guide reactions to environmental stimuli promotes flexible behavior. Remarkably little research has

Development of hippocampal subfield volumes from 4 to 22 years.

PubMed

Krogsrud, Stine K; Tamnes, Christian K; Fjell, Anders M; Amlien, Inge; Grydeland, Håkon; Sulutvedt, Unni; Due-Tønnessen, Paulina; Bjørnerud, Atle; Sølsnes, Anne E; Håberg, Asta K; Skrane, Jon; Walhovd, Kristine B

2014-11-01

The hippocampus supports several important cognitive functions known to undergo substantial development during childhood and adolescence, for example, encoding and consolidation of vivid personal memories. However, diverging developmental effects on hippocampal volume have been observed across studies. It is possible that the inconsistent findings may attribute to varying developmental processes and functions related to different hippocampal subregions. Most studies to date have measured global hippocampal volume. We aimed to explore early hippocampal development both globally and regionally within subfields. Using cross-sectional 1.5 T magnetic resonance imaging data from 244 healthy participants aged 4-22 years, we performed automated hippocampal segmentation of seven subfield volumes; cornu ammonis (CA) 1, CA2/3, CA4/dentate gyrus (DG), presubiculum, subiculum, fimbria, and hippocampal fissure. For validation purposes, seven subjects were scanned at both 1.5 and 3 T, and all subfields except fimbria showed strong correlations across field strengths. Effects of age, left and right hemisphere, sex and their interactions were explored. Nonparametric local smoothing models (smoothing spline) were used to depict age-trajectories. Results suggested nonlinear age functions for most subfields where volume increases until 13-15 years, followed by little age-related changes during adolescence. Further, the results showed greater right than left hippocampal volumes that seemed to be augmenting in older age. Sex differences were also found for subfields; CA2/3, CA4/DG, presubiculum, subiculum, and CA1, mainly driven by participants under 13 years. These results provide a detailed characterization of hippocampal subfield development from early childhood. Copyright © 2014 Wiley Periodicals, Inc.

Nutritional deficits during early development affect hippocampal structure and spatial memory later in life.

PubMed

Pravosudov, Vladimir V; Lavenex, Pierre; Omanska, Alicja

2005-10-01

Development rates vary among individuals, often as a result of direct competition for food. Survival of young might depend on their learning abilities, but it remains unclear whether learning abilities are affected by nutrition during development. The authors demonstrated that compared with controls, 1-year-old Western scrub jays (Aphelocoma californica) that experienced nutritional deficits during early posthatching development had smaller hippocampi with fewer neurons and performed worse in a cache recovery task and in a spatial version of an associative learning task. In contrast, performance of nutritionally deprived birds was similar to that of controls in 2 color versions of an associative learning task. These findings suggest that nutritional deficits during early development have long-term consequences for hippocampal structure and spatial memory, which, in turn, are likely to have a strong impact on animals' future fitness.

Silent Atrial Fibrillation in Elderly Pacemaker Users: A Randomized Trial Using Home Monitoring.

PubMed

Lima, Ceb; Martinelli, M; Peixoto, G L; Siqueira, S F; Wajngarten, Maurício; Silva, Rodrigo Tavares; Costa, Roberto; Filho, Roberto; Ramires, José Antônio Franchini

2016-05-01

Pacemaker with remote monitoring (PRM) may be useful for silent atrial fibrillation (AF) detection. The aims of this study were to evaluate the incidence of silent AF, the role of PRM, and to determine predictors of silent AF occurrence. Three hundred elderly patients with permanent pacemaker (PPM) were randomly assigned to the remote group (RG) or control group (CG). All patients received PPM with remote monitoring capabilities. Primary end point was AF occurrence rate and the secondary end points were time to AF detection and number of days with AF. During the average follow-up of 15.7±7.7 months, AF episodes were detected in 21.6% (RG = 24% vs CG = 19.3%, P = 0.36]. There was no difference in the time to detect the first AF episode. However, the median time to detect AF recurrence in the RG was lower than that in the CG (54 days vs 100 days, P = 0.004). The average number of days with AF was 16.0 and 51.2 in the RG and CG, respectively (P = 0.028). Predictors of silent AF were left atrial diameter (odds ratio [OR] 1.2; 95% CI = 1.1-1.3; P < 0.001) and diastolic dysfunction (OR 4.8; 95% CI = 1.6-14.0; P = 0.005). The incidence of silent AF is high in elderly patients with pacemaker; left atrial diameter and diastolic dysfunction were predictors of its occurrence. AF monitoring by means of pacemaker is a valuable tool for silent AF detection and continuous remote monitoring allows early AF recurrence detection and reduces the number of days with AF. © 2015 Wiley Periodicals, Inc.

Preschool is a sensitive period for the influence of maternal support on the trajectory of hippocampal development.

PubMed

Luby, Joan L; Belden, Andy; Harms, Michael P; Tillman, Rebecca; Barch, Deanna M

2016-05-17

Building on well-established animal data demonstrating the effects of early maternal support on hippocampal development and adaptive coping, a few longitudinal studies suggest that early caregiver support also impacts human hippocampal development. How caregiving contributes to human hippocampal developmental trajectories, whether there are sensitive periods for these effects, as well as whether related variation in hippocampal development predicts later childhood emotion functioning are of major public health importance. The current study investigated these questions in a longitudinal study of preschoolers assessed annually for behavioral and emotional development, including observed caregiver support. One hundred and twenty-seven children participated in three waves of magnetic resonance brain imaging through school age and early adolescence. Multilevel modeling of the effects of preschool and school-age maternal support on hippocampal volumes across the three waves was conducted. Hippocampal volume increased faster for those with higher levels of preschool maternal support. Subjects with support 1 SD above the mean had a 2.06 times greater increase in total hippocampus volume across the three scans than those with 1 SD below the mean (2.70% vs. 1.31%). No effect of school-age support was found. Individual slopes of hippocampus volume were significantly associated with emotion regulation at scan 3. The findings demonstrate a significant effect of early childhood maternal support on hippocampal volume growth across school age and early adolescence and suggest an early childhood sensitive period for these effects. They also show that this growth trajectory is associated with later emotion functioning.

Secondary Students' Reading Attitudes and Achievement in a Scaffolded Silent Reading Program versus Traditional Sustained Silent Reading

ERIC Educational Resources Information Center

West, Chandra Lorene

2010-01-01

This study explored the reading attitudes and achievement, as well as genre knowledge, of tenth, eleventh, and twelfth-grade students who participated in Scaffolded Silent Reading, Sustained Silent Reading, or a control group. The Reading and You attitude survey, Degrees of Reading Power achievement measure, and Genre Assessment were administered…

Making Data-Driven Decisions: Silent Reading

ERIC Educational Resources Information Center

Trudel, Heidi

2007-01-01

Due in part to conflicting opinions and research results, the practice of sustained silent reading (SSR) in schools has been questioned. After a frustrating experience with SSR, the author of this article began a data-driven decision-making process to gain new insights on how to structure silent reading in a classroom, including a comparison…

Using Complexity Metrics to Assess Silent Reading Fluency: A Cross-Sectional Study Comparing Oral and Silent Reading

ERIC Educational Resources Information Center

O'Brien, Beth A.; Wallot, Sebastian; Haussmann, Anna; Kloos, Heidi

2014-01-01

Reading typically undergoes a qualitative shift around Grade 4, becoming more fluent and silent, but there is no established measure for fluency in children's silent reading. The present study presents a measure of self-paced reading in children, examining the use of complexity measures for time-series analyses recently established with…

Maternal anxiety and infants' hippocampal development: timing matters.

PubMed

Qiu, A; Rifkin-Graboi, A; Chen, H; Chong, Y-S; Kwek, K; Gluckman, P D; Fortier, M V; Meaney, M J

2013-09-24

Exposure to maternal anxiety predicts offspring brain development. However, because children's brains are commonly assessed years after birth, the timing of such maternal influences in humans is unclear. This study aimed to examine the consequences of antenatal and postnatal exposure to maternal anxiety upon early infant development of the hippocampus, a key structure for stress regulation. A total of 175 neonates underwent magnetic resonance imaging (MRI) at birth and among them 35 had repeated scans at 6 months of age. Maternal anxiety was assessed using the State-Trait Anxiety Inventory (STAI) at week 26 of pregnancy and 3 months after delivery. Regression analyses showed that antenatal maternal anxiety did not influence bilateral hippocampal volume at birth. However, children of mothers reporting increased anxiety during pregnancy showed slower growth of both the left and right hippocampus over the first 6 months of life. This effect of antenatal maternal anxiety upon right hippocampal growth became statistically stronger when controlling for postnatal maternal anxiety. Furthermore, a strong positive association between postnatal maternal anxiety and right hippocampal growth was detected, whereas a strong negative association between postnatal maternal anxiety and the left hippocampal volume at 6 months of life was found. Hence, the postnatal growth of bilateral hippocampi shows distinct responses to postnatal maternal anxiety. The size of the left hippocampus during early development is likely to reflect the influence of the exposure to perinatal maternal anxiety, whereas right hippocampal growth is constrained by antenatal maternal anxiety, but enhanced in response to increased postnatal maternal anxiety.

Silent Synapse-Based Circuitry Remodeling in Drug Addiction.

PubMed

Dong, Yan

2016-05-01

Exposure to cocaine, and likely other drugs of abuse, generates α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-silent glutamatergic synapses in the nucleus accumbens. These immature synaptic contacts evolve after drug withdrawal to redefine the neurocircuital properties. These results raise at least three critical questions: (1) what are the molecular and cellular mechanisms that mediate drug-induced generation of silent synapses; (2) how are neurocircuits remodeled upon generation and evolution of drug-generated silent synapses; and (3) what behavioral consequences are produced by silent synapse-based circuitry remodeling? This short review analyzes related experimental results, and extends them to some speculations. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Acute Hippocampal Slice Preparation and Hippocampal Slice Cultures

PubMed Central

Lein, Pamela J.; Barnhart, Christopher D.; Pessah, Isaac N.

2012-01-01

A major advantage of hippocampal slice preparations is that the cytoarchitecture and synaptic circuits of the hippocampus are largely retained. In neurotoxicology research, organotypic hippocampal slices have mostly been used as acute ex vivo preparations for investigating the effects of neurotoxic chemicals on synaptic function. More recently, hippocampal slice cultures, which can be maintained for several weeks to several months in vitro, have been employed to study how neurotoxic chemicals influence the structural and functional plasticity in hippocampal neurons. This chapter provides protocols for preparing hippocampal slices to be used acutely for electrophysiological measurements using glass microelectrodes or microelectrode arrays or to be cultured for morphometric assessments of individual neurons labeled using biolistics. PMID:21815062

Silent Starters

ERIC Educational Resources Information Center

Morris, Emma

2011-01-01

The "silent starter" is an idea that the author was reminded of during Christopher Martin's session at the ATM conference in 2011, entitled "Big Ideas". This was a nice idea for introducing, or practising mappings, but it was not the first time the author had encountered this powerful teaching tool. The idea is best explained…

Extent of hippocampal atrophy predicts degree of deficit in recall.

PubMed

Patai, Eva Zita; Gadian, David G; Cooper, Janine M; Dzieciol, Anna M; Mishkin, Mortimer; Vargha-Khadem, Faraneh

2015-10-13

Which specific memory functions are dependent on the hippocampus is still debated. The availability of a large cohort of patients who had sustained relatively selective hippocampal damage early in life enabled us to determine which type of mnemonic deficit showed a correlation with extent of hippocampal injury. We assessed our patient cohort on a test that provides measures of recognition and recall that are equated for difficulty and found that the patients' performance on the recall tests correlated significantly with their hippocampal volumes, whereas their performance on the equally difficult recognition tests did not and, indeed, was largely unaffected regardless of extent of hippocampal atrophy. The results provide new evidence in favor of the view that the hippocampus is essential for recall but not for recognition.

Controversies in cardiovascular care: silent myocardial ischemia

NASA Technical Reports Server (NTRS)

Hollenberg, N. K.

1987-01-01

The objective evidence of silent myocardial ischemia--ischemia in the absence of classical chest pain--includes ST-segment shifts (usually depression), momentary left ventricular failure, and perfusion defects on scintigraphic studies. Assessment of angina patients with 24-hour ambulatory monitoring may uncover episodes of silent ischemia, the existence of which may give important information regarding prognosis and may help structure a more effective therapeutic regimen. The emerging recognition of silent ischemia as a significant clinical entity may eventually result in an expansion of current therapy--not only to ameliorate chest pain, but to minimize or eliminate ischemia in the absence of chest pain.

Difficulty with Out-Loud and Silent Reading in Glaucoma

PubMed Central

Ramulu, Pradeep Y.; Swenor, Bonnielin K.; Jefferys, Joan L.; Friedman, David S.; Rubin, Gary S.

2013-01-01

Purpose. We evaluated the impact of glaucoma on out-loud and silent reading. Methods. Glaucoma patients with bilateral visual field (VF) loss and normally-sighted controls had the following parameters measured: speed reading an International Reading Speed Text (IReST) passage out loud, maximum out-loud MNRead chart reading speed, sustained (30 minutes) silent reading speed, and change in reading speed during sustained silent reading. Results. Glaucoma subjects read slower than controls on the IReST (147 vs. 163 words per minute [wpm], P < 0.001), MNRead (172 vs. 186 wpm, P < 0.001), and sustained silent (179 vs. 218 wpm, P < 0.001) tests. In multivariable analyses adjusting for age, race, sex, education, employment, and cognition, IReST and MNRead reading speeds were 12 wpm (6%–7%) slower among glaucoma subjects compared to controls (P < 0.01 for both), while sustained silent reading speed was 16% slower (95% confidence interval [CI] = −24 to −6%, P = 0.002). Each 5 decibel (dB) decrement in better-eye VF mean deviation was associated with 6 wpm slower IReST reading (95% CI = −9 to −3%, P < 0.001), 5 wpm slower MNRead reading (95% CI = −7 to −2%, P < 0.001), and 9% slower sustained silent reading (95% CI = −13 to −6%, P < 0.001). A reading speed decline of 0.5 wpm/min or more over the sustained silent reading period was more common among glaucoma subjects than controls (odds ratio [OR] = 2.2, 95% CI = 1.0–4.9, P < 0.05). Conclusions. Reading speed is slower among glaucoma patients with bilateral VF loss, with the greatest impact present during sustained silent reading. Persons with glaucoma fatigue during silent reading, resulting in slower reading over time. PMID:23074207

Modification of hormonal secretion in clinically silent pituitary adenomas.

PubMed

Daems, Tania; Verhelst, Johan; Michotte, Alex; Abrams, Pascale; De Ridder, Dirk; Abs, Roger

2009-01-01

Silent pituitary adenomas are a subtype of adenomas characterized by positive immunoreactivity for one or more hormones classically secreted by normal pituitary cells but without clinical expression, although in some occasions enhanced or changed secretory activity can develop over time. Silent corticotroph adenomas are the classical example of this phenomenon. A series of about 500 pituitary adenomas seen over a period of 20 years were screened for modification in hormonal secretion. Biochemical and immunohistochemical data were reviewed. Two cases were retrieved, one silent somatotroph adenoma and one thyrotroph adenoma, both without specific clinical features or biochemical abnormalities, which presented 20 years after initial surgery with evidence of acromegaly and hyperthyroidism, respectively. While the acromegaly was controlled by a combination of somatostatin analogs and growth hormone (GH) receptor antagonist therapy, neurosurgery was necessary to manage the thyrotroph adenoma. Immunohistochemical examination demonstrated an increase in the number of thyroid stimulating hormone (TSH)-immunoreactive cells compared to the first tissue. Apparently, the mechanisms responsible for the secretory modifications are different, being a change in secretory capacity in the silent somatotroph adenoma and a quantitative change in the silent thyrotroph adenoma. These two cases, one somatotroph and one thyrotroph adenoma, are an illustration that clinically silent pituitary adenomas may in rare circumstances evolve over time and become active, as previously demonstrated in silent corticotroph adenomas.

Early life stress stimulates hippocampal reelin gene expression in a sex-specific manner: evidence for corticosterone-mediated action.

PubMed

Gross, Claus M; Flubacher, Armin; Tinnes, Stefanie; Heyer, Andrea; Scheller, Marie; Herpfer, Inga; Berger, Mathias; Frotscher, Michael; Lieb, Klaus; Haas, Carola A

2012-03-01

Early life stress predisposes to the development of psychiatric disorders. In this context the hippocampal formation is of particular interest, because it is affected by stress on the structural and cognitive level. Since little is known how early life stress is translated on the molecular level, we mimicked early life stress in mouse models and analyzed the expression of the glycoprotein Reelin, a master molecule for development and differentiation of the hippocampus. From postnatal day 1 (P1) to P14, mouse pups were subjected to one of the following treatments: nonhandling (NH), handling (H), maternal separation (MS), and early deprivation (ED) followed by immediate (P15) or delayed (P70) real time RT-PCR analysis of reelin mRNA expression. We show that at P15, reelin mRNA levels were significantly increased in male H and ED groups when compared with the NH group. In contrast, no stress-induced alterations of reelin mRNA expression were found in female animals. This sex difference in stress-mediated stimulation of reelin expression was maintained into adulthood, since at P70 intergroup differences were still found in male, but not in female mice. On the cellular level, however, we did not find any significant differences in cell densities of Reelin-immunolabeled neurons between treatment groups or sexes, but an overall reduction of Reelin-expressing neurons in the adult hippocampus when compared to P15. To address the question whether corticosterone mediates the stress-induced up-regulation of reelin gene expression, we used age-matched hippocampal slice cultures derived from male and female mouse pups. Quantitative determination of mRNA levels revealed that corticosterone treatment significantly up-regulated reelin mRNA expression in male, but not in female hippocampi. Taken together, these results show a sex-specific regulation of reelin gene expression by early life experience, most likely mediated by corticosterone. Copyright © 2010 Wiley Periodicals, Inc.

Silent store detection and recording in memory storage

DOEpatents

Bose, Pradip; Cher, Chen-Yong; Nair, Ravi

2017-03-07

An aspect includes receiving a write request that includes a memory address and write data. Stored data is read from a memory location at the memory address. Based on determining that the memory location was not previously modified, the stored data is compared to the write data. Based on the stored data matching the write data, the write request is completed without writing the write data to the memory and a corresponding silent store bit, in a silent store bitmap is set. Based on the stored data not matching the write data, the write data is written to the memory location, the silent store bit is reset and a corresponding modified bit is set. At least one of an application and an operating system is provided access to the silent store bitmap.

Silent store detection and recording in memory storage

DOEpatents

Bose, Pradip; Cher, Chen-Yong; Nair, Ravi

2016-09-20

An aspect includes receiving a write request that includes a memory address and write data. Stored data is read from a memory location at the memory address. Based on determining that the memory location was not previously modified, the stored data is compared to the write data. Based on the stored data matching the write data, the write request is completed without writing the write data to the memory and a corresponding silent store bit, in a silent store bitmap is set. Based on the stored data not matching the write data, the write data is written to the memory location, the silent store bit is reset and a corresponding modified bit is set. At least one of an application and an operating system is provided access to the silent store bitmap.

Extent of hippocampal atrophy predicts degree of deficit in recall

PubMed Central

Patai, Eva Zita; Gadian, David G.; Cooper, Janine M.; Dzieciol, Anna M.; Mishkin, Mortimer; Vargha-Khadem, Faraneh

2015-01-01

Which specific memory functions are dependent on the hippocampus is still debated. The availability of a large cohort of patients who had sustained relatively selective hippocampal damage early in life enabled us to determine which type of mnemonic deficit showed a correlation with extent of hippocampal injury. We assessed our patient cohort on a test that provides measures of recognition and recall that are equated for difficulty and found that the patients' performance on the recall tests correlated significantly with their hippocampal volumes, whereas their performance on the equally difficult recognition tests did not and, indeed, was largely unaffected regardless of extent of hippocampal atrophy. The results provide new evidence in favor of the view that the hippocampus is essential for recall but not for recognition. PMID:26417089

Recurrent Silent Thyroiditis as a Sequela of Postpartum Thyroiditis

PubMed Central

Kim, Paul

2014-01-01

Thyroiditis encompasses a group of disorders characterized by thyroid inflammation. Though clinically indistinguishable from silent thyroiditis, postpartum thyroiditis occurs in women within 12 months after delivery. Recurrent postpartum thyroiditis in subsequent pregnancies is common, but recurrent silent thyroiditis is rare. We reported a case of patient with recurrent episodes of thyroiditis, unrelated to pregnancy, after an episode of postpartum thyroiditis. It is of interest that postpartum thyroiditis and silent thyroiditis could occur closely to each other; however, the link between these disorders is not well established. This report is to remind physicians of the possibility of recurrent silent thyroiditis in women with a history of postpartum thyroiditis. PMID:24987536

Additive gene-environment effects on hippocampal structure in healthy humans.

PubMed

Rabl, Ulrich; Meyer, Bernhard M; Diers, Kersten; Bartova, Lucie; Berger, Andreas; Mandorfer, Dominik; Popovic, Ana; Scharinger, Christian; Huemer, Julia; Kalcher, Klaudius; Pail, Gerald; Haslacher, Helmuth; Perkmann, Thomas; Windischberger, Christian; Brocke, Burkhard; Sitte, Harald H; Pollak, Daniela D; Dreher, Jean-Claude; Kasper, Siegfried; Praschak-Rieder, Nicole; Moser, Ewald; Esterbauer, Harald; Pezawas, Lukas

2014-07-23

Hippocampal volume loss has been related to chronic stress as well as genetic factors. Although genetic and environmental variables affecting hippocampal volume have extensively been studied and related to mental illness, limited evidence is available with respect to G × E interactions on hippocampal volume. The present MRI study investigated interaction effects on hippocampal volume between three well-studied functional genetic variants (COMT Val158Met, BDNF Val66Met, 5-HTTLPR) associated with hippocampal volume and a measure of environmental adversity (life events questionnaire) in a large sample of healthy humans (n = 153). All three variants showed significant interactions with environmental adversity with respect to hippocampal volume. Observed effects were additive by nature and driven by both recent as well as early life events. A consecutive analysis of hippocampal subfields revealed a spatially distinct profile for each genetic variant suggesting a specific role of 5-HTTLPR for the subiculum, BDNF Val66Met for CA4/dentate gyrus, and COMT Val158Met for CA2/3 volume changes. The present study underscores the importance of G × E interactions as determinants of hippocampal volume, which is crucial for the neurobiological understanding of stress-related conditions, such as mood disorders or post-traumatic stress disorder (PTSD). Copyright © 2014 the authors 0270-6474/14/349917-10$15.00/0.

Childhood maltreatment, psychopathology, and the development of hippocampal subregions during adolescence.

PubMed

Whittle, Sarah; Simmons, Julian G; Hendriksma, Sylke; Vijayakumar, Nandita; Byrne, Michelle L; Dennison, Meg; Allen, Nicholas B

2017-02-01

It is well established that childhood maltreatment has a detrimental impact on the brain, particularly the hippocampus. However, the hippocampus is a functionally and structurally heterogeneous region, and little is known about how maltreatment might affect hippocampal subregion development throughout important periods of plasticity. This study investigated whether childhood maltreatment was associated with the development of hippocampal subregion volumes from early to late adolescence. It also investigated associations between onset of psychiatric disorder and hippocampal subregion volume development. One hundred and sixty-six (85 male) adolescents took part in three magnetic resonance imaging assessments during adolescence (mean age at each assessment: 12.79 [ SD 0.43] years, 16.70 [ SD 0.52] years, and 19.08 [ SD 0.46] years), provided a self-report of childhood maltreatment, and were assessed for Axis I psychopathology. Childhood maltreatment was associated with the development of right total and left cornu ammonis 4 (CA4-DG) volumes from early to late adolescence. Early and late onset psychopathology was associated with the development of right presubiculum and right cornu ammonis 1 (CA1) volumes, respectively. Maltreatment findings appeared to be specific to males, whereas psychopathology findings appeared to be specific to females. These findings provide evidence for possible deleterious effects of childhood maltreatment and early onset psychiatric disorder on the development of different subregions of the hippocampus. Altered development of the right CA1, on the other hand, might precede the development of late-adolescent onset psychopathology. Our results highlight the importance of considering development in research examining associations between stress, mental illness, and hippocampal morphology.

Reinforcement of Rat Hippocampal LTP by Holeboard Training

ERIC Educational Resources Information Center

Frey, Julietta U.; Korz, Volker; Uzakov, Shukhrat

2005-01-01

Hippocampal long-term potentiation (LTP) can be dissociated in early-LTP lasting 4-5 h and late-LTP with a duration of more than 8 h, the latter of which requires protein synthesis and heterosynaptic activity during its induction. Previous studies in vivo have shown that early-LTP in the dentate gyrus can protein synthesis-dependently be…

Parafoveal processing in silent and oral reading: Reading mode influences the relative weighting of phonological and semantic information in Chinese.

PubMed

Pan, Jinger; Laubrock, Jochen; Yan, Ming

2016-08-01

We examined how reading mode (i.e., silent vs. oral reading) influences parafoveal semantic and phonological processing during the reading of Chinese sentences, using the gaze-contingent boundary paradigm. In silent reading, we found in 2 experiments that reading times on target words were shortened with semantic previews in early and late processing, whereas phonological preview effects mainly occurred in gaze duration or second-pass reading. In contrast, results showed that phonological preview information is obtained early on in oral reading. Strikingly, in oral reading, we observed a semantic preview cost on the target word in Experiment 1 and a decrease in the effect size of preview benefit from first- to second-pass measures in Experiment 2, which we hypothesize to result from increased preview duration. Taken together, our results indicate that parafoveal semantic information can be obtained irrespective of reading mode, whereas readers more efficiently process parafoveal phonological information in oral reading. We discuss implications for notions of information processing priority and saccade generation during silent and oral reading. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Silent store detection and recording in memory storage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bose, Pradip; Cher, Chen-Yong; Nair, Ravi

An aspect includes receiving a write request that includes a memory address and write data. Stored data is read from a memory location at the memory address. Based on determining that the memory location was not previously modified, the stored data is compared to the write data. Based on the stored data matching the write data, the write request is completed without writing the write data to the memory and a corresponding silent store bit, in a silent store bitmap is set. Based on the stored data not matching the write data, the write data is written to the memorymore » location, the silent store bit is reset and a corresponding modified bit is set. At least one of an application and an operating system is provided access to the silent store bitmap.« less

Silent Reading Fluency Using Underlining: Evidence for an Alternative Method of Assessment

ERIC Educational Resources Information Center

Price, Katherine W.; Meisinger, Elizabeth B.; Louwerse, Max M.; D'Mello, Sidney K.

2012-01-01

Assessing silent reading fluency in classroom environments is challenging. This article reports on a method of assessing silent reading using underlining, an approach that solves many problems other silent reading fluency assessment measures face. This method computationally monitors readers' silent reading fluency by the speed they underline…

Evidence for presynaptically silent synapses in the immature hippocampus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, Jae Young; Choi, Sukwoo

Silent synapses show NMDA receptor (NMDAR)-mediated synaptic responses, but not AMPAR-mediated synaptic responses. A prevailing hypothesis states that silent synapses contain NMDARs, but not AMPARs. However, alternative presynaptic hypotheses, according to which AMPARs are present at silent synapses, have been proposed; silent synapses show slow glutamate release via a fusion pore, and glutamate spillover from the neighboring synaptic terminals. Consistent with these presynaptic hypotheses, the peak glutamate concentrations at silent synapses have been estimated to be ≪170 μM, much lower than those seen at functional synapses. Glutamate transients predicted based on the two presynaptic mechanisms have been shown to activate onlymore » high-affinity NMDARs, but not low-affinity AMPARs. Interestingly, a previous study has developed a new approach to distinguish between the two presynaptic mechanisms using dextran, an inert macromolecule that reduces the diffusivity of released glutamate: postsynaptic responses through the fusion pore mechanism, but not through the spillover mechanism, are potentiated by reduced glutamate diffusivity. Therefore, we reasoned that if the fusion pore mechanism underlies silent synapses, dextran application would reveal AMPAR-mediated synaptic responses at silent synapses. In the present study, we recorded AMPAR-mediated synaptic responses at the CA3-CA1 synapses in neonatal rats in the presence of blockers for NMDARs and GABAARs. Bath application of dextran revealed synaptic responses at silent synapses. GYKI53655, a selective AMPAR-antagonist, completely inhibited the unsilenced synaptic responses, indicating that the unsilenced synaptic responses are mediated by AMPARs. The dextran-mediated reduction in glutamate diffusivity would also lead to the activation of metabotropic glutamate receptors (mGluRs), which might induce unsilencing via the activation of unknown intracellular signaling. Hence, we determined whether m

The influence of negative life events on hippocampal and amygdala volumes in old age: a life-course perspective.

PubMed

Gerritsen, L; Kalpouzos, G; Westman, E; Simmons, A; Wahlund, L O; Bäckman, L; Fratiglioni, L; Wang, H X

2015-04-01

Psychosocial stress has been related to changes in the nervous system, with both adaptive and maladaptive consequences. The aim of this study was to examine the relationship of negative events experienced throughout the entire lifespan and hippocampal and amygdala volumes in older adults. In 466 non-demented old adults (age range 60-96 years, 58% female), hippocampal and amygdala volumes were segmented using Freesurfer. Negative life events and the age at which these events occurred were assessed by means of a structured questionnaire. Using generalized linear models, hippocampal and amygdala volumes were estimated with life events as independent variables. The statistical analyses were adjusted for age, gender, intracranial volume, lifestyle factors, cardiovascular risk factors, depressive symptoms, and cognitive functioning. Total number of negative life events and of late-life events, but not of early-life, early-adulthood, or middle-adulthood events, was related to larger amygdala volume. There were interactions of early-life events with age and gender. Participants who reported two or more early-life events had significantly smaller amygdala and hippocampal volumes with increasing age. Furthermore, smaller hippocampal volume was found in men who reported two or more early-life events, but not in women. These results suggest that the effect of negative life events on the brain depends on the time when the events occurred, with the strongest effects observed during the critical time periods of early and late life.

Description and Validation of a Test to Evaluate Sustained Silent Reading

PubMed Central

Ramulu, Pradeep Y.; Swenor, Bonnielin K.; Jefferys, Joan L.; Rubin, Gary S.

2013-01-01

Purpose. To construct and validate a test of sustained silent reading. Methods. Standardized 7300 and 7600 word passages were written to evaluate sustained silent reading. Two hundred forty subjects validated whether comprehension questions could discriminate subjects who did and did not read the passage. To evaluate test–retest properties, 49 subjects silently read the standardized passages on separate days. Sixty glaucoma suspect controls and 64 glaucoma subjects had their out loud reading evaluated with the MNRead card and an International Reading Speed Texts (IReST) passage, and their silent reading measured using the 7300 word passage. Sustained silent reading parameters included reading speed and reading speed slope over time. Results. Comprehension questions distinguished individuals who had and had not read passage materials. Bland-Altman analyses of intersession sustained reading speed and reading speed slope demonstrated 95% coefficients of repeatability of 57 words per minute (wpm) and 2.76 wpm/minute. Sustained silent reading speed was less correlated with MNRead (r = 0.59) or IReST passage (r = 0.68) reading speeds than the correlation of these two measures of out loud reading speed with each other (r = 0.72). Sustained silent reading speed was more likely to differ from IReST reading speed by more than 50% in rapid silent readers (odds ratio [OR] = 29, 95% confidence interval [CI] = 10–87), and comparisons of sustained and out loud reading speeds demonstrated proportional error in Bland-Altman analyses. Conclusions. Tests of out loud reading do not accurately reflect silent reading speed in individuals with normal vision or glaucoma. The described test offers a standardized way to evaluate the impact of eye disease and/or visual rehabilitation on sustained silent reading. PMID:23258146

Unspoken Content: Silent Film in the ESL Classroom.

ERIC Educational Resources Information Center

Kasper, Loretta F.; Singer, Robert

2001-01-01

Describes how one short silent film, "The Painted Lady," may be used to build language and content knowledge in English-as-a-second-language (ESL) courses. Provides a representative list of titles and corresponding content areas to assist instructors in their efforts to incorporate silent film into ESL courses. (SG)

Relativistic numerical cosmology with silent universes

NASA Astrophysics Data System (ADS)

Bolejko, Krzysztof

2018-01-01

Relativistic numerical cosmology is most often based either on the exact solutions of the Einstein equations, or perturbation theory, or weak-field limit, or the BSSN formalism. The silent universe provides an alternative approach to investigate relativistic evolution of cosmological systems. The silent universe is based on the solution of the Einstein equations in 1  +  3 comoving coordinates with additional constraints imposed. These constraints include: the gravitational field is sourced by dust and cosmological constant only, both rotation and magnetic part of the Weyl tensor vanish, and the shear is diagnosable. This paper describes the code simsilun (free software distributed under the terms of the reposi General Public License), which implements the equations of the silent universe. The paper also discusses applications of the silent universe and it uses the Millennium simulation to set up the initial conditions for the code simsilun. The simulation obtained this way consists of 16 777 216 worldlines, which are evolved from z  =  80 to z  =  0. Initially, the mean evolution (averaged over the whole domain) follows the evolution of the background ΛCDM model. However, once the evolution of cosmic structures becomes nonlinear, the spatial curvature evolves from ΩK =0 to ΩK ≈ 0.1 at the present day. The emergence of the spatial curvature is associated with ΩM and Ω_Λ being smaller by approximately 0.05 compared to the ΛCDM.

Longitudinal study of hippocampal volumes in heavy cannabis users.

PubMed

Koenders, L; Lorenzetti, V; de Haan, L; Suo, C; Vingerhoets, Wam; van den Brink, W; Wiers, R W; Meijer, C J; Machielsen, Mwj; Goudriaan, A E; Veltman, D J; Yücel, M; Cousijn, J

2017-08-01

Cannabis exposure, particularly heavy cannabis use, has been associated with neuroanatomical alterations in regions rich with cannabinoid receptors such as the hippocampus in some but not in other (mainly cross-sectional) studies. However, it remains unclear whether continued heavy cannabis use alters hippocampal volume, and whether an earlier age of onset and/or a higher dosage exacerbate these changes. Twenty heavy cannabis users (mean age 21 years, range 18-24 years) and 23 matched non-cannabis using healthy controls were submitted to a comprehensive psychological assessment and magnetic resonance imaging scan at baseline and at follow-up (average of 39 months post-baseline; standard deviation=2.4). Cannabis users started smoking around 16 years and smoked on average five days per week. A novel aspect of the current study is that hippocampal volume estimates were obtained from manual tracing the hippocampus on T1-weighted anatomical magnetic resonance imaging scans, using a previously validated protocol. Compared to controls, cannabis users did not show hippocampal volume alterations at either baseline or follow-up. Hippocampal volumes increased over time in both cannabis users and controls, following similar trajectories of increase. Cannabis dose and age of onset of cannabis use did not affect hippocampal volumes. Continued heavy cannabis use did not affect hippocampal neuroanatomical changes in early adulthood. This contrasts with prior evidence on alterations in this region in samples of older adult cannabis users. In young adults using cannabis at this level, cannabis use may not be heavy enough to affect hippocampal neuroanatomy.

Longitudinal study of hippocampal volumes in heavy cannabis users

PubMed Central

Koenders, L; Lorenzetti, V; de Haan, L; Suo, C; Vingerhoets, WAM; van den Brink, W; Wiers, RW; Meijer, CJ; Machielsen, MWJ; Goudriaan, AE; Veltman, DJ; Yücel, M; Cousijn, J

2017-01-01

Background: Cannabis exposure, particularly heavy cannabis use, has been associated with neuroanatomical alterations in regions rich with cannabinoid receptors such as the hippocampus in some but not in other (mainly cross-sectional) studies. However, it remains unclear whether continued heavy cannabis use alters hippocampal volume, and whether an earlier age of onset and/or a higher dosage exacerbate these changes. Methods: Twenty heavy cannabis users (mean age 21 years, range 18–24 years) and 23 matched non-cannabis using healthy controls were submitted to a comprehensive psychological assessment and magnetic resonance imaging scan at baseline and at follow-up (average of 39 months post-baseline; standard deviation=2.4). Cannabis users started smoking around 16 years and smoked on average five days per week. A novel aspect of the current study is that hippocampal volume estimates were obtained from manual tracing the hippocampus on T1-weighted anatomical magnetic resonance imaging scans, using a previously validated protocol. Results: Compared to controls, cannabis users did not show hippocampal volume alterations at either baseline or follow-up. Hippocampal volumes increased over time in both cannabis users and controls, following similar trajectories of increase. Cannabis dose and age of onset of cannabis use did not affect hippocampal volumes. Conclusions: Continued heavy cannabis use did not affect hippocampal neuroanatomical changes in early adulthood. This contrasts with prior evidence on alterations in this region in samples of older adult cannabis users. In young adults using cannabis at this level, cannabis use may not be heavy enough to affect hippocampal neuroanatomy. PMID:28741422

Silent Flange Coupling Design Used for the Schenck Eddy Current Dynamometer

NASA Astrophysics Data System (ADS)

Schinteie, D.; Croitorescu, V.

2016-11-01

The silent flange used for coupling different machines/systems to an eddy current dynamometer represents one of the modular components each test-bench should use. By introducing a silent flange into a dynamometer, the coupling steps are easier and faster. For an appropriate design, the silent flange was analyzed using dedicated software during different operation procedures and scenarios, for materials that allow easy manufacturing. This study shows that the design for this silent flange model has no danger of failure due to the small deformation and the values for the equivalent stresses. The silent flange coupling is suitable for the dynamometer for his high positioning accuracy, the zero backlash and the fact that there is no motion between the shafts.

Ventricular Fibrillation Associated With Dynamic Changes in J-Point Elevation in a Patient With Silent Thyroiditis.

PubMed

Karashima, Shigehiro; Tsuda, Toyonobu; Wakabayashi, Yusuke; Kometani, Mitsuhiro; Demura, Masashi; Ichise, Taro; Kawashiri, Masa-Aki; Takeda, Yoshiyu; Hayashi, Kenshi; Yoneda, Takashi

2018-02-01

A J wave is a common electrocardiographic finding in the general population. Individuals with prominent J waves in multiple electrocardiogram (ECG) leads have a higher risk of lethal arrhythmias than those with low-amplitude J waves. There are few reports about the relationship between thyroid function and J-wave amplitude. We report the case of a 45-year-old man who had unexpected ventricular fibrillation (VF). He had dynamic J-point elevation in multiple ECG leads. Possible early repolarization syndrome was diagnosed. He also had thyrotoxicosis caused by silent thyroiditis, and his J-wave amplitude decreased according to changes in thyroid function because of spontaneous remission of silent thyroiditis. There was a positive correlation between serum triiodothyronine levels and J-wave amplitudes. The findings in case suggested silent thyroiditis may contribute to the occurrence of VF in a patient with dynamic changes in J-point elevation in multiple ECG leads. Thyrotoxicosis is a relatively common endocrine disease; therefore, clinicians should pay attention to J-wave amplitude in the ECG of patients with thyrotoxicosis.

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. © 2017 The Authors. Hippocampus Published by Wiley Periodicals, Inc.

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

Hippocampal multimodal structural changes and subclinical depression in healthy individuals.

PubMed

Spalletta, Gianfranco; Piras, Fabrizio; Caltagirone, Carlo; Fagioli, Sabrina

2014-01-01

Several neuroimaging studies report reduced hippocampal volume in depressed patients. However, it is still unclear if hippocampal changes in healthy individuals can be considered a risk factor for progression to clinical depression. Here, we investigated subclinical depression and its hippocampal correlates in a non-clinical sample of healthy individuals, with particular regard to gender differences. One-hundred-two participants underwent a comprehensive clinical assessment, a high-resolution T1-weighted magnetic resonance imaging and diffusion tensor imaging protocol using a 3T MRI scanner. Data of macro-(volume) and micro-(mean diffusivity, MD) structural changes of the hippocampus were analyzed with reference to the Beck Depression Inventory score. Results of multivariate regression analyses revealed reduced bilateral volume, along with increased bilateral MD in hippocampal formation predicting subclinical depressive phenomenology only in healthy males. Conversely, subclinical depressive phenomenology in healthy female was accounted for by only lower educational level, in the absence of any hippocampal structure variations. To date, this is the only evidence reporting a relationship between subclinical depressive phenomenology and changes in hippocampal formation in healthy individuals. Our findings demonstrated that reduced volume, along with increased MD in hippocampal formation, is significantly associated with subclinical depressive phenomenology in healthy males. This encourages to study the hypothesis that early macro- and microstructural changes in hippocampi associated with subclinical depression may constitute a risk factor of developing depressive disorders in males. © 2013 Elsevier B.V. All rights reserved.

Differences in autonomic nerve function in patients with silent and symptomatic myocardial ischaemia.

PubMed Central

Shakespeare, C. F.; Katritsis, D.; Crowther, A.; Cooper, I. C.; Coltart, J. D.; Webb-Peploe, M. W.

1994-01-01

BACKGROUND--Autonomic neuropathy provides a mechanism for the absence of symptoms in silent myocardial ischaemia, but characterisation of the type of neuropathy is lacking. AIM--To characterise and compare autonomic nerve function in patients with silent and symptomatic myocardial ischaemia. METHODS AND RESULTS--The Valsalva manoeuvre, heart rate variation (HRV) in response to deep breathing and standing, lower body negative pressure, isometric handgrip, and the cold pressor test were performed by patients with silent (n = 25) and symptomatic (n = 25) ambulatory ischaemia and by controls (n = 21). No difference in parasympathetic efferent function between patients with silent and symptomatic ischaemia was recorded, but both had significantly less HRV in response to standing than the controls (p < 0.005 for silent and p < 0.01 for symptomatic). Patients with silent ischaemia showed an increased propensity for peripheral vasodilatation compared with symptomatic patients (p < 0.02) and controls (p < 0.04). Impaired sympathetic function was found in patients with pure silent ischaemia (n = 4) compared with the remaining patients with silent ischaemia whose pain pathways were presumed to be intact. CONCLUSIONS--Patients with silent ischaemia and pain pathways presumed to be intact have an enhanced peripheral vasodilator response, and if this applied to the coronary vasculature it could provide a mechanism for limiting ischaemia to below the pain threshold. Patients with pure silent ischaemia have evidence of sympathetic autonomic dysfunction. Images PMID:8297687

Multiple hippocampal transections for intractable hippocampal epilepsy: Seizure outcome.

PubMed

Koubeissi, Mohamad Z; Kahriman, Emine; Fastenau, Philip; Bailey, Christopher; Syed, Tanvir; Amina, Shahram; Miller, Jonathan; Munyon, Charles; Tanner, Adriana; Karanec, Kristina; Tuxhorn, Ingrid; Lüders, Hans

2016-05-01

The purpose of this study was to evaluate the seizure outcomes after transverse multiple hippocampal transections (MHTs) in 13 patients with intractable TLE. Thirteen patients with normal memory scores, including 8 with nonlesional hippocampi on MRI, had temporal lobe epilepsy (TLE) necessitating depth electrode implantation. After confirming hippocampal seizure onset, they underwent MHT. Intraoperative monitoring was done with 5-6 hippocampal electrodes spaced at approximately 1-cm intervals and spike counting for 5-8min before each cut. The number of transections ranged between 4 and 7. Neuropsychological assessment was completed preoperatively and postoperatively for all patients and will be reported separately. Duration of epilepsy ranged between 5 and 55years. There were no complications. Intraoperatively, MHT resulted in marked spike reduction (p=0.003, paired t-test). Ten patients (77%) are seizure-free (average follow-up was 33months, range 20-65months) without medication changes. One of the 3 patients with persistent seizures had an MRI revealing incomplete transections, another had an additional neocortical seizure focus (as suggested by pure aphasic seizures), and the third had only 2 seizures in 4years, one of which occurred during antiseizure medication withdrawal. Verbal and visual memory outcomes will be reported separately. Right and left hippocampal volumes were not different preoperatively (n=12, p=0.64, Wilcoxon signed-rank test), but the transected hippocampal volume decreased postoperatively (p=0.0173). Multiple hippocampal transections provide an effective intervention and a safe alternative to temporal lobectomy in patients with hippocampal epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Poor school and cognitive functioning with silent cerebral infarcts and sickle cell disease.

PubMed

Schatz, J; Brown, R T; Pascual, J M; Hsu, L; DeBaun, M R

2001-04-24

The authors evaluated education attainment and neuropsychological deficits in children with sickle cell disease (SCD) and silent cerebral infarcts. Children with silent infarcts had twice the rate of school difficulties as children without infarcts. Eighty percent of silent infarct cases had clinically significant cognitive deficits, whereas 35% had deficits in academic skills. Children with silent cerebral infarcts show high rates of poor educational attainment, cognitive deficits, and frontal lobe injury. Poor school performance in SCD is one indicator of silent infarcts.

Peripheral telomere length and hippocampal volume in adolescents with major depressive disorder.

PubMed

Henje Blom, E; Han, L K M; Connolly, C G; Ho, T C; Lin, J; LeWinn, K Z; Simmons, A N; Sacchet, M D; Mobayed, N; Luna, M E; Paulus, M; Epel, E S; Blackburn, E H; Wolkowitz, O M; Yang, T T

2015-11-10

Several studies have reported that adults with major depressive disorder have shorter telomere length and reduced hippocampal volumes. Moreover, studies of adult populations without major depressive disorder suggest a relationship between peripheral telomere length and hippocampal volume. However, the relationship of these findings in adolescents with major depressive disorder has yet to be explored. We examined whether adolescent major depressive disorder is associated with altered peripheral telomere length and hippocampal volume, and whether these measures relate to one another. In 54 unmedicated adolescents (13-18 years) with major depressive disorder and 63 well-matched healthy controls, telomere length was assessed from saliva using quantitative polymerase chain reaction methods, and bilateral hippocampal volumes were measured with magnetic resonance imaging. After adjusting for age and sex (and total brain volume in the hippocampal analysis), adolescents with major depressive disorder exhibited significantly shorter telomere length and significantly smaller right, but not left hippocampal volume. When corrected for age, sex, diagnostic group and total brain volume, telomere length was not significantly associated with left or right hippocampal volume, suggesting that these cellular and neural processes may be mechanistically distinct during adolescence. Our findings suggest that shortening of telomere length and reduction of hippocampal volume are already present in early-onset major depressive disorder and thus unlikely to be only a result of accumulated years of exposure to major depressive disorder.

Functional organization of the medial temporal lobe memory system following neonatal hippocampal lesion in rhesus monkeys.

PubMed

Chareyron, Loïc J; Banta Lavenex, Pamela; Amaral, David G; Lavenex, Pierre

2017-12-01

Hippocampal damage in adult humans impairs episodic and semantic memory, whereas hippocampal damage early in life impairs episodic memory but leaves semantic learning relatively preserved. We have previously shown a similar behavioral dissociation in nonhuman primates. Hippocampal lesion in adult monkeys prevents allocentric spatial relational learning, whereas spatial learning persists following neonatal lesion. Here, we quantified the number of cells expressing the immediate-early gene c-fos, a marker of neuronal activity, to characterize the functional organization of the medial temporal lobe memory system following neonatal hippocampal lesion. Ninety minutes before brain collection, three control and four adult monkeys with bilateral neonatal hippocampal lesions explored a novel environment to activate brain structures involved in spatial learning. Three other adult monkeys with neonatal hippocampal lesions remained in their housing quarters. In unlesioned monkeys, we found high levels of c-fos expression in the intermediate and caudal regions of the entorhinal cortex, and in the perirhinal, parahippocampal, and retrosplenial cortices. In lesioned monkeys, spatial exploration induced an increase in c-fos expression in the intermediate field of the entorhinal cortex, the perirhinal, parahippocampal, and retrosplenial cortices, but not in the caudal entorhinal cortex. These findings suggest that different regions of the medial temporal lobe memory system may require different types of interaction with the hippocampus in support of memory. The caudal perirhinal cortex, the parahippocampal cortex, and the retrosplenial cortex may contribute to spatial learning in the absence of functional hippocampal circuits, whereas the caudal entorhinal cortex may require hippocampal output to support spatial learning.

Cortisol, learning, memory, and attention in relation to smaller hippocampal volume in police officers with posttraumatic stress disorder.

PubMed

Lindauer, Ramón J L; Olff, Miranda; van Meijel, Els P M; Carlier, Ingrid V E; Gersons, Berthold P R

2006-01-15

A proposed explanation for memory impairments in posttraumatic stress disorder (PTSD) is stress-induced hippocampal damage due to elevated cortisol levels. We have previously reported smaller hippocampi in police officers with PTSD. In this study, we examined changes in and associations between cortisol, learning, memory, attention, and hippocampal volume in PTSD. In a case-matched control study, 12 police officers with PTSD and 12 traumatized police officers without lifetime PTSD were examined with magnetic resonance imaging (for hippocampal volume), salivary cortisol tests, and neurocognitive assessments. Significantly smaller hippocampi and higher early morning salivary cortisol levels were found in PTSD. Subjects with PTSD performed worse on a delayed visual memory recall task at trend level, and made more perseverations and intrusions on a verbal memory task. Negative correlations were found between PTSD symptom severity and immediate recall function, and between re-experiencing symptoms and left hippocampal volume. A positive correlation was found between salivary cortisol level in early morning and right hippocampal volume; however, hippocampal volume did not correlate with memory. Smaller hippocampi, higher cortisol levels, and memory impairments were associated with PTSD but were not directly correlated to one another. Memory impairments in PTSD do not seem to be a direct consequence of hippocampal size.

Atrial fibrillation and silent stroke: links, risks, and challenges.

PubMed

Hahne, Kathrin; Mönnig, Gerold; Samol, Alexander

2016-01-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia, with a projected number of 1 million affected subjects in Germany. Changes in age structure of the Western population allow for the assumption that the number of concerned people is going to be doubled, maybe tripled, by the year 2050. Large epidemiological investigations showed that AF leads to a significant increase in mortality and morbidity. Approximately one-third of all strokes are caused by AF and, due to thromboembolic cause, these strokes are often more severe than those caused by other etiologies. Silent brain infarction is defined as the presence of cerebral infarction in the absence of corresponding clinical symptomatology. Progress in imaging technology simplifies diagnostic procedures of these lesions and leads to a large amount of diagnosed lesions, but there is still no final conclusion about frequency, risk factors, and clinical relevance of these infarctions. The prevalence of silent strokes in patients with AF is higher compared to patients without AF, and several studies reported high incidence rates of silent strokes after AF ablation procedures. While treatment strategies to prevent clinically apparent strokes in patients with AF are well investigated, the role of anticoagulatory treatment for prevention of silent infarctions is unclear. This paper summarizes developments in diagnosis of silent brain infarction and its context to AF.

Abnormalities of hippocampal-cortical connectivity in temporal lobe epilepsy patients with hippocampal sclerosis

NASA Astrophysics Data System (ADS)

Li, Wenjing; He, Huiguang; Lu, Jingjing; Wang, Chunheng; Li, Meng; Lv, Bin; Jin, Zhengyu

2011-03-01

Hippocampal sclerosis (HS) is the most common damage seen in the patients with temporal lobe epilepsy (TLE). In the present study, the hippocampal-cortical connectivity was defined as the correlation between the hippocampal volume and cortical thickness at each vertex throughout the whole brain. We aimed to investigate the differences of ipsilateral hippocampal-cortical connectivity between the unilateral TLE-HS patients and the normal controls. In our study, the bilateral hippocampal volumes were first measured in each subject, and we found that the ipsilateral hippocampal volume significantly decreased in the left TLE-HS patients. Then, group analysis showed significant thinner average cortical thickness of the whole brain in the left TLE-HS patients compared with the normal controls. We found significantly increased ipsilateral hippocampal-cortical connectivity in the bilateral superior temporal gyrus, the right cingulate gyrus and the left parahippocampal gyrus of the left TLE-HS patients, which indicated structural vulnerability related to the hippocampus atrophy in the patient group. However, for the right TLE-HS patients, no significant differences were found between the patients and the normal controls, regardless of the ipsilateral hippocampal volume, the average cortical thickness or the patterns of hippocampal-cortical connectivity, which might be related to less atrophies observed in the MRI scans. Our study provided more evidence for the structural abnormalities in the unilateral TLE-HS patients.

Phlebotomy-induced anemia alters hippocampal neurochemistry in neonatal mice

PubMed Central

Wallin, Diana J.; Tkac, Ivan; Stucker, Sara; Ennis, Kathleen M.; Sola-Visner, Martha; Rao, Raghavendra; Georgieff, Michael K.

2015-01-01

Background Phlebotomy-induced anemia (PIA) is common in preterm infants. The hippocampus undergoes rapid differentiation during late fetal/early neonatal life and relies on adequate oxygen and iron to support oxidative metabolism necessary for development. Anemia shortchanges these two critical substrates, potentially altering hippocampal development and function. Methods PIA (hematocrit <25%) was induced in neonatal mice pups from postnatal day (P)3 to P14. Neurochemical concentrations in the hippocampus were determined using in vivo 1H NMR spectroscopy at 9.4T and compared with control animals at P14. Gene expression was assessed using qRT-PCR. Results PIA decreased brain iron concentration, increased hippocampal lactate and creatine concentrations, and decreased phosphoethanolamine (PE) concentration and the phosphocreatine/creatine ratio. Hippocampal transferrin receptor (Tfrc) gene expression was increased, while the expression of calcium/calmodulin-dependent protein kinase type II alpha (CamKIIα) was decreased in PIA mice. Conclusion This clinically relevant model of neonatal anemia alters hippocampal energy and phospholipid metabolism and gene expression during a critical developmental period. Low target hematocrits for preterm neonates in the NICU may have potential adverse neural implications. PMID:25734245

Environmental enrichment protects spatial learning and hippocampal neurons from the long-lasting effects of protein malnutrition early in life.

PubMed

Soares, Roberto O; Horiquini-Barbosa, Everton; Almeida, Sebastião S; Lachat, João-José

2017-09-29

As early protein malnutrition has a critically long-lasting impact on the hippocampal formation and its role in learning and memory, and environmental enrichment has demonstrated great success in ameliorating functional deficits, here we ask whether exposure to an enriched environment could be employed to prevent spatial memory impairment and neuroanatomical changes in the hippocampus of adult rats maintained on a protein deficient diet during brain development (P0-P35). To elucidate the protective effects of environmental enrichment, we used the Morris water task and neuroanatomical analysis to determine whether changes in spatial memory and number and size of CA1 neurons differed significantly among groups. Protein malnutrition and environmental enrichment during brain development had significant effects on the spatial memory and hippocampal anatomy of adult rats. Malnourished but non-enriched rats (MN) required more time to find the hidden platform than well-nourished but non-enriched rats (WN). Malnourished but enriched rats (ME) performed better than the MN and similarly to the WN rats. There was no difference between well-nourished but non-enriched and enriched rats (WE). Anatomically, fewer CA1 neurons were found in the hippocampus of MN rats than in those of WN rats. However, it was also observed that ME and WN rats retained a similar number of neurons. These results suggest that environmental enrichment during brain development alters cognitive task performance and hippocampal neuroanatomy in a manner that is neuroprotective against malnutrition-induced brain injury. These results could have significant implications for malnourished infants expected to be at risk of disturbed brain development. Copyright © 2017 Elsevier B.V. All rights reserved.

Silent reminders: geologic wonders of the George Washington and Jefferson National Forests

USGS Publications Warehouse

,; ,

2001-01-01

The iron industry played a vital role in the industrialization of the United States and in the development of the U.S. economy and society. Much of the early history of the iron industry took place in Virginia. The remains of 11 iron furnaces and nearby mines in the George Washington and Jefferson National Forests in Virginia and West Virginia are silent reminders of a time when iron mines and furnaces operated along a belt that extended through the Appalachian Mountains from New York State to Alabama.

Verbal and non-verbal memory and hippocampal volumes in a memory clinic population.

PubMed

Bonner-Jackson, Aaron; Mahmoud, Shamseldeen; Miller, Justin; Banks, Sarah J

2015-10-15

Better characterization of the relationship between episodic memory and hippocampal volumes is crucial in early detection of neurodegenerative disease. We examined these relationships in a memory clinic population. Participants (n = 226) underwent structural magnetic resonance imaging and tests of verbal (Hopkins Verbal Learning Test-Revised, HVLT-R) and non-verbal (Brief Visuospatial Memory Test-Revised, BVMT-R) memory. Correlational analyses were performed, and analyses on clinical subgroups (i.e., amnestic Mild Cognitive Impairment, non-amnestic Mild Cognitive Impairment, probable Alzheimer's disease, intact memory) were conducted. Positive associations were identified between bilateral hippocampal volumes and both memory measures, and BVMT-R learning slope was more strongly positively associated with hippocampal volumes than HVLT-R learning slope. Amnestic Mild Cognitive Impairment (aMCI) participants showed specific positive associations between BVMT-R performance and hippocampal volumes bilaterally. Additionally, analyses of the aMCI group showed trend-level evidence of material-specific lateralization, such that retention of verbal information was positively associated with left hippocampal volume, whereas learning curve and retention of non-verbal information was positively associated with right hippocampal volume. Findings support the link between episodic memory and hippocampal volumes in a memory clinic population. Non-verbal memory measures also may have higher diagnostic value, particularly in individuals at elevated risk for Alzheimer's disease.

Silent pituitary macroadenoma co-secreting growth hormone and thyroid stimulating hormone.

PubMed

Sen, Orhan; Ertorer, M Eda; Aydin, M Volkan; Erdogan, Bulent; Altinors, Nur; Zorludemir, Suzan; Guvener, Nilgun

2005-04-01

Silent pituitary adenomas are a group of tumors showing heterogenous morphological features with no hormonal function observed clinically. To date no explanation has been provided as to why these tumors remain "silent". We report a case of a silent macroadenoma with both growth hormone (GH) and thyroid stimulating hormone (TSH) staining and secretion but with no clinical manifestations, in particular, the absence of features of acromegaly or hyperthyroidism. The relevant literature is reviewed.

Classic hippocampal sclerosis and hippocampal-onset epilepsy produced by a single “cryptic” episode of focal hippocampal excitation in awake rats

PubMed Central

Norwood, Braxton A.; Bumanglag, Argyle V.; Osculati, Francesco; Sbarbati, Andrea; Marzola, Pasquina; Nicolato, Elena; Fabene, Paolo F.; Sloviter, Robert S.

2010-01-01

In refractory temporal lobe epilepsy, seizures often arise from a shrunken hippocampus exhibiting a pattern of selective neuron loss called “classic hippocampal sclerosis.” No single experimental injury has reproduced this specific pathology, suggesting that hippocampal atrophy might be a progressive “endstage” pathology resulting from years of spontaneous seizures. We posed the alternate hypothesis that classic hippocampal sclerosis results from a single excitatory event that has never been successfully modeled experimentally because convulsive status epilepticus, the insult most commonly used to produce epileptogenic brain injury, is too severe and necessarily terminated before the hippocampus receives the needed duration of excitation. We tested this hypothesis by producing prolonged hippocampal excitation in awake rats without causing convulsive status epilepticus. Two daily 30-minute episodes of perforant pathway stimulation in Sprague-Dawley rats increased granule cell paired-pulse inhibition, decreased epileptiform afterdischarge durations during 8 hours of subsequent stimulation, and prevented convulsive status epilepticus. Similarly, one 8-hour episode of reduced-intensity stimulation in Long-Evans rats, which are relatively resistant to developing status epilepticus, produced hippocampal discharges without causing status epilepticus. Both paradigms immediately produced the extensive neuronal injury that defines classic hippocampal sclerosis, without giving any clinical indication during the insult that an injury was being inflicted. Spontaneous hippocampal-onset seizures began 16–25 days post-injury, before hippocampal atrophy developed, as demonstrated by sequential magnetic resonance imaging. These results indicate that classic hippocampal sclerosis is uniquely produced by a single episode of clinically “cryptic” excitation. Epileptogenic insults may often involve prolonged excitation that goes undetected at the time of injury. PMID

Silent subtype 3 pituitary adenomas are not always silent and represent poorly differentiated monomorphous plurihormonal Pit-1 lineage adenomas.

PubMed

Mete, Ozgur; Gomez-Hernandez, Karen; Kucharczyk, Walter; Ridout, Rowena; Zadeh, Gelareh; Gentili, Fred; Ezzat, Shereen; Asa, Sylvia L

2016-02-01

Originally classified as a variant of silent corticotroph adenoma, silent subtype 3 adenomas are a distinct histologic variant of pituitary adenoma of unknown cytogenesis. We reviewed the clinical, biochemical, radiological, immunohistochemical and ultrastructural features of 31 silent subtype 3 adenomas to clarify their cellular origin. Among 25 with clinical and/or radiological data, all were macroadenomas; there was cavernous sinus invasion in 30% of cases and involvement of the clivus in 17% of cases. Almost 90% of patients were symptomatic; 67% had mass effect symptoms, 37% were hypogonadal and 8% had secondary adrenal insufficiency. Significant hormonal excess in 29% of cases included hyperthyroidism in 17%, acromegaly in 8% and hyperprolactinemia above 150 μg/l in 4%. Two individuals with hyperprolactinemia who were younger than 30 years had multiple endocrine neoplasia type 1. Immunohistochemically, all 31 tumors were diffusely positive for the pituitary lineage-specific transcription factor Pit-1. Although three only expressed Pit-1, others revealed variable positivity for one or more hormones of Pit-1 cell lineage (growth hormone, prolactin, thyroid-stimulating hormone), as well as alpha-subunit and estrogen receptor. Most tumors exhibited perinuclear reactivity for keratins with the CAM5.2 antibody; scattered fibrous bodies were noted in five (16%) tumors. The mean MIB-1 labeling index was 4% (range, 1-9%). Fourteen cases examined by electron microscopy were composed of a monomorphous population of large polygonal or elongated cells with nuclear spheridia. Sixty-five percent of patients had residual disease after surgery; after a mean follow-up of 48.4 months (median 41.5; range=2-171) disease progression was documented in 53% of those cases. These data identify silent subtype 3 adenomas as aggressive monomorphous plurihormonal adenomas of Pit-1 lineage that may be associated with hyperthyroidism, acromegaly or galactorrhea and amenorrhea. Our

Hippocampal shape variations at term equivalent age in very preterm infants compared with term controls: perinatal predictors and functional significance at age 7

PubMed Central

Thompson, Deanne K.; Adamson, Christopher; Roberts, Gehan; Faggian, Nathan; Wood, Stephen J.; Warfield, Simon K.; Doyle, Lex W.; Anderson, Peter J.; Egan, Gary F.; Inder, Terrie E.

2013-01-01

The hippocampus undergoes rapid growth and development in the perinatal months. Infants born very preterm (VPT) are vulnerable to hippocampal alterations, and can provide a model of disturbed early hippocampal development. Hippocampal shape alterations have previously been associated with memory impairment, but have never been investigated in infants. The aims of this study were to determine hippocampal shape differences between 184 VPT infants (<30 weeks’ gestation or <1250 g at birth) and 32 full-term infants, effects of perinatal factors, and associations between infant hippocampal shape and volume, and 7 year verbal and visual memory (California Verbal Learning Test- Children’s Version and Dot Locations). Infants underwent 1.5T magnetic resonance imaging at term equivalent age. Hippocampi were segmented, and spherical harmonics-point distribution model shape analysis was undertaken. VPT infants’ hippocampi were less infolded than full-term infants, being less curved toward the midline and less arched superior-inferiorly. Straighter hippocampi were associated with white matter injury and postnatal corticosteroid exposure. There were no significant associations between infant hippocampal shape and 7 year memory measures. However, larger infant hippocampal volumes were associated with better verbal memory scores. Altered hippocampal shape in VPT infants at term equivalent age may reflect delayed or disrupted development. This study provides further insight into early hippocampal development and the nature of hippocampal abnormalities in prematurity. PMID:23296179

Human handedness and asymmetry of the motor cortical silent period.

PubMed

Priori, A; Oliviero, A; Donati, E; Callea, L; Bertolasi, L; Rothwell, J C

1999-10-01

We performed transcranial magnetic stimulation of the motor cortex in 22 left-handed and 25 right-handed subjects during active contraction of a small hand muscle. Motor evoked potentials had the same latency, amplitude and threshold on both sides of the body, whilst the silent period duration was shorter in the dominant hand. Silent periods elicited by nerve and brainstem stimulation were the same in both hands. Since the latter part of the cortical silent period is due mainly to withdrawal of corticospinal input to spinal motoneurones, we speculate that the results are compatible with the suggestion that tonic contractions of the non-dominant hand are associated with a greater involvement of the corticospinal tract than those of the dominant hand. It also seems likely that there is an asymmetry in the excitability of cortical inhibitory mechanisms with those responsible for the cortical silent period being less excitable in the dominant motor cortex.

Hippocampal Functioning and Verbal Associative Memory in Adolescents with Congenital Hypothyroidism

PubMed Central

Wheeler, Sarah M.; McLelland, Victoria C.; Sheard, Erin; McAndrews, Mary Pat; Rovet, Joanne F.

2015-01-01

Thyroid hormone (TH) is essential for normal development of the hippocampus, which is critical for memory and particularly for learning and recalling associations between visual and verbal stimuli. Adolescents with congenital hypothyroidism (CH), who lack TH in late gestation and early life, demonstrate weak verbal recall abilities, reduced hippocampal volumes, and abnormal hippocampal functioning for visually associated material. However, it is not known if their hippocampus functions abnormally when remembering verbal associations. Our objective was to assess hippocampal functioning in CH using functional magnetic resonance imaging (fMRI). Fourteen adolescents with CH and 14 typically developing controls (TDC) were studied. Participants studied pairs of words and then, during fMRI acquisition, made two types of recognition decisions: in one they judged whether the pairs were the same as when seen originally and in the other, whether individual words were seen before regardless of pairing. Hippocampal activation was greater for pairs than items in both groups, but this difference was only significant in TDC. When we directly compared the groups, the right anterior hippocampus was the primary region in which the TDC and CH groups differed for this pair memory effect. Results signify that adolescents with CH show abnormal hippocampal functioning during verbal memory processing. PMID:26539162

The Silent Film Era: Silent Films, NAD Films, and the Deaf Community's Response

ERIC Educational Resources Information Center

Schuchman, John S.

2004-01-01

Older citizens who are deaf or hard of hearing recall the years of silent films (1893-1929) as a "golden era" in the cultural history of the American Deaf community. It was golden for several reasons. First, this period represents the one brief time that deaf and hard of hearing citizens had comparatively equal access to motion pictures--a…

Silent memory engrams as the basis for retrograde amnesia.

PubMed

Roy, Dheeraj S; Muralidhar, Shruti; Smith, Lillian M; Tonegawa, Susumu

2017-11-14

Recent studies identified neuronal ensembles and circuits that hold specific memory information (memory engrams). Memory engrams are retained under protein synthesis inhibition-induced retrograde amnesia. These engram cells can be activated by optogenetic stimulation for full-fledged recall, but not by stimulation using natural recall cues (thus, amnesia). We call this state of engrams "silent engrams" and the cells bearing them "silent engram cells." The retention of memory information under amnesia suggests that the time-limited protein synthesis following learning is dispensable for memory storage, but may be necessary for effective memory retrieval processes. Here, we show that the full-fledged optogenetic recall persists at least 8 d after learning under protein synthesis inhibition-induced amnesia. This long-term retention of memory information correlates with equally persistent retention of functional engram cell-to-engram cell connectivity. Furthermore, inactivation of the connectivity of engram cell ensembles with its downstream counterparts, but not upstream ones, prevents optogenetic memory recall. Consistent with the previously reported lack of retention of augmented synaptic strength and reduced spine density in silent engram cells, optogenetic memory recall under amnesia is stimulation strength-dependent, with low-power stimulation eliciting only partial recall. Finally, the silent engram cells can be converted to active engram cells by overexpression of α-p-21-activated kinase 1, which increases spine density in engram cells. These results indicate that memory information is retained in a form of silent engram under protein synthesis inhibition-induced retrograde amnesia and support the hypothesis that memory is stored as the specific connectivity between engram cells.

Early and sustained exposure to high-sucrose diet triggers hippocampal ER stress in young rats.

PubMed

Pinto, Bruno Araújo Serra; Melo, Thamys Marinho; Flister, Karla Frida Torres; França, Lucas Martins; Kajihara, Daniela; Tanaka, Leonardo Yuji; Laurindo, Francisco Rafael Martins; Paes, Antonio Marcus de Andrade

2016-08-01

Early-life environmental insults have been shown to promote long-term development of chronic non-communicable diseases, including metabolic disturbances and mental illnesses. As such, premature consumption of high-sugar foods has been associated to early onset of detrimental outcomes, whereas underlying mechanisms are still poorly understood. In the present study, we sought to investigate whether early and sustained exposure to high-sucrose diet promotes metabolic disturbances that ultimately might anticipate neurological injuries. At postnatal day 21, weaned male rats started to be fed a standard chow (10 % sucrose, CTR) or a high-sucrose diet (25 % sucrose, HSD) for 9 weeks prior to euthanasia at postnatal day 90. HSD did not alter weight gain and feed efficiency between groups, but increased visceral, non-visceral and brown adipose tissue accumulation. HSD rats demonstrated elevated blood glucose levels in both fasting and fed states, which were associated to impaired glucose tolerance. Peripheral insulin sensitivity did not change, whereas hepatic insulin resistance was supported by increased serum triglyceride levels, as well as higher TyG index values. Assessment of hippocampal gene expression showed endoplasmic reticulum (ER) stress pathways were activated in HSD rats, as compared to CTR. HSD rats had overexpression of unfolded protein response sensors, PERK and ATF6; ER chaperone, PDIA2 and apoptosis-related genes, CHOP and Caspase 3; but decreased expression of chaperone GRP78. Finally, HSD rats demonstrated impaired neuromuscular function and anxious behavior, but preserved cognitive parameters. In conclusion, our data indicate that early exposure to HSD promote metabolic disturbances, which disrupt hippocampus homeostasis and might precociously affect its neurobehavioral functions.

Differential effects of subtype-specific nicotinic acetylcholine receptor agonists on early and late hippocampal LTP.

PubMed

Kroker, Katja S; Rast, Georg; Rosenbrock, Holger

2011-12-05

Brain nicotinic acetylcholine receptors are involved in several neuropsychiatric disorders, e.g. Alzheimer's and Parkinson's diseases, Tourette's syndrome, schizophrenia, depression, autism, attention deficit hyperactivity disorder, and anxiety. Currently, approaches selectively targeting the activation of specific nicotinic acetylcholine receptors are in clinical development for treatment of memory impairment of Alzheimer's disease patients. These are α4β2 and α7 nicotinic acetylcholine receptor agonists which are believed to enhance cholinergic and glutamatergic neurotransmission, respectively. In order to gain a better insight into the mechanistic role of these two nicotinic acetylcholine receptors in learning and memory, we investigated the effects of the α4β2 nicotinic acetylcholine receptor agonist TC-1827 and the α7 nicotinic acetylcholine receptor partial agonist SSR180711 on hippocampal long-term potentiation (LTP), a widely accepted cellular experimental model of memory formation. Generally, LTP is distinguished in an early and a late form, the former being protein-synthesis independent and the latter being protein-synthesis dependent. TC-1827 was found to increase early LTP in a bell-shaped dose dependent manner, but did not affect late LTP. In contrast, the α7 nicotinic acetylcholine receptor partial agonist SSR180711 showed enhancing effects on both early and late LTP in a bell-shaped manner. Furthermore, SSR180711 not only increased early LTP, but also transformed it into late LTP, which was not observed with the α4β2 nicotinic acetylcholine receptor agonist. Therefore, based on these findings α7 nicotinic acetylcholine receptor (partial) agonists appear to exhibit stronger efficacy on memory improvement than α4β2 nicotinic acetylcholine receptor agonists. Copyright © 2011 Elsevier B.V. All rights reserved.

Silent Conversations in the Labyrinth of Artistic Research and Practice

ERIC Educational Resources Information Center

Eis, Andrea

2013-01-01

This essay explores silent conversations with the past, but also navigates through the labyrinth of artistic process, with its manifold passages of research, chance occurrence and aesthetic experimentation. The double metaphors of silent conversations and labyrinths apply to the essay and the artwork within it, to the research and to the practice.…

Interventions for preventing silent cerebral infarcts in people with sickle cell disease

PubMed Central

Estcourt, Lise J; Fortin, Patricia M; Hopewell, Sally; Trivella, Marialena; Doree, Carolyn; Abboud, Miguel R

2017-01-01

Background Sickle cell disease (SCD) is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Silent cerebral infarcts are the commonest neurological complication in children and probably adults with SCD. Silent cerebral infarcts also affect academic performance, increase cognitive deficits and may lower intelligence quotient. Objectives To assess the effectiveness of interventions to reduce or prevent silent cerebral infarcts in people with SCD. Search methods We searched for relevant trials in the Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Transfusion Evidence Library (from 1980), and ongoing trial databases; all searches current to 19 September 2016. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register: 06 October 2016. Selection criteria Randomised controlled trials comparing interventions to prevent silent cerebral infarcts in people with SCD. There were no restrictions by outcomes examined, language or publication status. Data collection and analysis We used standard Cochrane methodological procedures. Main results We included five trials (660 children or adolescents) published between 1998 and 2016. Four of the five trials were terminated early. The vast majority of participants had the haemoglobin (Hb)SS form of SCD. One trial focused on preventing silent cerebral infarcts or stroke; three trials were for primary stroke prevention and one trial dealt with secondary stroke prevention. Three trials compared the use of regular long-term red blood cell transfusions to standard care. Two of these trials included children with no previous long-term transfusions: one in children with normal transcranial doppler (TCD) velocities; and one in children with abnormal TCD velocities. The third trial included children and adolescents on

Silent initial conditions for cosmological perturbations with a change of spacetime signature

NASA Astrophysics Data System (ADS)

Mielczarek, Jakub; Linsefors, Linda; Barrau, Aurelien

Recent calculations in loop quantum cosmology suggest that a transition from a Lorentzian to a Euclidean spacetime might take place in the very early universe. The transition point leads to a state of silence, characterized by a vanishing speed of light. This behavior can be interpreted as a decoupling of different space points, similar to the one characterizing the BKL phase. In this study, we address the issue of imposing initial conditions for the cosmological perturbations at the transition point between the Lorentzian and Euclidean phases. Motivated by the decoupling of space points, initial conditions characterized by a lack of correlations are investigated. We show that the “white noise” gains some support from analysis of the vacuum state in the deep Euclidean regime. Furthermore, the possibility of imposing the silent initial conditions at the trans-Planckian surface, characterized by a vanishing speed for the propagation of modes with wavelengths of the order of the Planck length, is studied. Such initial conditions might result from the loop deformations of the Poincaré algebra. The conversion of the silent initial power spectrum to a scale-invariant one is also examined.

A Radiation-Induced Hippocampal Vascular Injury Surrogate Marker Predicts Late Neurocognitive Dysfunction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farjam, Reza; Pramanik, Priyanka; Aryal, Madhava P.

Purpose: We aimed to develop a hippocampal vascular injury surrogate marker for early prediction of late neurocognitive dysfunction in patients receiving brain radiation therapy (RT). Methods and Materials: Twenty-seven patients (17 males and 10 females, 31-80 years of age) were enrolled in an institutional review board-approved prospective longitudinal study. Patients received diagnoses of low-grade glioma or benign tumor and were treated by (3D) conformal or intensity-modulated RT with a median dose of 54 Gy (50.4-59.4 Gy in 1.8-Gy fractions). Six dynamic-contrast enhanced MRI scans were performed from pre-RT to 18-month post-RT, and quantified for vascular parameters related to blood-brain barrier permeability, K{sup trans},more » and the fraction of blood plasma volume, V{sub p}. The temporal changes in the means of hippocampal transfer constant K{sup trans} and V{sub p} after starting RT were modeled by integrating the dose effects with age, sex, hippocampal laterality, and presence of tumor or edema near a hippocampus. Finally, the early vascular dose response in hippocampi was correlated with neurocognitive dysfunction at 6 and 18 months post-RT. Results: The mean K{sup trans} Increased significantly from pre-RT to 1-month post-RT (P<.0004), which significantly depended on sex (P<.0007) and age (P<.00004), with the dose response more pronounced in older females. Also, the vascular dose response in the left hippocampus of females correlated significantly with changes in memory function at 6 (r=−0.95, P<.0006) and 18-months (r=−0.88, P<.02) post-RT. Conclusions: The early hippocampal vascular dose response could be a predictor of late neurocognitive dysfunction. A personalized hippocampus sparing strategy may be considered in the future.« less

Silent memory engrams as the basis for retrograde amnesia

PubMed Central

Roy, Dheeraj S.; Muralidhar, Shruti; Smith, Lillian M.

2017-01-01

Recent studies identified neuronal ensembles and circuits that hold specific memory information (memory engrams). Memory engrams are retained under protein synthesis inhibition-induced retrograde amnesia. These engram cells can be activated by optogenetic stimulation for full-fledged recall, but not by stimulation using natural recall cues (thus, amnesia). We call this state of engrams “silent engrams” and the cells bearing them “silent engram cells.” The retention of memory information under amnesia suggests that the time-limited protein synthesis following learning is dispensable for memory storage, but may be necessary for effective memory retrieval processes. Here, we show that the full-fledged optogenetic recall persists at least 8 d after learning under protein synthesis inhibition-induced amnesia. This long-term retention of memory information correlates with equally persistent retention of functional engram cell-to-engram cell connectivity. Furthermore, inactivation of the connectivity of engram cell ensembles with its downstream counterparts, but not upstream ones, prevents optogenetic memory recall. Consistent with the previously reported lack of retention of augmented synaptic strength and reduced spine density in silent engram cells, optogenetic memory recall under amnesia is stimulation strength-dependent, with low-power stimulation eliciting only partial recall. Finally, the silent engram cells can be converted to active engram cells by overexpression of α-p-21–activated kinase 1, which increases spine density in engram cells. These results indicate that memory information is retained in a form of silent engram under protein synthesis inhibition-induced retrograde amnesia and support the hypothesis that memory is stored as the specific connectivity between engram cells. PMID:29078397

Temporal lobe epilepsy patients with severe hippocampal neuron loss but normal hippocampal volume: Extracellular matrix molecules are important for the maintenance of hippocampal volume.

PubMed

Peixoto-Santos, Jose Eduardo; Velasco, Tonicarlo Rodrigues; Galvis-Alonso, Orfa Yineth; Araujo, David; Kandratavicius, Ludmyla; Assirati, Joao Alberto; Carlotti, Carlos Gilberto; Scandiuzzi, Renata Caldo; Santos, Antonio Carlos dos; Leite, Joao Pereira

2015-10-01

Hippocampal sclerosis is a common finding in patients with temporal lobe epilepsy (TLE), and magnetic resonance imaging (MRI) studies associate the reduction of hippocampal volume with the neuron loss seen on histologic evaluation. Astrogliosis and increased levels of chondroitin sulfate, a major component of brain extracellular matrix, are also seen in hippocampal sclerosis. Our aim was to evaluate the association between hippocampal volume and chondroitin sulfate, as well as neuronal and astroglial populations in the hippocampus of patients with TLE. Patients with drug-resistant TLE were subdivided, according to hippocampal volume measured by MRI, into two groups: hippocampal atrophy (HA) or normal volume (NV) cases. Hippocampi from TLE patients and age-matched controls were submitted to immunohistochemistry to evaluate neuronal population, astroglial population, and chondroitin sulfate expression with antibodies against neuron nuclei protein (NeuN), glial fibrillary acidic protein (GFAP), and chondroitin sulfate (CS-56) antigens, respectively. Both TLE groups were clinically similar. NV cases had higher hippocampal volume, both ipsilateral and contralateral, when compared to HA. Compared to controls, NV and HA patients had reduced neuron density, and increased GFAP and CS-56 immunopositive area. There was no statistical difference between NV and HA groups in neuron density or immunopositive areas for GFAP and CS-56. Hippocampal volume correlated positively with neuron density in CA1 and prosubiculum, and with immunopositive areas for CS-56 in CA1, and negatively with immunopositive area for GFAP in CA1. Multiple linear regression analysis indicated that both neuron density and CS-56 immunopositive area in CA1 were statistically significant predictors of hippocampal volume. Our findings indicate that neuron density and chondroitin sulfate immunopositive area in the CA1 subfield are crucial for the hippocampal volume, and that chondroitin sulfate is important for

Neuroplastic effects of music lessons on hippocampal volume in children with congenital hypothyroidism.

PubMed

Zendel, Benjamin Rich; Willoughby, Karen A; Rovet, Joanne F

2013-12-04

Children with congenital hypothyroidism (CH) who experience a neonatal thyroid hormone deficiency have reduced hippocampal volumes compared with healthy controls. Interestingly, evidence suggests that musical training can contribute to structural plasticity in a number of brain areas, including the hippocampus. Therefore, we investigated whether taking music lessons could ameliorate the volumetric reductions of the hippocampus in children with CH. Left and right hippocampal volumes were measured in four groups of children: children with CH with and without music lessons, and healthy controls with and without music lessons. We found that the volume of the right hippocampus was comparable between children with CH who had taken music lessons and the healthy controls. Children with CH who had not taken music lessons had reduced hippocampal volumes compared with the other three groups. These results suggest that music lessons may induce structural neuroplasticity in children with atypical hippocampal development because of early thyroid hormone deficiencies.

Acid Rain: The Silent Environmental Threat.

ERIC Educational Resources Information Center

Zmud, Mia

1992-01-01

Describes the silent environmental threat posed by acid rain. Caused mainly by manmade pollutants, acid rain damages water and trees, decreases visibility, corrodes monuments, and threatens public health. The article includes guidelines for action. (SM)

SNAP-25 requirement for dendritic growth of hippocampal neurons.

PubMed

Grosse, G; Grosse, J; Tapp, R; Kuchinke, J; Gorsleben, M; Fetter, I; Höhne-Zell, B; Gratzl, M; Bergmann, M

1999-06-01

Structure and dimension of the dendritic arbor are important determinants of information processing by the nerve cell, but mechanisms and molecules involved in dendritic growth are essentially unknown. We investigated early mechanisms of dendritic growth using mouse fetal hippocampal neurons in primary culture, which form processes during the first week in vitro. We detected a key component of regulated exocytosis, SNAP-25 (synaptosomal associated protein of 25 kDa), in axons and axonal terminals as well as in dendrites identified by the occurrence of the dendritic markers transferrin receptor and MAP2. Selective inactivation of SNAP-25 by botulinum neurotoxin A (BoNTA) resulted in inhibition of axonal growth and of vesicle recycling in axonal terminals. In addition, dendritic growth of hippocampal pyramidal and granule neurons was significantly inhibited by BoNTA. In contrast, cleavage of synaptobrevin by tetanus toxin had an effect on neither axonal nor dendritic growth. Our observations indicate that SNAP-25, but not synaptobrevin, is involved in constitutive axonal growth and dendrite formation by hippocampal neurons.

Migraine with aura and silent brain infarcts lack of mediation of patent foramen ovale.

PubMed

Calviere, L; Tall, P; Massabuau, P; Bonneville, F; Larrue, V

2013-12-01

Population-based studies have shown a heightened prevalence of clinically silent brain infarcts in subjects who have migraine with aura (MA). We sought to determine whether this association could be confirmed in young patients with cryptogenic ischemic stroke, and explored the role of patent foramen ovale (PFO) as a potential underlying mechanism. Patients were selected from a registry of young patients consecutively treated for ischemic stroke in a tertiary university hospital among those without definite cause of stroke. Patients with PFO were matched for age and gender with patients with normal atrial septum. Migraine and MA were evaluated after patient selection and matching. Silent brain infarcts were independently evaluated on MRI. We included 100 patients [60 men; mean age (SD), 44.8 years (8.3)], 50 patients with PFO. We found silent brain infarcts in 36 patients and MA in 13 patients. MA was more frequent in patients with silent brain infarcts than in patients without silent brain infarcts (25.0% vs. 6.3%; OR, 5; 95% CI, 1.4-17.6; P = 0.01). Traditional cardiovascular risk factors were not associated with silent brain infarcts. PFO was neither associated with MA (OR, 1.7; 95% CI, 0.5-5.3) nor silent brain infarcts (OR, 0.7; 95% CI, 0.3-1.5). The association of MA with silent brain infarcts was not altered after adjustment for PFO. Findings suggest that silent brain infarcts in young patients with cryptogenic stroke is associated with MA. We found no evidence for a mediating effect of PFO on this association. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

Prosodic Encoding in Silent Reading.

ERIC Educational Resources Information Center

Wilkenfeld, Deborah

In silent reading, short-memory tasks, such as semantic and syntactic processing, require a stage of phonetic encoding between visual representation and the actual extraction of meaning, and this encoding includes prosodic as well as segmental features. To test for this suprasegmental coding, an experiment was conducted in which subjects were…

How Fast Can We Read in the Mind? Developmental Trajectories of Silent Reading Fluency

ERIC Educational Resources Information Center

Ciuffo, Massimo; Myers, Jane; Ingrassia, Massimo; Milanese, Antonio; Venuti, Maria; Alquino, Ausilia; Baradello, Alice; Stella, Giacomo; Gagliano, Antonella

2017-01-01

The silent reading fluency is not an observable behaviour and, therefore, its evaluation is perceived as more challenging and less reliable than oral reading fluency. The present research is aimed to measure the silent reading speed in a sample of proficient students, assessed by an original silent reading fluency task, based on behavioural…

Does Phonological Recoding Occur during Silent Reading, and Is It Necessary for Orthographic Learning?

ERIC Educational Resources Information Center

de Jong, Peter F.; Bitter, Danielle J. L.; van Setten, Margot; Marinus, Eva

2009-01-01

Two studies were conducted to test the central claim of the self-teaching hypothesis (i.e., phonological recoding is necessary for orthographic learning) in silent reading. The first study aimed to demonstrate the use of phonological recoding during silent reading. Texts containing pseudowords were read silently or aloud. Two days later, target…

Inhibited Temperament and Hippocampal Volume in Offspring of Parents with Bipolar Disorder.

PubMed

Kim, Eunjoo; Garrett, Amy; Boucher, Spencer; Park, Min-Hyeon; Howe, Meghan; Sanders, Erica; Kelley, Ryan G; Reiss, Allan L; Chang, Kiki D; Singh, Manpreet K

2017-04-01

Prior studies have suggested that inhibited temperament may be associated with an increased risk for developing anxiety or mood disorder, including bipolar disorder. However, the neurobiological basis for this increased risk is unknown. The aim of this study was to examine temperament in symptomatic and asymptomatic child offspring of parents with bipolar disorder (OBD) and to investigate whether inhibited temperament is associated with aberrant hippocampal volumes compared with healthy control (HC) youth. The OBD group consisted of 45 youth, 24 of whom had current psychiatric symptoms (OBD + s) and 21 without any psychiatric symptoms (OBD - s), and were compared with 24 HC youth. Temperament characteristics were measured by using the Revised Dimensions of Temperament Survey. Magnetic resonance imaging was used to measure hippocampal volumes. The association between temperament and hippocampal volumes was tested by using multiple regression analysis. Compared with the OBD - s group, the OBD + s group had significantly more inhibited temperament traits, less flexibility, more negative mood, and less regular rhythm in their daily routines. In contrast, the OBD - s group was more likely to approach novel situations compared with OBD + s or HC groups. Within the OBD + s group, a more inhibited temperament was associated with smaller right hippocampal volumes. In this study, symptomatic OBD were characterized by an inhibited temperament that was inversely correlated with hippocampal volume. Additional longitudinal studies are needed to determine whether inverse correlations between hippocampal volume and inhibited temperament represent early markers of risk for later developing bipolar disorder.

Diagnosis and body mass index effects on hippocampal volumes and neurochemistry in bipolar disorder.

PubMed

Bond, D J; Silveira, L E; MacMillan, E L; Torres, I J; Lang, D J; Su, W; Honer, W G; Lam, R W; Yatham, L N

2017-03-28

We previously reported that higher body mass index (BMI) was associated with greater hippocampal glutamate+glutamine in people with bipolar disorder (BD), but not in non-BD healthy comparator subjects (HSs). In the current report, we extend these findings by examining the impact of BD diagnosis and BMI on hippocampal volumes and the concentrations of several additional neurochemicals in 57 early-stage BD patients and 31 HSs. Using 3-T magnetic resonance imaging and magnetic resonance spectroscopy, we measured bilateral hippocampal volumes and the hippocampal concentrations of four neurochemicals relevant to BD: N-acetylaspartate+N-acteylaspartylglutamate (tNAA), creatine+phosphocreatine (Cre), myoinositol (Ins) and glycerophosphocholine+phosphatidylcholine (Cho). We used multivariate factorial analysis of covariance to investigate the impact of diagnosis (patient vs HS) and BMI category (normal weight vs overweight/obese) on these variables. We found a main effect of diagnosis on hippocampal volumes, with patients having smaller hippocampi than HSs. There was no association between BMI and hippocampal volumes. We found diagnosis and BMI effects on hippocampal neurochemistry, with patients having lower Cre, Ins and Cho, and overweight/obese subjects having higher levels of these chemicals. In patient-only models that controlled for clinical and treatment variables, we detected an additional association between higher BMI and lower tNAA that was absent in HSs. To our knowledge, this was the first study to investigate the relative contributions of BD diagnosis and BMI to hippocampal volumes, and only the second to investigate their contributions to hippocampal chemistry. It provides further evidence that diagnosis and elevated BMI both impact limbic brain areas relevant to BD.

Reading, writing, and reserve: Literacy activities are linked to hippocampal volume and memory in multiple sclerosis.

PubMed

Sumowski, James F; Rocca, Maria A; Leavitt, Victoria M; Riccitelli, Gianna; Meani, Alessandro; Comi, Giancarlo; Filippi, Massimo

2016-10-01

Engagement in cognitive leisure activities during early adulthood has been linked to preserved memory and larger hippocampal volume in persons with multiple sclerosis (MS). To investigate which specific types of cognitive leisure activities contribute to hippocampal volume and memory. We investigated links between three types of cognitive activities (Reading-Writing, Art-Music, Games-Hobbies) and (a) hippocampal volume within independent samples of Italian (n=187) and American (n=55) MS patients and (b) memory in subsamples of Italian (n=97) and American (n=53) patients. Reading-Writing was the only predictor of hippocampal volume (rp=.204, p=.002), and the best predictor of memory (rp=.288, p=.001). Findings inform the development of targeted evidence-based enrichment programs aiming to bolster reserve against memory decline. © The Author(s), 2016.

Silent Sentry

NASA Technical Reports Server (NTRS)

1980-01-01

NASA developed personal security system, commercialized by Sentry Products, Inc. enables resident to summon instant help in case of medical emergency or threatened violence. Its principal elements are a pen-shaped signaling device, "silent" because its ultrasonic alert signal is inaudible to the human ear, and a system of receivers interconnected with a constantly-monitored aster console. SCAN pen weighs only two ounces and is worn on necklace or attached by a clip to the user's clothing. The person in trouble simply presses a clasp, releasing a hammer inside the pen which strikes an aluminum bar. The impact causes the bar to resonate like a tuning fork and emit the ultrasonic signal, which is detected by the nearest receiver.

Adverse early life environment increases hippocampal microglia abundance in conjunction with decreased neural stem cells in juvenile mice.

PubMed

Cohen, Susan; Ke, Xingrao; Liu, Qiuli; Fu, Qi; Majnik, Amber; Lane, Robert

2016-12-01

Adverse maternal lifestyle resulting in adverse early life environment (AELE) increases risks for neuropsychiatric disorders in offspring. Neuropsychiatric disorders are associated with impaired neurogenesis and neuro-inflammation in the hippocampus (HP). Microglia are neuro-inflammatory cells in the brain that regulate neurogenesis via toll-like receptors (TLR). TLR-9 is implicated in neurogenesis inhibition and is responsible for stress-related inflammatory responses. We hypothesized that AELE would increase microglia cell count and increase TLR-9 expression in juvenile mouse HP. These increases in microglia cell count and TLR-9 expression would be associated with decrease neural stem cell count and neuronal cell count. We developed a mouse model of AELE combining Western diet and a stress environment. Stress environment consisted of random change from embryonic day 13 (E13) to E17 as well as static change in maternal environment from E13 to postnatal day 21(P21). At P21, we measured hippocampal cell numbers of microglia, neural stem cell and neuron, as well as hippocampal TLR-9 expression. AELE significantly increased total microglia number and TLR-9 expression in the hippocampus. Concurrently, AELE significantly decreased neural stem cell and neuronal numbers. AELE increased the neuro-inflammatory cellular response in the juvenile HP. We speculate that increased neuro-inflammatory responses may contribute to impaired neurogenesis seen in this model. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

The Contributions of Oral and Silent Reading Fluency to Reading Comprehension

ERIC Educational Resources Information Center

Price, Katherine W.; Meisinger, Elizabeth B.; Louwerse, Max M.; D'Mello, Sidney

2016-01-01

Silent reading fluency has received limited attention in the school-based literatures across the past decade. We fill this gap by examining both oral and silent reading fluency and their relation to overall abilities in reading comprehension in fourth-grade students. Lower-level reading skills (word reading, rapid automatic naming) and vocabulary…

The written voice: implicit memory effects of voice characteristics following silent reading and auditory presentation.

PubMed

Abramson, Marianne

2007-12-01

After being familiarized with two voices, either implicit (auditory lexical decision) or explicit memory (auditory recognition) for words from silently read sentences was assessed among 32 men and 32 women volunteers. In the silently read sentences, the sex of speaker was implied in the initial words, e.g., "He said, ..." or "She said...". Tone in question versus statement was also manipulated by appropriate punctuation. Auditory lexical decision priming was found for sex- and tone-consistent items following silent reading, but only up to 5 min. after silent reading. In a second study, similar lexical decision priming was found following listening to the sentences, although these effects remained reliable after a 2-day delay. The effect sizes for lexical decision priming showed that tone-consistency and sex-consistency were strong following both silent reading and listening 5 min. after studying. These results suggest that readers create episodic traces of text from auditory images of silently read sentences as they do during listening.

Ethanol exposure in early adolescence inhibits intrinsic neuronal plasticity via sigma-1 receptor activation in hippocampal CA1 neurons

PubMed Central

Sabeti, Jilla

2011-01-01

Background We demonstrated previously that rats exposed to chronic intermittent ethanol (CIE) vapors in early adolescence show increased magnitudes of long-term potentiation (LTP) of excitatory transmission when recorded at dendritic synapses in hippocampus. Large amplitude LTP following CIE exposure is mediated by sigma-1 receptors; however, not yet addressed is the role of sigma-1 receptors in modulating the intrinsic properties of neurons to alter their action potential firing during LTP. Methods Activity-induced plasticity of spike firing was investigated using rat hippocampal slice recordings to measure changes in both field excitatory postsynaptic potentials (fEPSPs) and population spikes (pop. spikes) concomitantly at dendritic inputs and soma of CA1 pyramidal neurons, respectively. Results We observed unique modifications in plasticity of action potential firing in hippocampal slices from CIE exposed adolescent rats, where the induction of large amplitude LTP by 100 Hz stimulations was accompanied by reduced CA1 neuronal excitability—reflected as decreased pop. spike efficacy and impaired activity-induced fEPSP-to-spike (E-S) potentiation. By contrast, LTP induction in ethanol-naïve control slices resulted in increased spike efficacy and robust E-S potentiation. E-S potentiation impairments emerged at 24 hr after CIE treatment cessation, but not before the alcohol withdrawal period, and were restored with bath-application of the sigma-1 receptor selective antagonist BD1047, but not the NMDA receptor antagonist D-AP5. Further evidence revealed a significantly shortened somatic fEPSP time course in adolescent CIE-withdrawn hippocampal slices during LTP; however, paired-pulse data show no apparent correspondence between E-S dissociation and altered recurrent feedback inhibition. Conclusions Results here suggest that acute withdrawal from adolescent CIE exposure triggers sigma-1 receptors that act to depress the efficacy of excitatory inputs in triggering

Silent IL2RG Gene Editing in Human Pluripotent Stem Cells.

PubMed

Li, Li B; Ma, Chao; Awong, Geneve; Kennedy, Marion; Gornalusse, German; Keller, Gordon; Kaufman, Dan S; Russell, David W

2016-03-01

Many applications of pluripotent stem cells (PSCs) require efficient editing of silent chromosomal genes. Here, we show that a major limitation in isolating edited clones is silencing of the selectable marker cassette after homologous recombination and that this can be overcome by using a ubiquitous chromatin opening element (UCOE) promoter-driven transgene. We use this strategy to edit the silent IL2RG locus in human PSCs with a recombinant adeno-associated virus (rAAV)-targeting vector in the absence of potentially genotoxic, site-specific nucleases and show that IL2RG is required for natural killer and T-cell differentiation of human PSCs. Insertion of an active UCOE promoter into a silent locus altered the histone modification and cytosine methylation pattern of surrounding chromatin, but these changes resolved when the UCOE promoter was removed. This same approach could be used to correct IL2RG mutations in X-linked severe combined immunodeficiency patient-derived induced PSCs (iPSCs), to prevent graft versus host disease in regenerative medicine applications, or to edit other silent genes.

Computerized Silent Reading Rate and Strategy Instruction for Fourth Graders at Risk in Silent Reading Rate

ERIC Educational Resources Information Center

Niedo, Jasmin; Lee, Yen-Ling; Breznitz, Zvia; Berninger, Virginia W.

2014-01-01

Fourth graders whose silent word reading and/or sentence reading rate was, on average, two-thirds standard deviation below their oral reading of real and pseudowords and reading comprehension accuracy were randomly assigned to treatment ("n" = 7) or wait-listed ("n" = 7) control groups. Following nine sessions combining…

Progressive contralateral hippocampal atrophy following surgery for medically refractory temporal lobe epilepsy.

PubMed

Elliott, Cameron A; Gross, Donald W; Wheatley, B Matt; Beaulieu, Christian; Sankar, Tejas

2016-09-01

Determine the extent and time course of volumetric changes in the contralateral hippocampus following surgery for medically refractory temporal lobe epilepsy (TLE). Serial T1-weighted MRI brain scans were obtained in 26 TLE patients pre- and post-temporal lobe epilepsy surgery as well as in 12 control subjects of similar age. Patients underwent either anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy (SAH). Blinded, manual hippocampal volumetry (head, body, and tail) was performed in two groups: 1) two scan group [ATL (n=6); SAH (n=10)], imaged pre-surgery and on average at 5.4 years post-surgery; and 2) longitudinal group [ATL (n=8); SAH (n=2)] imaged pre-surgery and on post-operative day 1, 2, 3, 6, 60, 120 and a delayed time point (average 2.4 years). In the two scan group, there was atrophy by 12% of the unresected contralateral hippocampus (p<0.001), with atrophy being most pronounced (27%) in the hippocampal body (p<0.001) with no significant differences seen for the hippocampal head or tail. In the longitudinal group, significant atrophy was also observed for the whole hippocampus and the body with atrophy seen as early as post-operative day #1 which progressed significantly over the first post-operative week (1.3%/day and 3.0%./day, respectively) before stabilizing over the long-term to a 13% reduction in total volume. There was no significant difference in atrophy compared by surgical approach (ATL vs. SAH; p=0.94) or side (p=0.31); however, atrophy was significantly more pronounced in patients with ongoing post-operative seizures (hippocampal body, p=0.019; whole hippocampus, p=0.048). There were no detectable post-operative neuropsychological deficits attributable to contralateral hippocampal atrophy. Significant contralateral hippocampal atrophy occurs following TLE surgery, which begins immediately and progresses over the first post-operative week. The observation that seizure free patients had significantly less atrophy of the

How does the brain deal with cumulative stress? A review with focus on developmental stress, HPA axis function and hippocampal structure in humans.

PubMed

Frodl, Thomas; O'Keane, Veronica

2013-04-01

There is evidence that excessive stress exposure of the brain, mediated through the neurotoxic effects of cortisol and possibly neuroinflammation, causes damage to brain structure and function: the glucocorticoid cascade hypothesis. Functional changes of hypothalamic-pituitary-adrenal (HPA) axis as well as alterations in brain structures like the hippocampus have been consistently reported in major depression. However, there has not been a lot of emphasis on bringing findings from studies on early childhood stress, HPA axis functioning and hippocampal imaging together. This is the subject for this systematic review of the literature on how developmental stress, specifically childhood maltreatment, may impact on HPA axis function and hippocampal structure. We will also review the literature on the relationship between HPA axis function and hippocampal volume in healthy, depressed and other disease states. There is evidence that prenatal stress and childhood maltreatment is associated with an abnormally developing HPA system, as well as hippocampal volume reduction. Smaller hippocampal volumes are associated with increased cortisol secretion during the day. We conclude that a model integrating childhood maltreatment, cortisol abnormalities and hippocampal volume may need to take other factors into account, such as temperament, genetics or the presence of depression; to provide a cohesive explanation of all the findings. Finally, we have to conclude that the cascade hypothesis, mainly based on preclinical studies, has not been translated enough into humans. While there is evidence that early life maltreatment results in structural hippocampal changes and these are in turn more prominent in subjects with higher continuous cortisol secretion it is less clear which role early life maltreatment plays in HPA axis alteration. Copyright © 2012 Elsevier Inc. All rights reserved.

The "Silent Cough" Method for Vocal Hyperfunction

ERIC Educational Resources Information Center

Zwitman, Daniel H.; Calcaterra, Thomas C.

1973-01-01

A method of silent coughing is recommended as an alternative to coughing and throat clearing which are described as vocally abusive activities that can be directly related to laryngeal disease. (Author/GW)

How emotional abilities modulate the influence of early life stress on hippocampal functioning.

PubMed

Aust, Sabine; Alkan Härtwig, Elif; Koelsch, Stefan; Heekeren, Hauke R; Heuser, Isabella; Bajbouj, Malek

2014-07-01

Early life stress (ELS) is known to have considerable influence on brain development, mental health and affective functioning. Previous investigations have shown that alexithymia, a prevalent personality trait associated with difficulties experiencing and verbalizing emotions, is particularly related to ELS. The aim of the present study was to investigate how neural correlates of emotional experiences in alexithymia are altered in the presence and absence of ELS. Therefore, 50 healthy individuals with different levels of alexithymia were matched regarding ELS and investigated with respect to neural correlates of audio-visually induced emotional experiences via functional magnetic resonance imaging. The main finding was that ELS modulated hippocampal responses to pleasant (>neutral) stimuli in high-alexithymic individuals, whereas there was no such modulation in low-alexithymic individuals matched for ELS. Behavioral and psychophysiological results followed a similar pattern. When considered independent of ELS, alexithymia was associated with decreased responses in insula (pleasant > neutral) and temporal pole (unpleasant > neutral). Our results show that the influence of ELS on emotional brain responses seems to be modulated by an individual's degree of alexithymia. Potentially, protective and adverse effects of emotional abilities on brain responses to emotional experiences are discussed. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Concurrent silent strokes impair motor function by limiting behavioral compensation.

PubMed

Faraji, Jamshid; Kurio, Kristyn; Metz, Gerlinde A

2012-08-01

Silent strokes occur more frequently than classic strokes; however, symptoms may go unreported in spite of lasting tissue damage. A silent stroke may indicate elevated susceptibility to recurrent stroke, which may eventually result in apparent and lasting impairments. Here we investigated if multiple silent strokes to the motor system challenge the compensatory capacity of the brain to cumulatively result in permanent functional deficits. Adult male rats with focal ischemia received single focal ischemic mini-lesions in the sensorimotor cortex (SMC) or the dorsolateral striatum (DLS), or multiple lesions affecting both SMC and DLS. The time course and outcome of motor compensation and recovery were determined by quantitative and qualitative assessment of skilled reaching and skilled walking. Rats with SMC or DLS lesion alone did not show behavioral deficits in either task. However, the combination of focal ischemic lesions in SMC and DLS perturbed skilled reaching accuracy and disrupted forelimb placement in the ladder rung walking task. These observations suggest that multiple focal infarcts, each resembling a silent stroke, gradually compromise the plastic capacity of the motor system to cause permanent motor deficits. Moreover, these findings support the notion that cortical and subcortical motor systems cooperate when adopting beneficial compensatory movement strategies. Copyright © 2012 Elsevier Inc. All rights reserved.

Regulation of Hippocampal α1d Adrenergic Receptor mRNA by Corticosterone in Adrenalectomized Rats

PubMed Central

Day, Heidi E.W.; Kryskow, Elisa M.; Watson, Stanley J.; Akil, Huda; Campeau, Serge

2008-01-01

The hippocampal formation receives extensive noradrenergic projections and expresses high levels of mineralocorticoid (MR) and glucocorticoid (GR) receptors. Considerable evidence suggests that the noradrenergic system influences hippocampal corticosteroid receptors. However, there is relatively little data describing the influence of glucocorticoids on noradrenergic receptors in the hippocampal formation. α1d adrenergic receptor (ADR) mRNA is expressed at high levels in the hippocampal formation, within cells that express MR or GR. In order to determine whether expression of α1d ADR mRNA is influenced by circulating glucocorticoids, male rats underwent bilateral adrenalectomy (ADX) or sham surgery, and were killed after 1, 3, 7 or 14 days. Levels of α1d ADR mRNA were profoundly decreased in hippocampal subfields CA1, CA2 and CA3 and the medial and lateral blades of the dentate gyrus, as early as 1 day after ADX, as determined by in situ hybridization. The effect was specific for the hippocampal formation, with levels of α1d mRNA unaltered by ADX in the lateral amygdala, reticular thalamic nucleus, retrosplenial cortex or primary somatosensory cortex. Additional rats underwent ADX or sham surgery and received a corticosterone pellet (10 or 50 mg) or placebo for 7 days. Corticosterone replacement prevented the ADX-induced decrease in hippocampal α1d ADR mRNA, with the magnitude of effect depending on corticosterone dose and hippocampal subregion. These data indicate that α1d ADR mRNA expression in the hippocampal formation is highly sensitive to circulating levels of corticosterone, and provides further evidence for a close interaction between glucocorticoids and the noradrenergic system in the hippocampus. PMID:18534559

Oral Reading Fluency as a Predictor of Silent Reading Fluency at Secondary and Postsecondary Levels

ERIC Educational Resources Information Center

Seok, Soonhwa; DaCosta, Boaventura

2014-01-01

This research investigated oral reading fluency as a predictor of silent reading fluency at the secondary and postsecondary levels. Several measures were used, including the Gray Oral Reading Test, the Test of Silent Word Reading Fluency, the Test of Silent Contextual Reading Fluency, and the Reading Observation Scale. A total of 223 students…

Membrane Potential Dynamics of CA1 Pyramidal Neurons During Hippocampal Ripples in Awake Mice

PubMed Central

Hulse, Brad K.; Moreaux, Laurent C.; Lubenov, Evgueniy V.; Siapas, Athanassios G.

2016-01-01

Ripples are high-frequency oscillations associated with population bursts in area CA1 of the hippocampus that play a prominent role in theories of memory consolidation. While spiking during ripples has been extensively studied, our understanding of the subthreshold behavior of hippocampal neurons during these events remains incomplete. Here, we combine in vivo whole-cell and multisite extracellular recordings to characterize the membrane potential dynamics of identified CA1 pyramidal neurons during ripples. We find that the subthreshold depolarization during ripples is uncorrelated with the net excitatory input to CA1, while the post-ripple hyperpolarization varies proportionately. This clarifies the circuit mechanism keeping most neurons silent during ripples. On a finer time scale, the phase delay between intracellular and extracellular ripple oscillations varies systematically with membrane potential. Such smoothly varying delays are inconsistent with models of intracellular ripple generation involving perisomatic inhibition alone. Instead, they suggest that ripple-frequency excitation leading inhibition shapes intracellular ripple oscillations. PMID:26889811

Tobacco use in silent film: precedents of modern-day substance use portrayals.

PubMed

St Romain, Theresa; Hawley, Suzanne R; Ablah, Elizabeth; Kabler, Bethany S; Molgaard, Craig A

2007-12-01

Much research has been done into tobacco use portrayals in film since the mid-twentieth century, but the earlier years of Hollywood history have been overlooked. Yet the first decades of the twentieth century saw annual per capita cigarette consumption increase from under 100 in 1900 upto 1,500 in 1930. The current study looks at frequency and context (gender, age range, socioeconomic status, type of portrayal) of tobacco use in 20 top-grossing silent films spanning the silent feature era (1915-1928). The sample averaged 23.31 tobacco uses per hour. Tobacco use was most often associated with positive characterizations, working/middle class status, masculinity, and youth. Previous research has verified the influence of the film industry on tobacco consumption in modern years, and this potential connection should not be ignored for the silent film era. Top-grossing silent films set a precedent for positive media portrayals of substance use that have persisted to the present day.

Community violence exposure in early adolescence: Longitudinal associations with hippocampal and amygdala volume and resting state connectivity.

PubMed

Saxbe, Darby; Khoddam, Hannah; Piero, Larissa Del; Stoycos, Sarah A; Gimbel, Sarah I; Margolin, Gayla; Kaplan, Jonas T

2018-06-11

Community violence exposure is a common stressor, known to compromise youth cognitive and emotional development. In a diverse, urban sample of 22 adolescents, participants reported on community violence exposure (witnessing a beating or illegal drug use, hearing gun shots, or other forms of community violence) in early adolescence (average age 12.99), and underwent a neuroimaging scan 3-5 years later (average age 16.92). Community violence exposure in early adolescence predicted smaller manually traced left and right hippocampal and amygdala volumes in a model controlling for age, gender, and concurrent community violence exposure, measured in late adolescence. Community violence continued to predict hippocampus (but not amygdala) volumes after we also controlled for family aggression exposure in early adolescence. Community violence exposure was also associated with stronger resting state connectivity between the right hippocampus (using the manually traced structure as a seed region) and bilateral frontotemporal regions including the superior temporal gyrus and insula. These resting state connectivity results held after controlling for concurrent community violence exposure, SES, and family aggression. Although this is the first study focusing on community violence in conjunction with brain structure and function, these results dovetail with other research linking childhood adversity with smaller subcortical volumes in adolescence and adulthood, and with altered frontolimbic resting state connectivity. Our findings suggest that even community-level exposure to neighborhood violence can have detectable neural correlates in adolescents. © 2018 John Wiley & Sons Ltd.

The clinical dilemma of "silent desensitization" in aspirin-exacerbated respiratory disease.

PubMed

White, Andrew A; Bosso, John V; Stevenson, Donald D

2013-01-01

Aspirin desensitization is a treatment option for patients with aspirin-exacerbated respiratory disease (AERD). Some patients with an excellent history of aspirin or nonsteroidal anti-inflammatory drug (NSAID) reactions have negative aspirin challenges/desensitization. This study discusses the clinical entity of silent desensitization in AERD and the dilemma that this presents to the practicing allergist/immunologist. We discuss a series of patients with a strong history of NSAID reactions who initially underwent a negative challenge/silent desensitization. These patients were subsequently proven to have AERD after a second positive aspirin challenge. Silent desensitization is an uncommon but important outcome to recognize in AERD. Clinicians performing aspirin desensitization should understand that this can occur and consider a second confirmatory aspirin challenge in some patients.

Arsenic: The Silent Killer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Foster, Andrea

2006-02-28

Andrea Foster uses x-rays to determine the forms of potentially toxic elements in environmentally-important matrices such as water, sediments, plants, and microorganisms. In this free public lecture, Foster will discuss her research on arsenic, which is called the silent killer because dissolved in water, it is colorless, odorless, and tasteless, yet consumption of relatively small doses of this element in its most toxic forms can cause rapid and violent death. Arsenic is a well-known poison, and has been used as such since ancient times. Less well known is the fact that much lower doses of the element, consumed over years,more » can lead to a variety of skin and internal cancers that can also be fatal. Currently, what has been called the largest mass poisoning in history is occurring in Bangladesh, where most people are by necessity drinking ground water that is contaminated with arsenic far in excess of the maximum amounts determined to be safe by the World Health Organization. This presentation will review the long and complicated history with arsenic, describe how x-rays have helped explain the high yet spatially variable arsenic concentrations in Bangladesh, discuss the ways in which land use in Bangladesh may be exacerbating the problem, and summarize the impact of this silent killer on drinking water systems worldwide.« less

The Silent Spring of Rachel Carson.

ERIC Educational Resources Information Center

Kerstetter, Ned

1996-01-01

Presents a lesson plan examining Rachel Carson's call to arms concerning the harmful consequences of pesticides. Students view a video documentary on Carson's work and read a synopsis of her book, "Silent Spring." Assessment is provided by various activities including writing assignments, creating posters, and editorial cartoons. (MJP)

Silent method for mathematics instruction: An overview of teaching subsets

NASA Astrophysics Data System (ADS)

Sugiman, Apino, Ezi

2017-05-01

Generally, teachers use oral communication for teaching mathematics. Taking an opposite perspective, this paper describes how instructional practices for mathematics can be carried out namely a silent method. Silent method uses body language, written, and oral communication for classroom interaction. This research uses a design research approach consisting of four phases: preliminary, prototyping and developing the instruction, and assessment. There are four stages of silent method. The first stage is conditioning stage in which the teacher introduces the method and makes agreement about the `rule of the game'. It is followed by the second one, elaborating stage, where students guess and explore alternative answers. The third stage is developing mathematical thinking by structuring and symbolizing. Finally, the method is ended by reinforcing stage which aims at strengthening and reflecting student's understanding. In this paper, every stage is described on the basis of practical experiences in a real mathematics classroom setting.

Silent ureteral stones: impact on kidney function--can treatment of silent ureteral stones preserve kidney function?

PubMed

Marchini, Giovanni S; Vicentini, Fabio C; Mazzucchi, Eduardo; Brito, Arthur; Ebaid, Gustavo; Srougi, Miguel

2012-02-01

To report our experience with silent ureteral stones and expose their true influence on renal function. We analyzed 506 patients who had undergone ureterolithotripsy from January 2005 to May 2010. Silent ureteral stones were calculi found in the absence of any specific or subjective ureteral stone-related symptoms. Of the 506 patients, 27 (5.3%) met these criteria (global cohort). All patients were assessed postoperatively with dimercaptosuccinic acid scintigraphy (DMSA). A difference in relative kidney function of >10% was considered abnormal. Pre- and postoperative comparative DMSA analyses were electively obtained for 9 patients (kidney function cohort). A t test was used to assess the numeric variables, and the chi-square test or Fisher's exact test was used for categorical variables. Two-tailed P<.05 was considered statistically significant. Stones were diagnosed by radiologic abdominal evaluation for nonurologic diseases in 40% and after previous nephrolithiasis treatment in 33%. The primary therapy was ureterolithotripsy in 88%. The mean follow-up time was 23 months. The overall ureteral stone-free rate after 1 and 2 procedures was 96% and 100%, respectively. In the global cohort, the mean pre- and postoperative serum creatinine levels were similar (P=.39), and the mean postoperative function on DMSA was 31%. In the kidney function cohort, no difference was found between the pre- and postoperative DMSA findings (22%±12.1% vs 20%±11.8%; P=.83) and serum creatinine (0.8±0.13 mg/dL vs 1.0±0.21 mg/dL; P=.45). Silent ureteral stones are associated with decreased kidney function present at the diagnosis. Hydronephrosis tends to diminish after stone removal, and kidney function remains unaltered. Copyright © 2012 Elsevier Inc. All rights reserved.

Transient oxytocin signaling primes the development and function of excitatory hippocampal neurons

PubMed Central

Ripamonti, Silvia; Ambrozkiewicz, Mateusz C; Guzzi, Francesca; Gravati, Marta; Biella, Gerardo; Bormuth, Ingo; Hammer, Matthieu; Tuffy, Liam P; Sigler, Albrecht; Kawabe, Hiroshi; Nishimori, Katsuhiko; Toselli, Mauro; Brose, Nils; Parenti, Marco; Rhee, JeongSeop

2017-01-01

Beyond its role in parturition and lactation, oxytocin influences higher brain processes that control social behavior of mammals, and perturbed oxytocin signaling has been linked to the pathogenesis of several psychiatric disorders. However, it is still largely unknown how oxytocin exactly regulates neuronal function. We show that early, transient oxytocin exposure in vitro inhibits the development of hippocampal glutamatergic neurons, leading to reduced dendrite complexity, synapse density, and excitatory transmission, while sparing GABAergic neurons. Conversely, genetic elimination of oxytocin receptors increases the expression of protein components of excitatory synapses and excitatory synaptic transmission in vitro. In vivo, oxytocin-receptor-deficient hippocampal pyramidal neurons develop more complex dendrites, which leads to increased spine number and reduced γ-oscillations. These results indicate that oxytocin controls the development of hippocampal excitatory neurons and contributes to the maintenance of a physiological excitation/inhibition balance, whose disruption can cause neurobehavioral disturbances. DOI: http://dx.doi.org/10.7554/eLife.22466.001 PMID:28231043

Empathy in Hippocampal Amnesia

PubMed Central

Beadle, J. N.; Tranel, D.; Cohen, N. J.; Duff, M. C.

2013-01-01

Empathy is critical to the quality of our relationships with others and plays an important role in life satisfaction and well-being. The scientific investigation of empathy has focused on characterizing its cognitive and neural substrates, and has pointed to the importance of a network of brain regions involved in emotional experience and perspective taking (e.g., ventromedial prefrontal cortex, amygdala, anterior insula, cingulate). While the hippocampus has rarely been the focus of empathy research, the hallmark properties of the hippocampal declarative memory system (e.g., representational flexibility, relational binding, on-line processing capacity) make it well-suited to meet some of the crucial demands of empathy, and a careful investigation of this possibility could make a significant contribution to the neuroscientific understanding of empathy. The present study is a preliminary investigation of the role of the hippocampal declarative memory system in empathy. Participants were three patients (1 female) with focal, bilateral hippocampal (HC) damage and severe declarative memory impairments and three healthy demographically matched comparison participants. Empathy was measured as a trait through a battery of gold standard questionnaires and through on-line ratings and prosocial behavior in response to a series of empathy inductions. Patients with hippocampal amnesia reported lower cognitive and emotional trait empathy than healthy comparison participants. Unlike healthy comparison participants, in response to the empathy inductions hippocampal patients reported no increase in empathy ratings or prosocial behavior. The results provide preliminary evidence for a role for hippocampal declarative memory in empathy. PMID:23526601

Genetic Evidence for a Silent SUC Gene in Yeast

PubMed Central

Carlson, Marian; Osmond, Barbara C.; Botstein, David

1981-01-01

The SUC genes (SUC1–SUC7) of Saccharomyces are a family of genes that are dispersed in the yeast genome. A SUC+ allele at any locus confers the ability to produce the enzyme invertase and, thus, to ferment sucrose. Most yeast strains do not carry SUC+ alleles at all possible SUC loci. We have investigated the naturally occurring negative (suc0) alleles present at SUC loci with the aim of distinguishing between two possible models for the structure of suc0 alleles: (1) suc0 alleles correspond to a simple absence of SUC genetic information; (2) suc0 alleles are "silent" SUC genes that either produce a defective product or are not expressed. To facilitate these studies, sucrose-nonfermenting strains were constructed that are congenic to S. cerevisiae strain S288C (SUC2+), but carry at the SUC2 locus the naturally occurring negative allele, suc20, of strain FL100 (Lacroute 1968). These strains were used to study the genetic properties of the suc20 allele of FL100 and the suc0 alleles (suc10, suc30, etc.) of S288C. The suc20 allele was shown to revert to an active Suc+ state and to provide functional information at three points in the SUC2 gene in recombination experiments; this suc20 gene thus appears to be a "silent" gene. Similar tests for silent SUC genes in S288C (corresponding to loci other than SUC2) failed to reveal any additional silent genes. PMID:7040164

Evidence for Prosody in Silent Reading

ERIC Educational Resources Information Center

Gross, Jennifer; Millett, Amanda L.; Bartek, Brian; Bredell, Kyle Hampton; Winegard, Bo

2014-01-01

English speakers and expressive readers emphasize new content in an ongoing discourse. Do silent readers emphasize new content in their inner voice? Because the inner voice cannot be directly observed, we borrowed the cap-emphasis technique (e.g., "toMAYto") from the pronunciation guides of dictionaries to elicit prosodic emphasis.…

Effects of low-level sarin and cyclosarin exposure on hippocampal microstructure in Gulf War Veterans.

PubMed

Chao, Linda L; Zhang, Yu

2018-05-04

In early March 1991, shortly after the end of the Gulf War (GW), a munitions dump was destroyed at Khamisiyah, Iraq. Later, in 1996, the dump was found to have contained the organophosphorus (OP) nerve agents sarin and cyclosarin. We previously reported evidence of smaller hippocampal volumes in GW veterans with predicted exposure to the Khamisiyah plume compared to unexposed GW veterans. To investigate whether these macroscopic hippocampal volume changes are accompanied by microstructural alterations in the hippocampus, the current study acquired diffusion-tensor imaging (DTI), T1-, and T2-weighted images from 170 GW veterans (mean age: 53 ± 7 years), 81 of whom had predicted exposure to the Khamisiyah plume according to Department of Defense (DOD) plume modeling. We examined fractional anisotropy (FA), mean diffusivity (MD), and grey matter (GM) density from a hippocampal region of interest (ROI). Results indicate that, even after accounting for total hippocampal GM density (or hippocampal volume), age, sex, apolipoprotein ε4 genotype, and potential confounding OP pesticide exposures, hippocampal MD significantly predicted Khamisiyah exposure status (model p = 0.005, R 2  = 0.215, standardized coefficient β = 0.26, t = 2.85). Hippocampal MD was also inversely correlated with verbal memory learning performance in the entire study sample (p = 0.001). There were no differences in hippocampal FA or GM density; however, veterans with predicted Khamisiyah exposure had smaller hippocampal volumes compared to unexposed veterans. Because MD is sensitive to general microstructural disruptions that lead to increased extracellular spaces due to neuronal death, inflammation and gliosis, and/or to axonal loss or demyelination, these findings suggest that low-level exposure to the Khamisiyah plume has a detrimental, lasting effects on both macro- and micro-structure of the hippocampus. Copyright © 2018. Published by Elsevier Inc.

The Keefe Inventory of Silent Reading: A Window into the Reading Process.

ERIC Educational Resources Information Center

Keefe, Donald

1993-01-01

Contains part of the Keefe Inventory of Silent Reading, a silent informal reading inventory. Presents a case study of a student to whom it was administered, including analysis of this individual's reading ability and description of the specific strategies used with this individual on the basis of the results of the inventory. (RS)

Genetic deletion of melanin-concentrating hormone neurons impairs hippocampal short-term synaptic plasticity and hippocampal-dependent forms of short-term memory.

PubMed

Le Barillier, Léa; Léger, Lucienne; Luppi, Pierre-Hervé; Fort, Patrice; Malleret, Gaël; Salin, Paul-Antoine

2015-11-01

The cognitive role of melanin-concentrating hormone (MCH) neurons, a neuronal population located in the mammalian postero-lateral hypothalamus sending projections to all cortical areas, remains poorly understood. Mainly activated during paradoxical sleep (PS), MCH neurons have been implicated in sleep regulation. The genetic deletion of the only known MCH receptor in rodent leads to an impairment of hippocampal dependent forms of memory and to an alteration of hippocampal long-term synaptic plasticity. By using MCH/ataxin3 mice, a genetic model characterized by a selective deletion of MCH neurons in the adult, we investigated the role of MCH neurons in hippocampal synaptic plasticity and hippocampal-dependent forms of memory. MCH/ataxin3 mice exhibited a deficit in the early part of both long-term potentiation and depression in the CA1 area of the hippocampus. Post-tetanic potentiation (PTP) was diminished while synaptic depression induced by repetitive stimulation was enhanced suggesting an alteration of pre-synaptic forms of short-term plasticity in these mice. Behaviorally, MCH/ataxin3 mice spent more time and showed a higher level of hesitation as compared to their controls in performing a short-term memory T-maze task, displayed retardation in acquiring a reference memory task in a Morris water maze, and showed a habituation deficit in an open field task. Deletion of MCH neurons could thus alter spatial short-term memory by impairing short-term plasticity in the hippocampus. Altogether, these findings could provide a cellular mechanism by which PS may facilitate memory encoding. Via MCH neuron activation, PS could prepare the day's learning by increasing and modulating short-term synaptic plasticity in the hippocampus. © 2015 Wiley Periodicals, Inc.

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.

Bilateral Hippocampal Dysfunction in Schizophrenia

PubMed Central

Hanlon, Faith M.; Houck, Jon M.; Pyeatt, Clinton J.; Lundy, S. Laura; Euler, Matthew J.; Weisend, Michael P.; Thoma, Robert J.; Bustillo, Juan R.; Miller, Gregory A.; Tesche, Claudia D.

2014-01-01

The hippocampus has long been known to be important for memory, with the right hippocampus particularly implicated in nonverbal/visuo-spatial memory and left in verbal/narrative or episodic memory. Despite this hypothesized lateralized functional difference, there has not been a single task that has been shown to activate both the right and left hippocampus differentially, dissociating the two, using neuroimaging. The transverse patterning (TP) task is a strong candidate for this purpose, as it has been shown in human and nonhuman animal studies to theoretically and empirically depend on the hippocampus. In TP, participants choose between stimuli presented in pairs, with the correct choice being a function of the specific pairing. In this project, TP was used to assess lateralized hippocampal function by varying its dependence on verbal material, with the goal of dissociating the two hippocampi. Magnetoencephalographic (MEG) data were collected while controls performed verbal and nonverbal versions of TP in order to verify and validate lateralized activation within the hippocampi. Schizophrenia patients were evaluated to determine whether they exhibited a lateralized hippocampal deficit. As hypothesized, patients’ mean level of behavioral performance was poorer than controls’ on both verbal and nonverbal TP. In contrast, patients had no decrement in performance on a verbal and nonverbal non-hippocampal-dependent matched control task. Also, controls but not patients showed more right hippocampal activation during nonverbal TP and more left hippocampal activation during verbal TP. These data demonstrate the capacity to assess lateralized hippocampal function and suggest a bilateral hippocampal behavioral and activation deficit in schizophrenia. PMID:21763438

Letters to Silent Teachers in Tzu Chi Medical School: A Spiritual Interaction

ERIC Educational Resources Information Center

Chen, Guo-Ming; Chang, Chien; Yu, Tong

2011-01-01

This article examines the spiritual communication between medical students and the donated dead body they anatomized, referred to as the "silent teacher." Data were obtained from the medical school of Tzu Chi University in Taiwan, where students are required to write a letter to the silent teacher at the end of the semester after they…

Instrument Development Procedures for Silent Reading Measures. Technical Report Number 08-03

ERIC Educational Resources Information Center

Liu, Kimy; Sundstrom-Hebert, Krystal; Ketterlin-Geller, Leanne R.; Tindal, Gerald

2008-01-01

The purpose of this study was to develop and gather validity evidence for silent reading fluency passages. A number of passages were written following a traditional story grammar structure (character, setting, events) and placed on a computer for students to read silently. We describe in detail, the manner in which content-related evidence was…

Novel genetic loci associated with hippocampal volume.

PubMed

Hibar, Derrek P; Adams, Hieab H H; Jahanshad, Neda; Chauhan, Ganesh; Stein, Jason L; Hofer, Edith; Renteria, Miguel E; Bis, Joshua C; Arias-Vasquez, Alejandro; Ikram, M Kamran; Desrivières, Sylvane; Vernooij, Meike W; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S; Armstrong, Nicola J; Athanasiu, Lavinia; Axelsson, Tomas; Beecham, Ashley H; Beiser, Alexa; Bernard, Manon; Blanton, Susan H; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brickman, Adam M; Carmichael, Owen; Chakravarty, M Mallar; Chen, Qiang; Ching, Christopher R K; Chouraki, Vincent; Cuellar-Partida, Gabriel; Crivello, Fabrice; Den Braber, Anouk; Doan, Nhat Trung; Ehrlich, Stefan; Giddaluru, Sudheer; Goldman, Aaron L; Gottesman, Rebecca F; Grimm, Oliver; Griswold, Michael E; Guadalupe, Tulio; Gutman, Boris A; Hass, Johanna; Haukvik, Unn K; Hoehn, David; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Jørgensen, Kjetil N; Karbalai, Nazanin; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Liewald, David C M; Lopez, Lorna M; Luciano, Michelle; Macare, Christine; Marquand, Andre F; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; McKay, David R; Milaneschi, Yuri; Muñoz Maniega, Susana; Nho, Kwangsik; Nugent, Allison C; Nyquist, Paul; Loohuis, Loes M Olde; Oosterlaan, Jaap; Papmeyer, Martina; Pirpamer, Lukas; Pütz, Benno; Ramasamy, Adaikalavan; Richards, Jennifer S; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rommelse, Nanda; Ropele, Stefan; Rose, Emma J; Royle, Natalie A; Rundek, Tatjana; Sämann, Philipp G; Saremi, Arvin; Satizabal, Claudia L; Schmaal, Lianne; Schork, Andrew J; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V; Sprooten, Emma; Strike, Lachlan T; Teumer, Alexander; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Trompet, Stella; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Lee, Sven J; Van der Meer, Dennis; Van Donkelaar, Marjolein M J; Van Eijk, Kristel R; Van Erp, Theo G M; Van Rooij, Daan; Walton, Esther; Westlye, Lars T; Whelan, Christopher D; Windham, Beverly G; Winkler, Anderson M; Wittfeld, Katharina; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Yanek, Lisa R; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P; Agartz, Ingrid; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A; Arepalli, Sampath; Assareh, Amelia A; Barral, Sandra; Bastin, Mark E; Becker, Diane M; Becker, James T; Bennett, David A; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I; Brodaty, Henry; Brouwer, Rachel M; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bulayeva, Kazima B; Cahn, Wiepke; Calhoun, Vince D; Cannon, Dara M; Cavalleri, Gianpiero L; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Dale, Anders M; Davies, Gareth E; De Craen, Anton J M; De Geus, Eco J C; De Jager, Philip L; De Zubicaray, Greig I; Deary, Ian J; Debette, Stéphanie; DeCarli, Charles; Delanty, Norman; Depondt, Chantal; DeStefano, Anita; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C; Duggirala, Ravi; Dyer, Thomas D; Enzinger, Christian; Erk, Susanne; Espeseth, Thomas; Fedko, Iryna O; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E; Fleischman, Debra A; Ford, Ian; Fornage, Myriam; Foroud, Tatiana M; Fox, Peter T; Francks, Clyde; Fukunaga, Masaki; Gibbs, J Raphael; Glahn, David C; Gollub, Randy L; Göring, Harald H H; Green, Robert C; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Håberg, Asta K; Hansell, Narelle K; Hardy, John; Hartman, Catharina A; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G; Heslenfeld, Dirk J; Ho, Beng-Choon; Hoekstra, Pieter J; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Huentelman, Matthew; Hulshoff Pol, Hilleke E; Ikeda, Masashi; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G; Jukema, J Wouter; Kahn, René S; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L; Lopez, Oscar L; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S; McDonald, Colm; McIntosh, Andrew M; McMahon, Francis J; McMahon, Katie L; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W; Morris, Derek W; Mosley, Thomas H; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Nalls, Michael A; Nauck, Matthias; Nichols, Thomas E; Niessen, Wiro J; Nöthen, Markus M; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L; Ophoff, Roel A; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W J H; Pike, G Bruce; Potkin, Steven G; Psaty, Bruce M; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L; Romanczuk-Seiferth, Nina; Rotter, Jerome I; Ryten, Mina; Sacco, Ralph L; Sachdev, Perminder S; Saykin, Andrew J; Schmidt, Reinhold; Schmidt, Helena; Schofield, Peter R; Sigursson, Sigurdur; Simmons, Andrew; Singleton, Andrew; Sisodiya, Sanjay M; Smith, Colin; Smoller, Jordan W; Soininen, Hilkka; Steen, Vidar M; Stott, David J; Sussmann, Jessika E; Thalamuthu, Anbupalam; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Tsolaki, Magda; Tzourio, Christophe; Uitterlinden, Andre G; Hernández, Maria C Valdés; Van der Brug, Marcel; van der Lugt, Aad; van der Wee, Nic J A; Van Haren, Neeltje E M; van 't Ent, Dennis; Van Tol, Marie-Jose; Vardarajan, Badri N; Vellas, Bruno; Veltman, Dick J; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M; Wassink, Thomas H; Weale, Michael E; Weinberger, Daniel R; Weiner, Michael W; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y; Wright, Clinton B; Zielke, Ronald H; Zonderman, Alan B; Martin, Nicholas G; Van Duijn, Cornelia M; Wright, Margaret J; Longstreth, W T; Schumann, Gunter; Grabe, Hans J; Franke, Barbara; Launer, Lenore J; Medland, Sarah E; Seshadri, Sudha; Thompson, Paul M; Ikram, M Arfan

2017-01-18

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r g =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.

Novel genetic loci associated with hippocampal volume

PubMed Central

Hibar, Derrek P.; Adams, Hieab H. H.; Jahanshad, Neda; Chauhan, Ganesh; Stein, Jason L.; Hofer, Edith; Renteria, Miguel E.; Bis, Joshua C.; Arias-Vasquez, Alejandro; Ikram, M. Kamran; Desrivières, Sylvane; Vernooij, Meike W.; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S.; Armstrong, Nicola J.; Athanasiu, Lavinia; Axelsson, Tomas; Beecham, Ashley H.; Beiser, Alexa; Bernard, Manon; Blanton, Susan H.; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brickman, Adam M.; Carmichael, Owen; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Chouraki, Vincent; Cuellar-Partida, Gabriel; Crivello, Fabrice; Den Braber, Anouk; Doan, Nhat Trung; Ehrlich, Stefan; Giddaluru, Sudheer; Goldman, Aaron L.; Gottesman, Rebecca F.; Grimm, Oliver; Griswold, Michael E.; Guadalupe, Tulio; Gutman, Boris A.; Hass, Johanna; Haukvik, Unn K.; Hoehn, David; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Jørgensen, Kjetil N.; Karbalai, Nazanin; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Liewald, David C. M.; Lopez, Lorna M.; Luciano, Michelle; Macare, Christine; Marquand, Andre F.; Matarin, Mar; Mather, Karen A.; Mattheisen, Manuel; McKay, David R.; Milaneschi, Yuri; Muñoz Maniega, Susana; Nho, Kwangsik; Nugent, Allison C.; Nyquist, Paul; Loohuis, Loes M. Olde; Oosterlaan, Jaap; Papmeyer, Martina; Pirpamer, Lukas; Pütz, Benno; Ramasamy, Adaikalavan; Richards, Jennifer S.; Risacher, Shannon L.; Roiz-Santiañez, Roberto; Rommelse, Nanda; Ropele, Stefan; Rose, Emma J.; Royle, Natalie A.; Rundek, Tatjana; Sämann, Philipp G.; Saremi, Arvin; Satizabal, Claudia L.; Schmaal, Lianne; Schork, Andrew J.; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V.; Sprooten, Emma; Strike, Lachlan T.; Teumer, Alexander; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Trompet, Stella; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Lee, Sven J.; Van der Meer, Dennis; Van Donkelaar, Marjolein M. J.; Van Eijk, Kristel R.; Van Erp, Theo G. M.; Van Rooij, Daan; Walton, Esther; Westlye, Lars T.; Whelan, Christopher D.; Windham, Beverly G.; Winkler, Anderson M.; Wittfeld, Katharina; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Yanek, Lisa R.; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P.; Agartz, Ingrid; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A.; Arepalli, Sampath; Assareh, Amelia A.; Barral, Sandra; Bastin, Mark E.; Becker, Diane M.; Becker, James T.; Bennett, David A.; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I.; Brodaty, Henry; Brouwer, Rachel M.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Bulayeva, Kazima B.; Cahn, Wiepke; Calhoun, Vince D.; Cannon, Dara M.; Cavalleri, Gianpiero L.; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R.; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E.; Czisch, Michael; Dale, Anders M.; Davies, Gareth E.; De Craen, Anton J. M.; De Geus, Eco J. C.; De Jager, Philip L.; De Zubicaray, Greig I.; Deary, Ian J.; Debette, Stéphanie; DeCarli, Charles; Delanty, Norman; Depondt, Chantal; DeStefano, Anita; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C.; Duggirala, Ravi; Dyer, Thomas D.; Enzinger, Christian; Erk, Susanne; Espeseth, Thomas; Fedko, Iryna O.; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E.; Fleischman, Debra A.; Ford, Ian; Fornage, Myriam; Foroud, Tatiana M.; Fox, Peter T.; Francks, Clyde; Fukunaga, Masaki; Gibbs, J. Raphael; Glahn, David C.; Gollub, Randy L.; Göring, Harald H. H.; Green, Robert C.; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Håberg, Asta K.; Hansell, Narelle K.; Hardy, John; Hartman, Catharina A.; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G.; Heslenfeld, Dirk J.; Ho, Beng-Choon; Hoekstra, Pieter J.; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Huentelman, Matthew; Pol, Hilleke E. Hulshoff; Ikeda, Masashi; Jack Jr, Clifford R.; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G.; Jukema, J. Wouter; Kahn, René S.; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L.; Lopez, Oscar L.; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S.; McDonald, Colm; McIntosh, Andrew M.; McMahon, Francis J.; McMahon, Katie L.; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W.; Morris, Derek W.; Mosley, Thomas H.; Mühleisen, Thomas W.; Müller-Myhsok, Bertram; Nalls, Michael A.; Nauck, Matthias; Nichols, Thomas E.; Niessen, Wiro J.; Nöthen, Markus M.; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L.; Ophoff, Roel A.; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W. J. H.; Pike, G. Bruce; Potkin, Steven G.; Psaty, Bruce M.; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L.; Romanczuk-Seiferth, Nina; Rotter, Jerome I.; Ryten, Mina; Sacco, Ralph L.; Sachdev, Perminder S.; Saykin, Andrew J.; Schmidt, Reinhold; Schmidt, Helena; Schofield, Peter R.; Sigursson, Sigurdur; Simmons, Andrew; Singleton, Andrew; Sisodiya, Sanjay M.; Smith, Colin; Smoller, Jordan W.; Soininen, Hilkka; Steen, Vidar M.; Stott, David J.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Tsolaki, Magda; Tzourio, Christophe; Uitterlinden, Andre G.; Hernández, Maria C. Valdés; Van der Brug, Marcel; van der Lugt, Aad; van der Wee, Nic J. A.; Van Haren, Neeltje E. M.; van 't Ent, Dennis; Van Tol, Marie-Jose; Vardarajan, Badri N.; Vellas, Bruno; Veltman, Dick J.; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M.; Wassink, Thomas H.; Weale, Michael E.; Weinberger, Daniel R.; Weiner, Michael W.; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y.; Wright, Clinton B.; Zielke, Ronald H.; Zonderman, Alan B.; Martin, Nicholas G.; Van Duijn, Cornelia M.; Wright, Margaret J.; Longstreth, W. T.; Schumann, Gunter; Grabe, Hans J.; Franke, Barbara; Launer, Lenore J.; Medland, Sarah E.; Seshadri, Sudha; Thompson, Paul M.; Ikram, M. Arfan

2017-01-01

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg=−0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness. PMID:28098162

Image quality assessment of silent T2 PROPELLER sequence for brain imaging in infants.

PubMed

Kim, Hyun Gi; Choi, Jin Wook; Yoon, Soo Han; Lee, Sieun

2018-02-01

Infants are vulnerable to high acoustic noise. Acoustic noise generated by MR scanning can be reduced by a silent sequence. The purpose of this study is to compare the image quality of the conventional and silent T2 PROPELLER sequences for brain imaging in infants. A total of 36 scans were acquired from 24 infants using a 3 T MR scanner. Each patient underwent both conventional and silent T2 PROPELLER sequences. Acoustic noise level was measured. Quantitative and qualitative assessments were performed with the images taken with each sequence. The sound pressure level of the conventional T2 PROPELLER imaging sequence was 92.1 dB and that of the silent T2 PROPELLER imaging sequence was 73.3 dB (reduction of 20%). On quantitative assessment, the two sequences (conventional vs silent T2 PROPELLER) did not show significant difference in relative contrast (0.069 vs 0.068, p value = 0.536) and signal-to-noise ratio (75.4 vs 114.8, p value = 0.098). Qualitative assessment of overall image quality (p value = 0.572), grey-white differentiation (p value = 0.986), shunt-related artefact (p value > 0.999), motion artefact (p value = 0.801) and myelination degree in different brain regions (p values ≥ 0.092) did not show significant difference between the two sequences. The silent T2 PROPELLER sequence reduces acoustic noise and generated comparable image quality to that of the conventional sequence. Advances in knowledge: This is the first report to compare silent T2 PROPELLER images with that of conventional T2 PROPELLER images in children.

Dissociation between Complete Hippocampal Context Memory Formation and Context Fear Acquisition

ERIC Educational Resources Information Center

Leake, Jessica; Zinn, Raphael; Corbit, Laura; Vissel, Bryce

2017-01-01

Rodents require a minimal time period to explore a context prior to footshock to display plateau-level context fear at test. To investigate whether this rapid fear plateau reflects complete memory formation within that short time-frame, we used the immediate-early gene product Arc as an indicator of hippocampal context memory formation-related…

Hippocampal and diencephalic pathology in developmental amnesia.

PubMed

Dzieciol, Anna M; Bachevalier, Jocelyne; Saleem, Kadharbatcha S; Gadian, David G; Saunders, Richard; Chong, W K Kling; Banks, Tina; Mishkin, Mortimer; Vargha-Khadem, Faraneh

2017-01-01

Developmental amnesia (DA) is a selective episodic memory disorder associated with hypoxia-induced bilateral hippocampal atrophy of early onset. Despite the systemic impact of hypoxia-ischaemia, the resulting brain damage was previously reported to be largely limited to the hippocampus. However, the thalamus and the mammillary bodies are parts of the hippocampal-diencephalic network and are therefore also at risk of injury following hypoxic-ischaemic events. Here, we report a neuroimaging investigation of diencephalic damage in a group of 18 patients with DA (age range 11-35 years), and an equal number of controls. Importantly, we uncovered a marked degree of atrophy in the mammillary bodies in two thirds of our patients. In addition, as a group, patients had mildly reduced thalamic volumes. The size of the anterior-mid thalamic (AMT) segment was correlated with patients' visual memory performance. Thus, in addition to the hippocampus, the diencephalic structures also appear to play a role in the patients' memory deficit. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Maturation- and sex-sensitive depression of hippocampal excitatory transmission in a rat schizophrenia model.

PubMed

Patrich, Eti; Piontkewitz, Yael; Peretz, Asher; Weiner, Ina; Attali, Bernard

2016-01-01

Schizophrenia is associated with behavioral and brain structural abnormalities, of which the hippocampus appears to be one of the most consistent region affected. Previous studies performed on the poly I:C model of schizophrenia suggest that alterations in hippocampal synaptic transmission and plasticity take place in the offspring. However, these investigations yielded conflicting results and the neurophysiological alterations responsible for these deficits are still unclear. Here we performed for the first time a longitudinal study examining the impact of prenatal poly I:C treatment and of gender on hippocampal excitatory neurotransmission. In addition, we examined the potential preventive/curative effects of risperidone (RIS) treatment during the peri-adolescence period. Excitatory synaptic transmission was determined by stimulating Schaffer collaterals and monitoring fiber volley amplitude and slope of field-EPSP (fEPSP) in CA1 pyramidal neurons in male and female offspring hippocampal slices from postnatal days (PNDs) 18-20, 34, 70 and 90. Depression of hippocampal excitatory transmission appeared at juvenile age in male offspring of the poly I:C group, while it expressed with a delay in female, manifesting at adulthood. In addition, a reduced hippocampal size was found in both adult male and female offspring of poly I:C treated dams. Treatment with RIS at the peri-adolescence period fully restored in males but partly repaired in females these deficiencies. A maturation- and sex-dependent decrease in hippocampal excitatory transmission occurs in the offspring of poly I:C treated pregnant mothers. Pharmacological intervention with RIS during peri-adolescence can cure in a gender-sensitive fashion early occurring hippocampal synaptic deficits. Copyright © 2015 Elsevier Inc. All rights reserved.

The Nuts and Bolts of Transcriptionally Silent Chromatin in Saccharomyces cerevisiae

PubMed Central

Gartenberg, Marc R.; Smith, Jeffrey S.

2016-01-01

Transcriptional silencing in Saccharomyces cerevisiae occurs at several genomic sites including the silent mating-type loci, telomeres, and the ribosomal DNA (rDNA) tandem array. Epigenetic silencing at each of these domains is characterized by the absence of nearly all histone modifications, including most prominently the lack of histone H4 lysine 16 acetylation. In all cases, silencing requires Sir2, a highly-conserved NAD+-dependent histone deacetylase. At locations other than the rDNA, silencing also requires additional Sir proteins, Sir1, Sir3, and Sir4 that together form a repressive heterochromatin-like structure termed silent chromatin. The mechanisms of silent chromatin establishment, maintenance, and inheritance have been investigated extensively over the last 25 years, and these studies have revealed numerous paradigms for transcriptional repression, chromatin organization, and epigenetic gene regulation. Studies of Sir2-dependent silencing at the rDNA have also contributed to understanding the mechanisms for maintaining the stability of repetitive DNA and regulating replicative cell aging. The goal of this comprehensive review is to distill a wide array of biochemical, molecular genetic, cell biological, and genomics studies down to the “nuts and bolts” of silent chromatin and the processes that yield transcriptional silencing. PMID:27516616

Silent Thyroiditis

PubMed Central

Walker, Peter

1984-01-01

Silent or painless thyroiditis is a frequent cause of transient hyperthyroidism, which is characterized by recent onset of symptoms in a patient with a normal to modestly enlarged and firm thyroid gland. The hallmarks of the disease are the absence of thyroidal pain or tenderness and a markedly reduced radioiodine uptake. Histologically, the gland is characterized by an important lymphocytic infiltration, occasionally to the point of lymphoid follicle formation. However, other indices of an autoimmune cause are usually absent. The disease appears to have a predilection for the postpartum period. Relapses may occur with subsequent pregnancies. Otherwise, the course is usually benign and transient, requiring moderate doses of β-adrenergic blocking agents for symptomatic relief. No pathogenetic factors are known, but the disease may conceivably have an autoimmune basis, particularly in the postpartum patient. PMID:21278944

GENETIC INFLUENCE OF APOE4 GENOTYPE ON HIPPOCAMPAL MORPHOMETRY - AN N=725 SURFACE-BASED ADNI STUDY

PubMed Central

Shi, Jie; Leporé, Natasha; Gutman, Boris A.; Thompson, Paul M.; Baxter, Leslie C.; Caselli, Richard L.; Wang, Yalin

2014-01-01

The apolipoprotein E (APOE) e4 allele is the most prevalent genetic risk factor for Alzheimer’s disease (AD). Hippocampal volumes are generally smaller in AD patients carrying the e4 allele compared to e4 non-carriers. Here we examined the effect of APOE e4 on hippocampal morphometry in a large imaging database – the Alzheimer’s Disease Neuroimaging Initiative (ADNI). We automatically segmented and constructed hippocampal surfaces from the baseline MR images of 725 subjects with known APOE genotype information including 167 with AD, 354 with mild cognitive impairment (MCI), and 204 normal controls. High-order correspondences between hippocampal surfaces were enforced across subjects with a novel inverse consistent surface fluid registration method. Multivariate statistics consisting of multivariate tensor-based morphometry (mTBM) and radial distance were computed for surface deformation analysis. Using Hotelling’s T2 test, we found significant morphological deformation in APOE e4 carriers relative to non-carriers in the entire cohort as well as in the non-demented (pooled MCI and control) subjects, affecting the left hippocampus more than the right, and this effect was more pronounced in e4 homozygotes than heterozygotes. Our findings are consistent with previous studies that showed e4 carriers exhibit accelerated hippocampal atrophy; we extend these findings to a novel measure of hippocampal morphometry. Hippocampal morphometry has significant potential as an imaging biomarker of early stage AD. PMID:24453132

Integrating longitudinal information in hippocampal volume measurements for the early detection of Alzheimer's disease.

PubMed

Chincarini, Andrea; Sensi, Francesco; Rei, Luca; Gemme, Gianluca; Squarcia, Sandro; Longo, Renata; Brun, Francesco; Tangaro, Sabina; Bellotti, Roberto; Amoroso, Nicola; Bocchetta, Martina; Redolfi, Alberto; Bosco, Paolo; Boccardi, Marina; Frisoni, Giovanni B; Nobili, Flavio

2016-01-15

Structural MRI measures for monitoring Alzheimer's Disease (AD) progression are becoming instrumental in the clinical practice, and more so in the context of longitudinal studies. This investigation addresses the impact of four image analysis approaches on the longitudinal performance of the hippocampal volume. We present a hippocampal segmentation algorithm and validate it on a gold-standard manual tracing database. We segmented 460 subjects from ADNI, each subject having been scanned twice at baseline, 12-month and 24month follow-up scan (1.5T, T1 MRI). We used the bilateral hippocampal volume v and its variation, measured as the annualized volume change Λ=δv/year(mm(3)/y). Four processing approaches with different complexity are compared to maximize the longitudinal information, and they are tested for cohort discrimination ability. Reference cohorts are Controls vs. Alzheimer's Disease (CTRL/AD) and CTRL vs. Mild Cognitive Impairment who subsequently progressed to AD dementia (CTRL/MCI-co). We discuss the conditions on v and the added value of Λ in discriminating subjects. The age-corrected bilateral annualized atrophy rate (%/year) were: -1.6 (0.6) for CTRL, -2.2 (1.0) for MCI-nc, -3.2 (1.2) for MCI-co and -4.0 (1.5) for AD. Combined (v, Λ) discrimination ability gave an Area under the ROC curve (auc)=0.93 for CTRL vs AD and auc=0.88 for CTRL vs MCI-co. Longitudinal volume measurements can provide meaningful clinical insight and added value with respect to the baseline provided the analysis procedure embeds the longitudinal information. Copyright © 2015 Elsevier Inc. All rights reserved.

Enhanced oscillatory activity in the hippocampal-prefrontal network is related to short-term memory function after early-life seizures

PubMed Central

Kleen, Jonathan K.; Wu, Edie X.; Holmes, Gregory L.; Scott, Rod C.; Lenck-Santini, Pierre-Pascal

2011-01-01

Neurological insults during development are associated with later impairments in learning and memory. Although remedial training can help restore cognitive function, the neural mechanisms of this recovery in memory systems are largely unknown. To examine this issue we measured electrophysiological oscillatory activity in the hippocampus (both CA3 and CA1) and prefrontal cortex of adult rats that had experienced repeated seizures in the first weeks of life, while they were remedially trained on a delayed-nonmatch-to-sample memory task. Seizure-exposed rats showed initial difficulties learning the task but performed similar to control rats after extra training. Whole-session analyses illustrated enhanced theta power in all three structures while seizure rats learned response tasks prior to the memory task. Whilst performing the memory task, dynamic oscillation patterns revealed that prefrontal cortex theta power was increased among seizure-exposed rats. This enhancement appeared after the first memory training steps using short delays and plateaued at the most difficult steps which included both short and long delays. Further, seizure rats showed enhanced CA1-prefrontal theta coherence in correct trials compared to incorrect trials when long delays were imposed, suggesting increased hippocampal-prefrontal synchrony for the task in this group when memory demand was high. Seizure-exposed rats also showed heightened gamma power and coherence among all three structures during the trials. Our results demonstrate the first evidence of hippocampal-prefrontal enhancements following seizures in early development. Dynamic compensatory changes in this network and interconnected circuits may underpin cognitive rehabilitation following other neurological insults to higher cognitive systems. PMID:22031886

Semaphorin 5A inhibits synaptogenesis in early postnatal- and adult-born hippocampal dentate granule cells.

PubMed

Duan, Yuntao; Wang, Shih-Hsiu; Song, Juan; Mironova, Yevgeniya; Ming, Guo-li; Kolodkin, Alex L; Giger, Roman J

2014-10-14

Human SEMAPHORIN 5A (SEMA5A) is an autism susceptibility gene; however, its function in brain development is unknown. In this study, we show that mouse Sema5A negatively regulates synaptogenesis in early, developmentally born, hippocampal dentate granule cells (GCs). Sema5A is strongly expressed by GCs and regulates dendritic spine density in a cell-autonomous manner. In the adult mouse brain, newly born Sema5A-/- GCs show an increase in dendritic spine density and increased AMPA-type synaptic responses. Sema5A signals through PlexinA2 co-expressed by GCs, and the PlexinA2-RasGAP activity is necessary to suppress spinogenesis. Like Sema5A-/- mutants, PlexinA2-/- mice show an increase in GC glutamatergic synapses, and we show that Sema5A and PlexinA2 genetically interact with respect to GC spine phenotypes. Sema5A-/- mice display deficits in social interaction, a hallmark of autism-spectrum-disorders. These experiments identify novel intra-dendritic Sema5A/PlexinA2 interactions that inhibit excitatory synapse formation in developmentally born and adult-born GCs, and they provide support for SEMA5A contributions to autism-spectrum-disorders.

The association between saliva control, silent saliva penetration, aspiration, and videofluoroscopic findings in Parkinson's disease patients

PubMed Central

Rajaei, Ali; Ashtari, Fereshteh; Azargoon, Seyed Abolfazl; Chitsaz, Ahmad; Nilforoush, Mohammad Hussein; Taheri, Masoud; Sadeghi, Saba

2015-01-01

Background: Dysphagia is a common disorder among patients with Parkinson's disease (PD). It occurs in up to 80% of all (PD) patients during the early stages of the disease and up to 95% in the advanced stages; but professionals may not hear from the patients about dysphagia symptoms until these symptoms reach an advanced stage and lead to medical complications. Materials and Methods: Thirty-three PD patients (mean age 66.09 ± 9.4 years; 24 men, nine women) participated in this study at our Neurology Institute, between April 20, 2013, and October 26, 2013. They were asked two questions; one about saliva control and the other about silent saliva penetration and aspiration. Next, they underwent the videofluoroscopic swallowing study (VFSS). Results: The Pearson Correlation coefficient between the Penetration–Aspiration Scale (PAS) scores and question 1 scores was 0.48 (P < 0.05, =0.25), and there was a significant correlation between the PAS scores and question 2 scores, and also question 1 scores + question 2 scores (r = 0.589, P < 0.05, =0 and r = 0589, P < 0.05, =0). Conclusions: This study showed a significant correlation between the questions about saliva control, silent saliva penetration, and aspiration, and laryngeal penetration and aspiration during VFSS. Therefore, by using these two questions, the potential silent laryngeal penetration and aspiration during meals could be detected before it led to aspiration pneumonia. Taking the benefit of these questions, as a part of the swallowing assessment of PD patients, is recommended. PMID:26261810

Morphology and spelling in French students with dyslexia: the case of silent final letters.

PubMed

Quémart, Pauline; Casalis, Séverine

2017-04-01

Spelling is a challenge for individuals with dyslexia. Phoneme-to-grapheme correspondence rules are highly inconsistent in French, which make them very difficult to master, in particular for dyslexics. One recurrent manifestation of this inconsistency is the presence of silent letters at the end of words. Many of these silent letters perform a morphological function. The current study examined whether students with dyslexia (aged between 10 and 15 years) benefit from the morphological status of silent final letters when spelling. We compared, their ability to spell words with silent final letters that are either morphologically justified (e.g., tricot, "knit," where the final "t" is pronounced in morphologically related words such as tricoter, "to knit" and tricoteur "knitter") or not morphologically justified (e.g., effort, "effort") to that of a group of younger children matched for reading and spelling level. Results indicated that the dyslexic students' spelling of silent final letters was impaired in comparison to the control group. Interestingly, morphological status helped the dyslexics improve the accuracy of their choice of final letters, contrary to the control group. This finding provides new evidence of morphological processing in dyslexia during spelling.

The effect of increased genetic risk for Alzheimer’s disease on hippocampal and amygdala volume

PubMed Central

Lupton, Michelle K.; Strike, Lachlan; Hansell, Narelle K.; Wen, Wei; Mather, Karen A.; Armstrong, Nicola J.; Thalamuthu, Anbupalam; McMahon, Katie L.; de Zubicaray, Greig I.; Assareh, Amelia A.; Simmons, Andrew; Proitsi, Petroula; Powell, John F.; Montgomery, Grant W.; Hibar, Derrek P.; Westman, Eric; Tsolaki, Magda; Kloszewska, Iwona; Soininen, Hilkka; Mecocci, Patrizia; Velas, Bruno; Lovestone, Simon; Brodaty, Henry; Ames, David; Trollor, Julian N.; Martin, Nicholas G.; Thompson, Paul M.; Sachdev, Perminder S.; Wright, Margaret J.

2016-01-01

Reduction in hippocampal and amygdala volume measured via structural magnetic resonance imaging is an early marker of Alzheimer’s disease (AD). Whether genetic risk factors for AD exert an effect on these subcortical structures independent of clinical status has not been fully investigated. We examine whether increased genetic risk for AD influences hippocampal and amygdala volumes in case-control and population cohorts at different ages, in 1674 older (aged >53 years; 17% AD, 39% mild cognitive impairment [MCI]) and 467 young (16–30 years) adults. An AD polygenic risk score combining common risk variants excluding apolipoprotein E (APOE), and a single nucleotide polymorphism in TREM2, were both associated with reduced hippocampal volume in healthy older adults and those with MCI. APOE ɛ4 was associated with hippocampal and amygdala volume in those with AD and MCI but was not associated in healthy older adults. No associations were found in young adults. Genetic risk for AD affects the hippocampus before the clinical symptoms of AD, reflecting a neurodegenerative effect before clinical manifestations in older adults. PMID:26973105

Supporting the Development of Silent Reading Fluency: An Evidence-Based Framework for the Intermediate Grades (3-6)

ERIC Educational Resources Information Center

Reutzel, D. Ray; Juth, Stephanie

2014-01-01

Developing silent fluent reading is an important goal to be achieved in elementary literacy instruction. This article reviews characteristics of effective silent reading fluency instruction and practice. Next, the authors make the case for four components of effective silent reading fluency practice routines. Finally, the authors describe two…

Developmental and Adult GAP-43 Deficiency in Mice Dynamically Alters Hippocampal Neurogenesis and Mossy Fiber Volume

PubMed Central

Latchney, Sarah E.; Masiulis, Irene; Zaccaria, Kimberly J.; Lagace, Diane C.; Powell, Craig M.; McCasland, James S.; Eisch, Amelia J.

2014-01-01

Growth Associated Protein-43 (GAP-43) is a pre-synaptic protein that plays key roles in axonal growth and guidance and in modulating synapse formation. Previous work has demonstrated that mice lacking one allele of this gene [GAP-43(+/-) mice] exhibit hippocampal structural abnormalities and impaired spatial learning and stress-induced behavioral withdrawal and anxiety (Zaccaria et al., 2010), behaviors that are dependent on proper hippocampal circuitry and function. Given the correlation between hippocampal function, synaptic connectivity, and neurogenesis, we tested if behaviorally-naïve GAP-43(+/-) mice had alterations in either neurogenesis or synaptic connectivity in the hippocampus during early postnatal development and young adulthood, and following behavior testing in older adults. To test our hypothesis, we examined hippocampal cell proliferation (Ki67), number of immature neuroblasts (DCX), and mossy fiber volume (synaptoporin) in behaviorally-naïve postnatal (P) day 9 (P9), P26, and behaviorally-experienced 5-7 month old GAP-43(+/-) and (+/+) littermate mice. P9 GAP-43(+/-) mice had fewer Ki67+ and DCX+ cells compared to (+/+) mice, particularly in the posterior dentate gyrus, and smaller mossy fiber volume in the same region. In young adulthood, however, male GAP-43(+/-) mice had more Ki67+ and DCX+ cells and greater mossy fiber volume in the posterior dentate gyrus relative to male (+/+). These increases were not seen in females. In 5-7 month old GAP-43(+/-) mice whose behaviors were the focus of our prior publication (Zaccaria et al., 2010), there was no global change in number of proliferating or immature neurons relative to (+/+) mice. However, more detailed analysis revealed fewer proliferative DCX+ cells in the anterior dentate gyrus of male GAP-43(+/-) mice compared to male (+/+) mice. This reduction was not observed in females. These results suggest that young GAP-43(+/-) mice have decreased hippocampal neurogenesis and synaptic connectivity

Silent Reading Reconsidered: Reinterpreting Reading Instruction and Its Effects. Technical Report No. 390.

ERIC Educational Resources Information Center

Wilkinson, Ian; And Others

Results reported by Leinhardt, Zigmond, and Cooley (1981) have been interpreted as support for increased silent reading in classroom reading instruction. G. Leinhardt and colleagues examined a causal model of classroom processes influencing reading achievement and found that time spent in silent, rather than oral, reading was positively related to…

Childhood Trauma and COMT Genotype Interact to Increase Hippocampal Activation in Resilient Individuals.

PubMed

van Rooij, Sanne J H; Stevens, Jennifer S; Ely, Timothy D; Fani, Negar; Smith, Alicia K; Kerley, Kimberly A; Lori, Adriana; Ressler, Kerry J; Jovanovic, Tanja

2016-01-01

Both childhood trauma and a functional catechol-O-methyltransferase (COMT) genetic polymorphism have been associated with posttraumatic stress disorder (PTSD) and depression; however, it is still unclear whether the two interact and how this interaction relates to long-term risk or resilience. Imaging and genotype data were collected on 73 highly traumatized women. DNA extracted from saliva was used to determine COMT genotype (Val/Val, n = 38, Met carriers, n = 35). Functional MRI data were collected during a Go/NoGo task to investigate the neurocircuitry underlying response inhibition. Self-report measures of adult and childhood trauma exposure, PTSD and depression symptom severity, and resilience were collected. Childhood trauma was found to interact with COMT genotype to impact inhibition-related hippocampal activation. In Met carriers, more childhood trauma was associated with decreased hippocampal activation, whereas in the Val/Val group childhood trauma was related to increased hippocampal activation. Second, hippocampal activation correlated negatively with PTSD and depression symptoms and positively with trait resilience. Moreover, hippocampal activation mediated the relationship between childhood trauma and psychiatric risk or resilience in the Val/Val, but not in the Met carrier group. These data reveal a potential mechanism by which childhood trauma and COMT genotype interact to increase risk for trauma-related psychopathology or resilience. Hippocampal recruitment during inhibition may improve the ability to use contextual information to guide behavior, thereby enhancing resilience in trauma-exposed individuals. This finding may contribute to early identification of individuals at risk and suggests a mechanism that can be targeted in future studies aiming to prevent or limit negative outcomes.

Changes in fitness are associated with changes in hippocampal microstructure and hippocampal volume among older adults.

PubMed

Kleemeyer, Maike Margarethe; Kühn, Simone; Prindle, John; Bodammer, Nils Christian; Brechtel, Lars; Garthe, Alexander; Kempermann, Gerd; Schaefer, Sabine; Lindenberger, Ulman

2016-05-01

This study investigates the effects of fitness changes on hippocampal microstructure and hippocampal volume. Fifty-two healthy participants aged 59-74years with a sedentary lifestyle were randomly assigned to either of two levels of exercise intensity. Training lasted for six months. Physical fitness, hippocampal volumes, and hippocampal microstructure were measured before and after training. Hippocampal microstructure was assessed by mean diffusivity, which inversely reflects tissue density; hence, mean diffusivity is lower for more densely packed tissue. Mean changes in fitness did not differ reliably across intensity levels of training, so data were collapsed across groups. Multivariate modeling of pretest-posttest differences using structural equation modeling (SEM) revealed that individual differences in latent change were reliable for all three constructs. More positive changes in fitness were associated with more positive changes in tissue density (i.e., more negative changes in mean diffusivity), and more positive changes in tissue density were associated with more positive changes in volume. We conclude that fitness-related changes in hippocampal volume may be brought about by changes in tissue density. The relative contributions of angiogenesis, gliogenesis, and/or neurogenesis to changes in tissue density remain to be identified. Copyright © 2015 Elsevier Inc. All rights reserved.

Sex-specific association of sex hormones and gonadotropins, with brain amyloid and hippocampal neurodegeneration.

PubMed

Lee, Jun Ho; Byun, Min Soo; Yi, Dahyun; Choe, Young Min; Choi, Hyo Jung; Baek, Hyewon; Sohn, Bo Kyung; Lee, Jun-Young; Kim, Hyun Jung; Kim, Jee Wook; Lee, Younghwa; Kim, Yu Kyeong; Sohn, Chul-Ho; Woo, Jong Inn; Lee, Dong Young

2017-10-01

This study aimed to examine the sex-specific association between serum sex hormones and gonadotropins and the cerebral beta-amyloid (Aβ) burden and hippocampal neurodegeneration in subjects with normal cognition and impaired cognition. Two hundred sixty-five older subjects received clinical assessments, serum measurements of sex hormones, gonadotropins, 11 C-Pittsburgh compound B-positron emission tomography, and magnetic resonance imaging. In females, higher free testosterone and gonadotropin levels were associated with lower cerebral Aβ positivity. In males, free testosterone was positively related to hippocampal volume with significant interaction with cognitive status. Further subgroup analyses showed that the association was significant only in impaired cognition but not in normal cognition. Free estradiol was not associated with Aβ burden or hippocampal neurodegeneration in either sex. These results suggest that testosterone might inhibit the early pathological accumulation of Aβ in females and delay neurodegeneration in males. Copyright © 2017 Elsevier Inc. All rights reserved.

Human umbilical cord plasma proteins revitalize hippocampal function in aged mice

PubMed Central

Castellano, Joseph M.; Mosher, Kira I.; Abbey, Rachelle J.; McBride, Alisha A.; James, Michelle L.; Berdnik, Daniela; Shen, Jadon C.; Zou, Bende; Xie, Xinmin S.; Tingle, Martha; Hinkson, Izumi V.; Angst, Martin S.; Wyss-Coray, Tony

2017-01-01

Ageing drives changes in neuronal and cognitive function, the decline of which is a major feature of many neurological disorders. The hippocampus, a brain region subserving roles of spatial and episodic memory and learning, is sensitive to the detrimental effects of ageing at morphological and molecular levels. With advancing age, synapses in various hippocampal subfields exhibit impaired long-term potentiation1, an electrophysiological correlate of learning and memory. At the molecular level, immediate early genes are among the synaptic plasticity genes that are both induced by long-term potentiation2, 3, 4 and downregulated in the aged brain5, 6, 7, 8. In addition to revitalizing other aged tissues9, 10, 11, 12, 13, exposure to factors in young blood counteracts age-related changes in these central nervous system parameters14, 15, 16, although the identities of specific cognition-promoting factors or whether such activity exists in human plasma remains unknown17. We hypothesized that plasma of an early developmental stage, namely umbilical cord plasma, provides a reservoir of such plasticity-promoting proteins. Here we show that human cord plasma treatment revitalizes the hippocampus and improves cognitive function in aged mice. Tissue inhibitor of metalloproteinases 2 (TIMP2), a blood-borne factor enriched in human cord plasma, young mouse plasma, and young mouse hippocampi, appears in the brain after systemic administration and increases synaptic plasticity and hippocampal-dependent cognition in aged mice. Depletion experiments in aged mice revealed TIMP2 to be necessary for the cognitive benefits conferred by cord plasma. We find that systemic pools of TIMP2 are necessary for spatial memory in young mice, while treatment of brain slices with TIMP2 antibody prevents long-term potentiation, arguing for previously unknown roles for TIMP2 in normal hippocampal function. Our findings reveal that human cord plasma contains plasticity-enhancing proteins of high

Incidence and implications of silent hydronephrosis following percutaneous nephrolithotomy
.

PubMed

Dagrosa, Lawrence; Moses, Rachel; Pais, Vernon M

2017-01-01

While routine renal imaging following ureteroscopy for urinary calculi has been recommended to screen for asymptomatic "silent" obstruction, the rate of silent obstruction following percutaneous nephrolithotomy (PCNL) remains poorly defined, and no consensus recommendations exist on routine postoperative imaging. At our institution, we sought to assess the incidence of silent hydronephrosis (SH), as a screen for obstruction, following PCNL. The records of all 162 patients who met study inclusion criteria were reviewed. Of this group, 112 patients presented for their scheduled renal ultrasonography 4 - 6 weeks following stent removal to screen for SH. Asymptomatic patients found to have ultrasonographic evidence of hydronephrosis were further analyzed. SH was noted in 16% (18/112) of patients. Two required subsequent ureteroscopic stone extraction (1.8%), one of which also underwent endoureterotomy for a ureteral stricture. Four patients (22%) had stable hydronephrosis and declined functional imaging, 2 patients (11%) had a known partial ureteropelvic junction obstruction and declined intervention. SH resolved spontaneously in 50% (9/18) with a mean time to resolution of 6.3 months. There was no difference in stone complexity based on Guy's stone score between groups, 2.8 (± 0.92) vs. 2.4 (± 1.03), p = 0.34. Although not statistically significant, patients with SH were more likely to have had residual stone fragments postoperatively, 39% (7/18) vs. 19% (18/94), p = 0.067. SH following, PCNL was identified in 16% of this screened population, with the majority requiring no intervention. However, SH may be attributed to residual stone or stricture, which may have been otherwise unrecognized in up to 2% of patients undergoing PCNL. Consideration should be given for routine postoperative ultrasound to screen for silent obstruction following PCNL.
.

Hippocampal Atrophy Is Associated with Altered Hippocampus-Posterior Cingulate Cortex Connectivity in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis.

PubMed

Shih, Y C; Tseng, C E; Lin, F-H; Liou, H H; Tseng, W Y I

2017-03-01

Unilateral mesial temporal lobe epilepsy and hippocampal sclerosis have structural and functional abnormalities in the mesial temporal regions. To gain insight into the pathophysiology of the epileptic network in mesial temporal lobe epilepsy with hippocampal sclerosis, we aimed to clarify the relationships between hippocampal atrophy and the altered connection between the hippocampus and the posterior cingulate cortex in patients with mesial temporal lobe epilepsy with hippocampal sclerosis. Fifteen patients with left mesial temporal lobe epilepsy with hippocampal sclerosis and 15 healthy controls were included in the study. Multicontrast MR imaging, including high-resolution T1WI, diffusion spectrum imaging, and resting-state fMRI, was performed to measure the hippocampal volume, structural connectivity of the inferior cingulum bundle, and intrinsic functional connectivity between the hippocampus and the posterior cingulate cortex, respectively. Compared with controls, patients had decreased left hippocampal volume (volume ratio of the hippocampus and controls, 0.366% ± 0.029%; patients, 0.277% ± 0.063%, corrected P = .002), structural connectivity of the bilateral inferior cingulum bundle (generalized fractional anisotropy, left: controls, 0.234 ± 0.020; patients, 0.193 ± 0.022, corrected P = .0001, right: controls, 0.226 ± 0.022; patients, 0.208 ± 0.017, corrected P = .047), and intrinsic functional connectivity between the left hippocampus and the left posterior cingulate cortex (averaged z-value: controls, 0.314 ± 0.152; patients, 0.166 ± 0.062). The left hippocampal volume correlated with structural connectivity positively (standardized β = 0.864, P = .001), but it had little correlation with intrinsic functional connectivity (standardized β = -0.329, P = .113). On the contralesional side, the hippocampal volume did not show any significant correlation with structural connectivity or intrinsic functional connectivity ( F 2,12 = 0.284, P = .757, R 2

Comparison of Silent and Conventional MR Imaging for the Evaluation of Myelination in Children

PubMed Central

Matsuo-Hagiyama, Chisato; Watanabe, Yoshiyuki; Tanaka, Hisashi; Takahashi, Hiroto; Arisawa, Atsuko; Yoshioka, Eri; Nabatame, Shin; Nakano, Sayaka; Tomiyama, Noriyuki

2017-01-01

Purpose: Silent magnetic resonance imaging (MRI) scans produce reduced acoustic noise and are considered more gentle for sedated children. The aim of this study was to compare the validity of T1- (T1W) and T2-weighted (T2W) silent sequences for myelination assessment in children with conventional spin-echo sequences. Materials and Methods: A total of 30 children (21 boys, 9 girls; age range: 1–83 months, mean age: 35.5 months, median age: 28.5 months) were examined using both silent and spin-echo sequences. Acoustic noise levels were analyzed and compared. The degree of myelination was qualitatively assessed via consensus, and T1W and T2W signal intensities were quantitatively measured by percent contrast. Results: Acoustic noise levels were significantly lower during silent sequences than during conventional sequences (P < 0.0001 for both T1W and T2W). Inter-method comparison indicated overall good to excellent agreement (T1W and T2W images, κ = 0.76 and 0.80, respectively); however, agreement was poor for cerebellar myelination on T1W images (κ = 0.14). The percent contrast of silent and conventional MRI sequences had a strong correlation (T1W, correlation coefficient [CC] = 0.76; T1W excluding the middle cerebellar peduncle, CC = 0.82; T2W, CC = 0.91). Conclusions: For brain MRI, silent sequences significantly reduced acoustic noise and provided diagnostic image quality for myelination evaluations; however, the two methods differed with respect to cerebellar delineation on T1W sequences. PMID:27795484

Volume of hippocampal subfields and episodic memory in childhood and adolescence.

PubMed

Lee, Joshua K; Ekstrom, Arne D; Ghetti, Simona

2014-07-01

Episodic memory critically depends on the hippocampus to bind the features of an experience into memory. Episodic memory develops in childhood and adolescence, and hippocampal changes during this period may contribute to this development. Little is known, however, about how the hippocampus contributes to episodic memory development. The hippocampus is comprised of several cytoarchitectural subfields with functional significance for episodic memory. However, hippocampal subfields have not been assessed in vivo during child development, nor has their relation with episodic memory been assessed during this period. In the present study, high-resolution T2-weighted images of the hippocampus were acquired in 39 children and adolescents aged 8 to 14 years (M=11.30, SD=2.38), and hippocampal subfields were segmented using a protocol previously validated in adult populations. We first validated the method in children and adolescents and examined age-related differences in hippocampal subfields and correlations between subfield volumes and episodic memory. Significant age-related increases in the subfield volume were observed into early adolescence in the right CA3/DG and CA1. The right CA3/DG subfield volumes were positively correlated with accurate episodic memory for item-color relations, and the right CA3/DG and subiculum were negatively correlated with item false alarm rates. Subfield development appears to follow a protracted developmental trajectory, and likely plays a pivotal role in episodic memory development. Copyright © 2014 Elsevier Inc. All rights reserved.

Input-output features of anatomically identified CA3 neurons during hippocampal sharp wave/ripple oscillation in vitro.

PubMed

Hájos, Norbert; Karlócai, Mária R; Németh, Beáta; Ulbert, István; Monyer, Hannah; Szabó, Gábor; Erdélyi, Ferenc; Freund, Tamás F; Gulyás, Attila I

2013-07-10

Hippocampal sharp waves and the associated ripple oscillations (SWRs) are implicated in memory processes. These network events emerge intrinsically in the CA3 network. To understand cellular interactions that generate SWRs, we detected first spiking activity followed by recording of synaptic currents in distinct types of anatomically identified CA3 neurons during SWRs that occurred spontaneously in mouse hippocampal slices. We observed that the vast majority of interneurons fired during SWRs, whereas only a small portion of pyramidal cells was found to spike. There were substantial differences in the firing behavior among interneuron groups; parvalbumin-expressing basket cells were one of the most active GABAergic cells during SWRs, whereas ivy cells were silent. Analysis of the synaptic currents during SWRs uncovered that the dominant synaptic input to the pyramidal cell was inhibitory, whereas spiking interneurons received larger synaptic excitation than inhibition. The discharge of all interneurons was primarily determined by the magnitude and the timing of synaptic excitation. Strikingly, we observed that the temporal structure of synaptic excitation and inhibition during SWRs significantly differed between parvalbumin-containing basket cells, axoaxonic cells, and type 1 cannabinoid receptor (CB1)-expressing basket cells, which might explain their distinct recruitment to these synchronous events. Our data support the hypothesis that the active current sources restricted to the stratum pyramidale during SWRs originate from the synaptic output of parvalbumin-expressing basket cells. Thus, in addition to gamma oscillation, these GABAergic cells play a central role in SWR generation.

Hippocampal Sclerosis in Older Patients

PubMed Central

Cykowski, Matthew D.; Powell, Suzanne Z.; Schulz, Paul E.; Takei, Hidehiro; Rivera, Andreana L.; Jackson, Robert E.; Roman, Gustavo; Jicha, Gregory A.; Nelson, Peter T.

2018-01-01

Context Autopsy studies of the older population (≥65 years of age), and particularly of the “oldest-old” (≥85 years of age), have identified a significant proportion (~20%) of cognitively impaired patients in which hippocampal sclerosis is the major substrate of an amnestic syndrome. Hippocampal sclerosis may also be comorbid with frontotemporal lobar degeneration, Alzheimer disease, and Lewy body disease. Until recently, the terms hippocampal sclerosis of aging or hippocampal sclerosis dementia were applied in this context. Recent discoveries have prompted a conceptual expansion of hippocampal sclerosis of aging because (1) cellular inclusions of TAR DNA-binding protein 43 kDa (TDP-43) are frequent; (2) TDP-43 pathology may be found outside hippocampus; and (3) brain arteriolosclerosis is a common, possibly pathogenic, component. Objective To aid pathologists with recent recommendations for diagnoses of common neuropathologies in older persons, particularly hippocampal sclerosis, and highlight the recent shift in diagnostic terminology from HS-aging to cerebral age-related TDP-43 with sclerosis (CARTS). Data Sources Peer-reviewed literature and 5 autopsy examples that illustrate common age-related neuropathologies, including CARTS, and emphasize the importance of distinguishing CARTS from late-onset frontotemporal lobar degeneration with TDP-43 pathology and from advanced Alzheimer disease with TDP-43 pathology. Conclusions In advanced old age, the substrates of cognitive impairment are often multifactorial. This article demonstrates common and frequently comorbid neuropathologic substrates of cognitive impairment in the older population, including CARTS, to aid those practicing in this area of pathology. PMID:28467211

Revolutionary Concepts for Helicopter Noise Reduction: SILENT Program

NASA Technical Reports Server (NTRS)

Edwards, Bryan; Cox, Charles; Booth, Earl R., Jr. (Technical Monitor)

2002-01-01

As part of a NASA initiative to reduce helicopter main rotor noise, a Phase 1 study has been performed of candidate noise reduction concepts. Both conventional and novel design technologies have been analyzed that reduce the community impact of helicopter operations. In this study the noise reduction potential and design implications are assessed for conventional means of noise reduction, e.g., tip speed reduction, tip shapes and airfoil tailoring, and for two innovative design concepts: modulated blade spacing and x-force control. Main rotor designs that incorporate modulated blade spacing are shown to have reduced peak noise levels in most flight operations. X-force control alters the helicopter's force balance whereby the miss distance between main rotor blades and shed vortices can be controlled. This control provides a high potential to mitigate BVI noise radiation. Each concept is evaluated using best practice design and analysis methods, achieving the study's aim to significantly reduce noise with minimal performance degradation and no vibration increase. It is concluded that a SILENT main rotor design, incorporating the modulated blade spacing concept, offers significantly reduced noise levels and the potential of a breakthrough in how a helicopter's sound is perceived and judged. The SILENT rotor represents a definite advancement in the state-of-the-art and is selected as the design concept for demonstration in Phase 2. A Phase 2 Implementation Plan is developed for whirl cage and wind tunnel evaluations of a scaled model SILENT rotor.

High-throughput platform for the discovery of elicitors of silent bacterial gene clusters.

PubMed

Seyedsayamdost, Mohammad R

2014-05-20

Over the past decade, bacterial genome sequences have revealed an immense reservoir of biosynthetic gene clusters, sets of contiguous genes that have the potential to produce drugs or drug-like molecules. However, the majority of these gene clusters appear to be inactive for unknown reasons prompting terms such as "cryptic" or "silent" to describe them. Because natural products have been a major source of therapeutic molecules, methods that rationally activate these silent clusters would have a profound impact on drug discovery. Herein, a new strategy is outlined for awakening silent gene clusters using small molecule elicitors. In this method, a genetic reporter construct affords a facile read-out for activation of the silent cluster of interest, while high-throughput screening of small molecule libraries provides potential inducers. This approach was applied to two cryptic gene clusters in the pathogenic model Burkholderia thailandensis. The results not only demonstrate a prominent activation of these two clusters, but also reveal that the majority of elicitors are themselves antibiotics, most in common clinical use. Antibiotics, which kill B. thailandensis at high concentrations, act as inducers of secondary metabolism at low concentrations. One of these antibiotics, trimethoprim, served as a global activator of secondary metabolism by inducing at least five biosynthetic pathways. Further application of this strategy promises to uncover the regulatory networks that activate silent gene clusters while at the same time providing access to the vast array of cryptic molecules found in bacteria.

Aerobic fitness, hippocampal viscoelasticity, and relational memory performance

PubMed Central

Schwarb, Hillary; Johnson, Curtis L.; Daugherty, Ana M.; Hillman, Charles H.; Kramer, Arthur F.; Cohen, Neal J.; Barbey, Aron K.

2017-01-01

The positive relationship between hippocampal structure, aerobic fitness, and memory performance is often observed among children and older adults; but evidence of this relationship among young adults, for whom the hippocampus is neither developing nor atrophying, is less consistent. Studies have typically relied on hippocampal volumetry (a gross proxy of tissue composition) to assess individual differences in hippocampal structure. While volume is not specific to microstructural tissue characteristics, microstructural differences in hippocampal integrity may exist even among healthy young adults when volumetric differences are not diagnostic of tissue health or cognitive function. Magnetic resonance elastography (MRE) is an emerging noninvasive imaging technique for measuring viscoelastic tissue properties and provides quantitative measures of tissue integrity. We have previously demonstrated that individual differences in hippocampal viscoelasticity are related to performance on a relational memory task; however, little is known about health correlates to this novel measure. In the current study, we investigated the relationship between hippocampal viscoelasticity and cardiovascular health, and their mutual effect on relational memory in a group of healthy young adults (N=51). We replicated our previous finding that hippocampal viscoelasticity correlates with relational memory performance. We extend this work by demonstrating that better aerobic fitness, as measured by VO2max, was associated with hippocampal viscoelasticity that mediated the benefits of fitness on memory function. Hippocampal volume, however, did not account for individual differences in memory. Therefore, these data suggest that hippocampal viscoelasticity may provide a more sensitive measure to microstructural tissue organization and its consequences to cognition among healthy young adults. PMID:28366763

Evaluating Silent Reading Performance with an Eye Tracking System in Patients with Glaucoma

PubMed Central

Murata, Noriaki; Fukuchi, Takeo

2017-01-01

Objective To investigate the relationship between silent reading performance and visual field defects in patients with glaucoma using an eye tracking system. Methods Fifty glaucoma patients (Group G; mean age, 52.2 years, standard deviation: 11.4 years) and 20 normal controls (Group N; mean age, 46.9 years; standard deviation: 17.2 years) were included in the study. All participants in Group G had early to advanced glaucomatous visual field defects but better than 20/20 visual acuity in both eyes. Participants silently read Japanese articles written horizontally while the eye tracking system monitored and calculated reading duration per 100 characters, number of fixations per 100 characters, and mean fixation duration, which were compared with mean deviation and visual field index values from Humphrey visual field testing (24–2 and 10–2 Swedish interactive threshold algorithm standard) of the right versus left eye and the better versus worse eye. Results There was a statistically significant difference between Groups G and N in mean fixation duration (G, 233.4 msec; N, 215.7 msec; P = 0.010). Within Group G, significant correlations were observed between reading duration and 24–2 right mean deviation (rs = -0.280, P = 0.049), 24–2 right visual field index (rs = -0.306, P = 0.030), 24–2 worse visual field index (rs = -0.304, P = 0.032), and 10–2 worse mean deviation (rs = -0.326, P = 0.025). Significant correlations were observed between mean fixation duration and 10–2 left mean deviation (rs = -0.294, P = 0.045) and 10–2 worse mean deviation (rs = -0.306, P = 0.037), respectively. Conclusions The severity of visual field defects may influence some aspects of reading performance. At least concerning silent reading, the visual field of the worse eye is an essential element of smoothness of reading. PMID:28095478

A diet high in fat and sugar reverses anxiety-like behaviour induced by limited nesting in male rats: Impacts on hippocampal markers.

PubMed

Maniam, Jayanthi; Antoniadis, Christopher P; Le, Vivian; Morris, Margaret J

2016-06-01

Stress exposure during early development is known to produce long-term mental health deficits. Stress promotes poor lifestyle choices such as poor diet. Early life adversity and diets high in fat and sugar (HFHS) are known to affect anxiety and memory. However additive effects of HFHS and stress during early development are less explored. Here, we examined whether early life stress (ELS) simulated by limited nesting (LN) induces anxiety-like behaviour and cognitive deficits that are modulated by HFHS diet. We examined key hippocampal markers involved in anxiety and cognition, testing the hypothesis that post-weaning HFHS following ELS would ameliorate anxiety-like behaviour but worsen memory and associated hippocampal changes. Sprague-Dawley rats were exposed to LN, postnatal days 2-9, and at weaning, male siblings were given unlimited access to chow or HFHS resulting in (Con-Chow, Con-HFHS, LN-Chow, LN-HFHS, n=11-15/group). Anxiety-like behaviour was assessed by Elevated Plus Maze (EPM) at 10 weeks and spatial and object recognition tested at 11 weeks of age. Rats were culled at 13 weeks. Hippocampal mRNA expression was measured using TaqMan(®) Array Micro Fluidic cards (Life Technologies). As expected HFHS diet increased body weight; LN and control rats had similar weights at 13 weeks, energy intake was also similar across groups. LN-Chow rats showed increased anxiety-like behaviour relative to control rats, but this was reversed by HFHS diet. Spatial and object recognition memory were unaltered by LN exposure or consumption of HFHS diet. Hippocampal glucocorticoid receptor (GR) protein was not affected by LN exposure in chow rats, but was increased by 45% in HFHS rats relative to controls. Hippocampal genes involved in plasticity and mood regulation, GSKα and GSKβ were affected, with reductions in GSKβ under both diet conditions, and reduced GSKα only in LN-HFHS versus Con-HFHS. Interestingly, HFHS diet and LN exposure independently reduced expression of

Neocortical inhibitory activities and long-range afferents contribute to the synchronous onset of silent states of the neocortical slow oscillation.

PubMed

Lemieux, Maxime; Chauvette, Sylvain; Timofeev, Igor

2015-02-01

During slow-wave sleep, neurons of the thalamocortical network are engaged in a slow oscillation (<1 Hz), which consists of an alternation between the active and the silent states. Several studies have provided insights on the transition from the silent, which are essentially periods of disfacilitation, to the active states. However, the conditions leading to the synchronous onset of the silent state remain elusive. We hypothesized that a synchronous input to local inhibitory neurons could contribute to the transition to the silent state in the cat suprasylvian gyrus during natural sleep and under ketamine-xylazine anesthesia. After partial and complete deafferentation of the cortex, we found that the silent state onset was more variable among remote sites. We found that the transition to the silent state was preceded by a reduction in excitatory postsynaptic potentials and firing probability in cortical neurons. We tested the impact of chloride-mediated inhibition in the silent-state onset. We uncovered a long-duration (100-300 ms) inhibitory barrage occurring about 250 ms before the silent state onset in 3-6% of neurons during anesthesia and in 12-15% of cases during natural sleep. These inhibitory activities caused a decrease in cortical firing that reduced the excitatory drive in the neocortical network. That chain reaction of disfacilitation ends up on the silent state. Electrical stimuli could trigger a network silent state with a maximal efficacy in deep cortical layers. We conclude that long-range afferents to the neocortex and chloride-mediated inhibition play a role in the initiation of the silent state. Copyright © 2015 the American Physiological Society.

[Study of the predictive value of detection tests for silent aspirations].

PubMed

Woisard, V; Réhault, E; Brouard, C; Fichaux-Bourin, P; Puech, M; Grand, S

2009-01-01

Screening for aspiration in patients with swallowing disorders is important in preventing complications. The tests used in this regard are insufficient due to silent aspiration relating to abnormal protective reflexes in many patients with swallowing problems. The aim of this study is to determine the predictive values of simple tests in screening for silent aspiration. The reference test used was videofluoroscopic examination on swallowing. In the presence of aspiration (FR+) the presence (ME+) or not (ME-) of a cough of throat clearing was noted. The tests being studied were a nasal test with isotonic saline and swallowing according to a set time. For screening for aspiration the presence of a "wet voice" was considered to be a sign of reduced protective reflexes. 1) During the nasal test, the results are 100% for the positive predictive value (VPp) and 83.3% for the negative predictive value (VPn); 2) These results are respectively 84.6% and 35.9% during the swallowing test. Regarding screening for silent aspiration, 1) during the nasal test, the results are 62.5% for the positive predictive value (VPp) and 36.3% for the negative predictive value (VPn); 2) These results are respectively 54.5% and 26.6% during the swallowing test. This preliminary study points out the lack of predictive value of the nasal test and the swallow test for the silent aspirations. However the results could be useful for other researchers developing other tests in this area.

Iron deficiency impairs developing hippocampal neuron gene expression, energy metabolism and dendrite complexity

PubMed Central

Bastian, Thomas W.; von Hohenberg, William C.; Mickelson, Daniel J.; Lanier, Lorene M.; Georgieff, Michael K.

2016-01-01

Iron deficiency (ID), with and without anemia, affects an estimated 2 billion people worldwide. ID is particularly deleterious during early-life brain development, leading to long-term neurological impairments, including deficits in hippocampus-mediated learning and memory. Neonatal rats with fetal/neonatal ID anemia (IDA) have shorter hippocampal CA1 apical dendrites with disorganized branching. ID-induced dendritic structural abnormalities persist into adulthood despite normalization of iron status. However, the specific developmental effects of neuronal iron loss on hippocampal neuron dendrite growth and branching are unknown. Embryonic hippocampal neuron cultures were chronically treated with deferoxamine (DFO, an iron chelator) beginning at 3 days in vitro (DIV). Levels of mRNA for Tfr1 and Slc11a2, iron-responsive genes involved in iron uptake, were significantly elevated in DFO-treated cultures at 11DIV and 18DIV, indicating a similar degree of neuronal ID as seen in rodent ID models. DFO treatment decreased mRNA levels for genes indexing dendritic and synaptic development (i.e., BdnfVI, Camk2a, Vamp1, Psd95, Cfl1, Pfn1, Pfn2, and Gda) and mitochondrial function (i.e., Ucp2, Pink1, and Cox6a1). At 18DIV, DFO reduced key aspects of energy metabolism including basal respiration, maximal respiration, spare respiratory capacity, ATP production, and glycolytic rate, capacity, and reserve. Sholl analysis revealed a significant decrease in distal dendritic complexity in DFO-treated neurons at both 11DIV and 18DIV. At 11DIV, the length of primary dendrites and the number and length of branches in DFO-treated neurons was reduced. By 18DIV, a partial recovery of dendritic branch number in DFO-treated neurons was counteracted by a significant reduction in the number and length of primary dendrites and length of branches. Our findings suggest that early neuronal iron loss, at least partially driven through altered mitochondrial function and neuronal energy metabolism

Hippocampal sclerosis in advanced age: clinical and pathological features.

PubMed

Nelson, Peter T; Schmitt, Frederick A; Lin, Yushun; Abner, Erin L; Jicha, Gregory A; Patel, Ela; Thomason, Paula C; Neltner, Janna H; Smith, Charles D; Santacruz, Karen S; Sonnen, Joshua A; Poon, Leonard W; Gearing, Marla; Green, Robert C; Woodard, John L; Van Eldik, Linda J; Kryscio, Richard J

2011-05-01

Hippocampal sclerosis is a relatively common neuropathological finding (∼10% of individuals over the age of 85 years) characterized by cell loss and gliosis in the hippocampus that is not explained by Alzheimer's disease. Hippocampal sclerosis pathology can be associated with different underlying causes, and we refer to hippocampal sclerosis in the aged brain as hippocampal sclerosis associated with ageing. Much remains unknown about hippocampal sclerosis associated with ageing. We combined three different large autopsy cohorts: University of Kentucky Alzheimer's Disease Centre, the Nun Study and the Georgia Centenarian Study to obtain a pool of 1110 patients, all of whom were evaluated neuropathologically at the University of Kentucky. We focused on the subset of cases with neuropathology-confirmed hippocampal sclerosis (n=106). For individuals aged≥95 years at death (n=179 in our sample), each year of life beyond the age of 95 years correlated with increased prevalence of hippocampal sclerosis pathology and decreased prevalence of 'definite' Alzheimer's disease pathology. Aberrant TAR DNA protein 43 immunohistochemistry was seen in 89.9% of hippocampal sclerosis positive patients compared with 9.7% of hippocampal sclerosis negative patients. TAR DNA protein 43 immunohistochemistry can be used to demonstrate that the disease is usually bilateral even when hippocampal sclerosis pathology is not obvious by haematoxylin and eosin stains. TAR DNA protein 43 immunohistochemistry was negative on brain sections from younger individuals (n=10) after hippocampectomy due to seizures, who had pathologically confirmed hippocampal sclerosis. There was no association between cases with hippocampal sclerosis associated with ageing and apolipoprotein E genotype. Age of death and clinical features of hippocampal sclerosis associated with ageing (with or without aberrant TAR DNA protein 43) were distinct from previously published cases of frontotemporal lobar degeneration TAR

Hippocampal sclerosis in advanced age: clinical and pathological features

PubMed Central

Schmitt, Frederick A.; Lin, Yushun; Abner, Erin L.; Jicha, Gregory A.; Patel, Ela; Thomason, Paula C.; Neltner, Janna H.; Smith, Charles D.; Santacruz, Karen S.; Sonnen, Joshua A.; Poon, Leonard W.; Gearing, Marla; Green, Robert C.; Woodard, John L.; Van Eldik, Linda J.; Kryscio, Richard J.

2011-01-01

Hippocampal sclerosis is a relatively common neuropathological finding (∼10% of individuals over the age of 85 years) characterized by cell loss and gliosis in the hippocampus that is not explained by Alzheimer’s disease. Hippocampal sclerosis pathology can be associated with different underlying causes, and we refer to hippocampal sclerosis in the aged brain as hippocampal sclerosis associated with ageing. Much remains unknown about hippocampal sclerosis associated with ageing. We combined three different large autopsy cohorts: University of Kentucky Alzheimer’s Disease Centre, the Nun Study and the Georgia Centenarian Study to obtain a pool of 1110 patients, all of whom were evaluated neuropathologically at the University of Kentucky. We focused on the subset of cases with neuropathology-confirmed hippocampal sclerosis (n = 106). For individuals aged ≥95 years at death (n = 179 in our sample), each year of life beyond the age of 95 years correlated with increased prevalence of hippocampal sclerosis pathology and decreased prevalence of ‘definite’ Alzheimer’s disease pathology. Aberrant TAR DNA protein 43 immunohistochemistry was seen in 89.9% of hippocampal sclerosis positive patients compared with 9.7% of hippocampal sclerosis negative patients. TAR DNA protein 43 immunohistochemistry can be used to demonstrate that the disease is usually bilateral even when hippocampal sclerosis pathology is not obvious by haematoxylin and eosin stains. TAR DNA protein 43 immunohistochemistry was negative on brain sections from younger individuals (n = 10) after hippocampectomy due to seizures, who had pathologically confirmed hippocampal sclerosis. There was no association between cases with hippocampal sclerosis associated with ageing and apolipoprotein E genotype. Age of death and clinical features of hippocampal sclerosis associated with ageing (with or without aberrant TAR DNA protein 43) were distinct from previously published cases of frontotemporal lobar

BK potassium channels facilitate high-frequency firing and cause early spike frequency adaptation in rat CA1 hippocampal pyramidal cells

PubMed Central

Gu, Ning; Vervaeke, Koen; Storm, Johan F

2007-01-01

Neuronal potassium (K+) channels are usually regarded as largely inhibitory, i.e. reducing excitability. Here we show that BK-type calcium-activated K+ channels enhance high-frequency firing and cause early spike frequency adaptation in neurons. By combining slice electrophysiology and computational modelling, we investigated functions of BK channels in regulation of high-frequency firing in rat CA1 pyramidal cells. Blockade of BK channels by iberiotoxin (IbTX) selectively reduced the initial discharge frequency in response to strong depolarizing current injections, thus reducing the early spike frequency adaptation. IbTX also blocked the fast afterhyperpolarization (fAHP), slowed spike rise and decay, and elevated the spike threshold. Simulations with a computational model of a CA1 pyramidal cell confirmed that the BK channel-mediated rapid spike repolarization and fAHP limits activation of slower K+ channels (in particular the delayed rectifier potassium current (IDR)) and Na+ channel inactivation, whereas M-, sAHP- or SK-channels seem not to be important for the early facilitating effect. Since the BK current rapidly inactivates, its facilitating effect diminishes during the initial discharge, thus producing early spike frequency adaptation by an unconventional mechanism. This mechanism is highly frequency dependent. Thus, IbTX had virtually no effect at spike frequencies < 40 Hz. Furthermore, extracellular field recordings demonstrated (and model simulations supported) that BK channels contribute importantly to high-frequency burst firing in response to excitatory synaptic input to distal dendrites. These results strongly support the idea that BK channels play an important role for early high-frequency, rapidly adapting firing in hippocampal pyramidal neurons, thus promoting the type of bursting that is characteristic of these cells in vivo, during behaviour. PMID:17303637

How Silent Is the "Silent Period" for Young Bilinguals in Early Years Settings in England?

ERIC Educational Resources Information Center

Drury, Rose

2013-01-01

During the first decade of the twenty-first century there have been increasing numbers of bilingual children entering early years settings, many of whom are new to English. Twelve percent of school children in the UK are identified as having a mother tongue other than English and this number rises to 50% in urban areas such as inner London. In…

Early postnatal exposure to isoflurane causes cognitive deficits and disrupts development of newborn hippocampal neurons via activation of the mTOR pathway

PubMed Central

Lim, Sanghee; Kwak, Minhye; Gray, Christy D.; Xu, Michael; Choi, Jun H.; Junn, Sue; Kim, Jieun; Xu, Jing; Schaefer, Michele; Johns, Roger A.; Song, Hongjun; Ming, Guo-Li; Mintz, C. David

2017-01-01

Clinical and preclinical studies indicate that early postnatal exposure to anesthetics can lead to lasting deficits in learning and other cognitive processes. The mechanism underlying this phenomenon has not been clarified and there is no treatment currently available. Recent evidence suggests that anesthetics might cause persistent deficits in cognitive function by disrupting key events in brain development. The hippocampus, a brain region that is critical for learning and memory, contains a large number of neurons that develop in the early postnatal period, which are thus vulnerable to perturbation by anesthetic exposure. Using an in vivo mouse model we demonstrate abnormal development of dendrite arbors and dendritic spines in newly generated dentate gyrus granule cell neurons of the hippocampus after a clinically relevant isoflurane anesthesia exposure conducted at an early postnatal age. Furthermore, we find that isoflurane causes a sustained increase in activity in the mechanistic target of rapamycin pathway, and that inhibition of this pathway with rapamycin not only reverses the observed changes in neuronal development, but also substantially improves performance on behavioral tasks of spatial learning and memory that are impaired by isoflurane exposure. We conclude that isoflurane disrupts the development of hippocampal neurons generated in the early postnatal period by activating a well-defined neurodevelopmental disease pathway and that this phenotype can be reversed by pharmacologic inhibition. PMID:28683067

On Seeing Red with the "Silent Way".

ERIC Educational Resources Information Center

Seely, Jonathan

As a learner-oriented approach, Gattegno's "Silent Way" has recently been receiving much attention in the teaching of English as a second language. Whereas the cognitive approach to the teaching of language deserves praise, an integral aspect of Gattegno's method includes the introduction of a 37-color alphabet, used in a one-to-one…

Morphology and Spelling in French Students with Dyslexia: The Case of Silent Final Letters

ERIC Educational Resources Information Center

Quémart, Pauline; Casalis, Séverine

2017-01-01

Spelling is a challenge for individuals with dyslexia. Phoneme-to-grapheme correspondence rules are highly inconsistent in French, which make them very difficult to master, in particular for dyslexics. One recurrent manifestation of this inconsistency is the presence of silent letters at the end of words. Many of these silent letters perform a…

Toward the silent helicopter

NASA Astrophysics Data System (ADS)

Lewy, Serge; Marze, Henri-James

The development of a 'silent helicopter' program in Europe, whose aim would be noise reduction for both commercial and military helicopters over the next five years, is discussed. Attention is given to acoustic constraints for helicopters and to noise reduction techniques (with particular reference to the main rotor, the rear rotor, and the engines). For commercial helicopters, the noise reduction over the next five years is projected to be at least down to 6 dB below the OACI norms; for military helicopters, the aim is a variable-frequency signature in near-tactical-flight conditions, with a factor-of-two reduction in the maximum impulsivity in the far field.

Insulin treatment partially prevents cognitive and hippocampal alterations as well as glucocorticoid dysregulation in early-onset insulin-deficient diabetic rats.

PubMed

Marissal-Arvy, Nathalie; Campas, Marie-Neige; Semont, Audrey; Ducroix-Crepy, Céline; Beauvieux, Marie-Christine; Brossaud, Julie; Corcuff, Jean-Benoit; Helbling, Jean-Christophe; Vancassel, Sylvie; Bouzier-Sore, Anne-Karine; Touyarot, Katia; Ferreira, Guillaume; Barat, Pascal; Moisan, Marie-Pierre

2018-04-17

The diagnosis of Type 1 Diabetes (T1D) in ever younger children led us to question the impact of insulin deficiency or chronic hyperglycemia on cerebral development and memory performances. Here, we sought abnormalities in these traits in a model of streptozotocin-induced diabetes in juvenile rats treated or not by insulin. We made the assumption that such alterations would be related, at least in part, to excessive glucocorticoid exposition in hippocampal neurons. We have compared 3 groups of juvenile rats: controls, untreated diabetics and insulin-treated diabetics. Diabetes was induced by streptozotocin (65 mg/kg IP/day, 2 consecutive days), at postnatal days 21 and 22 and a subcutaneous pellet delivering 2 U of insulin/day was implanted in treated diabetic rats 3 days later. Three weeks after diabetes induction, cognitive performances (Y maze, object location and recognition tests), in vivo brain structure (brain volume and water diffusion by structural magnetic resonance imaging), and hippocampal neurogenesis (immunohistochemical labeling) measurements were undertaken. Corticosterone levels were evaluated in plasma under basal and stress conditions, and within hippocampus together with 11β-dehydrocorticosterone to assess 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity. The comparison of the three experimental groups revealed that, compared to controls, untreated diabetic rats showed decreased cognitive performances in Y-maze and object location test (p < 0.05), decreased brain and hippocampal microstructure (p < 0.05), and decreased maturation and survival of hippocampal newborn neurons (p < 0.05). These alterations were associated with increased plasma corticosterone at the baseline nadir of its secretion (p < 0.001) and during the recovery phase following a restraint stress (p < 0.001), as well as increased hippocampal corticosterone levels (p < 0.01) and 11β-HSD1 activity (p < 0.05). As untreated diabetic

Management of enophthalmos and superior sulcus deformity induced by the silent sinus syndrome.

PubMed

Ando, Andre; Cruz, Antonio Augusto Velasco

2005-01-01

Silent sinus syndrome is a dysfunction of the maxillary sinus that induces a progressive and asymptomatic enophthalmos with prominent deep superior sulcus deformity. Two cases of silent sinus syndrome are reported, and the simultaneous management of both enophthalmos and superior sulcus deformity caused by this syndrome is discussed. The patients underwent surgical endoscopic maxillary meatotomy and transconjunctival subperiosteal implantation of porous polyethylene sheets. The treatment successfully corrected both the enophthalmos and the upper eyelid sulcus deformity. However, small degrees of vertical eye dystopia were observed. Silent sinus syndrome is a rare cause of enophthalmos and superior sulcus deformity. Orbital floor implants can be used to increase the volume of the orbital contents, but vertical eye dystopia is likely to be induced if this method of treatment is the only option chosen.

Neonatal Hypoxia, Hippocampal Atrophy, and Memory Impairment: Evidence of a Causal Sequence

PubMed Central

Cooper, Janine M.; Gadian, David G.; Jentschke, Sebastian; Goldman, Allan; Munoz, Monica; Pitts, Georgia; Banks, Tina; Chong, W. Kling; Hoskote, Aparna; Deanfield, John; Baldeweg, Torsten; de Haan, Michelle; Mishkin, Mortimer; Vargha-Khadem, Faraneh

2015-01-01

Neonates treated for acute respiratory failure experience episodes of hypoxia. The hippocampus, a structure essential for memory, is particularly vulnerable to such insults. Hence, some neonates undergoing treatment for acute respiratory failure might sustain bilateral hippocampal pathology early in life and memory problems later in childhood. We investigated this possibility in a cohort of 40 children who had been treated neonatally for acute respiratory failure but were free of overt neurological impairment. The cohort had mean hippocampal volumes (HVs) significantly below normal control values, memory scores significantly below the standard population means, and memory quotients significantly below those predicted by their full scale IQs. Brain white matter volume also fell below the volume of the controls, but brain gray matter volumes and scores on nonmnemonic neuropsychological tests were within the normal range. Stepwise linear regression models revealed that the cohort's HVs were predictive of degree of memory impairment, and gestational age at treatment was predictive of HVs: the younger the age, the greater the atrophy. We conclude that many neonates treated for acute respiratory failure sustain significant hippocampal atrophy as a result of the associated hypoxia and, consequently, show deficient memory later in life. PMID:24343890

Early malnutrition results in long-lasting impairments in pattern-separation for overlapping novel object and novel location memories and reduced hippocampal neurogenesis.

PubMed

Pérez-García, Georgina; Guzmán-Quevedo, Omar; Da Silva Aragão, Raquel; Bolaños-Jiménez, Francisco

2016-02-17

Numerous epidemiological studies indicate that malnutrition during in utero development and/or childhood induces long-lasting learning disabilities and enhanced susceptibility to develop psychiatric disorders. However, animal studies aimed to address this question have yielded inconsistent results due to the use of learning tasks involving negative or positive reinforces that interfere with the enduring changes in emotional reactivity and motivation produced by in utero and neonatal malnutrition. Consequently, the mechanisms underlying the learning deficits associated with malnutrition in early life remain unknown. Here we implemented a behavioural paradigm based on the combination of the novel object recognition and the novel object location tasks to define the impact of early protein-restriction on the behavioural, cellular and molecular basis of memory processing. Adult rats born to dams fed a low-protein diet during pregnancy and lactation, exhibited impaired encoding and consolidation of memory resulting from impaired pattern separation. This learning deficit was associated with reduced production of newly born hippocampal neurons and down regulation of BDNF gene expression. These data sustain the existence of a causal relationship between early malnutrition and impaired learning in adulthood and show that decreased adult neurogenesis is associated to the cognitive deficits induced by childhood exposure to poor nutrition.

Early malnutrition results in long-lasting impairments in pattern-separation for overlapping novel object and novel location memories and reduced hippocampal neurogenesis

PubMed Central

Pérez-García, Georgina; Guzmán-Quevedo, Omar; Da Silva Aragão, Raquel; Bolaños-Jiménez, Francisco

2016-01-01

Numerous epidemiological studies indicate that malnutrition during in utero development and/or childhood induces long-lasting learning disabilities and enhanced susceptibility to develop psychiatric disorders. However, animal studies aimed to address this question have yielded inconsistent results due to the use of learning tasks involving negative or positive reinforces that interfere with the enduring changes in emotional reactivity and motivation produced by in utero and neonatal malnutrition. Consequently, the mechanisms underlying the learning deficits associated with malnutrition in early life remain unknown. Here we implemented a behavioural paradigm based on the combination of the novel object recognition and the novel object location tasks to define the impact of early protein-restriction on the behavioural, cellular and molecular basis of memory processing. Adult rats born to dams fed a low-protein diet during pregnancy and lactation, exhibited impaired encoding and consolidation of memory resulting from impaired pattern separation. This learning deficit was associated with reduced production of newly born hippocampal neurons and down regulation of BDNF gene expression. These data sustain the existence of a causal relationship between early malnutrition and impaired learning in adulthood and show that decreased adult neurogenesis is associated to the cognitive deficits induced by childhood exposure to poor nutrition. PMID:26882991

Sustained Silent Reading: Try It, You'll Like It!

ERIC Educational Resources Information Center

Anderson, Cynthia

2000-01-01

Recommends Sustained Silent Reading (SSR) in grades 2-12 to improve students' reading and to teach them to love to read. Outlines rules for SSR, and offers notes to the teacher on its implementation. (SR)

Hippocampal-targeted Theta-burst Stimulation Enhances Associative Memory Formation.

PubMed

Tambini, Arielle; Nee, Derek Evan; D'Esposito, Mark

2018-06-19

The hippocampus plays a critical role in episodic memory, among other cognitive functions. However, few tools exist to causally manipulate hippocampal function in healthy human participants. Recent work has targeted hippocampal-cortical networks by performing TMS to a region interconnected with the hippocampus, posterior inferior parietal cortex (pIPC). Such hippocampal-targeted TMS enhances associative memory and influences hippocampal functional connectivity. However, it is currently unknown which stages of mnemonic processing (encoding or retrieval) are affected by hippocampal-targeted TMS. Here, we examined whether hippocampal-targeted TMS influences the initial encoding of associations (vs. items) into memory. To selectively influence encoding and not retrieval, we performed continuous theta-burst TMS before participants encoded object-location associations and assessed memory after the direct effect of stimulation dissipated. Relative to control TMS and baseline memory, pIPC TMS enhanced associative memory success and confidence. Item memory was unaffected, demonstrating a selective influence on associative versus item memory. The strength of hippocampal-pIPC functional connectivity predicted TMS-related memory benefits, which was mediated by parahippocampal and retrosplenial cortices. Our findings indicate that hippocampal-targeted TMS can specifically modulate the encoding of new associations into memory without directly influencing retrieval processes and suggest that the ability to influence associative memory may be related to the fidelity of hippocampal TMS targeting. Our results support the notion that pIPC TMS may serve as a potential tool for manipulating hippocampal function in healthy participants. Nonetheless, future work combining hippocampal-targeted continuous theta-burst TMS with neuroimaging is needed to better understand the neural basis of TMS-induced memory changes.

Orthographic and Phonological Form Interference during Silent Reading

ERIC Educational Resources Information Center

Price, Iya Khelm; Witzel, Naoko; Witzel, Jeffrey

2015-01-01

This study reports 2 eye-tracking experiments investigating form interference during sentence-level silent reading. The items involved reduced and unreduced relative clauses (RCs) with words that were orthographically and phonologically similar "(injection-infection"; O+P+, Experiment 1) as well as with words that were orthographically…

Quantitative Neuroimaging Software for Clinical Assessment of Hippocampal Volumes on MR Imaging

PubMed Central

Ahdidan, Jamila; Raji, Cyrus A.; DeYoe, Edgar A.; Mathis, Jedidiah; Noe, Karsten Ø.; Rimestad, Jens; Kjeldsen, Thomas K.; Mosegaard, Jesper; Becker, James T.; Lopez, Oscar

2015-01-01

Background: Multiple neurological disorders including Alzheimer’s disease (AD), mesial temporal sclerosis, and mild traumatic brain injury manifest with volume loss on brain MRI. Subtle volume loss is particularly seen early in AD. While prior research has demonstrated the value of this additional information from quantitative neuroimaging, very few applications have been approved for clinical use. Here we describe a US FDA cleared software program, NeuroreaderTM, for assessment of clinical hippocampal volume on brain MRI. Objective: To present the validation of hippocampal volumetrics on a clinical software program. Method: Subjects were drawn (n = 99) from the Alzheimer Disease Neuroimaging Initiative study. Volumetric brain MR imaging was acquired in both 1.5 T (n = 59) and 3.0 T (n = 40) scanners in participants with manual hippocampal segmentation. Fully automated hippocampal segmentation and measurement was done using a multiple atlas approach. The Dice Similarity Coefficient (DSC) measured the level of spatial overlap between NeuroreaderTM and gold standard manual segmentation from 0 to 1 with 0 denoting no overlap and 1 representing complete agreement. DSC comparisons between 1.5 T and 3.0 T scanners were done using standard independent samples T-tests. Results: In the bilateral hippocampus, mean DSC was 0.87 with a range of 0.78–0.91 (right hippocampus) and 0.76–0.91 (left hippocampus). Automated segmentation agreement with manual segmentation was essentially equivalent at 1.5 T (DSC = 0.879) versus 3.0 T (DSC = 0.872). Conclusion: This work provides a description and validation of a software program that can be applied in measuring hippocampal volume, a biomarker that is frequently abnormal in AD and other neurological disorders. PMID:26484924

Hippocampal atrophy on MRI is predictive of histopathological patterns and surgical prognosis in mesial temporal lobe epilepsy with hippocampal sclerosis.

PubMed

Jardim, Anaclara Prada; Corso, Jeana Torres; Garcia, Maria Teresa Fernandes Castilho; Gaça, Larissa Botelho; Comper, Sandra Mara; Lancellotti, Carmen Lúcia Penteado; Centeno, Ricardo Silva; Carrete, Henrique; Cavalheiro, Esper Abrão; Scorza, Carla Alessandra; Yacubian, Elza Márcia Targas

2016-12-01

To correlate hippocampal volumes obtained from brain structural imaging with histopathological patterns of hippocampal sclerosis (HS), in order to predict surgical outcome. Patients with mesial temporal lobe epilepsy (MTLE) with HS were selected. Clinical data were assessed pre-operatively and surgical outcome in the first year post surgery. One block of mid hippocampal body was selected for HS classification according to ILAE criteria. NeuN-immunoreactive cell bodies were counted within hippocampal subfields, in four randomly visual fields, and cell densities were transformed into z-score values. FreeSurfer processing of 1.5T brain structural images was used for subcortical and cortical volumetric estimation of the ipsilateral hippocampus. Univariate analysis of variance and Pearson's correlation test were applied for statistical analyses. Sixty-two cases (31 female, 32 right HS) were included. ILAE type 1 HS was identified in 48 patients, type 2 in eight, type 3 in two, and four had no-HS. Better results regarding seizure control, i.e. ILAE 1, were achieved by patients with type 1 HS (58.3%). Patients with types 1 and 2 had smaller hippocampal volumes compared to those with no-HS (p<0.001 and p=0.004, respectively). Positive correlation was encountered between hippocampal volumes and CA1, CA3, CA4, and total estimated neuronal densities. CA2 was the only sector which did not correlate its neuronal density with hippocampal volume (p=0.390). This is the first study correlating hippocampal volume on MRI submitted to FreeSurfer processing with ILAE patterns of HS and neuronal loss within each hippocampal subfield, a fundamental finding to anticipate surgical prognosis for patients with drug-resistant MTLE and HS. Copyright © 2016 Elsevier B.V. All rights reserved.

Hippocampal MR volumetry

NASA Astrophysics Data System (ADS)

Haller, John W.; Botteron, K.; Brunsden, Barry S.; Sheline, Yvette I.; Walkup, Ronald K.; Black, Kevin J.; Gado, Mokhtar; Vannier, Michael W.

1994-09-01

Goal: To estimate hippocampal volumes from in vivo 3D magnetic resonance (MR) brain images and determine inter-rater and intra- rater repeatability. Objective: The precision and repeatability of hippocampal volume estimates using stereologic measurement methods is sought. Design: Five normal control and five schizophrenic subjects were MR scanned using a MPRAGE protocol. Fixed grid stereologic methods were used to estimate hippocampal volumes on a graphics workstation. The images were preprocessed using histogram analysis to standardize 3D MR image scaling from 16 to 8 bits and image volumes were interpolated to 0.5 mm3 isotropic voxels. The following variables were constant for the repeated stereologic measures: grid size, inter-slice distance (1.5 mm), voxel dimensions (0.5 mm3), number of hippocampi measured (10), total number of measurements per rater (40), and number of raters (5). Two grid sizes were tested to determine the coefficient of error associated with the number of sampled 'hits' (approximately 140 and 280) on the hippocampus. Starting slice and grid position were randomly varied to assure unbiased volume estimates. Raters were blind to subject identity, diagnosis, and side of the brain from which the image volumes were extracted and the order of subject presentation was randomized for each of the raters. Inter- and intra-rater intraclass correlation coefficients (ICC) were determined. Results: The data indicate excellent repeatability of fixed grid stereologic hippocampal volume measures when using an inter-slice distance of 1.5 mm and a 6.25 mm2 grid (inter-rater ICCs equals 0.86 - 0.97, intra- rater ICCs equals 0.85 - 0.97). One major advantage of the current study was the use of 3D MR data which significantly improved visualization of hippocampal boundaries by providing the ability to access simultaneous orthogonal views while counting stereological marks within the hippocampus. Conclusion: Stereological estimates of 3D volumes from 2D MR

Postoperative recovery of hippocampal contralateral diffusivity in medial temporal lobe epilepsy.

PubMed

Thivard, Lionel; Tanguy, Marie-Laure; Adam, Claude; Clémenceau, Stéphane; Dezamis, Edouard; Lehéricy, Stéphane; Dormont, Didier; Chiras, Jacques; Baulac, Michel; Dupont, Sophie

2007-03-01

To search for a recovery after surgery of mean diffusivity (MD) values in the contralateral nonsclerotic hippocampus of patients with medial temporal lobe epilepsy (MTLE) and hippocampal sclerosis (HS). Twenty-four MTLE patients (12 right-sided and 12 left-sided MTLE) and 36 healthy volunteers were investigated using diffusion tensor imaging. A region-of-interest approach was used to measure pre- and postoperative interictal hippocampal MD values in patients. Diffusion abnormalities in contralateral nonsclerotic hippocampus recovered after surgery (p<0.0001). A subgroup of 14 patients exhibited a clear increase in MD values whereas the remaining 10 patients were stable. No significant difference was found between the two subgroups for each of the electroclinical data studied including early postoperative outcome, all patients being either seizure free or with rare persistent auras. This finding suggests that diffusion abnormalities in contralateral hippocampus may represent a functional mechanism linked to the active epileptic process.

Consumption of the electric power inside silent discharge reactors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yehia, Ashraf, E-mail: yehia30161@yahoo.com

An experimental study was made in this paper to investigate the relation between the places of the dielectric barriers, which cover the surfaces of the electrodes in the coaxial cylindrical reactors, and the rate of change of the electric power that is consumed in forming silent discharges. Therefore, silent discharges have been formed inside three coaxial cylindrical reactors. The dielectric barriers in these reactors were pasted on both the internal surface of the outer electrode in the first reactor and the external surface of the inner electrode in the second reactor as well as the surfaces of the two electrodesmore » in the third reactor. The reactor under study has been fed by atmospheric air that flowed inside it with a constant rate at normal temperature and pressure, in parallel with the application of a sinusoidal ac voltage between the electrodes of the reactor. The electric power consumed in forming the silent discharges inside the three reactors was measured as a function of the ac peak voltage. The validity of the experimental results was investigated by applying Manley's equation on the same discharge conditions. The results have shown that the rate of consumption of the electric power relative to the ac peak voltage per unit width of the discharge gap improves by a ratio of either 26.8% or 80% or 128% depending on the places of the dielectric barriers that cover the surfaces of the electrodes inside the three reactors.« less

Lower Hippocampal Volume Predicts Decrements in Lane Control among Drivers with Amnestic MCI

PubMed Central

Griffith, H Randall; Okonkwo, Ozioma C; Stewart, Christopher C; Stoeckel, Luke E; den Hollander, Jan A; Elgin, Jennifer M; Harrell, Lindy E; Brockington, John C; Clark, David G; Ball, Karlene K; Owsley, Cynthia; Marson, Daniel C; Wadley, Virginia G

2014-01-01

Objectives There are few methods to discern driving risks in patients with early dementia and Mild Cognitive Impairment (MCI). We aimed to determine whether structural MRI of the hippocampus – a biomarker of probable Alzheimer pathology and a measure of disease severity in those affected – is linked to objective ratings of on-road driving performance in older adults with and without amnestic MCI. Methods 49 consensus-diagnosed participants from an Alzheimer's Disease Research Center (15 diagnosed with amnestic MCI and 34 demographically similar controls) underwent structural MRI and on-road driving assessments. Results Mild atrophy of the left hippocampus was associated with less-than-optimal ratings in lane control but not with other discrete driving skills. Decrements in left hippocampal volume conferred higher risk for less-than-optimal lane control ratings in the MCI patients (B = −1.63, SE = .74, Wald = 4.85, P = .028), but not in controls (B = 0.13, SE = .415, Wald = 0.10, P = .752). The odds ratio (OR) and 95% confidence interval (CI) for below optimal lane control in the MCI group was 4.41 (1.18, 16.36), which was attenuated to 3.46 (0.88, 13.60) after accounting for the contribution of left hippocampal volume. Conclusion These findings suggest that there may be a link between hippocampal atrophy and difficulties with lane control in persons with amnestic MCI. Further study appears warranted to better discern patterns of brain atrophy in MCI and AD and whether these could be early markers of clinically meaningful driving risk. PMID:24212246

Prenatal choline deficiency does not enhance hippocampal vulnerability after kainic acid-induced seizures in adulthood

PubMed Central

Wong-Goodrich, Sarah J.E.; Tognoni, Christina M.; Mellott, Tiffany J.; Glenn, Melissa J.; Blusztajn, Jan K.; Williams, Christina L.

2011-01-01

Choline is a vital nutrient needed during early development for both humans and rodents. Severe dietary choline deficiency during pregnancy leads to birth defects, while more limited deficiency during mid- to late pregnancy causes deficits in hippocampal plasticity in adult rodent offspring that are accompanied by cognitive deficits only when task demands are high. Because prenatal choline supplementation confers neuroprotection of the adult hippocampus against a variety of neural insults and aids memory, we hypothesized that prenatal choline deficiency may enhance vulnerability to neural injury. To examine this, adult offspring of rat dams either fed a control diet (CON) or one deficient in choline (DEF) during embryonic days 12–17 were given multiple injections (i.p.) of saline (control) or kainic acid to induce seizures and were euthanized 16 days later. Perhaps somewhat surprisingly, DEF rats were not more susceptible to seizure induction and showed similar levels of seizure-induced hippocampal histopathology, GAD expression loss, upregulated hippocampal GFAP and growth factor expression, and increased dentate cell and neuronal proliferation as that seen in CON rats. Although prenatal choline deficiency compromises adult hippocampal plasticity in the intact brain, it does not appear to exacerbate the neuropathological response to seizures in the adult hippocampus at least shortly after excitotoxic injury. PMID:21840511

Hippocampal dosimetry correlates with the change in neurocognitive function after hippocampal sparing during whole brain radiotherapy: a prospective study.

PubMed

Tsai, Ping-Fang; Yang, Chi-Cheng; Chuang, Chi-Cheng; Huang, Ting-Yi; Wu, Yi-Ming; Pai, Ping-Ching; Tseng, Chen-Kan; Wu, Tung-Ho; Shen, Yi-Liang; Lin, Shinn-Yn

2015-12-10

Whole brain radiotherapy (WBRT) has been the treatment of choice for patients with brain metastases. However, change/decline of neurocognitive functions (NCFs) resulting from impaired hippocampal neurogenesis might occur after WBRT. It is reported that conformal hippocampal sparing would provide the preservation of NCFs. Our study aims to investigate the hippocampal dosimetry and to demonstrate the correlation between hippocampal dosimetry and neurocognitive outcomes in patients receiving hippocampal sparing during WBRT (HS-WBRT). Forty prospectively recruited cancer patients underwent HS-WBRT for therapeutic or prophylactic purposes. Before receiving HS-WBRT, all participants received a battery of baseline neurocognitive assessment, including memory, executive functions and psychomotor speed. The follow-up neurocognitive assessment at 4 months after HS-WBRT was also performed. For the delivery of HS-WBRT, Volumetric Modulated Arc Therapy (VMAT) with two full arcs and two non-coplanar partial arcs was employed. For each treatment planning, dose volume histograms were generated for left hippocampus, right hippocampus, and the composite hippocampal structure respectively. Biologically equivalent doses in 2-Gy fractions (EQD2) assuming an alpha/beta ratio of 2 Gy were computed. To perform analyses addressing the correlation between hippocampal dosimetry and the change in scores of NCFs, pre- and post-HS-WBRT neurocognitive assessments were available in 24 patients in this study. Scores of NCFs were quite stable before and after HS-WBRT in terms of hippocampus-dependent memory. Regarding verbal memory, the corresponding EQD2 values of 0, 10, 50, 80 % irradiating the composite hippocampal structure with <12.60 Gy, <8.81, <7.45 Gy and <5.83 Gy respectively were significantly associated with neurocognitive preservation indicated by the immediate recall of Word List Test of Wechsler Memory Scale-III. According to logistic regression analyses, it was noted that dosimetric

Cognitive Processing in Oral and Silent Reading Comprehension.

ERIC Educational Resources Information Center

Salasoo, Aita

1986-01-01

Reading rates and comprehension measures that probed recognition of various levels of text structure were collected for passages read orally and silently by 16 college students. Results showed that memory traces of text microstructure created in oral reading were accessed faster during memory-based comprehension tasks than traces established by…

Early Hearing Detection and Intervention in Developing Countries: Current Status and Prospects

ERIC Educational Resources Information Center

Olusanya, Bolajoko O.

2006-01-01

Infant hearing screening is emerging rapidly as a silent global revolution for the early detection of children with congenital or early onset hearing loss to ensure timely enrollment in family-oriented intervention programs for the development of spoken language. This article examines the overriding and interrelated scientific, ethical and…

Bilateral silent sinus syndrome: A rare case and review of literature.

PubMed

Trope, Michal; Schwartz, Joseph S; Tajudeen, Bobby A; Kennedy, David W

2017-06-01

In this report, we presented a rare case of bilateral silent sinus syndrome (SSS) in an otherwise healthy 57-year-old man treated with functional endoscopic sinus surgery (FESS). A systematic review of the literature regarding bilateral SSS was performed. A 57-year-old man with well-controlled allergic rhinitis in the absence of previous surgery or trauma presented with bilateral SSS, which was successfully managed with bilateral FESS. A medical literature data base search of the terms "silent sinus syndrome" "maxillary atelectasis," "imploding antrum syndrome," and "bilateral silent sinus syndrome" was performed. The results were then narrowed to include only relevant articles. Relevant articles included three case reports and two articles that describe or mention bilateral SSS. Of the three case reports found, two patients presented with bilateral SSS, whereas the third patient presented metachronously, with the contralateral SSS manifesting 4 months after presentation of the initial ipsilateral SSS. The present literature regarding bilateral SSS is likely incomplete, and further investigation is required to provide greater insight into the prevalence of this disease. In this report, bilateral FESS was successful in resolving symptoms and preventing disease progression.

Hippocampal subfield segmentation in temporal lobe epilepsy: Relation to outcomes.

PubMed

Kreilkamp, B A K; Weber, B; Elkommos, S B; Richardson, M P; Keller, S S

2018-06-01

To investigate the clinical and surgical outcome correlates of preoperative hippocampal subfield volumes in patients with refractory temporal lobe epilepsy (TLE) using a new magnetic resonance imaging (MRI) multisequence segmentation technique. We recruited 106 patients with TLE and hippocampal sclerosis (HS) who underwent conventional T1-weighted and T2 short TI inversion recovery MRI. An automated hippocampal segmentation algorithm was used to identify twelve subfields in each hippocampus. A total of 76 patients underwent amygdalohippocampectomy and postoperative seizure outcome assessment using the standardized ILAE classification. Semiquantitative hippocampal internal architecture (HIA) ratings were correlated with hippocampal subfield volumes. Patients with left TLE had smaller volumes of the contralateral presubiculum and hippocampus-amygdala transition area compared to those with right TLE. Patients with right TLE had reduced contralateral hippocampal tail volumes and improved outcomes. In all patients, there were no significant relationships between hippocampal subfield volumes and clinical variables such as duration and age at onset of epilepsy. There were no significant differences in any hippocampal subfield volumes between patients who were rendered seizure free and those with persistent postoperative seizure symptoms. Ipsilateral but not contralateral HIA ratings were significantly correlated with gross hippocampal and subfield volumes. Our results suggest that ipsilateral hippocampal subfield volumes are not related to the chronicity/severity of TLE. We did not find any hippocampal subfield volume or HIA rating differences in patients with optimal and unfavorable outcomes. In patients with TLE and HS, sophisticated analysis of hippocampal architecture on MRI may have limited value for prediction of postoperative outcome. © 2018 The Authors. Acta Neurologica Scandinavica Published by John Wiley & Sons Ltd.

Automatic segmentation of the hippocampus for preterm neonates from early-in-life to term-equivalent age.

PubMed

Guo, Ting; Winterburn, Julie L; Pipitone, Jon; Duerden, Emma G; Park, Min Tae M; Chau, Vann; Poskitt, Kenneth J; Grunau, Ruth E; Synnes, Anne; Miller, Steven P; Mallar Chakravarty, M

2015-01-01

The hippocampus, a medial temporal lobe structure central to learning and memory, is particularly vulnerable in preterm-born neonates. To date, segmentation of the hippocampus for preterm-born neonates has not yet been performed early-in-life (shortly after birth when clinically stable). The present study focuses on the development and validation of an automatic segmentation protocol that is based on the MAGeT-Brain (Multiple Automatically Generated Templates) algorithm to delineate the hippocampi of preterm neonates on their brain MRIs acquired at not only term-equivalent age but also early-in-life. First, we present a three-step manual segmentation protocol to delineate the hippocampus for preterm neonates and apply this protocol on 22 early-in-life and 22 term images. These manual segmentations are considered the gold standard in assessing the automatic segmentations. MAGeT-Brain, automatic hippocampal segmentation pipeline, requires only a small number of input atlases and reduces the registration and resampling errors by employing an intermediate template library. We assess the segmentation accuracy of MAGeT-Brain in three validation studies, evaluate the hippocampal growth from early-in-life to term-equivalent age, and study the effect of preterm birth on the hippocampal volume. The first experiment thoroughly validates MAGeT-Brain segmentation in three sets of 10-fold Monte Carlo cross-validation (MCCV) analyses with 187 different groups of input atlases and templates. The second experiment segments the neonatal hippocampi on 168 early-in-life and 154 term images and evaluates the hippocampal growth rate of 125 infants from early-in-life to term-equivalent age. The third experiment analyzes the effect of gestational age (GA) at birth on the average hippocampal volume at early-in-life and term-equivalent age using linear regression. The final segmentations demonstrate that MAGeT-Brain consistently provides accurate segmentations in comparison to manually

Automatic segmentation of the hippocampus for preterm neonates from early-in-life to term-equivalent age

PubMed Central

Guo, Ting; Winterburn, Julie L.; Pipitone, Jon; Duerden, Emma G.; Park, Min Tae M.; Chau, Vann; Poskitt, Kenneth J.; Grunau, Ruth E.; Synnes, Anne; Miller, Steven P.; Mallar Chakravarty, M.

2015-01-01

Introduction The hippocampus, a medial temporal lobe structure central to learning and memory, is particularly vulnerable in preterm-born neonates. To date, segmentation of the hippocampus for preterm-born neonates has not yet been performed early-in-life (shortly after birth when clinically stable). The present study focuses on the development and validation of an automatic segmentation protocol that is based on the MAGeT-Brain (Multiple Automatically Generated Templates) algorithm to delineate the hippocampi of preterm neonates on their brain MRIs acquired at not only term-equivalent age but also early-in-life. Methods First, we present a three-step manual segmentation protocol to delineate the hippocampus for preterm neonates and apply this protocol on 22 early-in-life and 22 term images. These manual segmentations are considered the gold standard in assessing the automatic segmentations. MAGeT-Brain, automatic hippocampal segmentation pipeline, requires only a small number of input atlases and reduces the registration and resampling errors by employing an intermediate template library. We assess the segmentation accuracy of MAGeT-Brain in three validation studies, evaluate the hippocampal growth from early-in-life to term-equivalent age, and study the effect of preterm birth on the hippocampal volume. The first experiment thoroughly validates MAGeT-Brain segmentation in three sets of 10-fold Monte Carlo cross-validation (MCCV) analyses with 187 different groups of input atlases and templates. The second experiment segments the neonatal hippocampi on 168 early-in-life and 154 term images and evaluates the hippocampal growth rate of 125 infants from early-in-life to term-equivalent age. The third experiment analyzes the effect of gestational age (GA) at birth on the average hippocampal volume at early-in-life and term-equivalent age using linear regression. Results The final segmentations demonstrate that MAGeT-Brain consistently provides accurate segmentations

Lack of an association of BDNF Val66Met polymorphism and plasma BDNF with hippocampal volume and memory

PubMed Central

Kim, Ana; Fagan, Anne M; Goate, Alison M; Benzinger, Tammie LS; Morris, John C; Head, Denise

2015-01-01

Brain-derived neurotrophic factor (BDNF) has been shown to be important for neuronal survival and synaptic plasticity in the hippocampus in non-human animals. The Val66Met polymorphism in the BDNF gene, involving a valine (Val) to methionine (Met) substitution at codon 66, has been associated with lower BDNF secretion in vitro. However, there have been mixed results regarding associations between either circulating BDNF or the BDNF Val66Met polymorphism with hippocampal volume and memory in humans. The current study examined the association of BDNF genotype and plasma BDNF with hippocampal volume and memory in two large independent cohorts of middle-aged and older adults (both cognitively normal and early-stage dementia). Sample sizes ranged from 123 to 649. Measures of the BDNF genotype, plasma BDNF, MRI-based hippocampal volume and memory performance were obtained from the Knight Alzheimer Disease Research Center (ADRC) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). There were no significant differences between BDNF Met+ and Met- groups on either hippocampal volume or memory in either cohort. In addition, plasma BDNF was not significantly associated with either hippocampal volume or memory in either cohort. Neither age, cognitive status nor gender moderated any of the relationships. Overall, current findings suggest that BDNF genotype and plasma BDNF may not be robust predictors for variance in hippocampal volume and memory in middle age and older adult cohorts. PMID:25784293

The Effect of Hippocampal Damage in Children on Recalling the Past and Imagining New Experiences

ERIC Educational Resources Information Center

Cooper, Janine M.; Vargha-Khadem, Faraneh; Gadian, David G.; Maguire, Eleanor A.

2011-01-01

Compared to adults, relatively little is known about autobiographical memory and the ability to imagine fictitious and future scenarios in school-aged children, despite the importance of these functions for development and subsequent independent living. Even less is understood about the effect of early hippocampal damage on children's memory and…

Biochemically Silent Abdominal Paragangliomas in Patients with Mutations in the Succinate Dehydrogenase Subunit B Gene

PubMed Central

Timmers, Henri J. L. M.; Pacak, Karel; Huynh, Thanh T.; Abu-Asab, Mones; Tsokos, Maria; Merino, Maria J.; Baysal, Bora E.; Adams, Karen T.; Eisenhofer, Graeme

2008-01-01

Context: Patients with adrenal and extra-adrenal abdominal paraganglioma (PGL) almost invariably have increased plasma and urine concentrations of metanephrines, the O-methylated metabolites of catecholamines. We report four cases of biochemically silent abdominal PGL, in which metanephrines were normal despite extensive disease. Objective: Our objective was to identify the mechanism underlying the lack of catecholamine hypersecretion and metabolism to metanephrines in biochemically silent PGL. Design: This is a descriptive study. Setting: The study was performed at a referral center. Patients: One index case and three additional patients with large abdominal PGL and metastases but with the lack of evidence of catecholamine production, six patients with metastatic catecholamine-producing PGL and a mutation of the succinate dehydrogenase subunit B (SDHB) gene, and 136 random patients with catecholamine-producing PGL were included in the study. Main Outcome Measures: Plasma, urine, and tumor tissue concentrations of catecholamines and metabolites were calculated with electron microscopy and tyrosine hydroxylase immunohistochemistry. Results: All four patients with biochemically silent PGL had an underlying SDHB mutation. In the index case, the tumor tissue concentration of catecholamines (1.8 nmol/g) was less than 0.01% that of the median (20,410 nmol/g) for the 136 patients with catecholamine-producing tumors. Electron microscopy showed the presence of normal secretory granules in all four biochemically silent PGLs. Tyrosine hydroxylase immunoreactivity was negligible in the four biochemically silent PGLs but abundant in catecholamine-producing PGLs. Conclusions: Patients with SDHB mutations may present with biochemically silent abdominal PGLs due to defective catecholamine synthesis resulting from the absence of tyrosine hydroxylase. Screening for tumors in patients with SDHB mutations should not be limited to biochemical tests of catecholamine excess. PMID

Intracerebroventricular administration of okadaic acid induces hippocampal glucose uptake dysfunction and tau phosphorylation.

PubMed

Broetto, Núbia; Hansen, Fernanda; Brolese, Giovana; Batassini, Cristiane; Lirio, Franciane; Galland, Fabiana; Dos Santos, João Paulo Almeida; Dutra, Márcio Ferreira; Gonçalves, Carlos-Alberto

2016-06-01

Intraneuronal aggregates of neurofibrillary tangles (NFTs), together with beta-amyloid plaques and astrogliosis, are histological markers of Alzheimer's disease (AD). The underlying mechanism of sporadic AD remains poorly understood, but abnormal hyperphosphorylation of tau protein is suggested to have a role in NFTs genesis, which leads to neuronal dysfunction and death. Okadaic acid (OKA), a strong inhibitor of protein phosphatase 2A, has been used to induce dementia similar to AD in rats. We herein investigated the effect of intracerebroventricular (ICV) infusion of OKA (100 and 200ng) on hippocampal tau phosphorylation at Ser396, which is considered an important fibrillogenic tau protein site, and on glucose uptake, which is reduced early in AD. ICV infusion of OKA (at 200ng) induced a spatial cognitive deficit, hippocampal astrogliosis (based on GFAP increment) and increase in tau phosphorylation at site 396 in this model. Moreover, we observed a decreased glucose uptake in the hippocampal slices of OKA-treated rats. In vitro exposure of hippocampal slices to OKA altered tau phosphorylation at site 396, without any associated change in glucose uptake activity. Taken together, these findings further our understanding of OKA neurotoxicity, in vivo and vitro, particularly with regard to the role of tau phosphorylation, and reinforce the importance of the OKA dementia model for studying the neurochemical alterations that may occur in AD, such as NFTs and glucose hypometabolism. Copyright © 2016 Elsevier Inc. All rights reserved.

Adolescent social isolation stress unmasks the combined effects of adolescent exercise and adult inflammation on hippocampal neurogenesis and behavior.

PubMed

Hueston, Cara M; Cryan, John F; Nolan, Yvonne M

2017-12-04

Hippocampal neurogenesis and associated cognitive behaviors are regulated by a number of factors including stress, inflammation, and exercise. However, the interplay between these factors remains relatively unexplored, especially across the lifespan. In the current study, the effect of social isolation stress during the adolescent period on neurogenesis and hippocampal-dependent cognitive behaviors was examined. This period of the lifespan has been demonstrated to be an important time for hippocampal growth and plasticity, during which changes to hippocampal neurogenesis may have long lasting effects. Additionally, we aimed to determine whether a 'dual-hit' of adolescent stress and adult chronic neuroinflammation would potentiate any negative effects of either insult alone. Lastly, the potential positive effects of exercise during adolescence was examined to determine whether exercise could attenuate any negative impacts of these insults on hippocampal neurogenesis and behavior. The results from the current study demonstrate that social isolation stress during adolescence followed by intra-hippocampal exposure to the pro-inflammatory cytokine IL-1β in early adulthood produces deficits in both spontaneous alternations and novel object recognition. Exercise attenuated deficits in neurogenesis and novel object recognition in mice that had been exposed to the 'dual-hit' of stress and neuroinflammation. These findings indicate that adolescence represents a key period of the lifespan during which external factors such as stress and exercise can impact on hippocampal development, and may alter the response to challenges such as neuroinflammation in later life. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Librarians Provide Strongest Support for Sustained Silent Reading

ERIC Educational Resources Information Center

Gardiner, Steve

2007-01-01

Many schools have placed increased emphasis on literacy skills. Many state and federal programs require schools to demonstrate increased rates of literacy or improved tests scores based on literacy skills. And for many students, the fastest and most efficient method to achieve improved literacy skills is through Sustained Silent Reading (SSR). It…

Empowering Secondary Students to Promote Sustained Silent Reading

ERIC Educational Resources Information Center

Grant, Raymond Mead, III

2012-01-01

This study examines the efforts of student volunteers to motivate participation in a school-wide Sustained Silent Reading (SSR) program at a large urban high school. The researcher recruited a group of twenty student volunteers to visit classrooms and implement activities aimed at motivating their peers to read during SSR. Such activities help…

The effects of hormones and physical exercise on hippocampal structural plasticity.

PubMed

Triviño-Paredes, Juan; Patten, Anna R; Gil-Mohapel, Joana; Christie, Brian R

2016-04-01

The hippocampus plays an integral role in certain aspects of cognition. Hippocampal structural plasticity and in particular adult hippocampal neurogenesis can be influenced by several intrinsic and extrinsic factors. Here we review how hormones (i.e., intrinsic modulators) and physical exercise (i.e., an extrinsic modulator) can differentially modulate hippocampal plasticity in general and adult hippocampal neurogenesis in particular. Specifically, we provide an overview of the effects of sex hormones, stress hormones, and metabolic hormones on hippocampal structural plasticity and adult hippocampal neurogenesis. In addition, we also discuss how physical exercise modulates these forms of hippocampal plasticity, giving particular emphasis on how this modulation can be affected by variables such as exercise regime, duration, and intensity. Understanding the neurobiological mechanisms underlying the modulation of hippocampal structural plasticity by intrinsic and extrinsic factors will impact the design of new therapeutic approaches aimed at restoring hippocampal plasticity following brain injury or neurodegeneration. Copyright © 2016 Elsevier Inc. All rights reserved.

Underlying Skills of Oral and Silent Reading Fluency in Chinese: Perspective of Visual Rapid Processing

PubMed Central

Zhao, Jing; Kwok, Rosa K. W.; Liu, Menglian; Liu, Hanlong; Huang, Chen

2017-01-01

Reading fluency is a critical skill to improve the quality of our daily life and working efficiency. The majority of previous studies focused on oral reading fluency rather than silent reading fluency, which is a much more dominant reading mode that is used in middle and high school and for leisure reading. It is still unclear whether the oral and silent reading fluency involved the same underlying skills. To address this issue, the present study examined the relationship between the visual rapid processing and Chinese reading fluency in different modes. Fifty-eight undergraduate students took part in the experiment. The phantom contour paradigm and the visual 1-back task were adopted to measure the visual rapid temporal and simultaneous processing respectively. These two tasks reflected the temporal and spatial dimensions of visual rapid processing separately. We recorded the temporal threshold in the phantom contour task, as well as reaction time and accuracy in the visual 1-back task. Reading fluency was measured in both single-character and sentence levels. Fluent reading of single characters was assessed with a paper-and-pencil lexical decision task, and a sentence verification task was developed to examine reading fluency on a sentence level. The reading fluency test in each level was conducted twice (i.e., oral reading and silent reading). Reading speed and accuracy were recorded. The correlation analysis showed that the temporal threshold in the phantom contour task did not correlate with the scores of the reading fluency tests. Although, the reaction time in visual 1-back task correlated with the reading speed of both oral and silent reading fluency, the comparison of the correlation coefficients revealed a closer relationship between the visual rapid simultaneous processing and silent reading. Furthermore, the visual rapid simultaneous processing exhibited a significant contribution to reading fluency in silent mode but not in oral reading mode. These

Underlying Skills of Oral and Silent Reading Fluency in Chinese: Perspective of Visual Rapid Processing.

PubMed

Zhao, Jing; Kwok, Rosa K W; Liu, Menglian; Liu, Hanlong; Huang, Chen

2016-01-01

Reading fluency is a critical skill to improve the quality of our daily life and working efficiency. The majority of previous studies focused on oral reading fluency rather than silent reading fluency, which is a much more dominant reading mode that is used in middle and high school and for leisure reading. It is still unclear whether the oral and silent reading fluency involved the same underlying skills. To address this issue, the present study examined the relationship between the visual rapid processing and Chinese reading fluency in different modes. Fifty-eight undergraduate students took part in the experiment. The phantom contour paradigm and the visual 1-back task were adopted to measure the visual rapid temporal and simultaneous processing respectively. These two tasks reflected the temporal and spatial dimensions of visual rapid processing separately. We recorded the temporal threshold in the phantom contour task, as well as reaction time and accuracy in the visual 1-back task. Reading fluency was measured in both single-character and sentence levels. Fluent reading of single characters was assessed with a paper-and-pencil lexical decision task, and a sentence verification task was developed to examine reading fluency on a sentence level. The reading fluency test in each level was conducted twice (i.e., oral reading and silent reading). Reading speed and accuracy were recorded. The correlation analysis showed that the temporal threshold in the phantom contour task did not correlate with the scores of the reading fluency tests. Although, the reaction time in visual 1-back task correlated with the reading speed of both oral and silent reading fluency, the comparison of the correlation coefficients revealed a closer relationship between the visual rapid simultaneous processing and silent reading. Furthermore, the visual rapid simultaneous processing exhibited a significant contribution to reading fluency in silent mode but not in oral reading mode. These

Neonatal hypoxia, hippocampal atrophy, and memory impairment: evidence of a causal sequence.

PubMed

Cooper, Janine M; Gadian, David G; Jentschke, Sebastian; Goldman, Allan; Munoz, Monica; Pitts, Georgia; Banks, Tina; Chong, W Kling; Hoskote, Aparna; Deanfield, John; Baldeweg, Torsten; de Haan, Michelle; Mishkin, Mortimer; Vargha-Khadem, Faraneh

2015-06-01

Neonates treated for acute respiratory failure experience episodes of hypoxia. The hippocampus, a structure essential for memory, is particularly vulnerable to such insults. Hence, some neonates undergoing treatment for acute respiratory failure might sustain bilateral hippocampal pathology early in life and memory problems later in childhood. We investigated this possibility in a cohort of 40 children who had been treated neonatally for acute respiratory failure but were free of overt neurological impairment. The cohort had mean hippocampal volumes (HVs) significantly below normal control values, memory scores significantly below the standard population means, and memory quotients significantly below those predicted by their full scale IQs. Brain white matter volume also fell below the volume of the controls, but brain gray matter volumes and scores on nonmnemonic neuropsychological tests were within the normal range. Stepwise linear regression models revealed that the cohort's HVs were predictive of degree of memory impairment, and gestational age at treatment was predictive of HVs: the younger the age, the greater the atrophy. We conclude that many neonates treated for acute respiratory failure sustain significant hippocampal atrophy as a result of the associated hypoxia and, consequently, show deficient memory later in life. © The Author 2013. Published by Oxford University Press.

Exploring Silent Reading Fluency: Its Nature and Development

ERIC Educational Resources Information Center

Taylor, Stanford E.

2011-01-01

It is the goal of this book to provide unique and helpful information to reading and curriculum specialists who are looking for ways to improve the silent reading proficiency of their students. While the background information is, at times, technical, the recommendations as to the skill areas that require improvement as well as the computer…

YAC128 Huntington's disease transgenic mice show enhanced short-term hippocampal synaptic plasticity early in the course of the disease.

PubMed

Ghilan, Mohamed; Bostrom, Crystal A; Hryciw, Brett N; Simpson, Jessica M; Christie, Brian R; Gil-Mohapel, Joana

2014-09-18

Huntington's disease (HD) is a progressive and fatal neurodegenerative disorder caused by a polyglutamine expansion in the gene encoding the protein huntingtin. The disease progresses over decades, but often patients develop cognitive impairments that precede the onset of the classical motor symptoms. Similar to the disease progression in humans, the yeast artificial chromosome (YAC) 128 HD mouse model also exhibits cognitive dysfunction that precedes the onset of the neuropathological and motor impairments characteristic of HD. Thus, the purpose of this study was to evaluate whether short- and long-term synaptic plasticity in the hippocampus, two related biological models of learning and memory processes, were altered in YAC128 mice in early stages of disease progression. We show that the YAC128 hippocampal dentate gyrus (DG) displays marked reductions in paired-pulse depression both at 3 and 6 months of age. In addition, significantly enhanced post-tetanic and short-term potentiation are apparent in YAC128 mice after high-frequency stimulation at this time. Early and late forms of long-term plasticity were not altered at this stage. Together these findings indicate that there may be elevated neurotransmitter release in response to synaptic stimulation in YAC128 mice during the initial phase of disease progression. These abnormalities in short-term plasticity detected at this stage in YAC128 HD transgenic mice indicate that aberrant information processing at the level of the synapses may contribute, at least in part, to the early onset of cognitive deficits that are characteristic of this devastating neurodegenerative disorder. Copyright © 2014 Elsevier B.V. All rights reserved.

Etiology of hippocampal sclerosis

PubMed Central

Tsai, Meng-Han; Pardoe, Heath R.; Perchyonok, Yuliya; Fitt, Gregory J.; Scheffer, Ingrid E.; Berkovic, Samuel F.

2013-01-01

Objective: We sought evidence of a hereditary component for hippocampal sclerosis (HS) by determining whether close relatives of probands with temporal lobe epilepsy (TLE) with HS also had asymptomatic HS or subtle variation in hippocampal morphology. Methods: First-degree relatives from 15 families in which probands had TLE with HS and 32 age- and sex-matched controls were included in the study. Left and right hippocampal volumes and T2 relaxometry were measured using 3-tesla MRI. Results: Thirty-two asymptomatic first-degree relatives and 3 relatives with a history of seizures or epilepsy were studied. None of the first-degree relatives had HS on visual analysis and T2 relaxation times were normal, excluding the presence of HS. Mean hippocampal volume was smaller (6.4%) in asymptomatic relatives (2.94 ± 0.27 cm3, 95% confidence interval = 2.87–3.01) than in controls (3.14 ± 0.22 cm3, 95% confidence interval = 3.09–3.19, p < 0.005); the effect was greater in relatives of probands with a positive family history of epilepsy. The relatives also had more asymmetric hippocampi (asymmetric index 0.92 ± 0.05) than controls (0.96 ± 0.03, p = 0.001). Conclusions: Small asymmetric hippocampi in healthy relatives are likely to represent a familial developmental variant that may predispose to the formation of TLE with HS. The underlying histopathology of these small hippocampi is unknown. This observation may provide an imaging marker for future studies seeking susceptibility genes for HS. PMID:23749796

Hippocampal-neocortical functional reorganization underlies children's cognitive development

PubMed Central

Qin, Shaozheng; Cho, Soohyun; Chen, Tianwen; Rosenberg-Lee, Miriam; Geary, David C.; Menon, Vinod

2014-01-01

The importance of the hippocampal system for rapid learning and memory is well recognized, but its contributions to a cardinal feature of children's cognitive development – the transition from procedure-based to memory-based problem solving strategies – are unknown. Here we show that the hippocampal system is pivotal to this strategic transition. Longitudinal fMRI in children, ages 7 to 9, revealed that the transition from use of counting to memory-based retrieval parallels increased hippocampal and decreased prefrontal-parietal engagement during arithmetic problem solving. Critically, longitudinal improvements in retrieval strategy use were predicted by increased hippocampal-neocortical functional connectivity. Beyond childhood, retrieval strategy use continued to improve through adolescence into adulthood, and was associated with decreased activation but more stable inter-problem representations in the hippocampus. Our findings provide novel insights into the dynamic role of the hippocampus in the maturation of memory-based problem solving, and establish a critical link between hippocampal-neocortical reorganization and children's cognitive development. PMID:25129076

Hippocampal-neocortical functional reorganization underlies children's cognitive development.

PubMed

Qin, Shaozheng; Cho, Soohyun; Chen, Tianwen; Rosenberg-Lee, Miriam; Geary, David C; Menon, Vinod

2014-09-01

The importance of the hippocampal system for rapid learning and memory is well recognized, but its contributions to a cardinal feature of children's cognitive development-the transition from procedure-based to memory-based problem-solving strategies-are unknown. Here we show that the hippocampal system is pivotal to this strategic transition. Longitudinal functional magnetic resonance imaging (fMRI) in 7-9-year-old children revealed that the transition from use of counting to memory-based retrieval parallels increased hippocampal and decreased prefrontal-parietal engagement during arithmetic problem solving. Longitudinal improvements in retrieval-strategy use were predicted by increased hippocampal-neocortical functional connectivity. Beyond childhood, retrieval-strategy use continued to improve through adolescence into adulthood and was associated with decreased activation but more stable interproblem representations in the hippocampus. Our findings provide insights into the dynamic role of the hippocampus in the maturation of memory-based problem solving and establish a critical link between hippocampal-neocortical reorganization and children's cognitive development.

Hippocampal “Time Cells”: Time versus Path Integration

PubMed Central

Kraus, Benjamin J.; Robinson, Robert J.; White, John A.; Eichenbaum, Howard; Hasselmo, Michael E.

2014-01-01

SUMMARY Recent studies have reported the existence of hippocampal “time cells,” neurons that fire at particular moments during periods when behavior and location are relatively constant. However, an alternative explanation of apparent time coding is that hippocampal neurons “path integrate” to encode the distance an animal has traveled. Here, we examined hippocampal neuronal firing patterns as rats ran in place on a treadmill, thus “clamping” behavior and location, while we varied the treadmill speed to distinguish time elapsed from distance traveled. Hippocampal neurons were strongly influenced by time and distance, and less so by minor variations in location. Furthermore, the activity of different neurons reflected integration over time and distance to varying extents, with most neurons strongly influenced by both factors and some significantly influenced by only time or distance. Thus, hippocampal neuronal networks captured both the organization of time and distance in a situation where these dimensions dominated an ongoing experience. PMID:23707613

Tubular localization of silent calcium channels in crustacean skeletal muscle fibers.

PubMed

Monterrubio, J; Ortiz, G; Orkand, P M; Zuazaga, C

2002-01-01

Ca2+-induced Ca2+ release (CICR) in the superficial abdominal flexor muscle of the crustacean Atya lanipes appears to be mediated by a local control mechanism similar to that of vertebrate cardiac muscle, but with an unusually high gain. Thus, Ca2+ influx increases sufficiently the local concentration of Ca2+ in the immediate vicinity of the sarcoplasmic reticulum Ca2+ release channels to trigger the highly amplified release of Ca2+ required for contraction, but is too low to generate a macroscopic inward current (i.e., the Ca2+ channels are silent). To determine the localization of the silent Ca2+ Channels, the mechanical, electrophysiological and ultrastructural properties of the muscle were examined before and after formamide treatment, a procedure that produces the disruption of transverse tubules of striated muscle. We found that tubular disruption decreased tension generation by about 90%; reduced inward current (measured as Vmax, the maximum rate of rise of Sr2+ action potentials) by about 80%; and decreased membrane capacitance by about 77%. The results suggest that ca. 80% of the silent Ca2+ channels are located in the tubular system. Thus, these studies provide further evidence to support the local control mechanism of CICR in crustacean skeletal muscle.

Detecting Silent Data Corruption for Extreme-Scale Applications through Data Mining

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bautista-Gomez, Leonardo; Cappello, Franck

Supercomputers allow scientists to study natural phenomena by means of computer simulations. Next-generation machines are expected to have more components and, at the same time, consume several times less energy per operation. These trends are pushing supercomputer construction to the limits of miniaturization and energy-saving strategies. Consequently, the number of soft errors is expected to increase dramatically in the coming years. While mechanisms are in place to correct or at least detect some soft errors, a significant percentage of those errors pass unnoticed by the hardware. Such silent errors are extremely damaging because they can make applications silently produce wrongmore » results. In this work we propose a technique that leverages certain properties of high-performance computing applications in order to detect silent errors at the application level. Our technique detects corruption solely based on the behavior of the application datasets and is completely application-agnostic. We propose multiple corruption detectors, and we couple them to work together in a fashion transparent to the user. We demonstrate that this strategy can detect the majority of the corruptions, while incurring negligible overhead. We show that with the help of these detectors, applications can have up to 80% of coverage against data corruption.« less

Reading, Writing, and Reserve: Literacy Activities are linked to Hippocampal Volume and Memory in Multiple Sclerosis

PubMed Central

Sumowski, James F.; Rocca, Maria A.; Leavitt, Victoria M.; Riccitelli, Gianna; Meani, Alessandro; Comi, Giancarlo; Filippi, Massimo

2016-01-01

Consistent with basic research on enriched environments and the cognitive reserve literature, greater engagement in cognitive leisure activities during early adulthood has been linked to preserved memory and larger hippocampal volume in persons with multiple sclerosis (MS). Herein we investigated which specific types of cognitive leisure activities contribute to reserve. Reading-writing activities were positively linked to (a) hippocampal volume within independent samples of Italian (n=187) and American (n=55) MS patients, and (b) memory in subsamples of Italian (n=97) and American (n=53) patients with memory data. Art-music and games-hobbies did not contribute. Findings directly inform the development of targeted evidence-based enrichment programs aiming to bolster reserve against memory decline. PMID:26920377

Prenatal choline deficiency does not enhance hippocampal vulnerability after kainic acid-induced seizures in adulthood.

PubMed

Wong-Goodrich, Sarah J E; Tognoni, Christina M; Mellott, Tiffany J; Glenn, Melissa J; Blusztajn, Jan K; Williams, Christina L

2011-09-21

Choline is a vital nutrient needed during early development for both humans and rodents. Severe dietary choline deficiency during pregnancy leads to birth defects, while more limited deficiency during mid- to late pregnancy causes deficits in hippocampal plasticity in adult rodent offspring that are accompanied by cognitive deficits only when task demands are high. Because prenatal choline supplementation confers neuroprotection of the adult hippocampus against a variety of neural insults and aids memory, we hypothesized that prenatal choline deficiency may enhance vulnerability to neural injury. To examine this, adult offspring of rat dams either fed a control diet (CON) or one deficient in choline (DEF) during embryonic days 12-17 were given multiple injections (i.p.) of saline (control) or kainic acid to induce seizures and were euthanized 16 days later. Perhaps somewhat surprisingly, DEF rats were not more susceptible to seizure induction and showed similar levels of seizure-induced hippocampal histopathology, GAD expression loss, upregulated hippocampal GFAP and growth factor expression, and increased dentate cell and neuronal proliferation as that seen in CON rats. Although prenatal choline deficiency compromises adult hippocampal plasticity in the intact brain, it does not appear to exacerbate the neuropathological response to seizures in the adult hippocampus at least shortly after excitotoxic injury. Copyright © 2011 Elsevier B.V. All rights reserved.

Synergistic stress exacerbation in hippocampal neurons: Evidence favoring the dual-hit hypothesis of neurodegeneration.

PubMed

Heinemann, Scott D; Posimo, Jessica M; Mason, Daniel M; Hutchison, Daniel F; Leak, Rehana K

2016-08-01

The dual-hit hypothesis of neurodegeneration states that severe stress sensitizes vulnerable cells to subsequent challenges so that the two hits are synergistic in their toxic effects. Although the hippocampus is vulnerable to a number of neurodegenerative disorders, there are no models of synergistic cell death in hippocampal neurons in response to combined proteotoxic and oxidative stressors, the two major characteristics of these diseases. Therefore, a relatively high-throughput dual-hit model of stress synergy was developed in primary hippocampal neurons. In order to increase the rigor of the study and strengthen the interpretations, three independent, unbiased viability assays were employed at multiple timepoints. Stress synergy was elicited when hippocampal neurons were treated with the proteasome inhibitor MG132 followed by exposure to the oxidative toxicant paraquat, but only after 48 h. MG132 and paraquat only elicited additive effects 24 h after the final hit and even loss of heat shock protein 70 activity and glutathione did not promote stress synergy at this early timepoint. Dual hits of MG132 elicited modest glutathione loss and slightly synergistic toxic effects 48 h after the second hit, but only at some concentrations and only according to two viability assays (metabolic fitness and cytoskeletal integrity). The thiol N-acetyl cysteine protected hippocampal neurons against dual MG132/MG132 hits but not dual MG132/paraquat hits. These findings support the view that proteotoxic and oxidative stress propel and propagate each other in hippocampal neurons, leading to synergistically toxic effects, but not as the default response and only after a delay. The neuronal stress synergy observed here lies in contrast to astrocytic responses to dual hits, because astrocytes that survive severe proteotoxic stress resist additional cell loss following second hits. In conclusion, a new model of hippocampal vulnerability was developed for the testing of therapies

Synergistic stress exacerbation in hippocampal neurons: Evidence favoring the dual hit hypothesis of neurodegeneration

PubMed Central

Heinemann, Scott D.; Posimo, Jessica M.; Mason, Daniel M.; Hutchison, Daniel F.; Leak, Rehana K.

2016-01-01

The dual hit hypothesis of neurodegeneration states that severe stress sensitizes vulnerable cells to subsequent challenges so that the two hits are synergistic in their toxic effects. Although the hippocampus is vulnerable to a number of neurodegenerative disorders, there are no models of synergistic cell death in hippocampal neurons in response to combined proteotoxic and oxidative stressors, the two major characteristics of these diseases. Therefore, we developed a relatively high-throughput dual hit model of stress synergy in primary hippocampal neurons. In order to increase the rigor of our study and strengthen our interpretations, we employed three independent, unbiased viability assays at multiple timepoints. Stress synergy was elicited when hippocampal neurons were treated with the proteasome inhibitor MG132 followed by exposure to the oxidative toxicant paraquat, but only after 48h. MG132 and paraquat only elicited additive effects 24h after the final hit and even loss of heat shock protein 70 activity and glutathione did not promote stress synergy at this early timepoint. Dual hits of MG132 elicited modest glutathione loss and slightly synergistic toxic effects 48h after the second hit, but only at some concentrations and only according to two viability assays (metabolic fitness and cytoskeletal integrity). The thiol N-acetyl cysteine protected hippocampal neurons against dual MG132/MG132 hits but not dual MG132/paraquat hits. Our findings support the view that proteotoxic and oxidative stress propel and propagate each other in hippocampal neurons, leading to synergistically toxic effects, but not as the default response and only after a delay. The neuronal stress synergy observed here lies in contrast to astrocytic responses to dual hits, because astrocytes that survive severe proteotoxic stress resist additional cell loss following second hits. In conclusion, we present a new model of hippocampal vulnerability in which to test therapies, because

Micro-Experimental Analysis of the Small-Group Reading Lesson: Social and Cognitive Consequences of Silent Reading.

ERIC Educational Resources Information Center

Wilkinson, Ian A. G.; Anderson, Richard C.

This study examined a social-organizational hypothesis that explains how silent reading in small-group lessons might influence students' learning. One hundred children in four third-grade classes, each divided into three ability groups, received two silent and two oral reading lessons. Group dynamics were measured from videotapes of the lessons.…

Hippocampal neurogenesis enhancers promote forgetting of remote fear memory after hippocampal reactivation by retrieval

PubMed Central

Ishikawa, Rie; Fukushima, Hotaka; Frankland, Paul W; Kida, Satoshi

2016-01-01

Forgetting of recent fear memory is promoted by treatment with memantine (MEM), which increases hippocampal neurogenesis. The approaches for treatment of post-traumatic stress disorder (PTSD) using rodent models have focused on the extinction and reconsolidation of recent, but not remote, memories. Here we show that, following prolonged re-exposure to the conditioning context, enhancers of hippocampal neurogenesis, including MEM, promote forgetting of remote contextual fear memory. However, these interventions are ineffective following shorter re-exposures. Importantly, we find that long, but not short re-exposures activate gene expression in the hippocampus and induce hippocampus-dependent reconsolidation of remote contextual fear memory. Furthermore, remote memory retrieval becomes hippocampus-dependent after the long-time recall, suggesting that remote fear memory returns to a hippocampus dependent state after the long-time recall, thereby allowing enhanced forgetting by increased hippocampal neurogenesis. Forgetting of traumatic memory may contribute to the development of PTSD treatment. DOI: http://dx.doi.org/10.7554/eLife.17464.001 PMID:27669409

Silica nanoparticle exposure during the neonatal period impairs hippocampal precursor proliferation and social behavior later in life

PubMed Central

Gong, Linji; Ma, Yuanyuan; Xu, Haiwei; Gu, Zhanjun; Zhu, Jingci; Fan, Xiaotang

2018-01-01

Introduction Silica nanoparticles (SiO2-NPs) are currently among the most widely used nanomaterials, but their potentially adverse effects on brain development remain unknown. The developing brain is extremely sensitive to NP neurotoxicity during the early postnatal period. Materials and methods Herein, we investigated the effects of SiO2-NPs (doses of 10, 20, or 50 mg with a particle size of ~91 nm, equivalent to aerosol mass concentrations 55.56, 111.11, and 277.78 mg/m3, respectively) exposure from postnatal day (P) 1 to P7 on hippocampal precursor proliferation at P8 and long-term neurobehavior in adults. Results SiO2-NP exposure resulted in inflammatory cell infiltration in lung tissue, microglia over-activation in the hippocampal dentate gyrus (DG), and decreased hippocampal precursor proliferation in the DG-subgranular zone at P8. Moreover, after exposure to 20 mg of SiO2-NPs, mice exhibited social interaction deficits and slight anxiety-like behaviors in adulthood, but this exposure did not induce locomotor activity impairment, depression-like behavior, or short-term memory impairment. Discussion These findings suggest that early-age SiO2-NP exposure induced inflammation and inhibited precursor proliferation in the DG in a dose-dependent manner, which might be related to the social dysfunction observed in adulthood.

Hippocampal lesions, contextual retrieval, and autoshaping in pigeons.

PubMed

Richmond, Jenny; Colombo, Michael

2002-02-22

Both pigeons and rats with damage to the hippocampus are slow to acquire an autoshaped response and emit fewer overall responses than control animals. Experiment 1 explored the possibility that the autoshaping deficit was due to an impairment in contextual retrieval. Pigeons were trained for 14 days on an autoshaping task in which a red stimulus was followed by reinforcement in context A, and a green stimulus was followed by reinforcement in context B. On day 15, the subjects were given a context test in which the red and green stimuli were presented simultaneously in context A and then later in context B. Both control and hippocampal animals showed context specificity, that is, they responded more to the red stimulus in context A and to the green stimulus in context B. In Experiment 2 we video-recorded the control and hippocampal animals performing the autoshaping task. Hippocampal animals tended to miss-peck the key more often than control animals. In addition, the number of missed pecks increased across days for hippocampal animals but not for control animals, suggesting that while the control animals increased their pecking accuracy, the hippocampal animals actually decreased their pecking accuracy. Our findings suggest that impairments in moving through space may underlie the hippocampal autoshaping deficit.

Remembering preservation in hippocampal amnesia

PubMed Central

Clark, Ian A.; Maguire, Eleanor A.

2017-01-01

The lesion-deficit model dominates neuropsychology. This is unsurprising given powerful demonstrations that focal brain lesions can affect specific aspects of cognition. Nowhere is this more evident than in patients with bilateral hippocampal damage. In the last sixty years the amnesia and other impairments exhibited by these patients have helped to delineate the functions of the hippocampus and shape the field of memory. We do not question the value of this approach. However, less prominent are the cognitive processes that remain intact following hippocampal lesions. Here, we collate the piecemeal reports of preservation of function following focal bilateral hippocampal damage, highlighting a wealth of information often veiled by the field’s focus on deficits. We consider how a systematic understanding of what is preserved as well as what is lost could add an important layer of precision to models of memory and the hippocampus. PMID:26361051

Special report: silent disasters.

PubMed

Eriksson, Anneli

2007-12-01

Disasters occur not only in war and conflict or after natural events, such as earthquakes or floods. In fact, the death of hundreds of thousands of children in Niger every year, often for treatable conditions, could just as well qualify as a disaster situation. A lack of funding for health care and health-care staff and user fee policies for health care in very poor or unstable settings challenge international agreements that make statements about the right to health and access to health care for all people. This paper argues that although sustainable development is important, today many are without essential health care and die in the silent disasters of hunger and poverty. In other words, the development of health care appears to be stalled for the sake of sustainability.

Hippocampal subfield volume changes in subtypes of attention deficit hyperactivity disorder.

PubMed

Al-Amin, Mamun; Zinchenko, Artyom; Geyer, Thomas

2018-04-15

Attention-deficit hyperactivity disorder (ADHD) is accompanied by reduction of total hippocampal volume. However, disorder-related fine-grained structural alterations of hippocampal subfields remain unclear. Here we compared hippocampal subfield volumes in a large sample of patients with ADHD and healthy controls. We used T1-weighted structural 3-Tesla MRI images of 880 individuals (7-21 years old) from the ADHD-200 database. The images were acquired from 553 healthy individuals and 327 children and adolescents with combined (N = 196) and inattentive (N = 131) ADHD subtypes. Hippocampal subfields were segmented into the cornu amonis regions (CA1, CA2/3, CA4), fimbria, hippocampal fissure, presubiculum, subiculum, hippocampal tail, parasubiculum, granule cell layers of the dentate gyrus, molecular layer within the subiculum and the CA fields, and the hippocampal-amygdala transition area using an automatic algorithm available in Freesurfer 6.0. We found a significant reduction of total hippocampal volume in the combined ADHD group compared to healthy controls. This reduction was due to the atrophy of CA1, CA4, molecular layer, granule cell layers of the dentate gyrus, presubiculum, subiculum, and hippocampal tail. These differences were exclusively driven by the corresponding brain volume reduction in the combined ADHD-subtype, while hippocampal volumes in inattentive ADHD showed no reliable differences relative to controls. Finally, there were negative correlations between the reduced hippocampal subfields and behavioral ADHD indices. The present results point to a clear dissociation between inattentive and combined subtypes of ADHD. Therefore, hippocampal subfields may contribute towards understanding the pathophysiology of ADHD. Copyright © 2018 Elsevier B.V. All rights reserved.

Amnesia and the organization of the hippocampal system.

PubMed

Mishkin, M; Vargha-Khadem, F; Gadian, D G

1998-01-01

Early hippocampal injury in humans has been found to result in a limited form of global anterograde amnesia. At issue is whether the limitation is qualitative, with the amnesia reflecting substantially greater impairment in episodic than in semantic memory, or only quantitative, with both episodic and semantic memory being partially and equivalently impaired. Evidence from neuroanatomical and lesion studies in animals suggests that the hippocampus and subhippocampal cortices form a hierarchically organized system, such that the greatest convergence of information (and, by implication, the richest amount of association) takes place within the hippocampus, located at the top of the hierarchy. On the one hand, this evidence is consistent with the view that selective hippocampal damage produces a differential impairment in context-rich episodic memory as compared with context-free semantic memory, because only the latter can be supported by the subhippocampal cortices. On the other hand, given the system's hierarchical form of organization, this dissociation of deficits is difficult to prove, because a quantitatively limited deficit will nearly always be a viable alternative. A final choice between the alternative views is therefore likely to depend less on further evidence gathered in brain-injured patients than on which view accounts for more of the data gathered from converging approaches to the problem.

Fungal secondary metabolites - strategies to activate silent gene clusters.

PubMed

Brakhage, Axel A; Schroeckh, Volker

2011-01-01

Filamentous fungi produce a multitude of low molecular weight bioactive compounds. The increasing number of fungal genome sequences impressively demonstrated that their biosynthetic potential is far from being exploited. In fungi, the genes required for the biosynthesis of a secondary metabolite are clustered. Many of these bioinformatically newly discovered secondary metabolism gene clusters are silent under standard laboratory conditions. Consequently, no product can be found. This review summarizes the current strategies that have been successfully applied during the last years to activate these silent gene clusters in filamentous fungi, especially in the genus Aspergillus. The techniques take advantage of genome mining, vary from the simple search for compounds with bioinformatically predicted physicochemical properties up to methods that exploit a probable interaction of microorganisms. Until now, the majority of successful approaches have been based on molecular biology like the generation of gene "knock outs", promoter exchange, overexpression of transcription factors or other pleiotropic regulators. Moreover, strategies based on epigenetics opened a new avenue for the elucidation of the regulation of secondary metabolite formation and will certainly continue to play a significant role for the elucidation of cryptic natural products. The conditions under which a given gene cluster is naturally expressed are largely unknown. One technique is to attempt to simulate the natural habitat by co-cultivation of microorganisms from the same ecosystem. This has already led to the activation of silent gene clusters and the identification of novel compounds in Aspergillus nidulans. These simulation strategies will help discover new natural products in the future, and may also provide fundamental new insights into microbial communication. Copyright © 2010 Elsevier Inc. All rights reserved.

Later Life Changes in Hippocampal Neurogenesis and Behavioral Functions After Low-Dose Prenatal Irradiation at Early Organogenesis Stage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganapathi, Ramya; Manda, Kailash, E-mail: kailashmanda@gmail.com

Purpose: To investigate long-term changes in behavioral functions of mice after exposure to low-dose prenatal radiation at an early organogenesis stage. Methods and Materials: Pregnant C57BL/6J mice were irradiated (20 cGy) at postcoitus day 5.5. The male and female offspring were subjected to different behavioral assays for affective, motor, and cognitive functions at 3, 6, and 12 months of age. Behavioral functions were further correlated with the population of CA1 and CA3 pyramidal neurons and immature neurons in hippocampal dentate gyrus. Results: Prenatally exposed mice of different age groups showed a sex-specific pattern of sustained changes in behavioral functions. Male mice showed significantmore » changes in anxiety-like phenotypes, learning, and long-term memory at age 3 months. At 6 months of age such behavioral functions were recovered to a normal level but could not be sustained at age 12 months. Female mice showed an appreciable recovery in almost all behavioral functions at 12 months. Patterns of change in learning and long-term memory were comparable to the population of CA1 and CA3 pyramidal neurons and doublecortin-positive neurons in hippocampus. Conclusion: Our finding suggests that prenatal (early organogenesis stage) irradiation even at a lower dose level (20 cGy) is sufficient to cause potential changes in neurobehavioral function at later stages of life. Male mice showed relatively higher vulnerability to radiation-induced neurobehavioral changes as compared with female.« less

A Critical Proton MR Spectroscopy Marker of Alzheimer's Disease Early Neurodegenerative Change: Low Hippocampal NAA/Cr Ratio Impacts APOE ɛ4 Mexico City Children and Their Parents.

PubMed

Calderón-Garcidueñas, Lilian; Mora-Tiscareño, Antonieta; Melo-Sánchez, Gastón; Rodríguez-Díaz, Joel; Torres-Jardón, Ricardo; Styner, Martin; Mukherjee, Partha S; Lin, Weili; Jewells, Valerie

2015-01-01

Severe air pollution exposures produce systemic, respiratory, myocardial, and brain inflammation and Alzheimer's disease (AD) hallmarks in clinically healthy children. We tested whether hippocampal metabolite ratios are associated with contrasting levels of air pollution, APOE, and body mass index (BMI) in paired healthy children and one parent sharing the same APOE alleles. We used 1H-MRS to interrogate bilateral hippocampal single-voxel in 57 children (12.45 ± 3.4 years) and their 48 parents (37.5 ± 6.78 years) from a low pollution city versus Mexico City (MC). NAA/Cr, Cho/Cr, and mI/Cr metabolite ratios were analyzed. The right hippocampus NAA/Cr ratio was significantly different between cohorts (p = 0.007). The NAA/Cr ratio in right hippocampus in controls versus APOE ɛ4 MC children and in left hippocampus in MC APOE ɛ4 parents versus their children was significantly different after adjusting for age, gender, and BMI (p = 0.027 and 0.01, respectively). The NAA/Cr ratio is considered reflective of neuronal density/functional integrity/loss of synapses/higher pTau burden, thus a significant decrease in hippocampal NAA/Cr ratios may constitute a spectral marker of early neurodegeneration in young urbanites. Decreases in NAA/Cr correlate well with cognitive function, behavioral symptoms, and dementia severity; thus, since the progression of AD starts decades before clinical diagnosis, our findings support the hypothesis that under chronic exposures to fine particulate matter and ozone above the standards, neurodegenerative processes start in childhood and APOE ɛ4 carriers are at higher risk. Gene and environmental factors are critical in the development of AD and the identification and neuroprotection of young urbanites at high risk must become a public health priority.

Enduring, Handling-Evoked Enhancement of Hippocampal Memory Function and Glucocorticoid Receptor Expression Involves Activation of the Corticotropin-Releasing Factor Type 1 Receptor

PubMed Central

Fenoglio, Kristina A.; Brunson, Kristen L.; Avishai-Eliner, Sarit; Stone, Blake A.; Kapadia, Bhumika J.; Baram, Tallie Z.

2011-01-01

Early-life experience, including maternal care, influences hippocampus-dependent learning and memory throughout life. Handling of pups during postnatal d 2–9 (P2–9) stimulates maternal care and leads to improved memory function and stress-coping. The underlying molecular mechanisms may involve early (by P9) and enduring reduction of hypothalamic corticotropin-releasing factor (CRF) expression and subsequent (by P45) increase in hippocampal glucocorticoid receptor (GR) expression. However, whether hypothalamic CRF levels influence changes in hippocampal GR expression (and memory function), via reduced CRF receptor activation and consequent lower plasma glucocorticoid levels, is unclear. In this study we administered selective antagonist for the type 1 CRF receptor, NBI 30775, to nonhandled rats post hoc from P10–17 and examined hippocampus-dependent learning and memory later (on P50–70), using two independent paradigms, compared with naive and vehicle-treated nonhandled, and naive and antagonist-treated handled rats. Hippocampal GR and hypothalamic CRF mRNA levels and stress-induced plasma corticosterone levels were also examined. Transient, partial selective blockade of CRF1 in nonhandled rats improved memory functions on both the Morris watermaze and object recognition tests to levels significantly better than in naive and vehicle-treated controls and were indistinguishable from those in handled (naive, vehicle-treated, and antagonist-treated) rats. GR mRNA expression was increased in hippocampal CA1 and the dentate gyrus of CRF1-antagonist treated nonhandled rats to levels commensurate with those in handled cohorts. Thus, the extent of CRF1 activation, probably involving changes in hypothalamic CRF levels and release, contributes to the changes in hippocampal GR expression and learning and memory functions. PMID:15932935

"Small World" architecture in brain connectivity and hippocampal volume in Alzheimer's disease: a study via graph theory from EEG data.

PubMed

Vecchio, Fabrizio; Miraglia, Francesca; Piludu, Francesca; Granata, Giuseppe; Romanello, Roberto; Caulo, Massimo; Onofrj, Valeria; Bramanti, Placido; Colosimo, Cesare; Rossini, Paolo Maria

2017-04-01

Brain imaging plays an important role in the study of Alzheimer's disease (AD), where atrophy has been found to occur in the hippocampal formation during the very early disease stages and to progress in parallel with the disease's evolution. The aim of the present study was to evaluate a possible correlation between "Small World" characteristics of the brain connectivity architecture-as extracted from EEG recordings-and hippocampal volume in AD patients. A dataset of 144 subjects, including 110 AD (MMSE 21.3) and 34 healthy Nold (MMSE 29.8) individuals, was evaluated. Weighted and undirected networks were built by the eLORETA solutions of the cortical sources' activities moving from EEG recordings. The evaluation of the hippocampal volume was carried out on a subgroup of 60 AD patients who received a high-resolution T1-weighted sequence and underwent processing for surface-based cortex reconstruction and volumetric segmentation using the Freesurfer image analysis software. Results showed that, quantitatively, more correlation was observed in the right hemisphere, but the same trend was seen in both hemispheres. Alpha band connectivity was negatively correlated, while slow (delta) and fast-frequency (beta, gamma) bands positively correlated with hippocampal volume. Namely, the larger the hippocampal volume, the lower the alpha and the higher the delta, beta, and gamma Small World characteristics of connectivity. Accordingly, the Small World connectivity pattern could represent a functional counterpart of structural hippocampal atrophying and related-network disconnection.

Applying the Multiple Signal Classification Method to Silent Object Detection Using Ambient Noise

NASA Astrophysics Data System (ADS)

Mori, Kazuyoshi; Yokoyama, Tomoki; Hasegawa, Akio; Matsuda, Minoru

2004-05-01

The revolutionary concept of using ocean ambient noise positively to detect objects, called acoustic daylight imaging, has attracted much attention. The authors attempted the detection of a silent target object using ambient noise and a wide-band beam former consisting of an array of receivers. In experimental results obtained in air, using the wide-band beam former, we successfully applied the delay-sum array (DSA) method to detect a silent target object in an acoustic noise field generated by a large number of transducers. This paper reports some experimental results obtained by applying the multiple signal classification (MUSIC) method to a wide-band beam former to detect silent targets. The ocean ambient noise was simulated by transducers decentralized to many points in air. Both MUSIC and DSA detected a spherical target object in the noise field. The relative power levels near the target obtained with MUSIC were compared with those obtained by DSA. Then the effectiveness of the MUSIC method was evaluated according to the rate of increase in the maximum and minimum relative power levels.

Teen Depression and Suicide, A SILENT CRISIS.

PubMed

Kroning, Maureen; Kroning, Kayla

2016-01-01

Adolescent depression is a serious problem affecting 10.7% of all teens and 29.9% of high school students; 17% of high school students have contemplated suicide. Yet, depression in teens is often unrecognized. This article relays the tragic death of a 17-year-old, along with symptoms of depression and suicide in adolescents; DSM-5 criteria for depression; treatments including protective factors, psychotherapy, and medications; and imparts interventions for addressing this huge but silent crisis.

Risk factors associated with the occurrence of silent pulmonary embolism in patients with deep venous thrombosis of the lower limb.

PubMed

Li, Fenghe; Wang, Xuehu; Huang, Wen; Ren, Wei; Cheng, Jun; Zhang, Mao; Zhao, Yu

2014-08-01

The aim of our study is to investigate the prevalence of silent pulmonary embolism in patients with deep venous thrombosis in the lower limbs and to evaluate the associated risk factors. A total of 322 patients with acute deep venous thrombosis confirmed by CT venography or Doppler ultrasonography were studied. The diagnosis of silent pulmonary embolism was established by computed tomography pulmonary arteriography (CTPA). The association between covariates and the prevalence of silent pulmonary embolism in patients with deep venous thrombosis in lower limbs were assessed using chi-square test and multivariable regression. The incidence of silent pulmonary embolism was 33.5% (108 in 322 patients) in all patients with deep venous thrombosis in lower limbs. Chi-square test showed male gender, the right lower limb, proximal location of the thrombus, unprovoked venous thrombosis and coexisting heart diseases were related to a higher incidence of silent pulmonary embolism in patients with deep venous thrombosis in lower limbs. The multivariate regression analysis confirmed that the risk factors associated with silent pulmonary embolism in deep venous thrombosis patients included the right side and proximal location of the thrombus (odds ratio: 2.023, 95% CI: 1.215-3.368; odds ratio: 3.610, 95% CI: 1.772-7.354), unprovoked venous thrombosis (odds ratio: 2.037, 95% CI: 1.188-3.493), coexisting heart diseases (odds ratio: 4.507, 95% CI: 2.667-7.618). Silent pulmonary embolism occurred frequently in patients with deep venous thrombosis in lower limbs. The right side, the proximal location of the thrombus, unprovoked venous thrombosis and coexisting heart diseases increased the risk for the occurrence of silent pulmonary embolism. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Regional tau deposition and subregion atrophy of medial temporal structures in early Alzheimer's disease: A combined positron emission tomography/magnetic resonance imaging study.

PubMed

Sone, Daichi; Imabayashi, Etsuko; Maikusa, Norihide; Okamura, Nobuyuki; Furumoto, Shozo; Kudo, Yukitsuka; Ogawa, Masayo; Takano, Harumasa; Yokoi, Yuma; Sakata, Masuhiro; Tsukamoto, Tadashi; Kato, Koichi; Matsuda, Hiroshi

2017-01-01

Molecular imaging and selective hippocampal subfield atrophy are a focus of recent Alzheimer's disease (AD) research. Here, we investigated correlations between molecular imaging and hippocampal subfields in early AD. We investigated 18 patients with early AD and 18 healthy control subjects using 11 C-Pittsburgh compound-B (PIB) positron emission tomography (PET) and 18 F-THK5351 PET and automatic segmentation of hippocampal subfields with high-resolution T2-weighted magnetic resonance imaging. The PET images were normalized and underwent voxelwise regression analysis with each subregion volumes using SPM12. As for 18 F-THK5351 PET, the bilateral perirhinal cortex volumes were significantly associated with the ipsilateral or bilateral temporal lobar uptakes, whereas hippocampal subfields showed no correlations. 11 C-PIB PET showed relatively broad negative correlation with the right cornu ammonis 3 volumes. Regional tau deposition was correlated with extrahippocampal subregional atrophy and not with hippocampal subfields, possibly reflecting different underlying mechanisms of atrophy in early AD. Amyloid might be associated with right cornu ammonis 3 atrophy.

Harmony hurts: participation and silent conflict at an Indonesian fish pond.

PubMed

Tam, Chui-Ling

2006-07-01

Participatory environmental and resource management is premised on open communication to reach consensus. However, deliberate and open communication cannot adequately address silent conflict. This begs two questions. First, how is the existence of covert communication and silent conflict to be recognized and addressed? Second, how are the wider social relations and traditions that encompass communication and conflict to be described and explained? These questions revolve around communicative power. Communication of environmental knowledge is deeply embedded in social power structures, with direct implications for participatory resource planning and implementation. Ethnographic research conducted at a failed community-managed fish farming project in Southeast Sulawesi, Indonesia shows that a culture of harmony and respect for authority can silence environmental conflict in the hierarchical "community." Three propositions are offered. First, communication amnesia and exclusion jeopardize participation. Second, cultures of harmony and silent conflict shape planning processes and outcomes. Third, the weak use manipulation and communication strategy to acquire a "voice" while preserving harmony. These propositions address five unresolved issues in participatory resource management: analysis of groups, contextuality, social relationships, nonparticipants, and informal communication. Power, tradition, and social networks affect the valuing of knowledge relative to the power of different individuals and institutions to communicate priorities, values, and needs. These factors are critical to the inclusion of both participants and nonparticipants.

Rod Electroretinograms Elicited by Silent Substitution Stimuli from the Light-Adapted Human Eye

PubMed Central

Maguire, John; Parry, Neil R. A.; Kremers, Jan; Kommanapalli, Deepika; Murray, Ian J.; McKeefry, Declan J.

2016-01-01

Purpose To demonstrate that silent substitution stimuli can be used to generate electroretinograms (ERGs) that effectively isolate rod photoreceptor function in humans without the need for dark adaptation, and that this approach constitutes a viable alternative to current clinical standard testing protocols. Methods Rod-isolating and non-isolating sinusoidal flicker stimuli were generated on a 4 primary light-emitting diode (LED) Ganzfeld stimulator to elicit ERGs from participants with normal and compromised rod function who had not undergone dark-adaptation. Responses were subjected to Fourier analysis, and the amplitude and phase of the fundamental were used to examine temporal frequency and retinal illuminance response characteristics. Results Electroretinograms elicited by rod-isolating silent substitution stimuli exhibit low-pass temporal frequency response characteristics with an upper response limit of 30 Hz. Responses are optimal between 5 and 8 Hz and between 10 and 100 photopic trolands (Td). There is a significant correlation between the response amplitudes obtained with the silent substitution method and current standard clinical protocols. Analysis of signal-to-noise ratios reveals significant differences between subjects with normal and compromised rod function. Conclusions Silent substitution provides an effective method for the isolation of human rod photoreceptor function in subjects with normal as well as compromised rod function when stimuli are used within appropriate parameter ranges. Translational Relevance This method of generating rod-mediated ERGs can be achieved without time-consuming periods of dark adaptation, provides improved isolation of rod- from cone-based activity, and will lead to the development of faster clinical electrophysiologic testing protocols with improved selectivity. PMID:27617180

Constructing, Perceiving, and Maintaining Scenes: Hippocampal Activity and Connectivity

PubMed Central

Zeidman, Peter; Mullally, Sinéad L.; Maguire, Eleanor A.

2015-01-01

In recent years, evidence has accumulated to suggest the hippocampus plays a role beyond memory. A strong hippocampal response to scenes has been noted, and patients with bilateral hippocampal damage cannot vividly recall scenes from their past or construct scenes in their imagination. There is debate about whether the hippocampus is involved in the online processing of scenes independent of memory. Here, we investigated the hippocampal response to visually perceiving scenes, constructing scenes in the imagination, and maintaining scenes in working memory. We found extensive hippocampal activation for perceiving scenes, and a circumscribed area of anterior medial hippocampus common to perception and construction. There was significantly less hippocampal activity for maintaining scenes in working memory. We also explored the functional connectivity of the anterior medial hippocampus and found significantly stronger connectivity with a distributed set of brain areas during scene construction compared with scene perception. These results increase our knowledge of the hippocampus by identifying a subregion commonly engaged by scenes, whether perceived or constructed, by separating scene construction from working memory, and by revealing the functional network underlying scene construction, offering new insights into why patients with hippocampal lesions cannot construct scenes. PMID:25405941

How silent is silent reading? Intracerebral evidence for top-down activation of temporal voice areas during reading.

PubMed

Perrone-Bertolotti, Marcela; Kujala, Jan; Vidal, Juan R; Hamame, Carlos M; Ossandon, Tomas; Bertrand, Olivier; Minotti, Lorella; Kahane, Philippe; Jerbi, Karim; Lachaux, Jean-Philippe

2012-12-05

As you might experience it while reading this sentence, silent reading often involves an imagery speech component: we can hear our own "inner voice" pronouncing words mentally. Recent functional magnetic resonance imaging studies have associated that component with increased metabolic activity in the auditory cortex, including voice-selective areas. It remains to be determined, however, whether this activation arises automatically from early bottom-up visual inputs or whether it depends on late top-down control processes modulated by task demands. To answer this question, we collaborated with four epileptic human patients recorded with intracranial electrodes in the auditory cortex for therapeutic purposes, and measured high-frequency (50-150 Hz) "gamma" activity as a proxy of population level spiking activity. Temporal voice-selective areas (TVAs) were identified with an auditory localizer task and monitored as participants viewed words flashed on screen. We compared neural responses depending on whether words were attended or ignored and found a significant increase of neural activity in response to words, strongly enhanced by attention. In one of the patients, we could record that response at 800 ms in TVAs, but also at 700 ms in the primary auditory cortex and at 300 ms in the ventral occipital temporal cortex. Furthermore, single-trial analysis revealed a considerable jitter between activation peaks in visual and auditory cortices. Altogether, our results demonstrate that the multimodal mental experience of reading is in fact a heterogeneous complex of asynchronous neural responses, and that auditory and visual modalities often process distinct temporal frames of our environment at the same time.

Increased hippocampal blood volume and normal blood flow in schizophrenia

PubMed Central

Talati, Pratik; Rane, Swati; Skinner, Jack; Gore, John; Heckers, Stephan

2015-01-01

Neuroimaging studies have provided compelling evidence for abnormal hippocampal activity in schizophrenia. Most studies made inferences about baseline hippocampal activity using a single hemodynamic parameter (e.g., blood volume or blood flow). Here we studied several hemodynamic measures in the same cohort to test the hypothesis of increased hippocampal activity in schizophrenia. We used dynamic susceptibility contrast- (DSC-) magnetic resonance imaging to assess blood volume, blood flow, and mean transit time in the hippocampus of 15 patients with chronic schizophrenia and 15 healthy controls. Left and right hippocampal measurements were combined for absolute measures of cerebral blood volume (CBV), blood flow (CBF), and mean transit time (MTT). We found significantly increased hippocampal CBV, but normal CBF and MTT, in schizophrenia. The uncoupling of CBV and CBF could be due to several factors, including antipsychotic medication, loss of cerebral perfusion pressure, or angiogenesis. Further studies need to incorporate several complementary imaging modalities to better characterize hippocampal dysfunction in schizophrenia. PMID:25896442

Prevention of Stroke in Patients With Silent Cerebrovascular Disease: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association.

PubMed

Smith, Eric E; Saposnik, Gustavo; Biessels, Geert Jan; Doubal, Fergus N; Fornage, Myriam; Gorelick, Philip B; Greenberg, Steven M; Higashida, Randall T; Kasner, Scott E; Seshadri, Sudha

2017-02-01

Two decades of epidemiological research shows that silent cerebrovascular disease is common and is associated with future risk for stroke and dementia. It is the most common incidental finding on brain scans. To summarize evidence on the diagnosis and management of silent cerebrovascular disease to prevent stroke, the Stroke Council of the American Heart Association convened a writing committee to evaluate existing evidence, to discuss clinical considerations, and to offer suggestions for future research on stroke prevention in patients with 3 cardinal manifestations of silent cerebrovascular disease: silent brain infarcts, magnetic resonance imaging white matter hyperintensities of presumed vascular origin, and cerebral microbleeds. The writing committee found strong evidence that silent cerebrovascular disease is a common problem of aging and that silent brain infarcts and white matter hyperintensities are associated with future symptomatic stroke risk independently of other vascular risk factors. In patients with cerebral microbleeds, there was evidence of a modestly increased risk of symptomatic intracranial hemorrhage in patients treated with thrombolysis for acute ischemic stroke but little prospective evidence on the risk of symptomatic hemorrhage in patients on anticoagulation. There were no randomized controlled trials targeted specifically to participants with silent cerebrovascular disease to prevent stroke. Primary stroke prevention is indicated in patients with silent brain infarcts, white matter hyperintensities, or microbleeds. Adoption of standard terms and definitions for silent cerebrovascular disease, as provided by prior American Heart Association/American Stroke Association statements and by a consensus group, may facilitate diagnosis and communication of findings from radiologists to clinicians. © 2016 American Heart Association, Inc.

Adaptive top-down suppression of hippocampal activity and the purging of intrusive memories from consciousness.

PubMed

Benoit, Roland G; Hulbert, Justin C; Huddleston, Ean; Anderson, Michael C

2015-01-01

When reminded of unwanted memories, people often attempt to suppress these experiences from awareness. Prior work indicates that control processes mediated by the dorsolateral prefrontal cortex (DLPFC) modulate hippocampal activity during such retrieval suppression. It remains unknown whether this modulation plays a role in purging an intrusive memory from consciousness. Here, we combined fMRI and effective connectivity analyses with phenomenological reports to scrutinize a role for adaptive top-down suppression of hippocampal retrieval processes in terminating mnemonic awareness of intrusive memories. Participants either suppressed or recalled memories of pictures depicting faces or places. After each trial, they reported their success at regulating awareness of the memory. DLPFC activation was greatest when unwanted memories intruded into consciousness and needed to be purged, and this increased engagement predicted superior control of intrusive memories over time. However, hippocampal activity was decreased during the suppression of place memories only. Importantly, the inhibitory influence of the DLPFC on the hippocampus was linked to the ensuing reduction in intrusions of the suppressed memories. Individuals who exhibited negative top-down coupling during early suppression attempts experienced fewer involuntary memory intrusions later on. Over repeated suppressions, the DLPFC-hippocampus connectivity grew less negative with the degree that they no longer had to purge unwanted memories from awareness. These findings support a role of DLPFC in countermanding the unfolding recollection of an unwanted memory via the suppression of hippocampal processing, a mechanism that may contribute to adaptation in the aftermath of traumatic experiences.

Neuroprotective Effects of Ferruginol, Jatrophone, and Junicedric Acid Against Amyloid-β Injury in Hippocampal Neurons.

PubMed

Zolezzi, Juan M; Lindsay, Carolina B; Serrano, Felipe G; Ureta, Roxana C; Theoduloz, Cristina; Schmeda-Hirschmann, Guillermo; Inestrosa, Nibaldo C

2018-01-01

Soluble amyloid-β (Aβ) oligomers have been recognized as early neurotoxic intermediates with a key role in the synaptic dysfunction observed in Alzheimer's disease (AD). Aβ oligomers block hippocampal long-term potentiation (LTP) and impair rodent spatial memory. Additionally, the presence of Aβ oligomers is associated with imbalanced intracellular calcium levels and apoptosis in neurons. In this context, we evaluated the effects of three diterpenes (ferruginol, jatrophone, and junicedric acid) that are found in medicinal plants and have several forms of biological activity. The intracellular calcium levels in hippocampal neurons increased in the presence of ferruginol, jatrophone, and junicedric acid, a result that was consistent with the observed increase in CA1 synaptic transmission in mouse hippocampal slices. Additionally, assays using Aβ peptide demonstrated that diterpenes, particularly ferruginol, restore LTP and reduce apoptosis. Recovery of the Aβ oligomer-induced loss of the synaptic proteins PSD-95, synapsin, VGlut, and NMDA receptor subunit 2A was observed in mouse hippocampal slices treated with junicedric acid. This cascade of events may be associated with the regulation of kinases, e.g., protein kinase C (PKC) and calcium/calmodulin-dependent protein kinase II (CaMKII), in addition to the activation of the canonical Wnt signaling pathway and could thus provide protection against Aβ oligomers, which trigger synaptic dysfunction. Our results suggest a potential neuroprotective role for diterpenes against the Aβ oligomers-induced neurodegenerative alterations, which make them interesting molecules to be further studied in the context of AD.

Hippocampal contributions to recollection in retrograde and anterograde amnesia.

PubMed

Gilboa, Asaf; Winocur, Gordon; Rosenbaum, R Shayna; Poreh, Amir; Gao, Fuqiang; Black, Sandra E; Westmacott, Robyn; Moscovitch, Morris

2006-01-01

Lesions restricted to the hippocampal formation and/or extended hippocampal system (hippocampal formation, fornix, mammillary bodies, and anterior thalamic nuclei) can disrupt conscious recollection in anterograde amnesia, while leaving familiarity-based memory relatively intact. Familiarity may be supported by extra-hippocampal medial temporal lobe (MTL) structures. Within-task dissociations in recognition memory best exemplify this distinction in anterograde amnesia. The authors report for the first time comparable dissociations within recognition memory in retrograde amnesia. An amnesic patient (A.D.) with bilateral fornix and septal nuclei lesions failed to recognize details pertaining to personal past events only when recollection was required, during recognition of episodic details. His intact recognition of generic and semantic details pertaining to the same events was ascribed to intact familiarity processes. Recollective processes in the controls were reflected by asymmetrical Receiver's Operating Characteristic curves, whereas the patient's Receiver's Operating Characteristic was symmetrical, suggesting that his inferior recognition performance on episodic details was reliant on familiarity processes. Anterograde and retrograde memories were equally affected, with no temporal gradient for retrograde memories. By comparison, another amnesic person (K.C.) with extensive MTL damage (involving extra-hippocampal MTL structures in addition to hippocampal and fornix lesions) had very poor recognition and no recollection of either episodic or generic/semantic details. These data suggest that the extended hippocampal system is required to support recollection for both anterograde and retrograde memories, regardless of their age.

Management of the orbital floor in silent sinus syndrome.

PubMed

Thomas, Robert D; Graham, Scott M; Carter, Keith D; Nerad, Jeffrey A

2003-01-01

Enophthalmos in a patient with an opacified hypoplastic maxillary sinus, without sinus symptomatology, describes the silent sinus syndrome. A current trend is to perform endoscopic maxillary antrostomy and orbital floor reconstruction as a single-staged operation. A two-staged approach is performed at our institution to avoid placement of an orbital floor implant in the midst of potential infection and allow for the possibility that enophthalmos and global ptosis may resolve with endoscopic antrostomy alone, obviating the need for orbital floor reconstruction. A retrospective review identified four patients with silent sinus syndrome evaluated between June 1999 and August 2001. Patients presented to our ophthalmology department with ocular asymmetry, and computerized tomography (CT) scanning confirmed the diagnosis in each case. There were three men and one woman, with ages ranging from 27 to 40 years. All patients underwent endoscopic maxillary antrostomy. Preoperative enophthalmos determined by Hertel's measurements ranged from 3 to 4 mm. After endoscopic maxillary antrostomy, the range of reduction in enophthalmos was 1-2 mm. Case 2 had a preoperative CT scan and a CT scan 9 months after left endoscopic maxillary antrostomy. Volumetric analysis of the left maxillary sinus revealed a preoperative volume of 16.85 +/- 0.06 cm3 and a postoperative volume of 19.56 +/- 0.07 cm3. This represented a 16% increase in maxillary sinus volume postoperatively. Orbital floor augmentation was avoided in two patients because of satisfactory improvement in enophthalmos. In the other two patients, orbital reconstruction was performed as a second-stage procedure. There were no complications. Orbital floor augmentation can be offered as a second-stage procedure for patients with silent sinus syndrome. Some patients' enophthalmos may improve with endoscopic antrostomy alone.

A DUEL WITH SILENT NOISY GUN VERSUS NOISY GUN.

DTIC Science & Technology

A two person duel where the first person has one silent and one noisy shot to be fired in that order and the second person has one noisy shot is...analized for arbitrary continuously increasing, as the distance between duelists decreases, accuracy functions. The value of the duel and optimal strategies are computed. (Author)

Early developmental bisphenol-A exposure sex-independently impairs spatial memory by remodeling hippocampal dendritic architecture and synaptic transmission in rats

NASA Astrophysics Data System (ADS)

Liu, Zhi-Hua; Ding, Jin-Jun; Yang, Qian-Qian; Song, Hua-Zeng; Chen, Xiang-Tao; Xu, Yi; Xiao, Gui-Ran; Wang, Hui-Li

2016-08-01

Bisphenol-A (BPA, 4, 4‧-isopropylidene-2-diphenol), a synthetic xenoestrogen that widely used in the production of polycarbonate plastics, has been reported to impair hippocampal development and function. Our previous study has shown that BPA exposure impairs Sprague-Dawley (SD) male hippocampal dendritic spine outgrowth. In this study, the sex-effect of chronic BPA exposure on spatial memory in SD male and female rats and the related synaptic mechanism were further investigated. We found that chronic BPA exposure impaired spatial memory in both SD male and female rats, suggesting a dysfunction of hippocampus without gender-specific effect. Further investigation indicated that BPA exposure causes significant impairment of dendrite and spine structure, manifested as decreased dendritic complexity, dendritic spine density and percentage of mushroom shaped spines in hippocampal CA1 and dentate gyrus (DG) neurons. Furthermore, a significant reduction in Arc expression was detected upon BPA exposure. Strikingly, BPA exposure significantly increased the mIPSC amplitude without altering the mEPSC amplitude or frequency, accompanied by increased GABAARβ2/3 on postsynaptic membrane in cultured CA1 neurons. In summary, our study indicated that Arc, together with the increased surface GABAARβ2/3, contributed to BPA induced spatial memory deficits, providing a novel molecular basis for BPA achieved brain impairment.

A Comparison of Reading Rates, Comprehension, and Stamina in Oral and Silent Reading of Fourth-Grade Students

ERIC Educational Resources Information Center

Trainin, Guy; Hiebert, Elfrieda H.; Wilson, Kathleen M.

2015-01-01

This study examined the relationships between silent and oral reading fluency and comprehension. Findings indicated that fourth grade students had consistent levels of comprehension in both reading modes. Students of all reading levels showed a similar pattern across the segments of a text set in both oral and silent reading--a gradual increase in…

Radiation Dose–Dependent Hippocampal Atrophy Detected With Longitudinal Volumetric Magnetic Resonance Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seibert, Tyler M.; Karunamuni, Roshan; Bartsch, Hauke

Purpose: After radiation therapy (RT) to the brain, patients often experience memory impairment, which may be partially mediated by damage to the hippocampus. Hippocampal sparing in RT planning is the subject of recent and ongoing clinical trials. Calculating appropriate hippocampal dose constraints would be improved by efficient in vivo measurements of hippocampal damage. In this study we sought to determine whether brain RT was associated with dose-dependent hippocampal atrophy. Methods and Materials: Hippocampal volume was measured with magnetic resonance imaging (MRI) in 52 patients who underwent fractionated, partial brain RT for primary brain tumors. Study patients had high-resolution, 3-dimensional volumetric MRI beforemore » and 1 year after RT. Images were processed using software with clearance from the US Food and Drug Administration and Conformité Européene marking for automated measurement of hippocampal volume. Automated results were inspected visually for accuracy. Tumor and surgical changes were censored. Mean hippocampal dose was tested for correlation with hippocampal atrophy 1 year after RT. Average hippocampal volume change was also calculated for hippocampi receiving high (>40 Gy) or low (<10 Gy) mean RT dose. A multivariate analysis was conducted with linear mixed-effects modeling to evaluate other potential predictors of hippocampal volume change, including patient (random effect), age, hemisphere, sex, seizure history, and baseline volume. Statistical significance was evaluated at α = 0.05. Results: Mean hippocampal dose was significantly correlated with hippocampal volume loss (r=−0.24, P=.03). Mean hippocampal volume was significantly reduced 1 year after high-dose RT (mean −6%, P=.009) but not after low-dose RT. In multivariate analysis, both RT dose and patient age were significant predictors of hippocampal atrophy (P<.01). Conclusions: The hippocampus demonstrates radiation dose–dependent atrophy after treatment for

Toward early estimation and treatment of addiction vulnerability: radial arm maze and N-acetyl cysteine before cocaine sensitization or nicotine self-administration in neonatal ventral hippocampal lesion rats.

PubMed

Rao, Kalyan N; Sentir, Alena M; Engleman, Eric A; Bell, Richard L; Hulvershorn, Leslie A; Breier, Alan; Chambers, R Andrew

2016-12-01

Prefrontal cortical (PFC)-hippocampal-striatal circuits, interconnected via glutamatergic signaling, are dysfunctional in mental illnesses that involve addiction vulnerability. In healthy and neurodevelopmentally altered rats, we examined how Radial Arm Maze (RAM) performance estimates addiction vulnerability, and how starting a glutamatergic modulating agent, N-acetyl cysteine (NAC) in adolescence alters adult mental illness and/or addiction phenotypes. Rats with neonatal ventral hippocampal lesions (NVHL) vs. SHAM-operated controls were randomized to NAC vs. saline in adolescence followed by cognitive testing (RAM) in early adulthood and then cocaine behavioral sensitization (experiment 1; n = 80) or nicotine self-administration (experiment 2; n = 12). In experiment 1, NVHL rats showed over-consumption of food (Froot-Loops (FL)) baiting the RAM with poor working memory (low-arm entries to repeat (ETR)), producing an elevated FL to ETR ratio ("FLETR"; p < 0.001). FLETR was the best linear estimator (compared to FL or ETR) of magnitude of long-term cocaine sensitization (R 2  = 0.14, p < 0.001). NAC treatment did not alter FL, ETR, FLETR, or cocaine sensitization. In experiment 2, FLETR also significantly and uniquely correlated with subsequent drug seeking during nicotine-induced reinstatement after extinction of nicotine self-administration (R 2  = 0.47, p < 0.01). NAC did not alter RAM performance, but significantly reversed NVHL-induced increases in nicotine seeking during extinction and reinstatement. These findings demonstrate the utility of animal models of mental illness with addiction vulnerability for developing novel diagnostic measures of PFC-hippocampal-striatal circuit dysfunction that may reflect addiction risk. Such tests may direct pharmacological treatments prior to adulthood and addictive drug exposure, to prevent or treat adult addictions.

Focal CA3 hippocampal subfield atrophy following LGI1 VGKC-complex antibody limbic encephalitis

PubMed Central

Miller, Thomas D.; Chong, Trevor T.-J.; Aimola Davies, Anne M.; Ng, Tammy W.C.; Johnson, Michael R.; Irani, Sarosh R.; Vincent, Angela; Husain, Masud; Jacob, Saiju; Maddison, Paul; Kennard, Christopher; Gowland, Penny A.

2017-01-01

Magnetic resonance imaging has linked chronic voltage-gated potassium channel (VGKC) complex antibody-mediated limbic encephalitis with generalized hippocampal atrophy. However, autoantibodies bind to specific rodent hippocampal subfields. Here, human hippocampal subfield (subiculum, cornu ammonis 1-3, and dentate gyrus) targets of immunomodulation-treated LGI1 VGKC-complex antibody-mediated limbic encephalitis were investigated using in vivo ultra-high resolution (0.39 × 0.39 × 1.0 mm3) 7.0 T magnetic resonance imaging [n = 18 patients, 17 patients (94%) positive for LGI1 antibody and one patient negative for LGI1/CASPR2 but positive for VGKC-complex antibodies, mean age: 64.0 ± 2.55 years, median 4 years post-limbic encephalitis onset; n = 18 controls]. First, hippocampal subfield quantitative morphometry indicated significant volume loss confined to bilateral CA3 [F(1,34) = 16.87, P < 0.0001], despite hyperintense signal evident in 5 of 18 patients on presentation. Second, early and later intervention (<3 versus >3 months from symptom onset) were associated with CA3 atrophy. Third, whole-brain voxel-by-voxel morphometry revealed no significant grey matter loss. Fourth, CA3 subfield atrophy was associated with severe episodic but not semantic amnesia for postmorbid autobiographical events that was predicted by variability in CA3 volume. The results raise important questions about the links with histopathology, the impact of the observed focal atrophy on other CA3-mediated reconstructive and episodic mechanisms, and the role of potential antibody-mediated pathogenicity as part of the pathophysiology cascade in humans. PMID:28369215

Spectroscopic evidence of hippocampal abnormalities in neocortical epilepsy

PubMed Central

Mueller, S. G.; Laxer, K. D.; Cashdollar, N.; Lopez, R. C.; Weiner, M. W.

2009-01-01

Lesional neocortical epilepsy (NE) can be associated with hippocampal sclerosis or hippocampal spectroscopic abnormalities without atrophy (dual pathology). In this study, magnetic resonance spectroscopic imaging (MRSI) was used to determine the frequency of hippocampal damage/dysfunction in NE with and without structural lesion. Sixteen patients with NE [seven temporal NE (NE-T), nine extratemporal (NE-ET)] and 16 controls were studied with a 2D MRSI sequence (Repetition time/echo time (TR/TE) = 1800/135 ms) covering both hippocampi. Seven NE patients had MR visible lesions (NE-Les), nine had normal MRI (NE-no). In each hippocampus, 12 voxels were uniformly selected. In controls, mean (± SD) NAA/(Cr + Cho) values for each voxel were calculated and voxels with NAA/(Cr + Cho) ≤ (mean in controls – 2SD in controls) were defined as ‘pathological’ in patients. Eight of 16 NE patients had at least two ‘pathological’ voxel (mean 2.5, range 2–5) in one hippocampus. Four were NE-Les and four NE-no. Three (43%) NE-T patients, had evidence for hippocampal damage/dysfunction and five (56%) had NE-ET. The ipsilateral hippocampus was affected in six of eight NE patients. Evidence for unilateral hippocampal damage/dysfunction was demonstrated in 50% of the NE patients. The type of NE, i.e. NE-Les or NE-no, NE-T or NE-ET, had no influence on the occurrence of hippocampal damage/dysfunction. PMID:16618342

Clinical predictors of silent but substantial liver fibrosis in primary Sjogren's syndrome.

PubMed

Lee, Sang-Won; Kim, Beom Kyung; Park, Jun Yong; Kim, Do Young; Ahn, Sang Hoon; Song, Jungsik; Park, Yong-Beom; Lee, Soo-Kon; Han, Kwang-Hyub; Kim, Seung Up

2016-07-01

To investigate the prevalence and the predictors of silent but substantial liver fibrosis in patients with primary Sjogren's syndrome (pSS). We enrolled 101 pSS patients with normal liver function and structures, and without significant liver diseases or other conditions affecting liver fibrosis. The European league against rheumatism (EULAR) SS patients reported index (ESSPRI) and the EULAR SS disease activity index (ESSDAI) were analyzed. Liver stiffness (LS) was measured using transient elastography and 7.4 kPa was determined as the cutoff value for significant liver fibrosis. The median age of patients (91women) was 53 years and the median LS value was 4.7 kPa. The median ESSPRI and ESSDAI showed no correlation with LS values. Twelve patients (11.9%) had significant liver fibrosis. In multivariate logistic regression, white blood cells count ≤4000.0/mm(3) (Odds ratio [OR] 9.821), serum albumin ≤3.8 mg/dL (OR 16.770) and aspartate aminotransferase (AST) ≥ 27.0 IU/L (OR 20.858) independently predicted silent but substantial liver fibrosis in pSS patients. The prevalence of silent but substantial liver fibrosis was 11.9% in pSS and its predictors were leukopenia, decreased serum albumin and increased AST levels.

Effortful Retrieval Reduces Hippocampal Activity and Impairs Incidental Encoding

PubMed Central

Reas, Emilie T.; Brewer, James B.

2014-01-01

Functional imaging studies frequently report that the hippocampus is engaged by successful episodic memory retrieval. However, considering that concurrent encoding of the background environment occurs during retrieval and influences medial temporal lobe activity, it is plausible that hippocampal encoding functions are reduced with increased attentional engagement during effortful retrieval. Expanding upon evidence that retrieval efforts suppress activity in hippocampal regions implicated in encoding, this study examines the influence of retrieval effort on encoding performance and the interactive effects of encoding and retrieval on hippocampal and neocortical activity. Functional magnetic resonance imaging was conducted while subjects performed a word recognition task with incidental picture encoding. Both lower memory strength and increased search duration were associated with encoding failure and reduced hippocampal and default network activity. Activity in the anterior hippocampus tracked encoding, which was more strongly deactivated when incidental encoding was unsuccessful. These findings highlight potential contributions from background encoding processes to hippocampal activations during neuroimaging studies of episodic memory retrieval. PMID:23378272

Association between CSF biomarkers, hippocampal volume and cognitive function in patients with amnestic mild cognitive impairment (MCI).

PubMed

Nathan, Pradeep J; Lim, Yen Ying; Abbott, Rosemary; Galluzzi, Samantha; Marizzoni, Moira; Babiloni, Claudio; Albani, Diego; Bartres-Faz, David; Didic, Mira; Farotti, Lucia; Parnetti, Lucilla; Salvadori, Nicola; Müller, Bernhard W; Forloni, Gianluigi; Girtler, Nicola; Hensch, Tilman; Jovicich, Jorge; Leeuwis, Annebet; Marra, Camillo; Molinuevo, José Luis; Nobili, Flavio; Pariente, Jeremie; Payoux, Pierre; Ranjeva, Jean-Philippe; Rolandi, Elena; Rossini, Paolo Maria; Schönknecht, Peter; Soricelli, Andrea; Tsolaki, Magda; Visser, Pieter Jelle; Wiltfang, Jens; Richardson, Jill C; Bordet, Régis; Blin, Olivier; Frisoni, Giovanni B

2017-05-01

Few studies have examined the relationship between CSF and structural biomarkers, and cognitive function in MCI. We examined the relationship between cognitive function, hippocampal volume and cerebrospinal fluid (CSF) Aβ 42 and tau in 145 patients with MCI. Patients were assessed on cognitive tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB), the Geriatric Depression Scale and the Functional Activities Questionnaire. Hippocampal volume was measured using magnetic resonance imaging (MRI), and CSF markers of Aβ 42 , tau and p-tau 181 were also measured. Worse performance on a wide range of memory and sustained attention tasks were associated with reduced hippocampal volume, higher CSF tau and p-tau 181 and increased tau/Aβ 42 ratio. Memory tasks were also associated with lower ability to conduct functional activities of daily living, providing a link between AD biomarkers, memory performance and functional outcome. These results suggest that biomarkers of Aβ and tau are strongly related to cognitive performance as assessed by the CANTAB, and have implications for the early detection and characterization of incipient AD. Copyright © 2017 Elsevier Inc. All rights reserved.

Cholinergic modulation of hippocampal network function

PubMed Central

Teles-Grilo Ruivo, Leonor M.; Mellor, Jack R.

2013-01-01

Cholinergic septohippocampal projections from the medial septal area to the hippocampus are proposed to have important roles in cognition by modulating properties of the hippocampal network. However, the precise spatial and temporal profile of acetylcholine release in the hippocampus remains unclear making it difficult to define specific roles for cholinergic transmission in hippocampal dependent behaviors. This is partly due to a lack of tools enabling specific intervention in, and recording of, cholinergic transmission. Here, we review the organization of septohippocampal cholinergic projections and hippocampal acetylcholine receptors as well as the role of cholinergic transmission in modulating cellular excitability, synaptic plasticity, and rhythmic network oscillations. We point to a number of open questions that remain unanswered and discuss the potential for recently developed techniques to provide a radical reappraisal of the function of cholinergic inputs to the hippocampus. PMID:23908628

Canine hippocampal formation composited into three-dimensional structure using MPRAGE.

PubMed

Jung, Mi-Ae; Nahm, Sang-Soep; Lee, Min-Su; Lee, In-Hye; Lee, Ah-Ra; Jang, Dong-Pyo; Kim, Young-Bo; Cho, Zang-Hee; Eom, Ki-Dong

2010-07-01

This study was performed to anatomically illustrate the living canine hippocampal formation in three-dimensions (3D), and to evaluate its relationship to surrounding brain structures. Three normal beagle dogs were scanned on a MR scanner with inversion recovery segmented 3D gradient echo sequence (known as MP-RAGE: Magnetization Prepared Rapid Gradient Echo). The MRI data was manually segmented and reconstructed into a 3D model using the 3D slicer software tool. From the 3D model, the spatial relationships between hippocampal formation and surrounding structures were evaluated. With the increased spatial resolution and contrast of the MPRAGE, the canine hippocampal formation was easily depicted. The reconstructed 3D image allows easy understanding of the hippocampal contour and demonstrates the structural relationship of the hippocampal formation to surrounding structures in vivo.

Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition.

PubMed

Bast, Tobias; Pezze, Marie; McGarrity, Stephanie

2017-10-01

We review recent evidence concerning the significance of inhibitory GABA transmission and of neural disinhibition, that is, deficient GABA transmission, within the prefrontal cortex and the hippocampus, for clinically relevant cognitive functions. Both regions support important cognitive functions, including attention and memory, and their dysfunction has been implicated in cognitive deficits characterizing neuropsychiatric disorders. GABAergic inhibition shapes cortico-hippocampal neural activity, and, recently, prefrontal and hippocampal neural disinhibition has emerged as a pathophysiological feature of major neuropsychiatric disorders, especially schizophrenia and age-related cognitive decline. Regional neural disinhibition, disrupting spatio-temporal control of neural activity and causing aberrant drive of projections, may disrupt processing within the disinhibited region and efferent regions. Recent studies in rats showed that prefrontal and hippocampal neural disinhibition (by local GABA antagonist microinfusion) dysregulates burst firing, which has been associated with important aspects of neural information processing. Using translational tests of clinically relevant cognitive functions, these studies showed that prefrontal and hippocampal neural disinhibition disrupts regional cognitive functions (including prefrontal attention and hippocampal memory function). Moreover, hippocampal neural disinhibition disrupted attentional performance, which does not require the hippocampus but requires prefrontal-striatal circuits modulated by the hippocampus. However, some prefrontal and hippocampal functions (including inhibitory response control) are spared by regional disinhibition. We consider conceptual implications of these findings, regarding the distinct relationships of distinct cognitive functions to prefrontal and hippocampal GABA tone and neural activity. Moreover, the findings support the proposition that prefrontal and hippocampal neural disinhibition

Direct speech quotations promote low relative-clause attachment in silent reading of English.

PubMed

Yao, Bo; Scheepers, Christoph

2018-07-01

The implicit prosody hypothesis (Fodor, 1998, 2002) proposes that silent reading coincides with a default, implicit form of prosody to facilitate sentence processing. Recent research demonstrated that a more vivid form of implicit prosody is mentally simulated during silent reading of direct speech quotations (e.g., Mary said, "This dress is beautiful"), with neural and behavioural consequences (e.g., Yao, Belin, & Scheepers, 2011; Yao & Scheepers, 2011). Here, we explored the relation between 'default' and 'simulated' implicit prosody in the context of relative-clause (RC) attachment in English. Apart from confirming a general low RC-attachment preference in both production (Experiment 1) and comprehension (Experiments 2 and 3), we found that during written sentence completion (Experiment 1) or when reading silently (Experiment 2), the low RC-attachment preference was reliably enhanced when the critical sentences were embedded in direct speech quotations as compared to indirect speech or narrative sentences. However, when reading aloud (Experiment 3), direct speech did not enhance the general low RC-attachment preference. The results from Experiments 1 and 2 suggest a quantitative boost to implicit prosody (via auditory perceptual simulation) during silent production/comprehension of direct speech. By contrast, when reading aloud (Experiment 3), prosody becomes equally salient across conditions due to its explicit nature; indirect speech and narrative sentences thus become as susceptible to prosody-induced syntactic biases as direct speech. The present findings suggest a shared cognitive basis between default implicit prosody and simulated implicit prosody, providing a new platform for studying the effects of implicit prosody on sentence processing. Copyright © 2018 Elsevier B.V. All rights reserved.

Hippocampal amnesia disrupts creative thinking.

PubMed

Duff, Melissa C; Kurczek, Jake; Rubin, Rachael; Cohen, Neal J; Tranel, Daniel

2013-12-01

Creativity requires the rapid combination and recombination of existing mental representations to create novel ideas and ways of thinking. The hippocampal system, through its interaction with neocortical storage sites, provides a relational database necessary for the creation, updating, maintenance, and juxtaposition of mental representations used in service of declarative memory. Given this functionality, we hypothesized that hippocampus would play a critical role in creative thinking. We examined creative thinking, as measured by verbal and figural forms of the torrance tests of creative thinking (TTCT), in a group of participants with hippocampal damage and severe declarative memory impairment as well as in a group of demographically matched healthy comparison participants. The patients with bilateral hippocampal damage performed significantly worse than comparison participants on both the verbal and figural portions of the TTCT. These findings suggest that hippocampus plays a role critical in creative thinking, adding to a growing body of work pointing to the diverse ways the hallmark processing features of hippocampus serve a variety of behaviors that require flexible cognition. Copyright © 2013 Wiley Periodicals, Inc.

Beyond decoding: phonological processing during silent reading in beginning readers.

PubMed

Blythe, Hazel I; Pagán, Ascensión; Dodd, Megan

2015-07-01

In this experiment, the extent to which beginning readers process phonology during lexical identification in silent sentence reading was investigated. The eye movements of children aged seven to nine years and adults were recorded as they read sentences containing either a correctly spelled target word (e.g., girl), a pseudohomophone (e.g., gerl), or a spelling control (e.g., garl). Both children and adults showed a benefit from the valid phonology of the pseudohomophone, compared to the spelling control during reading. This indicates that children as young as seven years old exhibit relatively skilled phonological processing during reading, despite having moved past the use of overt phonological decoding strategies. In addition, in comparison to adults, children's lexical processing was more disrupted by the presence of spelling errors, suggesting a developmental change in the relative dependence upon phonological and orthographic processing in lexical identification during silent sentence reading. (c) 2015 APA, all rights reserved.

Abnormal hippocampal shape in offenders with psychopathy.

PubMed

Boccardi, Marina; Ganzola, Rossana; Rossi, Roberta; Sabattoli, Francesca; Laakso, Mikko P; Repo-Tiihonen, Eila; Vaurio, Olli; Könönen, Mervi; Aronen, Hannu J; Thompson, Paul M; Frisoni, Giovanni B; Tiihonen, Jari

2010-03-01

Posterior hippocampal volumes correlate negatively with the severity of psychopathy, but local morphological features are unknown. The aim of this study was to investigate hippocampal morphology in habitually violent offenders having psychopathy. Manual tracings of hippocampi from magnetic resonance images of 26 offenders (age: 32.5 +/- 8.4), with different degrees of psychopathy (12 high, 14 medium psychopathy based on the Psychopathy Checklist Revised), and 25 healthy controls (age: 34.6 +/- 10.8) were used for statistical modelling of local changes with a surface-based radial distance mapping method. Both offenders and controls had similar hippocampal volume and asymmetry ratios. Local analysis showed that the high psychopathy group had a significant depression along the longitudinal hippocampal axis, on both the dorsal and ventral aspects, when compared with the healthy controls and the medium psychopathy group. The opposite comparison revealed abnormal enlargement of the lateral borders in both the right and left hippocampi of both high and medium psychopathy groups versus controls, throughout CA1, CA2-3 and the subicular regions. These enlargement and reduction effects survived statistical correction for multiple comparisons in the main contrast (26 offenders vs. 25 controls) and in most subgroup comparisons. A statistical check excluded a possible confounding effect from amphetamine and polysubstance abuse. These results indicate that habitually violent offenders exhibit a specific abnormal hippocampal morphology, in the absence of total gray matter volume changes, that may relate to different autonomic modulation and abnormal fear-conditioning. 2009 Wiley-Liss, Inc.

Concurrent Validity of the Test of Silent Word Reading Fluency

ERIC Educational Resources Information Center

Bell, Sherry Mee; McCallum, R. Steve; Burton, Bobbie; Gray, Rebecca; Windingstad, Sunny; Moore, Jessica

2006-01-01

Relationships between the Test of Silent Word Reading Fluency (TOSWRF; Mather, Hammill, Allen, & Roberts, 2004), a recently developed measure of fluency, and other operationalizations of reading, including subtests from the Comprehensive Test of Basic Skills (CTBS; 1996), and the Woodcock-Johnson-III Tests of Achievement, (WJ-III; Woodcock,…

Roles of PTEN-induced putative kinase 1 and dynamin-related protein 1 in transient global ischemia-induced hippocampal neuronal injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Shang-Der, E-mail: chensd@adm.cgmh.org.tw; Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan; Lin, Tsu-Kung

Recent studies showed that increased mitochondrial fission is an early event of cell death during cerebral ischemia and dynamin-related protein 1 (Drp1) plays an important role in mitochondrial fission, which may be regulated by PTEN-induced putative kinase 1 (PINK1), a mitochondrial serine/threonine-protein kinase thought to protect cells from stress-induced mitochondrial dysfunction and regulate mitochondrial fission. However, the roles of PINK1 and Drp1 in hippocampal injury caused by transient global ischemia (TGI) remain unknown. We therefore tested the hypothesis that TGI may induce PINK1 causing downregulation of Drp1 phosphorylation to enhance hippocampal neuronal survival, thus functioning as an endogenous neuroprotective mechanism.more » We found progressively increased PINK1 expression in the hippocampal CA1 subfield1-48 h following TGI, reaching the maximal level at 4 h. Despite lack of changes in the expression level of total Drp1 and phosphor-Drp1 at Ser637, TGI induced a time-dependent increase of Drp1 phosphorlation at Ser616 that peaked after 24 h. Notably, PINK1-siRNA increased p-Drp1(Ser616) protein level in hippocampal CA1 subfield 24 h after TGI. The PINK1 siRNA also aggravated the TGI-induced oxidative DNA damage with an increased 8-hydroxy-deoxyguanosine (8-OHdG) content in hippocampal CA1 subfield. Furthermore, PINK1 siRNA also augmented TGI-induced apoptosis as evidenced by the increased numbers of TUNEL-positive staining and enhanced DNA fragmentation. These findings indicated that PINK1 is an endogenous protective mediator vital for neuronal survival under ischemic insult through regulating Drp1 phosphorylation at Ser616. - Highlights: • Transient global ischemia increases expression of PINK1 and p-Drp1 at Ser616 in hippocampal CA1 subfield. • PINK1-siRNA decreases PINK1 expression but increases p-Drp1 at Ser616 in hippocampal CA1 subfield. • PINK1-siRNA augments oxidative stress and neuronal damage in hippocampal CA1 subfield.« less

Early tissue damage and microstructural reorganization predict disease severity in experimental epilepsy

PubMed Central

Janz, Philipp; Schwaderlapp, Niels; Heining, Katharina; Häussler, Ute; Korvink, Jan G; von Elverfeldt, Dominik; Hennig, Jürgen; Egert, Ulrich

2017-01-01

Mesial temporal lobe epilepsy (mTLE) is the most common focal epilepsy in adults and is often refractory to medication. So far, resection of the epileptogenic focus represents the only curative therapy. It is unknown whether pathological processes preceding epilepsy onset are indicators of later disease severity. Using longitudinal multi-modal MRI, we monitored hippocampal injury and tissue reorganization during epileptogenesis in a mouse mTLE model. The prognostic value of MRI biomarkers was assessed by retrospective correlations with pathological hallmarks Here, we show for the first time that the extent of early hippocampal neurodegeneration and progressive microstructural changes in the dentate gyrus translate to the severity of hippocampal sclerosis and seizure burden in chronic epilepsy. Moreover, we demonstrate that structural MRI biomarkers reflect the extent of sclerosis in human hippocampi. Our findings may allow an early prognosis of disease severity in mTLE before its first clinical manifestations, thus expanding the therapeutic window. DOI: http://dx.doi.org/10.7554/eLife.25742.001 PMID:28746029

Preservation of hippocampal neuron numbers and hippocampal subfield volumes in behaviorally characterized aged tree shrews.

PubMed

Keuker, Jeanine I H; de Biurrun, Gabriel; Luiten, Paul G M; Fuchs, Eberhard

2004-01-19

Aging is associated with a decreased ability to store and retrieve information. The hippocampal formation plays a critical role in such memory processes, and its integrity is affected during normal aging. We used tree shrews (Tupaia belangeri) as an animal model of aging, because in many characteristics, tree shrews are closer to primates than they are to rodents. Young and aged male tree shrews performed a holeboard spatial memory task, which permits assessment of reference and working memory. Upon completion of the behavioral measurements, we carried out modified stereological analyses of neuronal numbers in various subdivisions of the hippocampus and used the Cavalieri method to calculate the volumes of these subfields. Results showed that the working memory of aged tree shrews was significantly impaired compared with that of young animals, whereas the hippocampus-dependent reference memory remained unchanged by aging. Estimation of the number of neurons revealed preserved neuron numbers in the subiculum, in the subregions CA1, CA2, CA3, and in the hilus of the dentate gyrus. Volume measurements showed no aging-related changes in the volume of any of these hippocampal subregions, or in the molecular and granule cell layers of the dentate gyrus of tree shrews. We conclude that the observed changes in memory performance in aging tree shrews are not accompanied by observable reductions of hippocampal neuron numbers or hippocampal volume, rather, the changes in memory performance are more likely the result of modified subcellular mechanisms that are affected by the aging process. Copyright 2003 Wiley-Liss, Inc.

The Effects of Oral and Silent Reading on Reading Comprehension

ERIC Educational Resources Information Center

Schimmel, Naomi; Ness, Molly

2017-01-01

This study examined the effects of reading mode (oral and silent) and text genre (narrative and expository) on fourth graders' reading comprehension. While controlling for prior reading ability of 48 participants, we measured comprehension. Using a repeated measured design, data were analyzed using analysis of covariance, paired t-tests, and…

Modeling hippocampal neurogenesis using human pluripotent stem cells.

PubMed

Yu, Diana Xuan; Di Giorgio, Francesco Paolo; Yao, Jun; Marchetto, Maria Carolina; Brennand, Kristen; Wright, Rebecca; Mei, Arianna; McHenry, Lauren; Lisuk, David; Grasmick, Jaeson Michael; Silberman, Pedro; Silberman, Giovanna; Jappelli, Roberto; Gage, Fred H

2014-03-11

The availability of human pluripotent stem cells (hPSCs) offers the opportunity to generate lineage-specific cells to investigate mechanisms of human diseases specific to brain regions. Here, we report a differentiation paradigm for hPSCs that enriches for hippocampal dentate gyrus (DG) granule neurons. This differentiation paradigm recapitulates the expression patterns of key developmental genes during hippocampal neurogenesis, exhibits characteristics of neuronal network maturation, and produces PROX1+ neurons that functionally integrate into the DG. Because hippocampal neurogenesis has been implicated in schizophrenia (SCZD), we applied our protocol to SCZD patient-derived human induced pluripotent stem cells (hiPSCs). We found deficits in the generation of DG granule neurons from SCZD hiPSC-derived hippocampal NPCs with lowered levels of NEUROD1, PROX1, and TBR1, reduced neuronal activity, and reduced levels of spontaneous neurotransmitter release. Our approach offers important insights into the neurodevelopmental aspects of SCZD and may be a promising tool for drug screening and personalized medicine.

The hippocampal formation: morphological changes induced by thyroid, gonadal and adrenal hormones.

PubMed

Gould, E; Woolley, C S; McEwen, B S

1991-01-01

The hippocampal formation is of considerable interest due to its proposed role in a number of important functions, including learning and memory processes. Manipulations of thyroid, gonadal and adrenal hormones have been shown to influence hippocampal physiology as well as learning and memory. The cellular events which underlie these hormone-induced functional changes are largely unexplored. However, studies suggest that hormonal manipulations during development and in adulthood result in dramatic morphological changes within the hippocampal formation. Because neuronal physiology has been suggested to depend upon neuronal morphology, we have been determining the morphologic sensitivity of hippocampal neurons to thyroid and steroid hormones in an effort to elucidate possible structural mechanisms to account for differences in hippocampal function. In this review, hormone-induced structural changes in the developing and adult hippocampal formation are discussed, with particular emphasis on their functional relevance. Sex differences, as well as the developmental effects of thyroid hormone and glucocorticoids, are described. Moreover, the effects of ovarian steroids, thyroid hormone and glucocorticoids on neuronal morphology in the hippocampal formation of the adult rat are reviewed. These hormone-induced structural changes may account, at least in part, for previously reported hormone-induced changes in hippocampal function.

Non-invasive Investigation of Human Hippocampal Rhythms Using Magnetoencephalography: A Review.

PubMed

Pu, Yi; Cheyne, Douglas O; Cornwell, Brian R; Johnson, Blake W

2018-01-01

Hippocampal rhythms are believed to support crucial cognitive processes including memory, navigation, and language. Due to the location of the hippocampus deep in the brain, studying hippocampal rhythms using non-invasive magnetoencephalography (MEG) recordings has generally been assumed to be methodologically challenging. However, with the advent of whole-head MEG systems in the 1990s and development of advanced source localization techniques, simulation and empirical studies have provided evidence that human hippocampal signals can be sensed by MEG and reliably reconstructed by source localization algorithms. This paper systematically reviews simulation studies and empirical evidence of the current capacities and limitations of MEG "deep source imaging" of the human hippocampus. Overall, these studies confirm that MEG provides a unique avenue to investigate human hippocampal rhythms in cognition, and can bridge the gap between animal studies and human hippocampal research, as well as elucidate the functional role and the behavioral correlates of human hippocampal oscillations.

MR-based in vivo hippocampal volumetrics: 2. Findings in neuropsychiatric disorders.

PubMed

Geuze, E; Vermetten, E; Bremner, J D

2005-02-01

Magnetic resonance imaging (MRI) has opened a new window to the brain. Measuring hippocampal volume with MRI has provided important information about several neuropsychiatric disorders. We reviewed the literature and selected all English-language, human subject, data-driven papers on hippocampal volumetry, yielding a database of 423 records. Smaller hippocampal volumes have been reported in epilepsy, Alzheimer's disease, dementia, mild cognitive impairment, the aged, traumatic brain injury, cardiac arrest, Parkinson's disease, Huntington's disease, Cushing's disease, herpes simplex encephalitis, Turner's syndrome, Down's syndrome, survivors of low birth weight, schizophrenia, major depression, posttraumatic stress disorder, chronic alcoholism, borderline personality disorder, obsessive-compulsive disorder, and antisocial personality disorder. Significantly larger hippocampal volumes have been correlated with autism and children with fragile X syndrome. Preservation of hippocampal volume has been reported in congenital hyperplasia, children with fetal alcohol syndrome, anorexia nervosa, attention-deficit and hyperactivity disorder, bipolar disorder, and panic disorder. Possible mechanisms of hippocampal volume loss in neuropsychiatric disorders are discussed.

Non-invasive Investigation of Human Hippocampal Rhythms Using Magnetoencephalography: A Review

PubMed Central

Pu, Yi; Cheyne, Douglas O.; Cornwell, Brian R.; Johnson, Blake W.

2018-01-01

Hippocampal rhythms are believed to support crucial cognitive processes including memory, navigation, and language. Due to the location of the hippocampus deep in the brain, studying hippocampal rhythms using non-invasive magnetoencephalography (MEG) recordings has generally been assumed to be methodologically challenging. However, with the advent of whole-head MEG systems in the 1990s and development of advanced source localization techniques, simulation and empirical studies have provided evidence that human hippocampal signals can be sensed by MEG and reliably reconstructed by source localization algorithms. This paper systematically reviews simulation studies and empirical evidence of the current capacities and limitations of MEG “deep source imaging” of the human hippocampus. Overall, these studies confirm that MEG provides a unique avenue to investigate human hippocampal rhythms in cognition, and can bridge the gap between animal studies and human hippocampal research, as well as elucidate the functional role and the behavioral correlates of human hippocampal oscillations. PMID:29755314

Enhanced Dopamine-Dependent Hippocampal Plasticity after Single MK-801 Application

PubMed Central

Bartsch, Julia C; Fidzinski, Pawel; Huck, Jojanneke HJ; Hörtnagl, Heide; Kovács, Richard; Liotta, Agustin; Priller, Josef; Wozny, Christian; Behr, Joachim

2015-01-01

Dopaminergic hyperfunction and N-methyl-D-aspartate receptor (NMDAR) hypofunction have both been implicated in psychosis. Dopamine-releasing drugs and NMDAR antagonists replicate symptoms associated with psychosis in healthy humans and exacerbate symptoms in patients with schizophrenia. Though hippocampal dysfunction contributes to psychosis, the impact of NMDAR hypofunction on hippocampal plasticity remains poorly understood. Here, we used an NMDAR antagonist rodent model of psychosis to investigate hippocampal long-term potentiation (LTP). We found that single systemic NMDAR antagonism results in a region-specific, presynaptic LTP at hippocampal CA1-subiculum synapses that is induced by activation of D1/D5 dopamine receptors and modulated by L-type voltage-gated Ca2+ channels. Thereby, our findings may provide a cellular mechanism how NMDAR antagonism can lead to an enhanced hippocampal output causing activation of the hippocampus-ventral tegmental area-loop and overdrive of the dopamine system. PMID:25315194

Focal CA3 hippocampal subfield atrophy following LGI1 VGKC-complex antibody limbic encephalitis.

PubMed

Miller, Thomas D; Chong, Trevor T-J; Aimola Davies, Anne M; Ng, Tammy W C; Johnson, Michael R; Irani, Sarosh R; Vincent, Angela; Husain, Masud; Jacob, Saiju; Maddison, Paul; Kennard, Christopher; Gowland, Penny A; Rosenthal, Clive R

2017-05-01

Magnetic resonance imaging has linked chronic voltage-gated potassium channel (VGKC) complex antibody-mediated limbic encephalitis with generalized hippocampal atrophy. However, autoantibodies bind to specific rodent hippocampal subfields. Here, human hippocampal subfield (subiculum, cornu ammonis 1-3, and dentate gyrus) targets of immunomodulation-treated LGI1 VGKC-complex antibody-mediated limbic encephalitis were investigated using in vivo ultra-high resolution (0.39 × 0.39 × 1.0 mm3) 7.0 T magnetic resonance imaging [n = 18 patients, 17 patients (94%) positive for LGI1 antibody and one patient negative for LGI1/CASPR2 but positive for VGKC-complex antibodies, mean age: 64.0 ± 2.55 years, median 4 years post-limbic encephalitis onset; n = 18 controls]. First, hippocampal subfield quantitative morphometry indicated significant volume loss confined to bilateral CA3 [F(1,34) = 16.87, P < 0.0001], despite hyperintense signal evident in 5 of 18 patients on presentation. Second, early and later intervention (<3 versus >3 months from symptom onset) were associated with CA3 atrophy. Third, whole-brain voxel-by-voxel morphometry revealed no significant grey matter loss. Fourth, CA3 subfield atrophy was associated with severe episodic but not semantic amnesia for postmorbid autobiographical events that was predicted by variability in CA3 volume. The results raise important questions about the links with histopathology, the impact of the observed focal atrophy on other CA3-mediated reconstructive and episodic mechanisms, and the role of potential antibody-mediated pathogenicity as part of the pathophysiology cascade in humans. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

The Impact of Sleep Loss on Hippocampal Function

ERIC Educational Resources Information Center

Prince, Toni-Moi; Abel, Ted

2013-01-01

Hippocampal cellular and molecular processes critical for memory consolidation are affected by the amount and quality of sleep attained. Questions remain with regard to how sleep enhances memory, what parameters of sleep after learning are optimal for memory consolidation, and what underlying hippocampal molecular players are targeted by sleep…

Posterior cingulate glucose metabolism, hippocampal glucose metabolism, and hippocampal volume in cognitively normal, late-middle-aged persons at 3 levels of genetic risk for Alzheimer disease.

PubMed

Protas, Hillary D; Chen, Kewei; Langbaum, Jessica B S; Fleisher, Adam S; Alexander, Gene E; Lee, Wendy; Bandy, Daniel; de Leon, Mony J; Mosconi, Lisa; Buckley, Shannon; Truran-Sacrey, Diana; Schuff, Norbert; Weiner, Michael W; Caselli, Richard J; Reiman, Eric M

2013-03-01

To characterize and compare measurements of the posterior cingulate glucose metabolism, the hippocampal glucose metabolism, and hippocampal volume so as to distinguish cognitively normal, late-middle-aged persons with 2, 1, or 0 copies of the apolipoprotein E (APOE) ε4 allele, reflecting 3 levels of risk for late-onset Alzheimer disease. Cross-sectional comparison of measurements of cerebral glucose metabolism using 18F-fluorodeoxyglucose positron emission tomography and measurements of brain volume using magnetic resonance imaging in cognitively normal ε4 homozygotes, ε4 heterozygotes, and noncarriers. Academic medical center. A total of 31 ε4 homozygotes, 42 ε4 heterozygotes, and 76 noncarriers, 49 to 67 years old, matched for sex, age, and educational level. The measurements of posterior cingulate and hippocampal glucose metabolism were characterized using automated region-of-interest algorithms and normalized for whole-brain measurements. The hippocampal volume measurements were characterized using a semiautomated algorithm and normalized for total intracranial volume. Although there were no significant differences among the 3 groups of participants in their clinical ratings, neuropsychological test scores, hippocampal volumes (P = .60), or hippocampal glucose metabolism measurements (P = .12), there were significant group differences in their posterior cingulate glucose metabolism measurements (P = .001). The APOE ε4 gene dose was significantly associated with posterior cingulate glucose metabolism (r = 0.29, P = .0003), and this association was significantly greater than those with hippocampal volume or hippocampal glucose metabolism (P < .05, determined by use of pairwise Fisher z tests). Although our findings may depend in part on the analysis algorithms used, they suggest that a reduction in posterior cingulate glucose metabolism precedes a reduction in hippocampal volume or metabolism in cognitively normal persons at increased genetic risk for

Posterior Cingulate Glucose Metabolism, Hippocampal Glucose Metabolism, and Hippocampal Volume in Cognitively Normal, Late-Middle-Aged Persons at 3 Levels of Genetic Risk for Alzheimer Disease

PubMed Central

Protas, Hillary D.; Chen, Kewei; Langbaum, Jessica B. S.; Fleisher, Adam S.; Alexander, Gene E.; Lee, Wendy; Bandy, Daniel; de Leon, Mony J.; Mosconi, Lisa; Buckley, Shannon; Truran-Sacrey, Diana; Schuff, Norbert; Weiner, Michael W.; Caselli, Richard J.; Reiman, Eric M.

2013-01-01

Objective To characterize and compare measurements of the posterior cingulate glucose metabolism, the hippocampal glucose metabolism, and hippocampal volume so as to distinguish cognitively normal, late-middle-aged persons with 2, 1, or 0 copies of the apolipoprotein E (APOE) ε4 allele, reflecting 3 levels of risk for late-onset Alzheimer disease. Design Cross-sectional comparison of measurements of cerebral glucose metabolism using 18F-fluorodeoxy-glucose positron emission tomography and measurements of brain volume using magnetic resonance imaging in cognitively normal ε4 homozygotes, ε4 heterozygotes, and noncarriers. Setting Academic medical center. Participants A total of 31 ε4 homozygotes, 42 ε4 heterozygotes, and 76 noncarriers, 49 to 67 years old, matched for sex, age, and educational level. Main Outcome Measures The measurements of posterior cingulate and hippocampal glucose metabolism were characterized using automated region-of-interest algorithms and normalized for whole-brain measurements. The hippocampal volume measurements were characterized using a semiautomated algorithm and normalized for total intracranial volume. Results Although there were no significant differences among the 3 groups of participants in their clinical ratings, neuropsychological test scores, hippocampal volumes (P=.60), or hippocampal glucose metabolism measurements (P = .12), there were significant group differences in their posterior cingulate glucose metabolism measurements (P=.001). The APOE ε4 gene dose was significantly associated with posterior cingulate glucose metabolism (r=0.29, P=.0003), and this association was significantly greater than those with hippocampal volume or hippocampal glucose metabolism (P<.05, determined by use of pairwise Fisher z tests). Conclusions Although our findings may depend in part on the analysis algorithms used, they suggest that a reduction in posterior cingulate glucose metabolism precedes a reduction in hippocampal volume or

Assessing hippocampal development and language in early childhood: Evidence from a new application of the Automatic Segmentation Adapter Tool.

PubMed

Lee, Joshua K; Nordahl, Christine W; Amaral, David G; Lee, Aaron; Solomon, Marjorie; Ghetti, Simona

2015-11-01

Volumetric assessments of the hippocampus and other brain structures during childhood provide useful indices of brain development and correlates of cognitive functioning in typically and atypically developing children. Automated methods such as FreeSurfer promise efficient and replicable segmentation, but may include errors which are avoided by trained manual tracers. A recently devised automated correction tool that uses a machine learning algorithm to remove systematic errors, the Automatic Segmentation Adapter Tool (ASAT), was capable of substantially improving the accuracy of FreeSurfer segmentations in an adult sample [Wang et al., 2011], but the utility of ASAT has not been examined in pediatric samples. In Study 1, the validity of FreeSurfer and ASAT corrected hippocampal segmentations were examined in 20 typically developing children and 20 children with autism spectrum disorder aged 2 and 3 years. We showed that while neither FreeSurfer nor ASAT accuracy differed by disorder or age, the accuracy of ASAT corrected segmentations were substantially better than FreeSurfer segmentations in every case, using as few as 10 training examples. In Study 2, we applied ASAT to 89 typically developing children aged 2 to 4 years to examine relations between hippocampal volume, age, sex, and expressive language. Girls had smaller hippocampi overall, and in left hippocampus this difference was larger in older than younger girls. Expressive language ability was greater in older children, and this difference was larger in those with larger hippocampi, bilaterally. Overall, this research shows that ASAT is highly reliable and useful to examinations relating behavior to hippocampal structure. © 2015 Wiley Periodicals, Inc.

Human Schedule Performance, Protocol Analysis, and the "Silent Dog" Methodology

ERIC Educational Resources Information Center

Cabello, Francisco; Luciano, Carmen; Gomez, Inmaculada; Barnes-Holmes, Dermot

2004-01-01

The purpose of the current experiment was to investigate the role of private verbal behavior on the operant performances of human adults, using a protocol analysis procedure with additional methodological controls (the "silent dog" method). Twelve subjects were exposed to fixed ratio 8 and differential reinforcement of low rate 3-s schedules. For…

Hippocampal volume and sensitivity to maternal aggressive behavior: a prospective study of adolescent depressive symptoms.

PubMed

Whittle, Sarah; Yap, Marie B H; Sheeber, Lisa; Dudgeon, Paul; Yücel, Murat; Pantelis, Christos; Simmons, Julian G; Allen, Nicholas B

2011-02-01

It has been suggested that biological factors confer increased sensitivity to environmental influences on depressive symptoms during adolescence, a crucial time for the onset of depressive disorders. Given the critical role of the hippocampus in sensitivity to stress and processing of contextual aspects of the environment, investigation of its role in determining sensitivity to environmental context seems warranted. This study prospectively examined hippocampal volume as a measure of sensitivity to the influence of aggressive maternal behavior on change in depressive symptoms from early to midadolescence. The interaction between aggressive maternal behavior and hippocampal volume was found to predict change in depressive symptoms. Significant sex differences also emerged, whereby only for girls were larger bilateral hippocampal volumes more sensitive to the effects of maternal aggressive behavior, particularly with respect to experiencing the protective effects of low levels of maternal aggressiveness. These findings help elucidate the complex relationships between brain structure, environmental factors such as maternal parenting style, and sensitivity to (i.e., risk for, and protection from) the emergence of depression during this life stage. Given that family context risk factors are modifiable, our findings suggest the potential utility of targeted parenting interventions for the prevention and treatment of adolescent depressive disorder.

The silent base flow and the sound sources in a laminar jet.

PubMed

Sinayoko, Samuel; Agarwal, Anurag

2012-03-01

An algorithm to compute the silent base flow sources of sound in a jet is introduced. The algorithm is based on spatiotemporal filtering of the flow field and is applicable to multifrequency sources. It is applied to an axisymmetric laminar jet and the resulting sources are validated successfully. The sources are compared to those obtained from two classical acoustic analogies, based on quiescent and time-averaged base flows. The comparison demonstrates how the silent base flow sources shed light on the sound generation process. It is shown that the dominant source mechanism in the axisymmetric laminar jet is "shear-noise," which is a linear mechanism. The algorithm presented here could be applied to fully turbulent flows to understand the aerodynamic noise-generation mechanism. © 2012 Acoustical Society of America

GSK-3β-induced Tau pathology drives hippocampal neuronal cell death in Huntington's disease: involvement of astrocyte-neuron interactions.

PubMed

L'Episcopo, F; Drouin-Ouellet, J; Tirolo, C; Pulvirenti, A; Giugno, R; Testa, N; Caniglia, S; Serapide, M F; Cisbani, G; Barker, R A; Cicchetti, F; Marchetti, B

2016-04-28

Glycogen synthase kinase-3β (GSK-3β) has emerged as a critical factor in several pathways involved in hippocampal neuronal maintenance and function. In Huntington's disease (HD), there are early hippocampal deficits both in patients and transgenic mouse models, which prompted us to investigate whether disease-specific changes in GSK-3β expression may underlie these abnormalities. Thirty-three postmortem hippocampal samples from HD patients (neuropathological grades 2-4) and age- and sex-matched normal control cases were analyzed using real-time quantitative reverse transcription PCRs (qPCRs) and immunohistochemistry. In vitro and in vivo studies looking at hippocampal pathology and GSK-3β were also undertaken in transgenic R6/2 and wild-type mice. We identified a disease and stage-dependent upregulation of GSK-3β mRNA and protein levels in the HD hippocampus, with the active isoform pGSK-3β-Tyr(216) being strongly expressed in dentate gyrus (DG) neurons and astrocytes at a time when phosphorylation of Tau at the AT8 epitope was also present in these same neurons. This upregulation of pGSK-3β-Tyr(216) was also found in the R6/2 hippocampus in vivo and linked to the increased vulnerability of primary hippocampal neurons in vitro. In addition, the increased expression of GSK-3β in the astrocytes of R6/2 mice appeared to be the main driver of Tau phosphorylation and caspase3 activation-induced neuronal death, at least in part via an exacerbated production of major proinflammatory mediators. This stage-dependent overactivation of GSK-3β in HD-affected hippocampal neurons and astrocytes therefore points to GSK-3β as being a critical factor in the pathological development of this condition. As such, therapeutic targeting of this pathway may help ameliorate neuronal dysfunction in HD.

GSK-3β-induced Tau pathology drives hippocampal neuronal cell death in Huntington's disease: involvement of astrocyte–neuron interactions

PubMed Central

L'Episcopo, F; Drouin-Ouellet, J; Tirolo, C; Pulvirenti, A; Giugno, R; Testa, N; Caniglia, S; Serapide, M F; Cisbani, G; Barker, R A; Cicchetti, F; Marchetti, B

2016-01-01

Glycogen synthase kinase-3β (GSK-3β) has emerged as a critical factor in several pathways involved in hippocampal neuronal maintenance and function. In Huntington's disease (HD), there are early hippocampal deficits both in patients and transgenic mouse models, which prompted us to investigate whether disease-specific changes in GSK-3β expression may underlie these abnormalities. Thirty-three postmortem hippocampal samples from HD patients (neuropathological grades 2–4) and age- and sex-matched normal control cases were analyzed using real-time quantitative reverse transcription PCRs (qPCRs) and immunohistochemistry. In vitro and in vivo studies looking at hippocampal pathology and GSK-3β were also undertaken in transgenic R6/2 and wild-type mice. We identified a disease and stage-dependent upregulation of GSK-3β mRNA and protein levels in the HD hippocampus, with the active isoform pGSK-3β-Tyr216 being strongly expressed in dentate gyrus (DG) neurons and astrocytes at a time when phosphorylation of Tau at the AT8 epitope was also present in these same neurons. This upregulation of pGSK-3β-Tyr216 was also found in the R6/2 hippocampus in vivo and linked to the increased vulnerability of primary hippocampal neurons in vitro. In addition, the increased expression of GSK-3β in the astrocytes of R6/2 mice appeared to be the main driver of Tau phosphorylation and caspase3 activation-induced neuronal death, at least in part via an exacerbated production of major proinflammatory mediators. This stage-dependent overactivation of GSK-3β in HD-affected hippocampal neurons and astrocytes therefore points to GSK-3β as being a critical factor in the pathological development of this condition. As such, therapeutic targeting of this pathway may help ameliorate neuronal dysfunction in HD. PMID:27124580

Direct brain recordings reveal hippocampal rhythm underpinnings of language processing.

PubMed

Piai, Vitória; Anderson, Kristopher L; Lin, Jack J; Dewar, Callum; Parvizi, Josef; Dronkers, Nina F; Knight, Robert T

2016-10-04

Language is classically thought to be supported by perisylvian cortical regions. Here we provide intracranial evidence linking the hippocampal complex to linguistic processing. We used direct recordings from the hippocampal structures to investigate whether theta oscillations, pivotal in memory function, track the amount of contextual linguistic information provided in sentences. Twelve participants heard sentences that were either constrained ("She locked the door with the") or unconstrained ("She walked in here with the") before presentation of the final word ("key"), shown as a picture that participants had to name. Hippocampal theta power increased for constrained relative to unconstrained contexts during sentence processing, preceding picture presentation. Our study implicates hippocampal theta oscillations in a language task using natural language associations that do not require memorization. These findings reveal that the hippocampal complex contributes to language in an active fashion, relating incoming words to stored semantic knowledge, a necessary process in the generation of sentence meaning.

Associative reinstatement memory measures hippocampal function in Parkinson's Disease.

PubMed

Cohn, Melanie; Giannoylis, Irene; De Belder, Maya; Saint-Cyr, Jean A; McAndrews, Mary Pat

2016-09-01

In Parkinson's Disease (PD), hippocampal atrophy is associated with rapid cognitive decline. Hippocampal function is typically assessed using memory tests but current clinical tools (e.g., free recall) also rely on executive functions or use material that is not optimally engaging hippocampal memory networks. Because of the ubiquity of executive dysfunction in PD, our ability to detect true memory deficits is suboptimal. Our previous behavioural and neuroimaging work in other populations suggests that an experimental memory task - Associative Reinstatement Memory (ARM) - may prove useful in investigating hippocampal function in PD. In this study, we investigated whether ARM is compromised in PD and we assessed its convergent and divergent validity by comparing it to standardized measures of memory and of attention and executive functioning in PD, respectively. Using fMRI, we also investigated whether performance in PD relates to degree of hippocampal engagement. Fifteen participants with PD and 13 age-matched healthy controls completed neuropsychological testing as well as an ARM fMRI recognition paradigm in which they were instructed to identify word pairs comprised of two studied words (intact or rearranged pairs) and those containing at least one new word (new or half new pairs). ARM is measured by the differences in hit rates between intact and rearranged pairs. Behaviourally, ARM was poorer in PD relative to controls and was correlated with verbal memory measures, but not with attention or executive functioning in the PD group. Hippocampal activation associated with ARM was reduced in PD relative to controls and covaried with ARM scores in both groups. To conclude, ARM is a sensitive measure of hippocampal memory function that is unaffected by attention or executive dysfunction in PD. Our study highlights the benefit of integrating cognitive neuroscience frameworks and novel experimental tasks to improve the practice of clinical neuropsychology in PD

Levetiracetam attenuates hippocampal expression of synaptic plasticity-related immediate early and late response genes in amygdala-kindled rats

PubMed Central

2010-01-01

Background The amygdala-kindled rat is a model for human temporal lobe epilepsy and activity-dependent synaptic plasticity. Hippocampal RNA isolated from amygdala-kindled rats at different kindling stages was analyzed to identify kindling-induced genes. Furthermore, effects of the anti-epileptic drug levetiracetam on kindling-induced gene expression were examined. Results Cyclooxygenase-2 (Cox-2), Protocadherin-8 (Pcdh8) and TGF-beta-inducible early response gene-1 (TIEG1) were identified and verified as differentially expressed transcripts in the hippocampus of kindled rats by in situ hybridization and quantitative RT-PCR. In addition, we identified a panel of 16 additional transcripts which included Arc, Egr3/Pilot, Homer1a, Ania-3, MMP9, Narp, c-fos, NGF, BDNF, NT-3, Synaptopodin, Pim1 kinase, TNF-α, RGS2, Egr2/krox-20 and β-A activin that were differentially expressed in the hippocampus of amygdala-kindled rats. The list consists of many synaptic plasticity-related immediate early genes (IEGs) as well as some late response genes encoding transcription factors, neurotrophic factors and proteins that are known to regulate synaptic remodelling. In the hippocampus, induction of IEG expression was dependent on the afterdischarge (AD) duration. Levetiracetam, 40 mg/kg, suppressed the development of kindling measured as severity of seizures and AD duration. In addition, single animal profiling also showed that levetiracetam attenuated the observed kindling-induced IEG expression; an effect that paralleled the anti-epileptic effect of the drug on AD duration. Conclusions The present study provides mRNA expression data that suggest that levetiracetam attenuates expression of genes known to regulate synaptic remodelling. In the kindled rat, levetiracetam does so by shortening the AD duration thereby reducing the seizure-induced changes in mRNA expression in the hippocampus. PMID:20105316

Distinct Single but Not Necessarily Repeated Tetanization Is Required to Induce Hippocampal Late-LTP in the Rat CA1

ERIC Educational Resources Information Center

Sajikumar, Sreedharan; Navakkode, Sheeja; Frey, Julietta U.

2008-01-01

The protein synthesis-dependent form of hippocampal long-term potentiation (late-LTP) is thought to underlie memory. Its induction requires a distinct stimulation strength, and the common opinion is that only repeated tetani result in late-LTP whereas as single tetanus only reveals a transient early-LTP. Properties of LTP induction were compared…

Stress and adolescent hippocampal neurogenesis: diet and exercise as cognitive modulators

PubMed Central

Hueston, C M; Cryan, J F; Nolan, Y M

2017-01-01

Adolescence is a critical period for brain maturation. Deciphering how disturbances to the central nervous system at this time affect structure, function and behavioural outputs is important to better understand any long-lasting effects. Hippocampal neurogenesis occurs during development and continues throughout life. In adulthood, integration of these new cells into the hippocampus is important for emotional behaviour, cognitive function and neural plasticity. During the adolescent period, maturation of the hippocampus and heightened levels of hippocampal neurogenesis are observed, making alterations to neurogenesis at this time particularly consequential. As stress negatively affects hippocampal neurogenesis, and adolescence is a particularly stressful time of life, it is important to investigate the impact of stressor exposure at this time on hippocampal neurogenesis and cognitive function. Adolescence may represent not only a time for which stress can have long-lasting effects, but is also a critical period during which interventions, such as exercise and diet, could ameliorate stress-induced changes to hippocampal function. In addition, intervention at this time may also promote life-long behavioural changes that would aid in fostering increased hippocampal neurogenesis and cognitive function. This review addresses both the acute and long-term stress-induced alterations to hippocampal neurogenesis and cognition during the adolescent period, as well as changes to the stress response and pubertal hormones at this time which may result in differential effects than are observed in adulthood. We hypothesise that adolescence may represent an optimal time for healthy lifestyle changes to have a positive and long-lasting impact on hippocampal neurogenesis, and to protect against stress-induced deficits. We conclude that future research into the mechanisms underlying the susceptibility of the adolescent hippocampus to stress, exercise and diet and the consequent effect

Stress and adolescent hippocampal neurogenesis: diet and exercise as cognitive modulators.

PubMed

Hueston, C M; Cryan, J F; Nolan, Y M

2017-04-04

Adolescence is a critical period for brain maturation. Deciphering how disturbances to the central nervous system at this time affect structure, function and behavioural outputs is important to better understand any long-lasting effects. Hippocampal neurogenesis occurs during development and continues throughout life. In adulthood, integration of these new cells into the hippocampus is important for emotional behaviour, cognitive function and neural plasticity. During the adolescent period, maturation of the hippocampus and heightened levels of hippocampal neurogenesis are observed, making alterations to neurogenesis at this time particularly consequential. As stress negatively affects hippocampal neurogenesis, and adolescence is a particularly stressful time of life, it is important to investigate the impact of stressor exposure at this time on hippocampal neurogenesis and cognitive function. Adolescence may represent not only a time for which stress can have long-lasting effects, but is also a critical period during which interventions, such as exercise and diet, could ameliorate stress-induced changes to hippocampal function. In addition, intervention at this time may also promote life-long behavioural changes that would aid in fostering increased hippocampal neurogenesis and cognitive function. This review addresses both the acute and long-term stress-induced alterations to hippocampal neurogenesis and cognition during the adolescent period, as well as changes to the stress response and pubertal hormones at this time which may result in differential effects than are observed in adulthood. We hypothesise that adolescence may represent an optimal time for healthy lifestyle changes to have a positive and long-lasting impact on hippocampal neurogenesis, and to protect against stress-induced deficits. We conclude that future research into the mechanisms underlying the susceptibility of the adolescent hippocampus to stress, exercise and diet and the consequent effect

Late-Onset Alzheimer's Disease Polygenic Risk Profile Score Predicts Hippocampal Function.

PubMed

Xiao, Ena; Chen, Qiang; Goldman, Aaron L; Tan, Hao Yang; Healy, Kaitlin; Zoltick, Brad; Das, Saumitra; Kolachana, Bhaskar; Callicott, Joseph H; Dickinson, Dwight; Berman, Karen F; Weinberger, Daniel R; Mattay, Venkata S

2017-11-01

We explored the cumulative effect of several late-onset Alzheimer's disease (LOAD) risk loci using a polygenic risk profile score (RPS) approach on measures of hippocampal function, cognition, and brain morphometry. In a sample of 231 healthy control subjects (19-55 years of age), we used an RPS to study the effect of several LOAD risk loci reported in a recent meta-analysis on hippocampal function (determined by its engagement with blood oxygen level-dependent functional magnetic resonance imaging during episodic memory) and several cognitive metrics. We also studied effects on brain morphometry in an overlapping sample of 280 subjects. There was almost no significant association of LOAD-RPS with cognitive or morphometric measures. However, there was a significant negative relationship between LOAD-RPS and hippocampal function (familywise error [small volume correction-hippocampal region of interest] p < .05). There were also similar associations for risk score based on APOE haplotype, and for a combined LOAD-RPS + APOE haplotype risk profile score (p < .05 familywise error [small volume correction-hippocampal region of interest]). Of the 29 individual single nucleotide polymorphisms used in calculating LOAD-RPS, variants in CLU, PICALM, BCL3, PVRL2, and RELB showed strong effects (p < .05 familywise error [small volume correction-hippocampal region of interest]) on hippocampal function, though none survived further correction for the number of single nucleotide polymorphisms tested. There is a cumulative deleterious effect of LOAD risk genes on hippocampal function even in healthy volunteers. The effect of LOAD-RPS on hippocampal function in the relative absence of any effect on cognitive and morphometric measures is consistent with the reported temporal characteristics of LOAD biomarkers with the earlier manifestation of synaptic dysfunction before morphometric and cognitive changes. Copyright © 2017 Society of Biological Psychiatry. All rights reserved.

Silent myocardial ischaemia: the Tan Tock Seng experience.

PubMed

Mak, K H; Tan, E K; Chew, L; Gan, S H; Chan, A L

1991-10-01

The results of treadmill exercise stress test (TMX) for ischaemia is based on ST-segment depression. Patients with positive test may or may not be symptomatic. This study examines if there are any differences between these two groups of patients. A total of thirty-nine patients with coronary artery disease and positive TMX results in 1988 was studied. There were 16 patients with chest pain and 23 without. They were followed-up for a mean period of 16.9 and 15.2 months respectively. The following factors were found not to be statistically significant between these two groups of patients: age, sex, race, height, weight, history of hypertension, diabetes mellitus or smoking, indication for the test, use of drugs, total and HDL-cholesterol, exercise duration and the initial double product. The difference between the maximal double product of the two groups was statistically significant (p = 0.004). In the follow-up period, in the group of patients with silent myocardial ischaemia, one had a cardiac event and one underwent revascularisation. While in the symptomatic group, two had cardiac events and seven underwent revascularisation. There were no deaths in either group. The difference in overall outcome was significant statistically (p = 0.002). Therefore, patients with silent myocardial ischaemia have a higher maximal double product in TMX; hence a higher maximal workload and a less adverse outcome compared to symptomatic patients.

Vesicular glutamate transporter VGLUT1 has a role in hippocampal long-term potentiation and spatial reversal learning.

PubMed

Balschun, Detlef; Moechars, Diederik; Callaerts-Vegh, Zsuzsanna; Vermaercke, Ben; Van Acker, Nathalie; Andries, Luc; D'Hooge, Rudi

2010-03-01

Vesicular glutamate transporters 1 and 2 (VGLUT1, VGLUT2) show largely complementary distribution in the mature rodent brain and tend to segregate to synapses with different physiological properties. In the hippocampus, VGLUT1 is the dominate subtype in adult animals, whereas VGLUT2 is transiently expressed during early postnatal development. We generated and characterized VGLUT1 knockout mice in order to examine the functional contribution of this transporter to hippocampal synaptic plasticity and hippocampus-dependent spatial learning. Because complete deletion of VGLUT1 resulted in postnatal lethality, we used heterozygous animals for analysis. Here, we report that deletion of VGLUT1 resulted in impaired hippocampal long-term potentiation (LTP) in the CA1 region in vitro. In contrast, heterozygous VGLUT2 mice that were investigated for comparison did not show any changes in LTP. The reduced ability of VGLUT1-deficient mice to express LTP was accompanied by a specific deficit in spatial reversal learning in the water maze. Our data suggest a functional role of VGLUT1 in forms of hippocampal synaptic plasticity that are required to adapt and modify acquired spatial maps to external stimuli and changes.

Early maternal separation followed by later stressors leads to dysregulation of the HPA-axis and increases in hippocampal NGF and NT-3 levels in a rat model.

PubMed

Faure, Jacqueline; Uys, Joachim D K; Marais, Lelanie; Stein, Dan J; Daniels, Willie M U

2006-09-01

Early adverse life events, followed by subsequent stressors, appear to increase susceptibility for subsequent onset of psychiatric disorders in humans. The molecular mechanisms that underlie this phenomenon remain unclear, but dysregulation of the HPA axis and alterations in neurotrophic factors have been implicated. The present study investigated the effects in rodents of early maternal separation, followed by stress in adolescence and adulthood on later HPA-axis activity and hippocampal neurotrophin levels (brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3). Animals subjected to repeated stressors showed a significant decrease in basal ACTH (p < 0.05) and CORT (p < 0.05) levels when compared to controls, as well as significantly increased levels of NGF in the dorsal (p < 0.001) and ventral hippocampus (p < 0.01), and of NT-3 in the dorsal hippocampus (p < 0.01). Dysregulation of the HPA axis after multiple stressors is consistent with previous preclinical and clinical work. Given that neurotrophins are important in neuronal survival and plasticity, it is possible to speculate that their elevation reflects a compensatory mechanism.

Early-life sugar consumption has long-term negative effects on memory function in male rats.

PubMed

Noble, Emily E; Hsu, Ted M; Liang, Joanna; Kanoski, Scott E

2017-09-25

Added dietary sugars contribute substantially to the diet of children and adolescents in the USA, and recent evidence suggests that consuming sugar-sweetened beverages (SSBs) during early life has deleterious effects on hippocampal-dependent memory function. Here, we test whether the effects of early-life sugar consumption on hippocampal function persist into adulthood when access to sugar is restricted to the juvenile/adolescent phase of development. Male rats were given ad libitum access to an 11% weight-by-volume sugar solution (made with high fructose corn syrup-55) throughout the adolescent phase of development (post-natal day (PN) 26-56). The control group received a second bottle of water instead, and both groups received ad libitum standard laboratory chow and water access throughout the study. At PN 56 sugar solutions were removed and at PN 175 rats were subjected to behavioral testing for hippocampal-dependent episodic contextual memory in the novel object in context (NOIC) task, for anxiety-like behavior in the Zero maze, and were given an intraperitoneal glucose tolerance test. Early-life exposure to SSBs conferred long-lasting impairments in hippocampal-dependent memory function later in life- yet had no effect on body weight, anxiety-like behavior, or glucose tolerance. A second experiment demonstrated that NOIC performance was impaired at PN 175 even when SSB access was limited to 2 hours daily from PN 26-56. Our data suggest that even modest SSB consumption throughout early life may have long-term negative consequences on memory function during adulthood.

Adult Hippocampal Neurogenesis in Natural Populations of Mammals

PubMed Central

Amrein, Irmgard

2015-01-01

This review will discuss adult hippocampal neurogenesis in wild mammals of different taxa and outline similarities with and differences from laboratory animals. It begins with a review of evidence for hippocampal neurogenesis in various mammals, and shows the similar patterns of age-dependent decline in cell proliferation in wild and domesticated mammals. In contrast, the pool of immature neurons that originate from proliferative activity varies between species, implying a selective advantage for mammals that can make use of a large number of these functionally special neurons. Furthermore, rapid adaptation of hippocampal neurogenesis to experimental challenges appears to be a characteristic of laboratory rodents. Wild mammals show species-specific, rather stable hippocampal neurogenesis, which appears related to demands that characterize the niche exploited by a species rather than to acute events in the life of its members. Studies that investigate adult neurogenesis in wild mammals are not numerous, but the findings of neurogenesis under natural conditions can provide new insights, and thereby also address the question to which cognitive demands neurogenesis may respond during selection. PMID:25934014

BDNF is Associated With Age-Related Decline in Hippocampal Volume

PubMed Central

Erickson, Kirk I.; Prakash, Ruchika Shaurya; Voss, Michelle W.; Chaddock, Laura; Heo, Susie; McLaren, Molly; Pence, Brandt D.; Martin, Stephen A.; Vieira, Victoria J.; Woods, Jeffrey A.; Kramer, Arthur F.

2010-01-01

Hippocampal volume shrinks in late adulthood, but the neuromolecular factors that trigger hippocampal decay in aging humans remains a matter of speculation. In rodents, brain derived neurotrophic factor (BDNF) promotes the growth and proliferation of cells in the hippocampus and is important in long-term potentiation and memory formation. In humans, circulating levels of BDNF decline with advancing age and a genetic polymorphism for BDNF has been related to gray matter volume loss in old age. In this study, we tested whether age-related reductions in serum levels of BDNF would be related to shrinkage of the hippocampus and memory deficits in older adults. Hippocampal volume was acquired by automated segmentation of magnetic resonance images in 142 older adults without dementia. The caudate nucleus was also segmented and examined in relation to levels of serum BDNF. Spatial memory was tested using a paradigm in which memory load was parametrically increased. We found that increasing age was associated with smaller hippocampal volumes, reduced levels of serum BDNF, and poorer memory performance. Lower levels of BDNF were associated with smaller hippocampi and poorer memory, even when controlling for the variation related to age. In an exploratory mediation analysis, hippocampal volume mediated the age-related decline in spatial memory and BDNF mediated the age-related decline in hippocampal volume. Caudate nucleus volume was unrelated to BDNF levels or spatial memory performance. Our results identify serum BDNF as a significant factor related to hippocampal shrinkage and memory decline in late adulthood. PMID:20392958

Nocturnal Mnemonics: Sleep and Hippocampal Memory Processing

PubMed Central

Saletin, Jared M.; Walker, Matthew P.

2012-01-01

As critical as waking brain function is to learning and memory, an established literature now describes an equally important yet complementary role for sleep in information processing. This overview examines the specific contribution of sleep to human hippocampal memory processing; both the detriments caused by a lack of sleep, and conversely, the proactive benefits that develop following the presence of sleep. First, a role for sleep before learning is discussed, preparing the hippocampus for initial memory encoding. Second, a role for sleep after learning is considered, modulating the post-encoding consolidation of hippocampal-dependent memory. Third, a model is outlined in which these encoding and consolidation operations are symbiotically accomplished, associated with specific NREM sleep physiological oscillations. As a result, the optimal network outcome is achieved: increasing hippocampal independence and hence overnight consolidation, while restoring next-day sparse hippocampal encoding capacity for renewed learning ability upon awakening. Finally, emerging evidence is considered suggesting that, unlike previous conceptions, sleep does not universally consolidate all information. Instead, and based on explicit as well as saliency cues during initial encoding, sleep executes the discriminatory offline consolidation only of select information. Consequently, sleep promotes the targeted strengthening of some memories while actively forgetting others; a proposal with significant theoretical and clinical ramifications. PMID:22557988

Silent reading of direct versus indirect speech activates voice-selective areas in the auditory cortex.

PubMed

Yao, Bo; Belin, Pascal; Scheepers, Christoph

2011-10-01

In human communication, direct speech (e.g., Mary said: "I'm hungry") is perceived to be more vivid than indirect speech (e.g., Mary said [that] she was hungry). However, for silent reading, the representational consequences of this distinction are still unclear. Although many of us share the intuition of an "inner voice," particularly during silent reading of direct speech statements in text, there has been little direct empirical confirmation of this experience so far. Combining fMRI with eye tracking in human volunteers, we show that silent reading of direct versus indirect speech engenders differential brain activation in voice-selective areas of the auditory cortex. This suggests that readers are indeed more likely to engage in perceptual simulations (or spontaneous imagery) of the reported speaker's voice when reading direct speech as opposed to meaning-equivalent indirect speech statements as part of a more vivid representation of the former. Our results may be interpreted in line with embodied cognition and form a starting point for more sophisticated interdisciplinary research on the nature of auditory mental simulation during reading.

Health Education Films of the Silent Era: A Historical Analysis

ERIC Educational Resources Information Center

Sofalvi, Alan

2011-01-01

Films have been used to present health messages throughout the history of the medium. The purpose of this article is to describe pictures from the silent film era that were designed to educate people about health issues. Films still available in at least one format were reviewed. Published reviews were also used to obtain information about these…

Typical and atypical (silent) subacute thyroiditis in a wife and husband

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morrison, J.; Caplan, R.H.

1978-01-01

Typical subacute thyroiditis was diagnosed in a woman. Three weeks later, signs and symptoms of hyperthyroidism developed in her husband. Although the right lobe of his thyroid gland was slightly enlarged, pain and tenderness were absent throughout the course of his illness. The free thyroxine equivalent (FTE) value and the sedimentation rate were elevated; the low uptake of radioactive iodine by the thyroid gland was consistent with ''silent'' subacute thyroiditis. We postulate that a common etiology, probably viral, was operative in both cases. Nine additional cases of hyperthyroidism with low levels of thyroidal uptake of radioactive iodine are described. Themore » thyroid glands of these patients were normal or slightly enlarged. Antithyroglobulin antibody levels determined in seven patients were not substantially elevated. The clinical course of these patients was characteristic of ''silent'' subacute thyroiditis. Although the origin of the syndrome remains unclear, the disease is self-limited and therapy, if any, is supportive.« less

Amygdalohippocampal MR volume measurements in the early stages of Alzheimer disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lehericy, S.; Baulac, M.; Chiras, J.

1994-05-01

To evaluate the accuracy of hippocampal and amygdala volume measurements in diagnosing patients in the early stages of Alzheimer disease. Measurements of the hippocampal formation, amygdala, amygdalohippocampal complex (the two measurements summed), caudate nucleus, and ventricles, normalized for total intracranial volume, were obtained on coronal sections (1.5 T, 400/13 [repetition time/echo time], 5 mm) of 13 patients in the mild (minimental status {ge} 21) and five patients in the moderate stages of Alzheimer disease (10 < minimental status < 21), and eight age-matched control subjects. For patients with a minimental status score of 21 or greater, atrophy was significant formore » the amygdala and hippocampal formation (-36% and -25% for amygdala/total intracranial volume and hippocampal formation/total intracranial volume, respectively), but not for the caudate nucleus. No significant ventricular enlargement was found. For patients with a minimental status score less than 21, atrophy was more severe in all structures studied (amygdala/total intracranial volume -40%; hippocampal formation/total intracranial volume, -45%; caudate nucleus/total intracranial volume, -21%), and ventricles were enlarged (63%). No overlap was found between Alzheimer disease and control values for the amygdalohippocampal volume, even in the mild stages of the disease. In Alzheimer disease patients, hippocampal formation volumes correlated with the minimental status. Hippocampal and amygdala atrophy is marked and significant in the mild stages of Alzheimer disease. Volumetric measurements of the amygdala and the amygdalohippocampal complex appear more accurate than those of the hippocampal formation alone in distinguishing patients with Alzheimer disease. 46 refs., 8 figs., 2 tabs.« less

Estradiol stimulates an anti-translocation expression pattern of glucocorticoid co-regulators in a hippocampal cell model

PubMed Central

Malviya, Sanjana A.; Kelly, Sean D.; Greenlee, Megan M.; Eaton, Douglas C.; Duke, Billie Jeanne; Bourke, Chase H.; Neigh, Gretchen N.

2013-01-01

A consistent clinical finding in patients with major depressive disorder (MDD) is hyperactivity of the hypothalamic–pituitary–adrenal (HPA) axis, the system in the body that facilitates the response to stress. It has been suggested that alterations in glucocorticoid receptor (GR)-mediated feedback prolong activation of the HPA axis, leading to the dysfunction observed in MDD. Additionally, the risk for developing MDD is heightened by several risk factors, namely gender, genetics and early life stress. Previous studies have demonstrated that GR translocation is sexually dimorphic and this difference may be facilitated by differential expression of GR co-regulators. The purpose of this study was to determine the extent to which ovarian hormones alter expression of GR and its co-regulators, Fkbp5 and Ppid, in HT-22 hippocampal neurons. The impact of corticosterone (cort), estradiol (E2), and progesterone (P4) treatments on the expression of the genes Nr3c1, Ppid, and Fkbp5 was assessed in HT-22 hippocampal neurons. Treatment of cells with increasing doses of cort increased the expression of Fkbp5, an effect that was potentiated by E2. Exposure of HT-22 cells to E2 decreased the expression of Ppid and simultaneous exposure to E2 and P4 had combinatory effects on Ppid expression. The effects of E2 on Ppid extend previous work which demonstrated that serum E2 concentrations correlate with hippocampal Ppid expression in female rats. The results presented here illustrate that E2 generates an anti-translocation pattern of GR co-regulators in hippocampal cells. PMID:23541378

Global and Regional Alterations of Hippocampal Anatomy in Long-Term Meditation Practitioners

PubMed Central

Luders, Eileen; Thompson, Paul M.; Kurth, Florian; Hong, Jui-Yang; Phillips, Owen R.; Wang, Yalin; Gutman, Boris A.; Chou, Yi-Yu; Narr, Katherine L.; Toga, Arthur W.

2014-01-01

Studies linking meditation and brain structure are still relatively sparse, but the hippocampus is consistently implicated as one of the structures altered in meditation practitioners. To explore hippocampal features in the framework of meditation, we analyzed high-resolution structural magnetic resonance imaging data from 30 long-term meditators and 30 controls, closely matched for sex, age, and handedness. Hippocampal formations were manually traced following established protocols. In addition to calculating left and right hippocampal volumes (global measures), regional variations in surface morphology were determined by measuring radial distances from the hippocampal core to spatially matched surface points (local measures). Left and right hippocampal volumes were larger in meditators than in controls, significantly so for the left hippocampus. The presence and direction of this global effect was confirmed locally by mapping the exact spatial locations of the group differences. Altogether, radial distances were larger in meditators compared to controls, with up to 15% difference. These local effects were observed in several hippocampal regions in the left and right hemisphere though achieved significance primarily in the left hippocampal head. Larger hippocampal dimensions in long-term meditators may constitute part of the underlying neurological substrate for cognitive skills, mental capacities, and/or personal traits associated with the practice of meditation. Alternatively, given that meditation positively affects autonomic regulation and immune activity, altered hippocampal dimensions may be one result of meditation-induced stress reduction. However, given the cross-sectional design, the lack of individual stress measures, and the limited resolution of brain data, the exact underlying neuronal mechanisms remain to be established. PMID:22815233

Hippocampal volume changes following electroconvulsive therapy: a systematic review and meta-analysis.

PubMed

Wilkinson, Samuel T; Sanacora, Gerard; Bloch, Michael H

2017-05-01

Reduced hippocampal volume is one of the most consistent morphological findings in Major Depressive Disorder (MDD). Electroconvulsive therapy (ECT) is the most effective therapy for MDD, yet its mechanism of action remains poorly understood. Animal models show that ECT induces several neuroplastic processes, which lead to hippocampal volume increases. We conducted a meta-analysis of ECT studies in humans to investigate its effects on hippocampal volume. PubMed was searched for studies examining hippocampal volume before and after ECT. A random-effects model was used for meta-analysis with standardized mean difference (SMD) of the change in hippocampal volume before and after ECT as the primary outcome. Nine studies involving 174 participants were included. Total hippocampal volumes increased significantly following ECT compared to pre-treatment values (SMD=1.10; 95% CI 0.80-1.39; z=7.34; p<0.001; k=9). Both right (SMD=1.01; 95% CI 0.72-1.30; z=6.76; p<0.001; k=7) and left (SMD=0.87; 95% CI 0.51-1.23; z=4.69; p<0.001; k=7) hippocampal volumes were also similarly increased significantly following ECT. We demonstrated no correlation between improvement in depression symptoms with ECT and change in total hippocampal volume (beta=-1.28, 95% CI -4.51-1.95, z=-0.78, p=0.44). We demonstrate fairly consistent increases in hippocampal volume bilaterally following ECT treatment. The relationship among these volumetric changes and clinical improvement and cognitive side effects of ECT should be explored by larger, multisite studies with harmonized imaging methods.

Face-Scanning Behavior to Silently-Talking Faces in 12-Month-Old Infants: The Impact of Pre-Exposed Auditory Speech

ERIC Educational Resources Information Center

Kubicek, Claudia; de Boisferon, Anne Hillairet; Dupierrix, Eve; Loevenbruck, Helene; Gervain, Judit; Schwarzer, Gudrun

2013-01-01

The present eye-tracking study aimed to investigate the impact of auditory speech information on 12-month-olds' gaze behavior to silently-talking faces. We examined German infants' face-scanning behavior to side-by-side presentation of a bilingual speaker's face silently speaking German utterances on one side and French on the other side, before…

Delayed recall, hippocampal volume and Alzheimer neuropathology: findings from the Nun Study.

PubMed

Mortimer, J A; Gosche, K M; Riley, K P; Markesbery, W R; Snowdon, D A

2004-02-10

To examine the associations of hippocampal volume and the severity of neurofibrillary lesions determined at autopsy with delayed verbal recall performance evaluated an average of 1 year prior to death. Hippocampal volumes were computed using postmortem brain MRI from the first 56 scanned participants of the Nun Study. Quantitative neuropathologic studies included lesion counts, Braak staging, and determination of whether neuropathologic criteria for Alzheimer disease (AD) were met. Multiple regression was used to assess the association of hippocampal volume and neuropathologic lesions with the number of words (out of 10) recalled on the Consortium to Establish a Registry for Alzheimer's Disease Delayed Word Recall Test administered an average of 1 year prior to death. When entered separately, hippocampal volume, Braak stage, and the mean neurofibrillary tangle counts in the CA-1 region of the hippocampus and the subiculum were strongly associated with the number of words recalled after a delay, adjusting for age and education. When hippocampal volume was entered together with each neuropathologic index, only hippocampal volume retained a significant association with the delayed recall measure. The association between hippocampal volume and the number of words recalled was present in both demented and nondemented individuals as well as in those with and without substantial AD neurofibrillary pathology. The association of neurofibrillary tangles with delayed verbal recall may reflect associated hippocampal atrophy.

Septo-hippocampal GABAergic signaling across multiple modalities in awake mice.

PubMed

Kaifosh, Patrick; Lovett-Barron, Matthew; Turi, Gergely F; Reardon, Thomas R; Losonczy, Attila

2013-09-01

Hippocampal interneurons receive GABAergic input from the medial septum. Using two-photon Ca(2+) imaging of axonal boutons in hippocampal CA1 of behaving mice, we found that populations of septo-hippocampal GABAergic boutons were activated during locomotion and salient sensory events; sensory responses scaled with stimulus intensity and were abolished by anesthesia. We found similar activity patterns among boutons with common putative postsynaptic targets, with low-dimensional bouton population dynamics being driven primarily by presynaptic spiking.

Remote semantic memory is impoverished in hippocampal amnesia

PubMed Central

Klooster, Nathaniel B.; Duff, Melissa C.

2015-01-01

The necessity of the hippocampus for acquiring new semantic concepts is a topic of considerable debate. However, it is generally accepted that any role the hippocampus plays in semantic memory is time limited and that previously acquired information becomes independent of the hippocampus over time. This view, along with intact naming and word-definition matching performance in amnesia, has led to the notion that remote semantic memory is intact in patients with hippocampal amnesia. Motivated by perspectives of word learning as a protracted process where additional features and senses of a word are added over time, and by recent discoveries about the time course of hippocampal contributions to on-line relational processing, reconsolidation, and the flexible integration of information, we revisit the notion that remote semantic memory is intact in amnesia. Using measures of semantic richness and vocabulary depth from psycholinguistics and first and second language-learning studies, we examined how much information is associated with previously acquired, highly familiar words in a group of patients with bilateral hippocampal damage and amnesia. Relative to healthy demographically matched comparison participants and a group of brain-damaged comparison participants, the patients with hippocampal amnesia performed significantly worse on both productive and receptive measures of vocabulary depth and semantic richness. These findings suggest that remote semantic memory is impoverished in patients with hippocampal amnesia and that the hippocampus may play a role in the maintenance and updating of semantic memory beyond its initial acquisition. PMID:26474741

Dynamics of hippocampal spatial representation in echolocating bats

PubMed Central

Ulanovsky, Nachum; Moss, Cynthia F.

2009-01-01

The ‘place fields‘ of hippocampal pyramidal neurons are not static. For example, upon a contextual change in the environment, place-fields may ‘remap‘ within typical timescales of ~1 minute. A few studies have shown more rapid dynamics in hippocampal activity, linked to internal processes, such as switches between spatial reference frames or changes within the theta cycle. However, little is known about rapid hippocampal place-field dynamics in response to external, sensory stimuli. Here, we studied this question in big brown bats, echolocating mammals in which we can readily measure rapid changes in sensory dynamics (sonar signals), as well as rapid behavioral switches between distal and proximal exploratory modes. First, we show that place-field size was modulated by the availability of sensory information, on a timescale of ~300-milliseconds: Bat hippocampal place-fields were smallest immediately after an echolocation call, but place-fields ‘diffused’ with the passage of time after the call, when echo information was no longer arriving. Second, we show rapid modulation of hippocampal place-fields as the animal switched between two exploratory modes. Third, we compared place fields and spatial-view fields of individual neurons and found that place tuning was much more pronounced than spatial-view tuning. In addition, dynamic fluctuations in spatial-view tuning were stronger than fluctuations in place tuning. Taken together, these results suggest that spatial representation in mammalian hippocampus can be very rapidly modulated by external sensory and behavioral events. PMID:20014379

Early remodeling of the neocortex upon episodic memory encoding

PubMed Central

Bero, Adam W.; Meng, Jia; Cho, Sukhee; Shen, Abra H.; Canter, Rebecca G.; Ericsson, Maria; Tsai, Li-Huei

2014-01-01

Understanding the mechanisms by which long-term memories are formed and stored in the brain represents a central aim of neuroscience. Prevailing theory suggests that long-term memory encoding involves early plasticity within hippocampal circuits, whereas reorganization of the neocortex is thought to occur weeks to months later to subserve remote memory storage. Here we report that long-term memory encoding can elicit early transcriptional, structural, and functional remodeling of the neocortex. Parallel studies using genome-wide RNA sequencing, ultrastructural imaging, and whole-cell recording in wild-type mice suggest that contextual fear conditioning initiates a transcriptional program in the medial prefrontal cortex (mPFC) that is accompanied by rapid expansion of the synaptic active zone and postsynaptic density, enhanced dendritic spine plasticity, and increased synaptic efficacy. To address the real-time contribution of the mPFC to long-term memory encoding, we performed temporally precise optogenetic inhibition of excitatory mPFC neurons during contextual fear conditioning. Using this approach, we found that real-time inhibition of the mPFC inhibited activation of the entorhinal–hippocampal circuit and impaired the formation of long-term associative memory. These findings suggest that encoding of long-term episodic memory is associated with early remodeling of neocortical circuits, identify the prefrontal cortex as a critical regulator of encoding-induced hippocampal activation and long-term memory formation, and have important implications for understanding memory processing in healthy and diseased brain states. PMID:25071187

Early postnatal exposure to methylphenidate alters stress reactivity and increases hippocampal ectopic granule cells in adult rats

PubMed Central

Torres-Reveron, Annelyn; Gray, Jason D.; Melton, Jay T.; Punsoni, Michael; Tabori, Nora E.; Ward, Mary J.; Frys, Kelly; Iadecola, Costantino; Milner, Teresa A.

2009-01-01

To mimic clinical treatment with methylphenidate (MPH; Ritalin) for attention deficit/hyperactivity disorder (ADHD), rat pups were injected with MPH (5 mg/kg, I.P.) or placebo twice daily during their nocturnal active phase from postnatal day (PND) 7 to 35. Thirty-nine days after the last MPH administration (PND76), four litters of rats experienced stressful conditions during the 2003 New York City blackout. MPH-treated rats that endured the blackout lost more weight and regained it at a slower pace than controls (p<0.05; N=7–11/group). Furthermore, MPH-treated rats had elevated systolic arterial blood pressure (from 115.6 ± 1.2 to 126 ± 1.8 mmHg; p<0.05), assessed on PND130 by tail cuff plethysmography. Immunocytochemical studies of transmitter systems in the brain demonstrated rearrangements of catecholamine and neuropeptide Y fibers in select brain regions at PND135, which did not differ between blackout and control groups. However, MPH-treated rats that endured the blackout had more ectopic granule cells in the hilus of the dorsal hippocampal dentate gyrus compared to controls at PND 135 (p<0.05; N=6/group). These findings indicate that early postnatal exposure to high therapeutic doses of MPH can have long lasting effects on the plasticity of select brain regions and can induce changes in the reactivity to stress that persist into adulthood. PMID:19100815

Maternal depression in childhood and aggression in young adulthood: evidence for mediation by offspring amygdala-hippocampal volume ratio.

PubMed

Gilliam, Mary; Forbes, Erika E; Gianaros, Peter J; Erickson, Kirk I; Brennan, Lauretta M; Shaw, Daniel S

2015-10-01

There is abundant evidence that offspring of depressed mothers are at increased risk for persistent behavior problems related to emotion regulation, but the mechanisms by which offspring incur this risk are not entirely clear. Early adverse caregiving experiences have been associated with structural alterations in the amygdala and hippocampus, which parallel findings of cortical regions altered in adults with behavior problems related to emotion regulation. This study examined whether exposure to maternal depression during childhood might predict increased aggression and/or depression in early adulthood, and whether offspring amygdala:hippocampal volume ratio might mediate this relationship. Participants were 258 mothers and sons at socioeconomic risk for behavior problems. Sons' trajectories of exposure to maternal depression were generated from eight reports collected prospectively from offspring ages 18 months to 10 years. Offspring brain structure, aggression, and depression were assessed at age 20 (n = 170). Persistent, moderately high trajectories of maternal depression during childhood predicted increased aggression in adult offspring. In contrast, stable and very elevated trajectories of maternal depression during childhood predicted depression in adult offspring. Increased amygdala: hippocampal volume ratios at age 20 were significantly associated with concurrently increased aggression, but not depression, in adult offspring. Offspring amygdala: hippocampal volume ratio mediated the relationship found between trajectories of moderately elevated maternal depression during childhood and aggression in adult offspring. Alterations in the relative size of brain structures implicated in emotion regulation may be one mechanism by which offspring of depressed mothers incur increased risk for the development of aggression. © 2014 Association for Child and Adolescent Mental Health.

Hippocampal Insulin Resistance Impairs Spatial Learning and Synaptic Plasticity

PubMed Central

Piroli, Gerardo G.; Lawrence, Robert C.; Wrighten, Shayna A.; Green, Adrienne J.; Wilson, Steven P.; Sakai, Randall R.; Kelly, Sandra J.; Wilson, Marlene A.; Mott, David D.; Reagan, Lawrence P.

2015-01-01

Insulin receptors (IRs) are expressed in discrete neuronal populations in the central nervous system, including the hippocampus. To elucidate the functional role of hippocampal IRs independent of metabolic function, we generated a model of hippocampal-specific insulin resistance using a lentiviral vector expressing an IR antisense sequence (LV-IRAS). LV-IRAS effectively downregulates IR expression in the rat hippocampus without affecting body weight, adiposity, or peripheral glucose homeostasis. Nevertheless, hippocampal neuroplasticity was impaired in LV-IRAS–treated rats. High-frequency stimulation, which evoked robust long-term potentiation (LTP) in brain slices from LV control rats, failed to evoke LTP in LV-IRAS–treated rats. GluN2B subunit levels, as well as the basal level of phosphorylation of GluA1, were reduced in the hippocampus of LV-IRAS rats. Moreover, these deficits in synaptic transmission were associated with impairments in spatial learning. We suggest that alterations in the expression and phosphorylation of glutamate receptor subunits underlie the alterations in LTP and that these changes are responsible for the impairment in hippocampal-dependent learning. Importantly, these learning deficits are strikingly similar to the impairments in complex task performance observed in patients with diabetes, which strengthens the hypothesis that hippocampal insulin resistance is a key mediator of cognitive deficits independent of glycemic control. PMID:26216852

Earthquakes triggered by silent slip events on Kīlauea volcano, Hawaii

USGS Publications Warehouse

Segall, Paul; Desmarais, Emily K.; Shelly, David; Miklius, Asta; Cervelli, Peter F.

2006-01-01

Slow-slip events, or ‘silent earthquakes’, have recently been discovered in a number of subduction zones including the Nankai trough1, 2, 3 in Japan, Cascadia4, 5, and Guerrero6 in Mexico, but the depths of these events have been difficult to determine from surface deformation measurements. Although it is assumed that these silent earthquakes are located along the plate megathrust, this has not been proved. Slow slip in some subduction zones is associated with non-volcanic tremor7, 8, but tremor is difficult to locate and may be distributed over a broad depth range9. Except for some events on the San Andreas fault10, slow-slip events have not yet been associated with high-frequency earthquakes, which are easily located. Here we report on swarms of high-frequency earthquakes that accompany otherwise silent slips on Kīlauea volcano, Hawaii. For the most energetic event, in January 2005, the slow slip began before the increase in seismicity. The temporal evolution of earthquakes is well explained by increased stressing caused by slow slip, implying that the earthquakes are triggered. The earthquakes, located at depths of 7–8 km, constrain the slow slip to be at comparable depths, because they must fall in zones of positive Coulomb stress change. Triggered earthquakes accompanying slow-slip events elsewhere might go undetected if background seismicity rates are low. Detection of such events would help constrain the depth of slow slip, and could lead to a method for quantifying the increased hazard during slow-slip events, because triggered events have the potential to grow into destructive earthquakes.

Preliminary evidence of hippocampal damage in chronic users of ecstasy.

PubMed

den Hollander, Bjørnar; Schouw, Marieke; Groot, Paul; Huisman, Henk; Caan, Matthan; Barkhof, Frederik; Reneman, Liesbeth

2012-01-01

Various studies have shown that ecstasy (3,4-methylenedioxymethamphetamine) users display significant memory impairments, whereas their performance on other cognitive tests is generally normal. The hippocampus plays an essential role in short-term memory. There are, however, no structural human data on the effects of ecstasy on the hippocampus. The objective of this study was to investigate whether the hippocampal volume of chronic ecstasy users is reduced when compared with healthy polydrug-using controls, as an indicator of hippocampal damage. The hippocampus was manually outlined in volumetric MRI scans in 10 male ecstasy users (mean age 25.4 years) and seven healthy age- and gender-matched control subjects (21.3 years). Other than the use of ecstasy, there were no statistically significant differences between both groups in exposure to other drugs of abuse and alcohol. The ecstasy users were on average drug-free for more than 2 months and had used on average 281 tablets over the past six and a half years. The hippocampal volume in the ecstasy using group was on average 10.5% smaller than the hippocampal volume in the control group (p=0.032). These data provide preliminary evidence that ecstasy users may be prone to incurring hippocampal damage, in line with previous reports of acute hippocampal sclerosis and subsequent atrophy in chronic users of this drug.

Calcified Neurocysticercosis Associates with Hippocampal Atrophy: A Population-Based Study

PubMed Central

Del Brutto, Oscar H.; Salgado, Perla; Lama, Julio; Del Brutto, Victor J.; Campos, Xavier; Zambrano, Mauricio; García, Héctor H.

2015-01-01

Calcified neurocysticercosis has been associated with hippocampal atrophy in patients with refractory epilepsy, but the relevance of this association in the population at large is unknown. We assessed calcified cysticerci and its association with hippocampal atrophy in elderly persons living in Atahualpa, an Ecuadorian village endemic for neurocysticercosis. All Atahualpa residents ≥ 60 years of age were invited to undergo computed tomography/magnetic resonance imaging for neurocysticercosis detection. Twenty-eight (11%) out of 248 enrolled persons had calcified cysticerci (case-patients) and were matched 1:1 by age, sex, and years of education to individuals without neurocysticercosis on computed tomography/magnetic resonance imaging (controls). Four case-patients and none of the controls had epilepsy (P = 0.134). Cognitive performance was similar across both groups. The Scheltens' medial temporal atrophy scale was used for hippocampal rating in case-patients and matched controls without neurocysticercosis. Mean score in the Scheltens' scale was higher in case-patients than in controls (P < 0.001). Atrophic hippocampi were noticed in 19 case-patients and five controls (P = 0.003). Atrophy was bilateral in 11 case-patients and unilateral in eight. All case-patients with unilateral hippocampal atrophy had at least one ipsilateral calcification. This study shows an association between calcified cysticerci and hippocampal atrophy and raises the possibility of an inflammation-mediated hippocampal damage as the responsible mechanism for these findings. PMID:25349375

Hippocampal Network Modularity Is Associated With Relational Memory Dysfunction in Schizophrenia.

PubMed

Avery, Suzanne N; Rogers, Baxter P; Heckers, Stephan

2018-05-01

Functional dysconnectivity has been proposed as a major pathophysiological mechanism for cognitive dysfunction in schizophrenia. The hippocampus is a focal point of dysconnectivity in schizophrenia, with decreased hippocampal functional connectivity contributing to the marked memory deficits observed in patients. Normal memory function relies on the interaction of complex corticohippocampal networks. However, only recent technological advances have enabled the large-scale exploration of functional networks with accuracy and precision. We investigated the modularity of hippocampal resting-state functional networks in a sample of 45 patients with schizophrenia spectrum disorders and 38 healthy control subjects. Modularity was calculated for two distinct functional networks: a core hippocampal-medial temporal lobe cortex network and an extended hippocampal-cortical network. As hippocampal function differs along its longitudinal axis, follow-up analyses examined anterior and posterior networks separately. To explore effects of resting network function on behavior, we tested associations between modularity and relational memory ability. Age, sex, handedness, and parental education were similar between groups. Network modularity was lower in schizophrenia patients, especially in the posterior hippocampal network. Schizophrenia patients also showed markedly lower relational memory ability compared with control subjects. We found a distinct brain-behavior relationship in schizophrenia that differed from control subjects by network and anterior/posterior division-while relational memory in control subjects was associated with anterior hippocampal-cortical modularity, schizophrenia patients showed an association with posterior hippocampal-medial temporal lobe cortex network modularity. Our findings support a model of abnormal resting-state corticohippocampal network coherence in schizophrenia, which may contribute to relational memory deficits. Copyright © 2018 Society of

Glycomics Laboratory for the Early Detection of Epithelial Ovarian Cancer | Division of Cancer Prevention

Cancer.gov

Ovarian cancer is a silent killer with few early symptoms and advanced disease present at the time of diagnosis. This cancer is the most lethal of all gynecologic malignancies with over 20,000 new cases diagnosed each year. The 5 year survival rates for ovarian cancer dramatically improve when the disease is diagnosed at an early stage. Therefore, the long term goal of the

Sex-Specific and Strain-Dependent Effects of Early Life Adversity on Behavioral and Epigenetic Outcomes

PubMed Central

Kundakovic, Marija; Lim, Sean; Gudsnuk, Kathryn; Champagne, Frances A.

2013-01-01

Early life adversity can have a significant long-term impact with implications for the emergence of psychopathology. Disruption to mother-infant interactions is a form of early life adversity that may, in particular, have profound programing effects on the developing brain. However, despite converging evidence from human and animal studies, the precise mechanistic pathways underlying adversity-associated neurobehavioral changes have yet to be elucidated. One approach to the study of mechanism is exploration of epigenetic changes associated with early life experience. In the current study, we examined the effects of postnatal maternal separation (MS) in mice and assessed the behavioral, brain gene expression, and epigenetic effects of this manipulation in offspring. Importantly, we included two different mouse strains (C57BL/6J and Balb/cJ) and both male and female offspring to determine strain- and/or sex-associated differential response to MS. We found both strain-specific and sex-dependent effects of MS in early adolescent offspring on measures of open-field exploration, sucrose preference, and social behavior. Analyses of cortical and hippocampal mRNA levels of the glucocorticoid receptor (Nr3c1) and brain-derived neurotrophic factor (Bdnf) genes revealed decreased hippocampal Bdnf expression in maternally separated C57BL/6J females and increased cortical Bdnf expression in maternally separated male and female Balb/cJ offspring. Analyses of Nr3c1and Bdnf (IV and IX) CpG methylation indicated increased hippocampal Nr3c1 methylation in maternally separated C57BL/6J males and increased hippocampal Bdnf IX methylation in male and female maternally separated Balb/c mice. Overall, though effect sizes were modest, these findings suggest a complex interaction between early life adversity, genetic background, and sex in the determination of neurobehavioral and epigenetic outcomes that may account for differential vulnerability to later-life disorder. PMID:23914177

Hippocampal Structure Predicts Statistical Learning and Associative Inference Abilities during Development.

PubMed

Schlichting, Margaret L; Guarino, Katharine F; Schapiro, Anna C; Turk-Browne, Nicholas B; Preston, Alison R

2017-01-01

Despite the importance of learning and remembering across the lifespan, little is known about how the episodic memory system develops to support the extraction of associative structure from the environment. Here, we relate individual differences in volumes along the hippocampal long axis to performance on statistical learning and associative inference tasks-both of which require encoding associations that span multiple episodes-in a developmental sample ranging from ages 6 to 30 years. Relating age to volume, we found dissociable patterns across the hippocampal long axis, with opposite nonlinear volume changes in the head and body. These structural differences were paralleled by performance gains across the age range on both tasks, suggesting improvements in the cross-episode binding ability from childhood to adulthood. Controlling for age, we also found that smaller hippocampal heads were associated with superior behavioral performance on both tasks, consistent with this region's hypothesized role in forming generalized codes spanning events. Collectively, these results highlight the importance of examining hippocampal development as a function of position along the hippocampal axis and suggest that the hippocampal head is particularly important in encoding associative structure across development.

Hippocampal structure predicts statistical learning and associative inference abilities during development

PubMed Central

Schlichting, Margaret L.; Guarino, Katharine F.; Schapiro, Anna C.; Turk-Browne, Nicholas B.; Preston, Alison R.

2016-01-01

Despite the importance of learning and remembering across the lifespan, little is known about how the episodic memory system develops to support the extraction of associative structure from the environment. Here, we relate individual differences in volumes along the hippocampal long axis to performance on statistical learning and associative inference tasks—both of which require encoding associations that span multiple episodes—in a developmental sample ranging from ages 6–30 years. Relating age to volume, we found dissociable patterns across the hippocampal long axis, with opposite nonlinear volume changes in the head and body. These structural differences were paralleled by performance gains across the age range on both tasks, suggesting improvements in the cross-episode binding ability from childhood to adulthood. Controlling for age, we also found that smaller hippocampal heads were associated with superior behavioral performance on both tasks, consistent with this region’s hypothesized role in forming generalized codes spanning events. Collectively, these results highlight the importance of examining hippocampal development as a function of position along the hippocampal axis and suggest that the hippocampal head is particularly important in encoding associative structure across development. PMID:27575916

Hippocampal volume and memory performance in children with perinatal stroke.

PubMed

Gold, Jeffrey J; Trauner, Doris A

2014-01-01

Pediatric neurologists and neonatologists often are asked to predict cognitive outcome after perinatal brain injury (including likely memory and learning outcomes). However, relatively few data exist on how accurate predictions can be made. Furthermore, although the consequences of brain injury on hippocampal volume and memory performance have been studied extensively in adults, little work has been done in children. We measured the volume of the hippocampus in 27 children with perinatal stroke and 19 controls, and measured their performance on standardized verbal and non-verbal memory tests. We discovered the following: (1) As a group, children with perinatal stroke had smaller left and right hippocampi compared with control children. (2) Individually, children with perinatal stroke demonstrated 1 of 3 findings: no hippocampal loss, unilateral hippocampal loss, or bilateral hippocampal volume loss compared with control children. (3) Hippocampal volume inversely correlated with memory test performance in the perinatal stroke group, with smaller left and right hippocampal volumes related to poorer verbal and non-verbal memory test performance, respectively. (4) Seizures played a significant role in determining memory deficit and extent of hippocampal volume reduction in patients with perinatal stroke. These findings support the view that, in the developing brain, the left and right hippocampi preferentially support verbal and nonverbal memory respectively, a consistent finding in the adult literature but a subject of debate in the pediatric literature. This is the first work to report that children with focal brain injury incurred from perinatal stroke have volume reduction in the hippocampus and impairments in certain aspects of declarative memory. Copyright © 2014 Elsevier Inc. All rights reserved.

Postnatal Loss of Hap1 Reduces Hippocampal Neurogenesis and Causes Adult Depressive-Like Behavior in Mice

PubMed Central

Xiang, Jianxing; Yan, Sen; Li, Shi-Hua; Li, Xiao-Jiang

2015-01-01

Depression is a serious mental disorder that affects a person’s mood, thoughts, behavior, physical health, and life in general. Despite our continuous efforts to understand the disease, the etiology of depressive behavior remains perplexing. Recently, aberrant early life or postnatal neurogenesis has been linked to adult depressive behavior; however, genetic evidence for this is still lacking. Here we genetically depleted the expression of huntingtin-associated protein 1 (Hap1) in mice at various ages or in selective brain regions. Depletion of Hap1 in the early postnatal period, but not later life, led to a depressive-like phenotype when the mice reached adulthood. Deletion of Hap1 in adult mice rendered the mice more susceptible to stress-induced depressive-like behavior. Furthermore, early Hap1 depletion impaired postnatal neurogenesis in the dentate gyrus (DG) of the hippocampus and reduced the level of c-kit, a protein expressed in neuroproliferative zones of the rodent brain and that is stabilized by Hap1. Importantly, stereotaxically injected adeno-associated virus (AAV) that directs the expression of c-kit in the hippocampus promoted postnatal hippocampal neurogenesis and ameliorated the depressive-like phenotype in conditional Hap1 KO mice, indicating a link between postnatal-born hippocampal neurons and adult depression. Our results demonstrate critical roles for Hap1 and c-kit in postnatal neurogenesis and adult depressive behavior, and also suggest that genetic variations affecting postnatal neurogenesis may lead to adult depression. PMID:25875952

Postnatal loss of hap1 reduces hippocampal neurogenesis and causes adult depressive-like behavior in mice.

PubMed

Xiang, Jianxing; Yan, Sen; Li, Shi-Hua; Li, Xiao-Jiang

2015-04-01

Depression is a serious mental disorder that affects a person's mood, thoughts, behavior, physical health, and life in general. Despite our continuous efforts to understand the disease, the etiology of depressive behavior remains perplexing. Recently, aberrant early life or postnatal neurogenesis has been linked to adult depressive behavior; however, genetic evidence for this is still lacking. Here we genetically depleted the expression of huntingtin-associated protein 1 (Hap1) in mice at various ages or in selective brain regions. Depletion of Hap1 in the early postnatal period, but not later life, led to a depressive-like phenotype when the mice reached adulthood. Deletion of Hap1 in adult mice rendered the mice more susceptible to stress-induced depressive-like behavior. Furthermore, early Hap1 depletion impaired postnatal neurogenesis in the dentate gyrus (DG) of the hippocampus and reduced the level of c-kit, a protein expressed in neuroproliferative zones of the rodent brain and that is stabilized by Hap1. Importantly, stereotaxically injected adeno-associated virus (AAV) that directs the expression of c-kit in the hippocampus promoted postnatal hippocampal neurogenesis and ameliorated the depressive-like phenotype in conditional Hap1 KO mice, indicating a link between postnatal-born hippocampal neurons and adult depression. Our results demonstrate critical roles for Hap1 and c-kit in postnatal neurogenesis and adult depressive behavior, and also suggest that genetic variations affecting postnatal neurogenesis may lead to adult depression.

Brevetoxin Depresses Synaptic Transmission in Guinea Pig Hippocampal Slices

DTIC Science & Technology

1993-01-01

Brevetoxin depresses synaptic transmission in guinea pig hippocampal slices. Brain Res Bull 31(1/2) 201-207, 1993.--Extracellular recordings were...obtained from area CA1 of guinea pig hippocampal slices. PbTx-3, a brevetoxin fraction isolated from the red tide dinoflagellate Ptychodiscus brevis, was

Hippocampal MRI volumetry at 3 Tesla: reliability and practical guidance.

PubMed

Jeukens, Cécile R L P N; Vlooswijk, Mariëlle C G; Majoie, H J Marian; de Krom, Marc C T F M; Aldenkamp, Albert P; Hofman, Paul A M; Jansen, Jacobus F A; Backes, Walter H

2009-09-01

Although volumetry of the hippocampus is considered to be an established technique, protocols reported in literature are not described in great detail. This article provides a complete and detailed protocol for hippocampal volumetry applicable to T1-weighted magnetic resonance (MR) images acquired at 3 Tesla, which has become the standard for structural brain research. The protocol encompasses T1-weighted image acquisition at 3 Tesla, anatomic guidelines for manual hippocampus delineation, requirements of delineation software, reliability measures, and criteria to assess and ensure sufficient reliability. Moreover, the validity of the correction for total intracranial volume size was critically assessed. The protocol was applied by 2 readers to the MR images of 36 patients with cryptogenic localization-related epilepsy, 4 patients with unilateral hippocampal sclerosis, and 20 healthy control subjects. The uncorrected hippocampal volumes were 2923 +/- 500 mm3 (mean +/- SD) (left) and 3120 +/- 416 mm3 (right) for the patient group and 3185 +/- 411 mm3 (left) and 3302 +/- 411 mm3 (right) for the healthy control group. The volume of the 4 pathologic hippocampi of the patients with unilateral hippocampal sclerosis was 2980 +/- 422 mm3. The inter-reader reliability values were determined: intraclass-correlation-coefficient (ICC) = 0.87 (left) and 0.86 (right), percentage volume difference (VD) = 7.0 +/- 4.7% (left) and 6.0 +/- 3.8% (right), and overlap ratio (OR) = 0.82 +/- 0.04 (left) and 0.82 +/- 0.03 (right). The positive Pearson correlation between hippocampal volume and total intracranial volume was found to be low: r = 0.48 (P = 0.03, left) and r = 0.62 (P = 0.004, right) and did not significantly reduce the volumetric variances, showing the limited benefit of the brain size correction. A protocol was described to determine hippocampal volumes based on 3 Tesla MR images with high inter-reader reliability. Although the reliability of hippocampal volumetry at 3 Tesla

Hippocampal volume in healthy controls given 3-day stress doses of hydrocortisone.

PubMed

Brown, E Sherwood; Jeon-Slaughter, Haekyung; Lu, Hanzhang; Jamadar, Rhoda; Issac, Sruthy; Shad, Mujeeb; Denniston, Daren; Tamminga, Carol; Nakamura, Alyson; Thomas, Binu P

2015-03-13

In animal models, corticosterone elevations are associated with hippocampal changes that can be prevented with phenytoin. In humans, Cushing's syndrome and long-term prescription corticosteroid use are associated with a reduction in the hippocampal volume. However, little is known about the effects of short-term corticosteroid administration on the hippocampus. The current report examines changes in the hippocampal volume during a brief hydrocortisone exposure and whether volumetric changes can be blocked by phenytoin. A randomized, double-blind, placebo-controlled, within-subject crossover study was conducted in healthy adults (n=17). Participants received hydrocortisone (160 mg/day)/placebo, phenytoin/placebo, both medications together, or placebo/placebo, with 21-day washouts between the conditions. Structural MRI scans and cortisol levels were obtained following each medication condition. No significant difference in the total brain volume was observed with hydrocortisone. However, hydrocortisone was associated with a significant 1.69% reduction in the total hippocampal volume compared with placebo. Phenytoin blocked the volume reduction associated with hydrocortisone. Reduction in hippocampal volume correlated with the change in cortisol levels (r=-0.58, P=0.03). To our knowledge, this is the first report of structural hippocampal changes with brief corticosteroid exposure. The correlation between the change in hippocampal volume and cortisol level suggests that the volume changes are related to cortisol elevation. Although the findings from this pilot study need replication, they suggest that the reductions in hippocampal volume occur even during brief exposure to corticosteroids, and that hippocampal changes can, as in animal models, be blocked by phenytoin. The results may have implications both for understanding the response of the hippocampus to stress as well as for patients receiving prescription corticosteroids.

Global and regional alterations of hippocampal anatomy in long-term meditation practitioners.

PubMed

Luders, Eileen; Thompson, Paul M; Kurth, Florian; Hong, Jui-Yang; Phillips, Owen R; Wang, Yalin; Gutman, Boris A; Chou, Yi-Yu; Narr, Katherine L; Toga, Arthur W

2013-12-01

Studies linking meditation and brain structure are still relatively sparse, but the hippocampus is consistently implicated as one of the structures altered in meditation practitioners. To explore hippocampal features in the framework of meditation, we analyzed high-resolution structural magnetic resonance imaging data from 30 long-term meditators and 30 controls, closely matched for sex, age, and handedness. Hippocampal formations were manually traced following established protocols. In addition to calculating left and right hippocampal volumes (global measures), regional variations in surface morphology were determined by measuring radial distances from the hippocampal core to spatially matched surface points (local measures). Left and right hippocampal volumes were larger in meditators than in controls, significantly so for the left hippocampus. The presence and direction of this global effect was confirmed locally by mapping the exact spatial locations of the group differences. Altogether, radial distances were larger in meditators compared to controls, with up to 15% difference. These local effects were observed in several hippocampal regions in the left and right hemisphere though achieved significance primarily in the left hippocampal head. Larger hippocampal dimensions in long-term meditators may constitute part of the underlying neurological substrate for cognitive skills, mental capacities, and/or personal traits associated with the practice of meditation. Alternatively, given that meditation positively affects autonomic regulation and immune activity, altered hippocampal dimensions may be one result of meditation-induced stress reduction. However, given the cross-sectional design, the lack of individual stress measures, and the limited resolution of brain data, the exact underlying neuronal mechanisms remain to be established. Copyright © 2012 Wiley Periodicals, Inc.

Hippocampal asymmetry in exploratory behavior to vasoactive intestinal polypeptide.

PubMed

Ivanova, Margarita; Ternianov, Alexandar; Belcheva, Stiliana; Tashev, Roman; Negrev, Negrin; Belcheva, Iren

2008-06-01

The effects of vasoactive intestinal polypeptide (VIP) microinjected uni- or bilaterally into the CA1 hippocampal area of male Wistar rats at a dose of 10, 50 and 100 ng on exploratory behavior were examined. VIP microinjected bilaterally at a high dose (100 ng) significantly decreased the horizontal movements, while at low doses (10 and 50 ng) had no effect on the exploratory activity. Microinjections of VIP into the left hippocampal CA1 area at doses 50 and 100 ng suppressed the exploratory activity, while right-side VIP administration at a dose 100 ng significantly increased horizontal movements compared to the respective controls. Vertical activity was stimulated only by VIP administered into the right hippocampal CA1 area at the three doses used. Neither bilateral nor left injections of VIP induced changes in the vertical movements. The main finding was the presence of hippocampal asymmetry in exploratory behavior to unilateral microinjections of VIP depending on the dose and the microinjected hemisphere.

Hippocampal mechanisms for the context-dependent retrieval of episodes

PubMed Central

Hasselmo, Michael E.; Eichenbaum, Howard B.

2008-01-01

Behaviors ranging from delivering newspapers to waiting tables depend on remembering previous episodes to avoid incorrect repetition. Physiologically, this requires mechanisms for long-term storage and selective retrieval of episodes based on time of occurrence, despite variable intervals and similarity of events in a familiar environment. Here, this process has been modeled based on physiological properties of the hippocampal formation, including mechanisms for sustained activity in entorhinal cortex and theta rhythm oscillations in hippocampal subregions. The model simulates the context-sensitive firing properties of hippocampal neurons including trial specific firing during spatial alternation and trial by trial changes in theta phase precession on a linear track. This activity is used to guide behavior, and lesions of the hippocampal network impair memory-guided behavior. The model links data at the cellular level to behavior at the systems level, describing a physiologically plausible mechanism for the brain to recall a given episode which occurred at a specific place and time. PMID:16263240

Effect of Age on Silent Gap Discrimination in Synthetic Speech Stimuli.

ERIC Educational Resources Information Center

Lister, Jennifer; Tarver, Kenton

2004-01-01

The difficulty that older listeners experience understanding conversational speech may be related to their limited ability to use information present in the silent intervals (i.e., temporal gaps) between dynamic speech sounds. When temporal gaps are present between nonspeech stimuli that are spectrally invariant (e.g., noise bands or sinusoids),…

Sustained Silent Reading in University Courses in EFL for Academic Purposes.

ERIC Educational Resources Information Center

Ducy-Perez, Ellen

This paper summarizes a study conducted to determine whether sustained silent reading (SSR) can contribute to improvement in grammar and reading comprehension in university academic English as a foreign language (EFL) courses. A total of 186 beginning and intermediate students enrolled in the English for Academic Purposes program at the…

Hippocampal theta activity is selectively associated with contingency detection but not discrimination in rabbit discrimination-reversal eyeblink conditioning.

PubMed

Nokia, Miriam S; Wikgren, Jan

2010-04-01

The relative power of the hippocampal theta-band ( approximately 6 Hz) activity (theta ratio) is thought to reflect a distinct neural state and has been shown to affect learning rate in classical eyeblink conditioning in rabbits. We sought to determine if the theta ratio is mostly related to the detection of the contingency between the stimuli used in conditioning or also to the learning of more complex inhibitory associations when a highly demanding delay discrimination-reversal eyeblink conditioning paradigm is used. A high hippocampal theta ratio was not only associated with a fast increase in conditioned responding in general but also correlated with slow emergence of discriminative responding due to sustained responding to the conditioned stimulus not paired with an unconditioned stimulus. The results indicate that the neural state reflected by the hippocampal theta ratio is specifically linked to forming associations between stimuli rather than to the learning of inhibitory associations needed for successful discrimination. This is in line with the view that the hippocampus is responsible for contingency detection in the early phase of learning in eyeblink conditioning. (c) 2009 Wiley-Liss, Inc.

The effect of adult-acquired hippocampal damage on memory retrieval: an fMRI study.

PubMed

Maguire, Eleanor A; Frith, Christopher D; Rudge, Peter; Cipolotti, Lisa

2005-08-01

Bilateral hippocampal pathology typically results in significant memory problems. Despite apparently similar structural damage, patients with such lesions can differ in the pattern of impairment and preservation of memory functions. Previously, an fMRI study of a developmental amnesic patient whose anoxic hippocampal damage was incurred perinatally revealed his residual hippocampal tissue to be active during memory retrieval. This hippocampal activity was apparent during the retrieval of personal and general facts relative to a control task. In this study, we used a similar fMRI paradigm to investigate whether residual hippocampal activation was present also in patient VC with adult-acquired anoxic hippocampal pathology. VC's performance and reaction times on the experimental personal and general fact tasks were comparable to age-matched control subjects. However, in contrast to the elderly control sample and the previous developmental amnesic patient, his residual hippocampal tissue did not show activation changes during the experimental tasks. This finding indicates that patient VC's successful retrieval of personal and general facts was achieved without a significant hippocampal contribution. It further suggests that the hippocampal activation observed in the elderly controls and previous developmental amnesic patient was not necessary for successful task performance. The reason for this difference in hippocampal responsivity between VC and the developmental amnesic patient remains to be determined. We speculate that it may relate to the age at which hippocampal damage occurred reflecting plasticity within the developing brain, or to cognitive differences between VC, the developmental amnesic patient, and the control subjects.

Inhibition of local estrogen synthesis in the hippocampus impairs hippocampal memory consolidation in ovariectomized female mice

PubMed Central

Tuscher, Jennifer J.; Szinte, Julia S.; Starrett, Joseph R.; Krentzel, Amanda A.; Fortress, Ashley M.; Remage-Healey, Luke; Frick, Karyn M.

2016-01-01

The potent estrogen 17β-Estradiol (E2) plays a critical role in mediating hippocampal function, yet the precise mechanisms through which E2 enhances hippocampal memory remain unclear. In young adult female rodents, the beneficial effects of E2 on memory are generally attributed to ovarian-synthesized E2. However, E2 is also synthesized in the adult brain in numerous species, where it regulates synaptic plasticity and is synthesized in response to experiences such as exposure to females or conspecific song. Although de novo E2 synthesis has been demonstrated in rodent hippocampal cultures, little is known about the functional role of local E2 synthesis in mediating hippocampal memory function. Therefore, the present study examined the role of hippocampal E2 synthesis in hippocampal memory consolidation. Using bilateral dorsal hippocampal infusions of the aromatase inhibitor letrozole, we first found that blockade of dorsal hippocampal E2 synthesis impaired hippocampal memory consolidation. We next found that elevated levels of E2 in dorsal hippocampus observed 30 min after object training were blocked by dorsal hippocampal infusion of letrozole, suggesting that behavioral experience increases acute and local E2 synthesis. Finally, aromatase inhibition did not prevent exogenous E2 from enhancing hippocampal memory consolidation, indicating that hippocampal E2 synthesis is not necessary for exogenous E2 to enhance hippocampal memory. Combined, these data are consistent with the hypothesis that hippocampally-synthesized E2 is necessary for hippocampus-dependent memory consolidation in rodents. PMID:27178577

Adult hippocampal neurogenesis in natural populations of mammals.

PubMed

Amrein, Irmgard

2015-05-01

This review will discuss adult hippocampal neurogenesis in wild mammals of different taxa and outline similarities with and differences from laboratory animals. It begins with a review of evidence for hippocampal neurogenesis in various mammals, and shows the similar patterns of age-dependent decline in cell proliferation in wild and domesticated mammals. In contrast, the pool of immature neurons that originate from proliferative activity varies between species, implying a selective advantage for mammals that can make use of a large number of these functionally special neurons. Furthermore, rapid adaptation of hippocampal neurogenesis to experimental challenges appears to be a characteristic of laboratory rodents. Wild mammals show species-specific, rather stable hippocampal neurogenesis, which appears related to demands that characterize the niche exploited by a species rather than to acute events in the life of its members. Studies that investigate adult neurogenesis in wild mammals are not numerous, but the findings of neurogenesis under natural conditions can provide new insights, and thereby also address the question to which cognitive demands neurogenesis may respond during selection. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

Thyroid hormone accelerates the differentiation of adult hippocampal progenitors.

PubMed

Kapoor, R; Desouza, L A; Nanavaty, I N; Kernie, S G; Vaidya, V A

2012-09-01

Disrupted thyroid hormone function evokes severe physiological consequences in the immature brain. In adulthood, although clinical reports document an effect of thyroid hormone status on mood and cognition, the molecular and cellular changes underlying these behavioural effects are poorly understood. More recently, the subtle effects of thyroid hormone on structural plasticity in the mature brain, in particular on adult hippocampal neurogenesis, have come to be appreciated. However, the specific stages of adult hippocampal progenitor development that are sensitive to thyroid hormone are not defined. Using nestin-green fluorescent protein reporter mice, we demonstrate that thyroid hormone mediates its effects on hippocampal neurogenesis by influencing Type 2b and Type 3 progenitors, although it does not alter proliferation of either the Type 1 quiescent progenitor or the Type 2a amplifying neural progenitor. Thyroid hormone increases the number of doublecortin (DCX)-positive Type 3 progenitors, and accelerates neuronal differentiation into both DCX-positive immature neurones and neuronal nuclei-positive granule cell neurones. Furthermore, we show that this increase in neuronal differentiation is accompanied by a significant induction of specific transcription factors involved in hippocampal progenitor differentiation. In vitro studies using the neurosphere assay support a direct effect of thyroid hormone on progenitor development because neurospheres treated with thyroid hormone are shifted to a more differentiated state. Taken together, our results indicate that thyroid hormone mediates its neurogenic effects via targeting Type 2b and Type 3 hippocampal progenitors, and suggests a role for proneural transcription factors in contributing to the effects of thyroid hormone on neuronal differentiation of adult hippocampal progenitors. © 2012 The Authors. Journal of Neuroendocrinology © 2012 British Society for Neuroendocrinology.

Towards Contactless Silent Speech Recognition Based on Detection of Active and Visible Articulators Using IR-UWB Radar

PubMed Central

Shin, Young Hoon; Seo, Jiwon

2016-01-01

People with hearing or speaking disabilities are deprived of the benefits of conventional speech recognition technology because it is based on acoustic signals. Recent research has focused on silent speech recognition systems that are based on the motions of a speaker’s vocal tract and articulators. Because most silent speech recognition systems use contact sensors that are very inconvenient to users or optical systems that are susceptible to environmental interference, a contactless and robust solution is hence required. Toward this objective, this paper presents a series of signal processing algorithms for a contactless silent speech recognition system using an impulse radio ultra-wide band (IR-UWB) radar. The IR-UWB radar is used to remotely and wirelessly detect motions of the lips and jaw. In order to extract the necessary features of lip and jaw motions from the received radar signals, we propose a feature extraction algorithm. The proposed algorithm noticeably improved speech recognition performance compared to the existing algorithm during our word recognition test with five speakers. We also propose a speech activity detection algorithm to automatically select speech segments from continuous input signals. Thus, speech recognition processing is performed only when speech segments are detected. Our testbed consists of commercial off-the-shelf radar products, and the proposed algorithms are readily applicable without designing specialized radar hardware for silent speech processing. PMID:27801867

Towards Contactless Silent Speech Recognition Based on Detection of Active and Visible Articulators Using IR-UWB Radar.

PubMed

Shin, Young Hoon; Seo, Jiwon

2016-10-29

People with hearing or speaking disabilities are deprived of the benefits of conventional speech recognition technology because it is based on acoustic signals. Recent research has focused on silent speech recognition systems that are based on the motions of a speaker's vocal tract and articulators. Because most silent speech recognition systems use contact sensors that are very inconvenient to users or optical systems that are susceptible to environmental interference, a contactless and robust solution is hence required. Toward this objective, this paper presents a series of signal processing algorithms for a contactless silent speech recognition system using an impulse radio ultra-wide band (IR-UWB) radar. The IR-UWB radar is used to remotely and wirelessly detect motions of the lips and jaw. In order to extract the necessary features of lip and jaw motions from the received radar signals, we propose a feature extraction algorithm. The proposed algorithm noticeably improved speech recognition performance compared to the existing algorithm during our word recognition test with five speakers. We also propose a speech activity detection algorithm to automatically select speech segments from continuous input signals. Thus, speech recognition processing is performed only when speech segments are detected. Our testbed consists of commercial off-the-shelf radar products, and the proposed algorithms are readily applicable without designing specialized radar hardware for silent speech processing.

When Spiders Bite: The Use, Misuse, and Unintended Consequences of ``Silent Information''

NASA Astrophysics Data System (ADS)

Keenan, Thomas P.

Spiders are the workhorses of the Internet, silently (and almost invisibly) traversing the online world, 24 hours a day, looking for information that may be of interest to someone. It is being archived, organized, and sold, usually without the knowledge or consent of the subject of the information. Serious consequences are starting to appear, such as the withdrawal of three candidates from the October 2008 Canadian Federal election because of previous online indiscretions. While these were intentional if mis-guided postings, information made available without our consent can have equally devastating effects. Advances in artificial intelligence, as well as the increasing tendency to post more and more information, such as videos, will make the gathering, aggregation, and republishing of this “silent information” an increasingly important issue that must be addressed from the technical, social, ethical and legal perspectives, and sooner rather than later.

Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline

DOE PAGES

Leal, Stephanie L.; Landau, Susan M.; Bell, Rachel K.; ...

2017-02-08

The amyloid hypothesis suggests that beta-amyloid (Aβ) deposition leads to alterations in neural function and ultimately to cognitive decline in Alzheimer’s disease. However, factors that underlie Aβ deposition are incompletely understood. One proposed model suggests that synaptic activity leads to increased Aβ deposition. More specifically, hyperactivity in the hippocampus may be detrimental and could be one factor that drives Aβ deposition. To test this model, we examined the relationship between hippocampal activity during a memory task using fMRI and subsequent longitudinal change in Aβ using PIB-PET imaging in cognitively normal older adults. We found that greater hippocampal activation at baselinemore » was associated with increased Aβ accumulation. Furthermore, increasing Aβ accumulation mediated the influence of hippocampal activation on declining memory performance, demonstrating a crucial role of Aβ in linking hippocampal activation and memory. These findings support a model linking increased hippocampal activation to subsequent Aβ deposition and cognitive decline.« less

Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leal, Stephanie L.; Landau, Susan M.; Bell, Rachel K.

The amyloid hypothesis suggests that beta-amyloid (Aβ) deposition leads to alterations in neural function and ultimately to cognitive decline in Alzheimer’s disease. However, factors that underlie Aβ deposition are incompletely understood. One proposed model suggests that synaptic activity leads to increased Aβ deposition. More specifically, hyperactivity in the hippocampus may be detrimental and could be one factor that drives Aβ deposition. To test this model, we examined the relationship between hippocampal activity during a memory task using fMRI and subsequent longitudinal change in Aβ using PIB-PET imaging in cognitively normal older adults. We found that greater hippocampal activation at baselinemore » was associated with increased Aβ accumulation. Furthermore, increasing Aβ accumulation mediated the influence of hippocampal activation on declining memory performance, demonstrating a crucial role of Aβ in linking hippocampal activation and memory. These findings support a model linking increased hippocampal activation to subsequent Aβ deposition and cognitive decline.« less

Remote semantic memory is impoverished in hippocampal amnesia.

PubMed

Klooster, Nathaniel B; Duff, Melissa C

2015-12-01

The necessity of the hippocampus for acquiring new semantic concepts is a topic of considerable debate. However, it is generally accepted that any role the hippocampus plays in semantic memory is time limited and that previously acquired information becomes independent of the hippocampus over time. This view, along with intact naming and word-definition matching performance in amnesia, has led to the notion that remote semantic memory is intact in patients with hippocampal amnesia. Motivated by perspectives of word learning as a protracted process where additional features and senses of a word are added over time, and by recent discoveries about the time course of hippocampal contributions to on-line relational processing, reconsolidation, and the flexible integration of information, we revisit the notion that remote semantic memory is intact in amnesia. Using measures of semantic richness and vocabulary depth from psycholinguistics and first and second language-learning studies, we examined how much information is associated with previously acquired, highly familiar words in a group of patients with bilateral hippocampal damage and amnesia. Relative to healthy demographically matched comparison participants and a group of brain-damaged comparison participants, the patients with hippocampal amnesia performed significantly worse on both productive and receptive measures of vocabulary depth and semantic richness. These findings suggest that remote semantic memory is impoverished in patients with hippocampal amnesia and that the hippocampus may play a role in the maintenance and updating of semantic memory beyond its initial acquisition. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hippocampal Volume in Healthy Controls Given 3-Day Stress Doses of Hydrocortisone

PubMed Central

Brown, E Sherwood; Jeon-Slaughter, Haekyung; Lu, Hanzhang; Jamadar, Rhoda; Issac, Sruthy; Shad, Mujeeb; Denniston, Daren; Tamminga, Carol; Nakamura, Alyson; Thomas, Binu P

2015-01-01

In animal models, corticosterone elevations are associated with hippocampal changes that can be prevented with phenytoin. In humans, Cushing's syndrome and long-term prescription corticosteroid use are associated with a reduction in the hippocampal volume. However, little is known about the effects of short-term corticosteroid administration on the hippocampus. The current report examines changes in the hippocampal volume during a brief hydrocortisone exposure and whether volumetric changes can be blocked by phenytoin. A randomized, double-blind, placebo-controlled, within-subject crossover study was conducted in healthy adults (n=17). Participants received hydrocortisone (160 mg/day)/placebo, phenytoin/placebo, both medications together, or placebo/placebo, with 21-day washouts between the conditions. Structural MRI scans and cortisol levels were obtained following each medication condition. No significant difference in the total brain volume was observed with hydrocortisone. However, hydrocortisone was associated with a significant 1.69% reduction in the total hippocampal volume compared with placebo. Phenytoin blocked the volume reduction associated with hydrocortisone. Reduction in hippocampal volume correlated with the change in cortisol levels (r=−0.58, P=0.03). To our knowledge, this is the first report of structural hippocampal changes with brief corticosteroid exposure. The correlation between the change in hippocampal volume and cortisol level suggests that the volume changes are related to cortisol elevation. Although the findings from this pilot study need replication, they suggest that the reductions in hippocampal volume occur even during brief exposure to corticosteroids, and that hippocampal changes can, as in animal models, be blocked by phenytoin. The results may have implications both for understanding the response of the hippocampus to stress as well as for patients receiving prescription corticosteroids. PMID:25409592

Decoding Mechanisms by which Silent Codon Changes Influence Protein Biogenesis and Function

PubMed Central

Bali, Vedrana; Bebok, Zsuzsanna

2015-01-01

Scope Synonymous codon usage has been a focus of investigation since the discovery of the genetic code and its redundancy. The occurrences of synonymous codons vary between species and within genes of the same genome, known as codon usage bias. Today, bioinformatics and experimental data allow us to compose a global view of the mechanisms by which the redundancy of the genetic code contributes to the complexity of biological systems from affecting survival in prokaryotes, to fine tuning the structure and function of proteins in higher eukaryotes. Studies analyzing the consequences of synonymous codon changes in different organisms have revealed that they impact nucleic acid stability, protein levels, structure and function without altering amino acid sequence. As such, synonymous mutations inevitably contribute to the pathogenesis of complex human diseases. Yet, fundamental questions remain unresolved regarding the impact of silent mutations in human disorders. In the present review we describe developments in this area concentrating on mechanisms by which synonymous mutations may affect protein function and human health. Purpose This synopsis illustrates the significance of synonymous mutations in disease pathogenesis. We review the different steps of gene expression affected by silent mutations, and assess the benefits and possible harmful effects of codon optimization applied in the development of therapeutic biologics. Physiological and medical relevance Understanding mechanisms by which synonymous mutations contribute to complex diseases such as cancer, neurodegeneration and genetic disorders, including the limitations of codon-optimized biologics, provides insight concerning interpretation of silent variants and future molecular therapies. PMID:25817479

A calcium-permeable cGMP-activated cation conductance in hippocampal neurons

NASA Technical Reports Server (NTRS)

Leinders-Zufall, T.; Rosenboom, H.; Barnstable, C. J.; Shepherd, G. M.; Zufall, F.

1995-01-01

Whole-cell patch clamp recordings detected a previously unidentified cGMP-activated membrane conductance in cultured rat hippocampal neurons. This conductance is nonselectively permeable for cations and is completely but reversibly blocked by external Cd2+. The Ca2+ permeability of the hippocampal cGMP-activated conductance was examined in detail, indicating that the underlying ion channels display a high relative permeability for Ca2+. The results indicate that hippocampal neurons contain a cGMP-activated membrane conductance that has some properties similar to the cyclic nucleotide-gated channels previously shown in sensory receptor cells and retinal neurons. In hippocampal neurons this conductance similarly could mediate membrane depolarization and Ca2+ fluxes in response to intracellular cGMP elevation.

Retinoic acid modulates intrahippocampal levels of corticosterone in middle-aged mice: consequences on hippocampal plasticity and contextual memory

PubMed Central

Bonhomme, Damien; Pallet, Véronique; Dominguez, Gaelle; Servant, Laure; Henkous, Nadia; Lafenêtre, Pauline; Higueret, Paul; Béracochéa, Daniel; Touyarot, Katia

2014-01-01

It is now established that vitamin A and its derivatives, retinoic acid (RA), are required for cognitive functions in adulthood. RA hyposignaling and hyperactivity of glucocorticoid (GC) pathway appear concomitantly during aging and would contribute to the deterioration of hippocampal synaptic plasticity and functions. Furthermore, recent data have evidenced counteracting effects of retinoids on GC signaling pathway. In the present study, we addressed the following issue: whether the stimulation of RA pathway could modulate intrahippocampal corticosterone (CORT) levels in middle-aged mice and thereby impact on hippocampal plasticity and cognitive functions. We firstly investigated the effects of vitamin A supplementation and RA treatment in middle-aged mice, on contextual serial discrimination task, a paradigm which allows the detection of early signs of age-related hippocampal-dependent memory dysfunction. We then measured intrahippocampal CORT concentrations by microdialysis before and after a novelty-induced stress. Our results show that both RA treatment and vitamin A supplementation improve “episodic-like” memory in middle-aged mice but RA treatment appears to be more efficient. Moreover, we show that the beneficial effect of RA on memory is associated to an increase in hippocampal PSD-95 expression. In addition, intrahippocampal CORT levels are reduced after novelty-induced stress in RA-treated animals. This effect cannot be related to a modulation of hippocampal 11β-HSD1 expression. Interestingly, RA treatment induces a modulation of RA receptors RARα and RARβ expression in middle-aged mice, a finding which has been correlated with the amplitude of intrahippocampal CORT levels after novelty-induced stress. Taken together, our results suggest that the preventive action of RA treatment on age-related memory deficits in middle-aged mice could be, at least in part, due to an inhibitory effect of retinoids on GC activity. PMID:24570662

Aerobic Fitness is Associated With Hippocampal Volume in Elderly Humans

PubMed Central

Erickson, Kirk I.; Prakash, Ruchika S.; Voss, Michelle W.; Chaddock, Laura; Hu, Liang; Morris, Katherine S.; White, Siobhan M.; Wójcicki, Thomas R.; McAuley, Edward; Kramer, Arthur F.

2010-01-01

Deterioration of the hippocampus occurs in elderly individuals with and without dementia, yet individual variation exists in the degree and rate of hippocampal decay. Determining the factors that influence individual variation in the magnitude and rate of hippocampal decay may help promote lifestyle changes that prevent such deterioration from taking place. Aerobic fitness and exercise are effective at preventing cortical decay and cognitive impairment in older adults and epidemiological studies suggest that physical activity can reduce the risk for developing dementia. However, the relationship between aerobic fitness and hippocampal volume in elderly humans is unknown. In this study, we investigated whether individuals with higher levels of aerobic fitness displayed greater volume of the hippocampus and better spatial memory performance than individuals with lower fitness levels. Furthermore, in exploratory analyses, we assessed whether hippocampal volume mediated the relationship between fitness and spatial memory. Using a region-of-interest analysis on magnetic resonance images in 165 nondemented older adults, we found a triple association such that higher fitness levels were associated with larger left and right hippocampi after controlling for age, sex, and years of education, and larger hippocampi and higher fitness levels were correlated with better spatial memory performance. Furthermore, we demonstrated that hippocampal volume partially mediated the relationship between higher fitness levels and enhanced spatial memory. Our results clearly indicate that higher levels of aerobic fitness are associated with increased hippocampal volume in older humans, which translates to better memory function. PMID:19123237

Inhibition of local estrogen synthesis in the hippocampus impairs hippocampal memory consolidation in ovariectomized female mice.

PubMed

Tuscher, Jennifer J; Szinte, Julia S; Starrett, Joseph R; Krentzel, Amanda A; Fortress, Ashley M; Remage-Healey, Luke; Frick, Karyn M

2016-07-01

The potent estrogen 17β-Estradiol (E2) plays a critical role in mediating hippocampal function, yet the precise mechanisms through which E2 enhances hippocampal memory remain unclear. In young adult female rodents, the beneficial effects of E2 on memory are generally attributed to ovarian-synthesized E2. However, E2 is also synthesized in the adult brain in numerous species, where it regulates synaptic plasticity and is synthesized in response to experiences such as exposure to females or conspecific song. Although de novo E2 synthesis has been demonstrated in rodent hippocampal cultures, little is known about the functional role of local E2 synthesis in mediating hippocampal memory function. Therefore, the present study examined the role of hippocampal E2 synthesis in hippocampal memory consolidation. Using bilateral dorsal hippocampal infusions of the aromatase inhibitor letrozole, we first found that blockade of dorsal hippocampal E2 synthesis impaired hippocampal memory consolidation. We next found that elevated levels of E2 in the dorsal hippocampus observed 30min after object training were blocked by dorsal hippocampal infusion of letrozole, suggesting that behavioral experience increases acute and local E2 synthesis. Finally, aromatase inhibition did not prevent exogenous E2 from enhancing hippocampal memory consolidation, indicating that hippocampal E2 synthesis is not necessary for exogenous E2 to enhance hippocampal memory. Combined, these data are consistent with the hypothesis that hippocampally-synthesized E2 is necessary for hippocampus-dependent memory consolidation in rodents. Copyright © 2016 Elsevier Inc. All rights reserved.

Uncovering temporal structure in hippocampal output patterns

PubMed Central

de Jong, Laurel Watkins; Pfeiffer, Brad E; Foster, David

2018-01-01

Place cell activity of hippocampal pyramidal cells has been described as the cognitive substrate of spatial memory. Replay is observed during hippocampal sharp-wave-ripple-associated population burst events (PBEs) and is critical for consolidation and recall-guided behaviors. PBE activity has historically been analyzed as a phenomenon subordinate to the place code. Here, we use hidden Markov models to study PBEs observed in rats during exploration of both linear mazes and open fields. We demonstrate that estimated models are consistent with a spatial map of the environment, and can even decode animals’ positions during behavior. Moreover, we demonstrate the model can be used to identify hippocampal replay without recourse to the place code, using only PBE model congruence. These results suggest that downstream regions may rely on PBEs to provide a substrate for memory. Additionally, by forming models independent of animal behavior, we lay the groundwork for studies of non-spatial memory. PMID:29869611

Uncovering temporal structure in hippocampal output patterns.

PubMed

Maboudi, Kourosh; Ackermann, Etienne; de Jong, Laurel Watkins; Pfeiffer, Brad E; Foster, David; Diba, Kamran; Kemere, Caleb

2018-06-05

Place cell activity of hippocampal pyramidal cells has been described as the cognitive substrate of spatial memory. Replay is observed during hippocampal sharp-wave-ripple-associated population burst events (PBEs) and is critical for consolidation and recall-guided behaviors. PBE activity has historically been analyzed as a phenomenon subordinate to the place code. Here, we use hidden Markov models to study PBEs observed in rats during exploration of both linear mazes and open fields. We demonstrate that estimated models are consistent with a spatial map of the environment, and can even decode animals' positions during behavior. Moreover, we demonstrate the model can be used to identify hippocampal replay without recourse to the place code, using only PBE model congruence. These results suggest that downstream regions may rely on PBEs to provide a substrate for memory. Additionally, by forming models independent of animal behavior, we lay the groundwork for studies of non-spatial memory. © 2018, Maboudi et al.

Does white matter structure or hippocampal volume mediate associations between cortisol and cognitive ageing?

PubMed Central

Cox, Simon R.; MacPherson, Sarah E.; Ferguson, Karen J.; Royle, Natalie A.; Maniega, Susana Muñoz; Hernández, Maria del C. Valdés; Bastin, Mark E.; MacLullich, Alasdair M.J.; Wardlaw, Joanna M.; Deary, Ian J.

2015-01-01

Elevated glucocorticoid (GC) levels putatively damage specific brain regions, which in turn may accelerate cognitive ageing. However, many studies are cross-sectional or have relatively short follow-up periods, making it difficult to relate GCs directly to changes in cognitive ability with increasing age. Moreover, studies combining endocrine, MRI and cognitive variables are scarce, measurement methods vary considerably, and formal tests of the underlying causal hypothesis (cortisol → brain → cognition) are absent. In this study, 90 men, aged 73 years, provided measures of fluid intelligence, processing speed and memory, diurnal and reactive salivary cortisol and two measures of white matter (WM) structure (WM hyperintensity volume from structural MRI and mean diffusivity averaged across 12 major tracts from diffusion tensor MRI), hippocampal volume, and also cognitive ability at age 11. We tested whether negative relationships between cognitive ageing differences (over more than 60 years) and salivary cortisol were significantly mediated by WM and hippocampal volume. Significant associations between reactive cortisol at 73 and cognitive ageing differences between 11 and 73 (r = −.28 to −.36, p < .05) were partially mediated by both WM structural measures, but not hippocampal volume. Cortisol-WM relationships were modest, as was the degree to which WM structure attenuated cortisol–cognition associations (<15%). These data support the hypothesis that GCs contribute to cognitive ageing differences from childhood to the early 70s, partly via brain WM structure. PMID:26298692

Fornix lesions decouple the induction of hippocampal arc transcription from behavior but not plasticity.

PubMed

Fletcher, Bonnie R; Calhoun, Michael E; Rapp, Peter R; Shapiro, Matthew L

2006-02-01

The immediate-early gene (IEG) Arc is transcribed after behavioral and physiological treatments that induce synaptic plasticity and is implicated in memory consolidation. The relative contributions of neuronal activity and learning-related plasticity to the behavioral induction of Arc remain to be defined. To differentiate the contributions of each, we assessed the induction of Arc transcription in rats with fornix lesions that impair hippocampal learning yet leave cortical connectivity and neuronal firing essentially intact. Arc expression was assessed after exploration of novel environments and performance of a novel water maze task during which normal rats learned the spatial location of an escape platform. During the same task, rats with fornix lesions learned to approach a visible platform but did not learn its spatial location. Rats with fornix lesions had normal baseline levels of hippocampal Arc mRNA, but unlike normal rats, expression was not increased in response to water maze training. The integrity of signaling pathways controlling Arc expression was demonstrated by stimulation of the medial perforant path, which induced normal synaptic potentiation and Arc in rats with fornix lesions. Together, the results demonstrate that Arc induction can be decoupled from behavior and is more likely to indicate the engagement of synaptic plasticity mechanisms than synaptic or neuronal activity per se. The results further imply that fornix lesions may impair memory in part by decoupling neuronal activity from signaling pathways required for long-lasting hippocampal synaptic plasticity.

Phonological Encoding in the Silent Speech of Persons Who Stutter

ERIC Educational Resources Information Center

Sasisekaran, Jayanthi; De Nil, Luc F.; Smyth, Ron; Johnson, Carla

2006-01-01

The purpose of the present study was to investigate the role of phonological encoding in the silent speech of persons who stutter (PWS) and persons who do not stutter (PNS). Participants were 10 PWS (M=30.4 years, S.D.=7.8), matched in age, gender, and handedness with 11 PNS (M=30.1 years, S.D.=7.8). Each participant performed five tasks: a…

Erythropoietin Improved Cognitive Function and Decreased Hippocampal Caspase Activity in Rat Pups after Traumatic Brain Injury

PubMed Central

Requena, Daniela F.; Block, Benjamin; Davis, Lizeth J.; Rodesch, Christopher; Casper, T. Charles; Juul, Sandra E.; Kesner, Raymond P.; Lane, Robert H.

2014-01-01

Abstract Traumatic brain injury (TBI) is a leading cause of acquired neurologic disability in children. Erythropoietin (EPO), an anti-apoptotic cytokine, improved cognitive outcome in adult rats after TBI. To our knowledge, EPO has not been studied in a developmental TBI model. Hypothesis: We hypothesized that EPO would improve cognitive outcome and increase neuron fraction in the hippocampus in 17-day-old (P17) rat pups after controlled cortical impact (CCI). Methods: EPO or vehicle was given at 1, 24, and 48 h after CCI and at post injury day (PID) 7. Cognitive outcome at PID14 was assessed using Novel Object Recognition (NOR). Hippocampal EPO levels, caspase activity, and mRNA levels of the apoptosis factors Bcl2, Bax, Bcl-xL, and Bad were measured during the first 14 days after injury. Neuron fraction and caspase activation in CA1, CA3, and DG were studied at PID2. Results: EPO normalized recognition memory after CCI. EPO blunted the increased hippocampal caspase activity induced by CCI at PID1, but not at PID2. EPO increased neuron fraction in CA3 at PID2. Brain levels of exogenous EPO appeared low relative to endogenous. Timing of EPO administration was associated with temporal changes in hippocampal mRNA levels of EPO and pro-apoptotic factors. Conclusion/Speculation: EPO improved recognition memory, increased regional hippocampal neuron fraction, and decreased caspase activity in P17 rats after CCI. We speculate that EPO improved cognitive outcome in rat pups after CCI as a result of improved neuronal survival via inhibition of caspase-dependent apoptosis early after injury. PMID:23972011

Prenatal choline availability modulates hippocampal neurogenesis and neurogenic responses to enriching experiences in adult female rats

PubMed Central

Glenn, Melissa J.; Gibson, Erin M.; Kirby, Elizabeth D.; Mellott, Tiffany J.; Blusztajn, Jan K.; Williams, Christina L.

2008-01-01

Increased dietary intake of choline early in life improves performance of adult rats on memory tasks and prevents their age-related memory decline. Because neurogenesis in the adult hippocampus also declines with age, we investigated whether prenatal choline availability affects hippocampal neurogenesis in adult Sprague–Dawley rats and modifies their neurogenic response to environmental stimulation. On embryonic days (ED) 12−17, pregnant rats ate a choline-supplemented (SUP-5 g/kg), choline sufficient (SFF-1.1 g/kg), or choline-free (DEF) semisynthetic diet. Adult offspring either remained in standard housing or were given 21 daily visits to explore a maze. On the last ten exploration days, all rats received daily injections of 5-bromo-2-deoxyuridine (BrdU, 100 mg/kg). The number of BrdU+ cells was significantly greater in the dentate gyrus in SUP rats compared to SFF or DEF rats. While maze experience increased the number of BrdU+ cells in SFF rats to the level seen in the SUP rats, this enriching experience did not alter cell proliferation in DEF rats. Similar patterns of cell proliferation were obtained with immunohistochemical staining for neuronal marker doublecortin, confirming that diet and exploration affected hippocampal neurogenesis. Moreover, hippocampal levels of the brain-derived neurotrophic factor (BDNF) were increased in SUP rats as compared to SFF and DEF animals. We conclude that prenatal choline intake has enduring effects on adult hippocampal neurogenesis, possibly via up-regulation of BDNF levels, and suggest that these alterations of neurogenesis may contribute to the mechanism of life-long changes in cognitive function governed by the availability of choline during gestation. PMID:17445242

Deficits in memory and visuospatial learning correlate with regional hippocampal atrophy in MS.

PubMed

Longoni, Giulia; Rocca, Maria A; Pagani, Elisabetta; Riccitelli, Gianna C; Colombo, Bruno; Rodegher, Mariaemma; Falini, Andrea; Comi, Giancarlo; Filippi, Massimo

2015-01-01

The hippocampus has a critical role in episodic memory and visuospatial learning and consolidation. We assessed the patterns of whole and regional hippocampal atrophy in a large group of multiple sclerosis (MS) patients, and their correlations with neuropsychological impairment. From 103 MS patients and 28 healthy controls (HC), brain dual-echo and high-resolution 3D T1-weighted images were acquired using a 3.0-Tesla scanner. All patients underwent a neuropsychological assessment of hippocampal-related cognitive functions, including Paired Associate Word Learning, Short Story, delayed recall of Rey-Osterrieth Complex Figure and Paced Auditory Serial Attention tests. The hippocampi were manually segmented and volumes derived. Regional atrophy distribution was assessed using a radial mapping analysis. Correlations between hippocampal atrophy and clinical, neuropsychological and MRI metrics were also evaluated. Hippocampal volume was reduced in MS patients vs HC (p < 0.001 for both right and hippocampus). In MS patients, radial atrophy affected CA1 subfield and subiculum of posterior hippocampus, bilaterally. The dentate hilus (DG:H) of the right hippocampal head was also affected. Regional hippocampal atrophy correlated with brain T2 and T1 lesion volumes, while no correlation was found with disability. Damage to the CA1 and subiculum was significantly correlated to the performances at hippocampal-targeted neuropsychological tests. These results show that hippocampal subregions have a different vulnerability to MS-related damage, with a relative sparing of the head of the left hippocampus. The assessment of regional hippocampal atrophy may help explain deficits of specific cognitive functions in MS patients, including memory and visuospatial abilities.

The Association Between Neurocysticercosis and Hippocampal Atrophy is Related to Age

PubMed Central

Del Brutto, Oscar H.; Issa, Naoum P.; Salgado, Perla; Del Brutto, Victor J.; Zambrano, Mauricio; Lama, Julio; García, Héctor H.

2017-01-01

Neurocysticercosis (NCC) has been associated with hippocampal atrophy, but the prevalence and pathogenic mechanisms implicated in this relationship are unknown. Using a population-based, case–control study design, residents in a rural village (Atahualpa) aged ≥ 40 years with calcified NCC were identified as cases and paired to NCC-free individuals (control subjects) matched by age, sex, and level of education. Cases and control subjects underwent magnetic resonance imaging for hippocampal rating according to the Scheltens' scale for medial temporal atrophy and were interviewed to identify those with a clinical seizure disorder. The prevalence of hippocampal atrophy was compared between cases and control subjects by the use of the McNemar's test for correlated proportions. Seventy-five individuals with calcified NCC and their matched control subjects were included in the analysis. Hippocampal atrophy was noted in 26 (34.7%) cases and nine (12%) control subjects (odds ratio: 4.4; 95% confidence interval: 1.6–14.9, P < 0.0021). Stratification of pairs according to tertiles of age revealed an age-related trend in this association, which became significant only in those aged ≥ 68 years (P = 0.027). Only five cases and one control had recurrent seizures (P = 0.221); three of these five cases had hippocampal atrophy, and the single control subject had normal hippocampi. This study confirms an association between NCC and hippocampal atrophy, and shows that this association is stronger in older age groups. This suggests that NCC-related hippocampal atrophy takes a long time to develop. PMID:28077750

Distinguishing cognitive state with multifractal complexity of hippocampal interspike interval sequences

PubMed Central

Fetterhoff, Dustin; Kraft, Robert A.; Sandler, Roman A.; Opris, Ioan; Sexton, Cheryl A.; Marmarelis, Vasilis Z.; Hampson, Robert E.; Deadwyler, Sam A.

2015-01-01

Fractality, represented as self-similar repeating patterns, is ubiquitous in nature and the brain. Dynamic patterns of hippocampal spike trains are known to exhibit multifractal properties during working memory processing; however, it is unclear whether the multifractal properties inherent to hippocampal spike trains reflect active cognitive processing. To examine this possibility, hippocampal neuronal ensembles were recorded from rats before, during and after a spatial working memory task following administration of tetrahydrocannabinol (THC), a memory-impairing component of cannabis. Multifractal detrended fluctuation analysis was performed on hippocampal interspike interval sequences to determine characteristics of monofractal long-range temporal correlations (LRTCs), quantified by the Hurst exponent, and the degree/magnitude of multifractal complexity, quantified by the width of the singularity spectrum. Our results demonstrate that multifractal firing patterns of hippocampal spike trains are a marker of functional memory processing, as they are more complex during the working memory task and significantly reduced following administration of memory impairing THC doses. Conversely, LRTCs are largest during resting state recordings, therefore reflecting different information compared to multifractality. In order to deepen conceptual understanding of multifractal complexity and LRTCs, these measures were compared to classical methods using hippocampal frequency content and firing variability measures. These results showed that LRTCs, multifractality, and theta rhythm represent independent processes, while delta rhythm correlated with multifractality. Taken together, these results provide a novel perspective on memory function by demonstrating that the multifractal nature of spike trains reflects hippocampal microcircuit activity that can be used to detect and quantify cognitive, physiological, and pathological states. PMID:26441562

Accelerated Age-Dependent Hippocampal Volume Loss in Parkinson Disease With Mild Cognitive Impairment.

PubMed

Schneider, Christine B; Donix, Markus; Linse, Katharina; Werner, Annett; Fauser, Mareike; Klingelhoefer, Lisa; Löhle, Matthias; von Kummer, Rüdiger; Reichmann, Heinz; Storch, Alexander

2017-09-01

Patients with Parkinson disease are at high risk of developing dementia. During the course of the disease, a substantial number of patients will experience a cognitive decline, indicating the dynamics of the underlying neuropathology. Magnetic resonance imaging (MRI) has become increasingly useful for identifying structural characteristics in radiological brain anatomy existing prior to clinical symptoms. Whether these changes reflect pathology, whether they are aging related, or both often remains unclear. We hypothesized that aging-associated brain structural changes would be more pronounced in the hippocampal region among patients with Parkinson disease having mild cognitive deficits relative to cognitively unimpaired patients. Using MRI, we investigated 30 cognitively healthy patients with Parkinson disease and 33 patients with nondemented Parkinson disease having mild cognitive impairment. All participants underwent structural MRI scanning and extensive clinical and neuropsychological assessments. Irrespective of the study participants' cognitive status, older age was associated with reduced cortical thickness in various neocortical regions. Having mild cognitive impairment was not associated with an increased rate of cortical thinning or volume loss in these regions, except in the hippocampus bilaterally. Patients with Parkinson disease having mild cognitive impairment show an accelerated age-dependent hippocampal volume loss when compared with cognitively healthy patients with Parkinson disease. This may indicate pathological processes in a key region for memory functioning in patients with Parkinson disease at risk of developing dementia. Structural MRI of the hippocampal region could potentially contribute to identifying patients who should receive early treatment aimed at delaying the clinical onset of dementia.

Silent Corticotroph Adenomas After Stereotactic Radiosurgery: A Case–Control Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Zhiyuan; Ellis, Scott; Lee, Cheng-Chia

Purpose: To investigate the safety and effectiveness of stereotactic radiosurgery (SRS) in patients with a silent corticotroph adenoma (SCA) compared with patients with other subtypes of non–adrenocorticotropic hormone staining nonfunctioning pituitary adenoma (NFA). Methods and Materials: The clinical features and outcomes of 104 NFA patients treated with SRS in our center between September 1994 and August 2012 were evaluated. Among them, 34 consecutive patients with a confirmatory SCA were identified. A control group of 70 patients with other subtypes of NFA were selected for review based on comparable baseline features, including sex, age at the time of SRS, tumor size, marginmore » radiation dose to the tumor, and duration of follow-up. Results: The median follow-up after SRS was 56 months (range, 6-200 months). No patients with an SCA developed Cushing disease during the follow-up. Tumor control was achieved in 21 of 34 patients (62%) in the SCA group, compared with 65 of 70 patients (93%) in the NFA group. The median progression-free survival (PFS) was 58 months in the SCA group. The actuarial PFS was 73%, 46%, and 31% in the SCA group and was 94%, 87%, and 87% in the NFA group at 3, 5, and 8 years, respectively. Silent corticotroph adenomas treated with a dose of ≥17 Gy exhibited improved PFS. New-onset loss of pituitary function developed in 10 patients (29%) in the SCA group, whereas it occurred in 18 patients (26%) in the NFA group. Eight patients (24%) in the SCA group experienced worsening of a visual field deficit or visual acuity attributed to the tumor progression, as did 6 patients (9%) in the NFA group. Conclusion: Silent corticotroph adenomas exhibited a more aggressive course with a higher progression rate than other subtypes of NFAs. Stereotactic radiosurgery is an important adjuvant treatment for control of tumor growth. Increased radiation dose may lead to improved tumor control in SCA patients.« less

Hyperbaric Oxygen Therapy Alleviates Carbon Monoxide Poisoning-Induced Delayed Memory Impairment by Preserving Brain-Derived Neurotrophic Factor-Dependent Hippocampal Neurogenesis.

PubMed

Liu, Wen-Chung; Yang, San-Nan; Wu, Chih-Wei J; Chen, Lee-Wei; Chan, Julie Y H

2016-01-01

suppression of adult neurogenesis by the carbon monoxide poisoning was appreciably alleviated by early treatment of hyperbaric oxygen. The hyperbaric oxygen treatment also promoted a sustained increase in hippocampal brain-derived neurotrophic factor level. Blockade of hippocampal brain-derived neurotrophic factor signaling with intracerebroventricular infusion of recombinant human TrkB-Fc chimera significantly blunted the protection by the hyperbaric oxygen on hippocampal neurogenesis; whereas intracerebroventricular infusion of brain-derived neurotrophic factor mimicked the action of hyperbaric oxygen and preserved hippocampal neurogenesis after acute carbon monoxide poisoning. Furthermore, acute carbon monoxide poisoning resulted in a delayed impairment of cognitive function. The hyperbaric oxygen treatment notably restored the cognitive impairment in a brain-derived neurotrophic factor-dependent manner. The early hyperbaric oxygen treatment may alleviate delayed memory impairment after acute carbon monoxide poisoning by preserving adult neurogenesis via an increase in hippocampal brain-derived neurotrophic factor content.

Undeclared Imports: Silent Borrowing in Educational Policy-Making and Research in Sweden

ERIC Educational Resources Information Center

Waldow, Florian

2009-01-01

Research on educational policy borrowing has mostly focused on explicit transfer processes, often highlighting how explicit reference to the international has served legitimatory purposes in the borrowing country. In contrast, this paper focuses on "silent" borrowing, i.e. non-acknowledged processes of policy transfer. The paper argues…

Role of adult neurogenesis in hippocampal-cortical memory consolidation

PubMed Central

2014-01-01

Acquired memory is initially dependent on the hippocampus (HPC) for permanent memory formation. This hippocampal dependency of memory recall progressively decays with time, a process that is associated with a gradual increase in dependency upon cortical structures. This process is commonly referred to as systems consolidation theory. In this paper, we first review how memory becomes hippocampal dependent to cortical dependent with an emphasis on the interactions that occur between the HPC and cortex during systems consolidation. We also review the mechanisms underlying the gradual decay of HPC dependency during systems consolidation from the perspective of memory erasures by adult hippocampal neurogenesis. Finally, we discuss the relationship between systems consolidation and memory precision. PMID:24552281

Value of speckle tracking echocardiography for detection of clinically silent left ventricular dysfunction in patients with β-thalassemia.

PubMed

Parsaee, Mozhgan; Saedi, Sedigheh; Joghataei, Pegah; Azarkeivan, Azita; Alizadeh Sani, Zahra

2017-10-01

β-Thalassemia is an inherited hemoglobin disorder resulting in chronic hemolytic anemia requiring chronic transfusion therapy. Cardiac involvement is the main cause of death in patients with thalassemia major. The narrow border is between overt myocardial dysfunction and clinically silent left ventricular (LV) dysfunction in patients with thalassemia. Therefore, we need novel parameters in different imaging techniques to discover cardiac involvement in an early and subtle stage. We explore to find a novel, straightforward and informative parameter in echocardiography as a noninvasive, economical and really routine in clinical practice. In this prospective study, 55 patients, who are known cases of β-thalassemia major, receiving long-term blood transfusions and undergoing iron chelation therapy were enrolled. Ferritin level, cardiac magnetic resonance (CMR) T2 * value, full conventional echocardiography and speckle tracking, LV regional circumferential and longitudinal strain values (%) and time-to-peak strain (ms) of 17 segments cardiac model in eyeball tomogram were measured. There was a significant reduction in global longitudinal strain (GLS) (-20.9% ± 1.9 vs. -22.2 ± 1.03) and also basal segments longitudinal strain compared to normal subjects group (-17.4% ± 2.7 vs. -19.6% ± 1.2). There was no significant difference in circumferential strain value between thalassemia patients and normal control group. Interestingly, there was no significant correlation between GLS and CMR T2 * values showing no association between cardiac iron load and longitudinal strain. Speckle tracking echocardiography could be used as a feasible method for evaluating subclinical myocardial dysfunction in patients with thalassemia major. Echocardiography, using GLS, could predict clinically silent myocardial dysfunction independent of CMR (T2 * value) and extension of iron deposition. Our study also puts forward other causes such as chronic tissue hypoxia resulting

Hippocampal subfield surface deformity in non-semantic primary progressive aphasia.

PubMed

Christensen, Adam; Alpert, Kathryn; Rogalski, Emily; Cobia, Derin; Rao, Julia; Beg, Mirza Faisal; Weintraub, Sandra; Mesulam, M-Marsel; Wang, Lei

2015-03-01

Alzheimer neuropathology (AD) is found in almost half of patients with non-semantic primary progressive aphasia (PPA). This study examined hippocampal abnormalities in PPA to determine similarities to those described in amnestic AD. In 37 PPA patients and 32 healthy controls, we generated hippocampal subfield surface maps from structural MRIs and administered a face memory test. We analyzed group and hemisphere differences for surface shape measures and their relationship with test scores and ApoE genotype. The hippocampus in PPA showed inward deformity (CA1 and subiculum subfields) and outward deformity (CA2-4+DG subfield) and smaller left than right volumes. Memory performance was related to hippocampal shape abnormalities in PPA patients, but not controls, even in the absence of memory impairments. Hippocampal deformity in PPA is related to memory test scores. This may reflect a combination of intrinsic degenerative phenomena with transsynaptic or Wallerian effects of neocortical neuronal loss.

Hippocampal Sleep Features: Relations to Human Memory Function

PubMed Central

Ferrara, Michele; Moroni, Fabio; De Gennaro, Luigi; Nobili, Lino

2012-01-01

The recent spread of intracranial electroencephalographic (EEG) recording techniques for presurgical evaluation of drug-resistant epileptic patients is providing new information on the activity of different brain structures during both wakefulness and sleep. The interest has been mainly focused on the medial temporal lobe, and in particular the hippocampal formation, whose peculiar local sleep features have been recently described, providing support to the idea that sleep is not a spatially global phenomenon. The study of the hippocampal sleep electrophysiology is particularly interesting because of its central role in the declarative memory formation. Recent data indicate that sleep contributes to memory formation. Therefore, it is relevant to understand whether specific patterns of activity taking place during sleep are related to memory consolidation processes. Fascinating similarities between different states of consciousness (wakefulness, REM sleep, non-REM sleep) in some electrophysiological mechanisms underlying cognitive processes have been reported. For instance, large-scale synchrony in gamma activity is important for waking memory and perception processes, and its changes during sleep may be the neurophysiological substrate of sleep-related deficits of declarative memory. Hippocampal activity seems to specifically support memory consolidation during sleep, through specific coordinated neurophysiological events (slow waves, spindles, ripples) that would facilitate the integration of new information into the pre-existing cortical networks. A few studies indeed provided direct evidence that rhinal ripples as well as slow hippocampal oscillations are correlated with memory consolidation in humans. More detailed electrophysiological investigations assessing the specific relations between different types of memory consolidation and hippocampal EEG features are in order. These studies will add an important piece of knowledge to the elucidation of the ultimate

Direct and Indirect Effects of Print Exposure on Silent Reading Fluency

ERIC Educational Resources Information Center

Mano, Quintino R.; Guerin, Julia M.

2018-01-01

Print exposure is an important causal factor in reading development. Little is known, however, of the mechanisms through which print exposure exerts an effect onto reading. To address this gap, we examined the direct and indirect effects of print exposure on silent reading fluency among college students (n = 52). More specifically, we focused on…

Reading and Company: Embodiment and Social Space in Silent Reading Practices

ERIC Educational Resources Information Center

Kuzmicová, Anežka; Dias, Patrícia; Vogrincic Cepic, Ana; Albrechtslund, Anne-Mette Bech; Casado, André; Kotrla Topic, Marina; Mínguez López, Xavier; Nilsson, Skans Kersti; Teixeira-Botelho, Inês

2018-01-01

Reading, even when silent and individual, is a social phenomenon and has often been studied as such. Complementary to this view, research has begun to explore how reading is embodied beyond simply being 'wired' in the brain. This article brings the social and embodied perspectives together in a very literal sense. Reporting a qualitative study of…

Association of human hippocampal neurochemistry, serotonin transporter genetic variation, and anxiety.

PubMed

Gallinat, Jürgen; Ströhle, Andreas; Lang, Undine E; Bajbouj, Malek; Kalus, Peter; Montag, Christiane; Seifert, Frank; Wernicke, Catrin; Rommelspacher, Hans; Rinneberg, Herbert; Schubert, Florian

2005-05-15

The impact of the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) on anxiety-related behavior and related cerebral activation has facilitated the understanding of neurobiological mechanisms of anxiety. However, the influence of the 5-HTTLPR genotype on hippocampal neuronal development and neurochemistry, which is relevant to anxiety behavior, has not been investigated. In 38 healthy subjects, absolute concentrations of N-acetylaspartate (NAA) were measured as a main surrogate parameter for hippocampal neurochemistry on a 3-T scanner. A significantly lower hippocampal NAA concentration in s allele carriers was observed as compared to l/l genotype. Other metabolites (choline, creatine + phosphocreatine, glutamate) were unaffected by genotype. The hippocampal NAA concentration was negatively correlated with trait anxiety scores (STAI). Metabolites measured in the anterior cingulate cortex (reference region) were not associated with genotype. The results are in accordance with the recently reported relationship between hippocampal neuronal development and anxiety behavior in adult animals and show an association between human limbic neurochemistry and genetically driven serotonergic neurotransmission relevant to anxiety.

Eye Movements during Silent and Oral Reading in a Regular Orthography: Basic Characteristics and Correlations with Childhood Cognitive Abilities and Adolescent Reading Skills

PubMed Central

Krieber, Magdalena; Bartl-Pokorny, Katrin D.; Pokorny, Florian B.; Zhang, Dajie; Landerl, Karin; Körner, Christof; Pernkopf, Franz; Pock, Thomas; Einspieler, Christa; Marschik, Peter B.

2017-01-01

The present study aimed to define differences between silent and oral reading with respect to spatial and temporal eye movement parameters. Eye movements of 22 German-speaking adolescents (14 females; mean age = 13;6 years;months) were recorded while reading an age-appropriate text silently and orally. Preschool cognitive abilities were assessed at the participants’ age of 5;7 (years;months) using the Kaufman Assessment Battery for Children. The participants’ reading speed and reading comprehension at the age of 13;6 (years;months) were determined using a standardized inventory to evaluate silent reading skills in German readers (Lesegeschwindigkeits- und -verständnistest für Klassen 6–12). The results show that (i) reading mode significantly influenced both spatial and temporal characteristics of eye movement patterns; (ii) articulation decreased the consistency of intraindividual reading performances with regard to a significant number of eye movement parameters; (iii) reading skills predicted the majority of eye movement parameters during silent reading, but influenced only a restricted number of eye movement parameters when reading orally; (iv) differences with respect to a subset of eye movement parameters increased with reading skills; (v) an overall preschool cognitive performance score predicted reading skills at the age of 13;6 (years;months), but not eye movement patterns during either silent or oral reading. However, we found a few significant correlations between preschool performances on subscales of sequential and simultaneous processing and eye movement parameters for both reading modes. Overall, the findings suggest that eye movement patterns depend on the reading mode. Preschool cognitive abilities were more closely related to eye movement patterns of oral than silent reading, while reading skills predicted eye movement patterns during silent reading, but less so during oral reading. PMID:28151950

Influence of slow oscillation on hippocampal activity and ripples through cortico-hippocampal synaptic interactions, analyzed by a cortical-CA3-CA1 network model.

PubMed

Taxidis, Jiannis; Mizuseki, Kenji; Mason, Robert; Owen, Markus R

2013-01-01

Hippocampal sharp wave-ripple complexes (SWRs) involve the synchronous discharge of thousands of cells throughout the CA3-CA1-subiculum-entorhinal cortex axis. Their strong transient output affects cortical targets, rendering SWRs a possible means for memory transfer from the hippocampus to the neocortex for long-term storage. Neurophysiological observations of hippocampal activity modulation by the cortical slow oscillation (SO) during deep sleep and anesthesia, and correlations between ripples and UP states, support the role of SWRs in memory consolidation through a cortico-hippocampal feedback loop. We couple a cortical network exhibiting SO with a hippocampal CA3-CA1 computational network model exhibiting SWRs, in order to model such cortico-hippocampal correlations and uncover important parameters and coupling mechanisms controlling them. The cortical oscillatory output entrains the CA3 network via connections representing the mossy fiber input, and the CA1 network via the temporoammonic pathway (TA). The spiking activity in CA3 and CA1 is shown to depend on the excitation-to-inhibition ratio, induced by combining the two hippocampal inputs, with mossy fiber input controlling the UP-state correlation of CA3 population bursts and corresponding SWRs, whereas the temporoammonic input affects the overall CA1 spiking activity. Ripple characteristics and pyramidal spiking participation to SWRs are shaped by the strength of the Schaffer collateral drive. A set of in vivo recordings from the rat hippocampus confirms a model-predicted segregation of pyramidal cells into subgroups according to the SO state where they preferentially fire and their response to SWRs. These groups can potentially play distinct functional roles in the replay of spike sequences.

Hippocampal Insulin Resistance Impairs Spatial Learning and Synaptic Plasticity.

PubMed

Grillo, Claudia A; Piroli, Gerardo G; Lawrence, Robert C; Wrighten, Shayna A; Green, Adrienne J; Wilson, Steven P; Sakai, Randall R; Kelly, Sandra J; Wilson, Marlene A; Mott, David D; Reagan, Lawrence P

2015-11-01

Insulin receptors (IRs) are expressed in discrete neuronal populations in the central nervous system, including the hippocampus. To elucidate the functional role of hippocampal IRs independent of metabolic function, we generated a model of hippocampal-specific insulin resistance using a lentiviral vector expressing an IR antisense sequence (LV-IRAS). LV-IRAS effectively downregulates IR expression in the rat hippocampus without affecting body weight, adiposity, or peripheral glucose homeostasis. Nevertheless, hippocampal neuroplasticity was impaired in LV-IRAS-treated rats. High-frequency stimulation, which evoked robust long-term potentiation (LTP) in brain slices from LV control rats, failed to evoke LTP in LV-IRAS-treated rats. GluN2B subunit levels, as well as the basal level of phosphorylation of GluA1, were reduced in the hippocampus of LV-IRAS rats. Moreover, these deficits in synaptic transmission were associated with impairments in spatial learning. We suggest that alterations in the expression and phosphorylation of glutamate receptor subunits underlie the alterations in LTP and that these changes are responsible for the impairment in hippocampal-dependent learning. Importantly, these learning deficits are strikingly similar to the impairments in complex task performance observed in patients with diabetes, which strengthens the hypothesis that hippocampal insulin resistance is a key mediator of cognitive deficits independent of glycemic control. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Reduced extinction of hippocampal-dependent memories in CPEB knockout mice.

PubMed

Berger-Sweeney, Joanne; Zearfoss, N Ruth; Richter, Joel D

2006-01-01

CPEB is a sequence-specific RNA binding protein that regulates translation at synapses. In neurons of CPEB knockout mice, synaptic efficacy is reduced. Here, we have performed a battery of behavioral tests and find that relative to wild-type animals, CPEB knockout mice, although similar on many baseline behaviors, have reduced extinction of memories on two hippocampal-dependent tasks. A corresponding microarray analysis reveals that about 0.14% of hippocampal genes have an altered expression in the CPEB knockout mouse. These data suggest that CPEB-dependent local protein synthesis may be an important cellular mechanism underlying extinction of hippocampal-dependent memories.

Secondary Teachers Perceptions of the Advantages and Disadvantages of Sustained Silent Reading

ERIC Educational Resources Information Center

Feliciani, Meghan Lynn

2013-01-01

Educators often use reading programs to address younger students' reading abilities and teachers' perceptions of those reading abilities; however, few researchers have examined teachers' perceptions of the effects of sustained silent reading on middle and high school students. The conceptual framework for this study was based on social learning…

Function Word Repetitions Emerge When Speakers Are Operantly Conditioned to Reduce Frequency of Silent Pauses

PubMed Central

Howell, Peter; Sackin, Stevie

2007-01-01

Beattie and Bradbury (1979) reported a study in which, in one condition, they punished speakers when they produced silent pauses (by lighting a light they were supposed to keep switched off). They found speakers were able to reduce silent pauses and that this was not achieved at the expense of reduced overall speech rate. They reported an unexpected increase in word repetition rate. A recent theory proposed by Howell, Au-Yeung, and Sackin (1999) predicts that the change in word repetition rate will occur on function, not content words. This hypothesis is tested and confirmed. The results are used to assess the theory and to consider practical applications of this conditioning procedure. PMID:11529422

Function word repetitions emerge when speakers are operantly conditioned to reduce frequency of silent pauses.

PubMed

Howell, P; Sackin, S

2001-09-01

Beattie and Bradbury (1979) reported a study in which, in one condition, they punished speakers when they produced silent pauses (by lighting a light they were supposed to keep switched off). They found speakers were able to reduce silent pauses and that this was not achieved at the expense of reduced overall speech rate. They reported an unexpected increase in word repetition rate. A recent theory proposed by Howell, Au-Yeung, and Sackin (1999) predicts that the change in word repetition rate will occur on function, not content words. This hypothesis is tested and confirmed. The results are used to assess the theory and to consider practical applications of this conditioning procedure.

Hippocampal Region-Specific Contributions to Memory Performance in Normal Elderly

ERIC Educational Resources Information Center

Chen, Karren H. M.; Chuah, Lisa Y. M.; Sim, Sam K. Y.; Chee, Michael W. L.

2010-01-01

To investigate the relationship between regional hippocampal volume and memory in healthy elderly, 147 community-based volunteers, aged 55-83 years, were evaluated using magnetic resonance imaging, the Groton Maze Learning Test, Visual Reproduction and the Rey Auditory Verbal Learning Test. Hippocampal volumes were determined by interactive…

Training labels for hippocampal segmentation based on the EADC-ADNI harmonized hippocampal protocol.

PubMed

Boccardi, Marina; Bocchetta, Martina; Morency, Félix C; Collins, D Louis; Nishikawa, Masami; Ganzola, Rossana; Grothe, Michel J; Wolf, Dominik; Redolfi, Alberto; Pievani, Michela; Antelmi, Luigi; Fellgiebel, Andreas; Matsuda, Hiroshi; Teipel, Stefan; Duchesne, Simon; Jack, Clifford R; Frisoni, Giovanni B

2015-02-01

The European Alzheimer's Disease Consortium and Alzheimer's Disease Neuroimaging Initiative (ADNI) Harmonized Protocol (HarP) is a Delphi definition of manual hippocampal segmentation from magnetic resonance imaging (MRI) that can be used as the standard of truth to train new tracers, and to validate automated segmentation algorithms. Training requires large and representative data sets of segmented hippocampi. This work aims to produce a set of HarP labels for the proper training and certification of tracers and algorithms. Sixty-eight 1.5 T and 67 3 T volumetric structural ADNI scans from different subjects, balanced by age, medial temporal atrophy, and scanner manufacturer, were segmented by five qualified HarP tracers whose absolute interrater intraclass correlation coefficients were 0.953 and 0.975 (left and right). Labels were validated as HarP compliant through centralized quality check and correction. Hippocampal volumes (mm(3)) were as follows: controls: left = 3060 (standard deviation [SD], 502), right = 3120 (SD, 897); mild cognitive impairment (MCI): left = 2596 (SD, 447), right = 2686 (SD, 473); and Alzheimer's disease (AD): left = 2301 (SD, 492), right = 2445 (SD, 525). Volumes significantly correlated with atrophy severity at Scheltens' scale (Spearman's ρ = <-0.468, P = <.0005). Cerebrospinal fluid spaces (mm(3)) were as follows: controls: left = 23 (32), right = 25 (25); MCI: left = 15 (13), right = 22 (16); and AD: left = 11 (13), right = 20 (25). Five subjects (3.7%) presented with unusual anatomy. This work provides reference hippocampal labels for the training and certification of automated segmentation algorithms. The publicly released labels will allow the widespread implementation of the standard segmentation protocol. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Episodic autobiographical memory is associated with variation in the size of hippocampal subregions.

PubMed

Palombo, Daniela J; Bacopulos, Agnes; Amaral, Robert S C; Olsen, Rosanna K; Todd, Rebecca M; Anderson, Adam K; Levine, Brian

2018-02-01

Striking individual differences exist in the human capacity to recollect past events, yet, little is known about the neural correlates of such individual differences. Studies investigating hippocampal volume in relation to individual differences in laboratory measures of episodic memory in young adults suggest that whole hippocampal volume is unrelated (or even negatively associated) with episodic memory. However, anatomical and functional specialization across hippocampal subregions suggests that individual differences in episodic memory may be linked to particular hippocampal subregions, as opposed to whole hippocampal volume. Given that the DG/CA 2/3 circuitry is thought to be especially critical for supporting episodic memory in humans, we predicted that the volume of this region would be associated with individual variability in episodic memory. This prediction was supported using high-resolution MRI of the hippocampal subfields and measures of real-world (autobiographical) episodic memory. In addition to the association with DG/CA 2/3 , we further observed a relationship between episodic autobiographical memory and subiculum volume, whereas no association was observed with CA 1 or with whole hippocampal volume. These findings provide insight into the possible neural substrates that mediate individual differences in real-world episodic remembering in humans. © 2017 Wiley Periodicals, Inc.

MK-801 Impairs Cognitive Coordination on a Rotating Arena (Carousel) and Contextual Specificity of Hippocampal Immediate-Early Gene Expression in a Rat Model of Psychosis

PubMed Central

Kubík, Štěpán; Buchtová, Helena; Valeš, Karel; Stuchlík, Aleš

2014-01-01

Flexible behavior in dynamic, real-world environments requires more than static spatial learning and memory. Discordant and unstable cues must be organized in coherent subsets to give rise to meaningful spatial representations. We model this form of cognitive coordination on a rotating arena – Carousel where arena- and room-bound spatial cues are dissociated. Hippocampal neuronal ensemble activity can repeatedly switch between multiple representations of such an environment. Injection of tetrodotoxin into one hippocampus prevents cognitive coordination during avoidance of a stationary room-defined place on the Carousel and increases coactivity of previously unrelated neurons in the uninjected hippocampus. Place avoidance on the Carousel is impaired after systemic administration of non-competitive NMDAr blockers (MK-801) used to model schizophrenia in animals and people. We tested if this effect is due to cognitive disorganization or other effect of NMDAr antagonism such as hyperlocomotion, spatial memory impairment, or general learning deficit. We also examined if the same dose of MK-801 alters patterns of immediate-early gene (IEG) expression in the hippocampus. IEG expression is triggered in neuronal nuclei in a context-specific manner after behavioral exploration and it is used to map activity in neuronal populations. IEG expression is critical for maintenance of synaptic plasticity and memory consolidation. We show that the same dose of MK-801 that impairs spatial coordination of rats on the Carousel also eliminates contextual specificity of IEG expression in hippocampal CA1 ensembles. This effect is due to increased similarity between ensembles activated in different environments, consistent with the idea that it is caused by increased coactivity between neurons, which did not previously fire together. Our data support the proposition of the Hypersynchrony theory that cognitive disorganization in psychosis is due to increased coactivity between unrelated

The Tzu Chi Silent Mentor Program: Application of Buddhist Ethics to Teach Student Physicians Empathy, Compassion, and Self-Sacrifice.

PubMed

Santibañez, Scott; Boudreaux, Debra; Tseng, Guo-Fang; Konkel, Kimberly

2016-10-01

The Buddhist Tzu Chi Silent Mentor Program promotes the donation of one's body to science as a selfless act by appealing to the Buddhist ethics of compassion and self-sacrifice. Together, faculty, families, and donors help medical students to learn the technical, spiritual, emotional, and psychological aspects of medicine. Students assigned to each "Silent Mentor" visit the family to learn about the donor's life. They see photos and hear family members' stories. Afterwards, students write a brief biography of the donor which is posted on the program website, in the medical school, and on the dissection table. In this paper, we: (1) summarize the Silent Mentor Program; (2) describe findings from an assessment of medical students who recently completed a new version of the program in Malaysia; and (3) explore how healthcare settings could benefit from this innovative program.

The effect of hippocampal damage in children on recalling the past and imagining new experiences.

PubMed

Cooper, Janine M; Vargha-Khadem, Faraneh; Gadian, David G; Maguire, Eleanor A

2011-06-01

Compared to adults, relatively little is known about autobiographical memory and the ability to imagine fictitious and future scenarios in school-aged children, despite the importance of these functions for development and subsequent independent living. Even less is understood about the effect of early hippocampal damage on children's memory and imagination abilities. To bridge this gap, we devised a novel naturalistic autobiographical memory task that enabled us to formally assess the memory for recent autobiographical experiences in healthy school-aged children. Contemporaneous with the autobiographical memories being formed, the children also imagined and described fictitious scenarios. Having established the performance of healthy school-aged children on these tasks, we proceeded to make comparisons with children (n=21) who had experienced neonatal hypoxia/ischaemia, and consequent bilateral hippocampal damage. Our results showed that healthy children could recall autobiographical events, including spatiotemporal information and specific episodic details. By contrast, children who had experienced neonatal hypoxia/ischaemia had impaired recall, with the specific details of episodes being lost. Despite this significant memory deficit they were able to construct fictitious scenarios. This is in clear contrast to adults with hippocampal damage, who typically have impaired autobiographical memory and deficits in the construction of fictitious and future scenarios. We speculate that the paediatric patients' relatively intact semantic memory and/or some functionality in their residual hippocampi may underpin their scene construction ability. Copyright © 2011 Elsevier Ltd. All rights reserved.

Oxidative Damage in the Guinea Pig Hippocampal Slice

DTIC Science & Technology

1989-01-01

Original Contribution OXIDATIVE DAMAGE IN THE GUINEA PIG HIPPOCAMPAL SLICE TIRRY C. Pnt.N1.iAR’ and KATIlRNN L. Nt-t-t- Physiology Department. Armed Forces...responses in the hippocampal slice isolated from the brains of guinea pigs . Electrical stim- ulation of afferents to neurons of the CA I region of...from the brains be secreted by the microglia invading a region of in- of euthanized male Hartley guinea pigs as previously Jury. ’ Another possible

Hippocampal subfield volumetry in mild cognitive impairment, Alzheimer's disease and semantic dementia.

PubMed

La Joie, Renaud; Perrotin, Audrey; de La Sayette, Vincent; Egret, Stéphanie; Doeuvre, Loïc; Belliard, Serge; Eustache, Francis; Desgranges, Béatrice; Chételat, Gaël

2013-01-01

Hippocampal atrophy is a well-known feature of Alzheimer's disease (AD), but sensitivity and specificity of hippocampal volumetry are limited. Neuropathological studies have shown that hippocampal subfields are differentially vulnerable to AD; hippocampal subfield volumetry may thus prove to be more accurate than global hippocampal volumetry to detect AD. CA1, subiculum and other subfields were manually delineated from 40 healthy controls, 18 AD, 17 amnestic Mild Cognitive Impairment (aMCI), and 8 semantic dementia (SD) patients using a previously developed high resolution MRI procedure. Non-parametric group comparisons and receiver operating characteristic (ROC) analyses were conducted. Complementary analyses were conducted to evaluate differences of hemispheric asymmetry and anterior-predominance between AD and SD patients and to distinguish aMCI patients with or without β-amyloid deposition as assessed by Florbetapir-TEP. Global hippocampi were atrophied in all three patient groups and volume decreases were maximal in the CA1 subfield (22% loss in aMCI, 27% in both AD and SD; all p < 0.001). In aMCI, CA1 volumetry was more accurate than global hippocampal measurement to distinguish patients from controls (areas under the ROC curve = 0.88 and 0.76, respectively; p = 0.05) and preliminary analyses suggest that it was independent from the presence of β-amyloid deposition. In patients with SD, whereas the degree of CA1 and subiculum atrophy was similar to that found in AD patients, hemispheric and anterior-posterior asymmetry were significantly more marked than in AD with greater involvement of the left and anterior hippocampal subfields. The findings suggest that CA1 measurement is more sensitive than global hippocampal volumetry to detect structural changes at the pre-dementia stage, although the predominance of CA1 atrophy does not appear to be specific to AD pathophysiological processes.

Gender differences in post-temporal lobectomy verbal memory and relationships between MRI hippocampal volumes and preoperative verbal memory.

PubMed

Trenerry, M R; Jack, C R; Cascino, G D; Sharbrough, F W; Ivnik, R J

1995-01-01

Thirty-three men and 42 women who underwent left, and 26 men and 24 women who underwent right temporal lobectomy (TL) were studied retrospectively to determine if there were sex differences in (1) verbal memory outcome, and (2) relationships between verbal memory and magnetic resonance imaging (MRI) hippocampal volumes. All patients were left hemisphere language dominant. The surgical specimen and MRI were consistent only with mesial temporal sclerosis (MTS). Verbal memory was evaluated by Logical Memory percent retention (LMPER) from the Wechsler Memory Scale-Revised (WMS-R). Women experienced a significant improvement while men experienced a significant decline in postoperative LMPER. The difference between right and left hippocampal volumes predicted verbal memory outcome in both men and women. Preoperative LMPER was positively correlated with both the left and right hippocampal volumes in left TL women only. No verbal memory sex differences or correlations between LMPER and MRI data were found in the right TL group. The data support the presence of human neurocognitive sexual dimorphism. Verbal memory abilities supported by the hippocampus are less lateralized in women with left temporal lobe epilepsy and mesial temporal sclerosis. Women appear to have greater verbal memory plasticity following early left mesial temporal lobe insult.

Prosodic expectations in silent reading: ERP evidence from rhyme scheme and semantic congruence in classic Chinese poems.

PubMed

Chen, Qingrong; Zhang, Jingjing; Xu, Xiaodong; Scheepers, Christoph; Yang, Yiming; Tanenhaus, Michael K

2016-09-01

In an ERP study, classic Chinese poems with a well-known rhyme scheme were used to generate an expectation of a rhyme in the absence of an expectation for a specific character. Critical characters were either consistent or inconsistent with the expected rhyme scheme and semantically congruent or incongruent with the content of the poem. These stimuli allowed us to examine whether a top-down rhyme scheme expectation would affect relatively early components of the ERP associated with character-to-sound mapping (P200) and lexically-mediated semantic processing (N400). The ERP data revealed that rhyme scheme congruence, but not semantic congruence modulated the P200: rhyme-incongruent characters elicited a P200 effect across the head demonstrating that top-down expectations influence early phonological coding of the character before lexical-semantic processing. Rhyme scheme incongruence also produced a right-lateralized N400-like effect. Moreover, compared to semantically congruous poems, semantically incongruous poems produced a larger N400 response only when the character was consistent with the expected rhyme scheme. The results suggest that top-down prosodic expectations can modulate early phonological processing in visual word recognition, indicating that prosodic expectations might play an important role in silent reading. They also suggest that semantic processing is influenced by general knowledge of text genre. Copyright © 2016 Elsevier B.V. All rights reserved.

Phoneme Monitoring in Silent Naming and Perception in Adults Who Stutter

ERIC Educational Resources Information Center

Sasisekaran, Jayanthi; De Nil, Luc F.

2006-01-01

The present study investigated phonological encoding skills in persons who stutter (PWS). Participants were 10 PWS (M=31.8 years, S.D.=5.9) matched for age, gender, and handedness with 12 persons who do not stutter (PNS) (M=24.3 years, S.D.=4.3). The groups were compared in a phoneme monitoring task performed during silent picture naming. The…

Occurrence of maternal and paternal spindles in unfertilized human oocytes: possible relationship to nucleation defects after silent fertilization.

PubMed

Van Blerkom, Jonathan; Davis, Patrick; Alexander, Samuel

2004-04-01

Experience with conventional clinical IVF indicates that a first cleavage can occur in the absence of detectable pronuclear formation (so-called silent fertilization). In these instances, the first division is often asymmetrical and delayed when compared with normally fertilized siblings. In this study, DNA configurations and spindle organization were examined by fluorescence microscopy in metaphase II human oocytes that remained unfertilized after conventional IVF and were considered likely candidates for silent fertilization. The results show comparatively high frequencies of penetration in the absence of detectable pronuclear evolution, and that both a maternal meiotic and a sperm-derived mitotic-like spindle can coexist in the same oocyte. Patterns of cell division and blastomere nucleation in silent fertilizations suggest the possibility that this division may involve uniparental chromosomal segregation in which maternal and paternal DNA is differentially partitioned into daughter blastomeres. This pattern of inheritance may generate certain types of ploidy and nucleation defects detected at the 2- to 4-cell stage.

Human Hippocampal Dynamics during Response Conflict.

PubMed

Oehrn, Carina R; Baumann, Conrad; Fell, Juergen; Lee, Hweeling; Kessler, Henrik; Habel, Ute; Hanslmayr, Simon; Axmacher, Nikolai

2015-08-31

Besides its relevance for declarative memory functions, hippocampal activation has been observed during disambiguation of uncertainty and conflict. Uncertainty and conflict may arise on various levels. On the perceptual level, the hippocampus has been associated with signaling of contextual deviance and disambiguation of similar items (i.e., pattern separation). Furthermore, conflicts can occur on the response level. Animal experiments showed a role of the hippocampus for inhibition of prevailing response tendencies and suppression of automatic stimulus-response mappings, potentially related to increased theta oscillations (3-8 Hz). In humans, a recent fMRI study demonstrated hippocampal involvement in approach-avoidance conflicts. However, the more general significance of hippocampal activity for dealing with response conflicts also on a cognitive level is still unknown. Here, we investigated the role of the hippocampus for response conflict in the Stroop task by combining intracranial electroencephalography (iEEG) recordings from the hippocampus of epilepsy patients with region of interest-based fMRI in healthy participants. Both methods revealed converging evidence that the hippocampus is recruited in a regionally specific manner during response conflict. Moreover, our iEEG data show that this activation depends on theta oscillations and is relevant for successful response conflict resolution. Copyright © 2015 Elsevier Ltd. All rights reserved.

Are hippocampal size differences in posttraumatic stress disorder mediated by sleep pathology?

PubMed

Mohlenhoff, Brian S; Chao, Linda L; Buckley, Shannon T; Weiner, Michael W; Neylan, Thomas C

2014-06-01

Posttraumatic stress disorder (PTSD) is associated with smaller volumes of the hippocampus, as has been demonstrated by meta-analyses. Proposed mechanistic relationships are reviewed briefly, including the hypothesis that sleep disturbances mediate the effects of PTSD on hippocampal volume. Evidence for this includes findings that insomnia and restricted sleep are associated with changes in hippocampal cell regulation and impairments in cognition. We present results of a new study of 187 subjects in whom neither PTSD nor poor sleep was associated with lower hippocampal volume. We outline a broad research agenda centered on the hypothesis that sleep changes mediate the relationship between PTSD and hippocampal volume. Copyright © 2014. Published by Elsevier Inc.

An investigation of the reduction of carbon dioxide in a silent electric discharge

NASA Technical Reports Server (NTRS)

Luce, R. S.; Greenough, B. (Editor)

1978-01-01

The reduction of CO2 to O2 and CO in a silent electric discharge was studied. It was found that current alone (in the ionized plasma induced by the silent electric discharge) was reponsible for the CO2 reduction process. Voltage and frequency were important only in so far as they induced current in the plasma. Pressure and temperature were of minimum influence in the process. The large power consumption in the process was recognized as resulting from the low power factor of the reactor vessel which electrically behaved like a capacitor. The power factor was subsequently improved by adding an inductive element to make the reactor vessel capacitance part of a resonant circuit. It was found that the CO2 reduction process was most efficient in terms of power vs reduction rate when a voltage was employed that was only slightly higher than that needed to induce the plasma.

Hippocampal sclerosis: volumetric evaluation of the substructures of the hippocampus by magnetic resonance imaging.

PubMed

Granados Sánchez, A M; Orejuela Zapata, J F

2018-05-25

The pathological classification of hippocampal sclerosis is based on the loss of neurons in the substructures of the hippocampus. This study aimed to evaluate these substructures in patients with hippocampal sclerosis by magnetic resonance imaging and to compare the usefulness of this morphological analysis compared to that of volumetric analysis of the entire hippocampus. We included 25 controls and 25 patients with hippocampal sclerosis whose diagnosis was extracted from the institutional epilepsy board. We used FreeSurfer to process the studies and obtain the volumetric data. We evaluated overall volume and volume by substructure: fimbria, subiculum, presubiculum, hippocampal sulcus, CA1, CA2-CA3, CA4, and dentate gyrus (DG). We considered p < 0.05 statistically significant. We observed statistically significant decreases in the volume of the hippocampus ipsilateral to the epileptogenic focus in 19 (76.0%) of the 25 cases. With the exception of the hippocampal sulcus, we observed a decrease in all ipsilateral hippocampal substructures in patients with right hippocampal sclerosis (CA1, p=0.0223; CA2-CA3, p=0.0066; CA4-GD, p=0.0066; fimbria, p=0.0046; presubiculum, p=0.0087; subiculum, p=0.0017) and in those with left hippocampal sclerosis (CA1, p<0.0001; CA2-CA3, p<0. 0001; CA4-GD, p<0. 0001; fimbria, p=0.0183; presubiculum, p<0. 0001; subiculum, p<0. 0001). In four patients with left hippocampal sclerosis, none of the substructures had statistically significant alterations, although a trend toward atrophy was observed, mainly in CA2-CA3 and CA4-GD. The findings suggest that it can be useful to assess the substructures of the hippocampus to improve the performance of diagnostic imaging in patients with hippocampal sclerosis. Copyright © 2018 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Choline-mediated modulation of hippocampal sharp wave-ripple complexes in vitro.

PubMed

Fischer, Viktoria; Both, Martin; Draguhn, Andreas; Egorov, Alexei V

2014-06-01

The cholinergic system is critically involved in the modulation of cognitive functions, including learning and memory. Acetylcholine acts through muscarinic (mAChRs) and nicotinic receptors (nAChRs), which are both abundantly expressed in the hippocampus. Previous evidence indicates that choline, the precursor and degradation product of Acetylcholine, can itself activate nAChRs and thereby affects intrinsic and synaptic neuronal functions. Here, we asked whether the cellular actions of choline directly affect hippocampal network activity. Using mouse hippocampal slices we found that choline efficiently suppresses spontaneously occurring sharp wave-ripple complexes (SPW-R) and can induce gamma oscillations. In addition, choline reduces synaptic transmission between hippocampal subfields CA3 and CA1. Surprisingly, these effects are mediated by activation of both mAChRs and α7-containing nAChRs. Most nicotinic effects became only apparent after local, fast application of choline, indicating rapid desensitization kinetics of nAChRs. Effects were still present following block of choline uptake and are, therefore, likely because of direct actions of choline at the respective receptors. Together, choline turns out to be a potent regulator of patterned network activity within the hippocampus. These actions may be of importance for understanding state transitions in normal and pathologically altered neuronal networks. In this study we asked whether choline, the precursor and degradation product of acetylcholine, directly affects hippocampal network activity. Using mouse hippocampal slices we found that choline efficiently suppresses spontaneously occurring sharp wave-ripple complexes (SPW-R). In addition, choline reduces synaptic transmission between hippocampal subfields. These effects are mediated by direct activation of muscarinic as well as nicotinic cholinergic pathways. Together, choline turns out to be a potent regulator of patterned activity within hippocampal

Aerobic exercise increases hippocampal volume and improves memory in multiple sclerosis: preliminary findings.

PubMed

Leavitt, V M; Cirnigliaro, C; Cohen, A; Farag, A; Brooks, M; Wecht, J M; Wylie, G R; Chiaravalloti, N D; DeLuca, J; Sumowski, J F

2014-01-01

Multiple sclerosis leads to prominent hippocampal atrophy, which is linked to memory deficits. Indeed, 50% of multiple sclerosis patients suffer memory impairment, with negative consequences for quality of life. There are currently no effective memory treatments for multiple sclerosis either pharmacological or behavioral. Aerobic exercise improves memory and promotes hippocampal neurogenesis in nonhuman animals. Here, we investigate the benefits of aerobic exercise in memory-impaired multiple sclerosis patients. Pilot data were collected from two ambulatory, memory-impaired multiple sclerosis participants randomized to non-aerobic (stretching) and aerobic (stationary cycling) conditions. The following baseline/follow-up measurements were taken: high-resolution MRI (neuroanatomical volumes), fMRI (functional connectivity), and memory assessment. Intervention was 30-minute sessions 3 times per week for 3 months. Aerobic exercise resulted in 16.5% increase in hippocampal volume and 53.7% increase in memory, as well as increased hippocampal resting-state functional connectivity. Improvements were specific, with no comparable changes in overall cerebral gray matter (+2.4%), non-hippocampal deep gray matter structures (thalamus, caudate: -4.0%), or in non-memory cognitive functioning (executive functions, processing speed, working memory: changes ranged from -11% to +4%). Non-aerobic exercise resulted in relatively no change in hippocampal volume (2.8%) or memory (0.0%), and no changes in hippocampal functional connectivity. This is the first evidence for aerobic exercise to increase hippocampal volume and connectivity and improve memory in multiple sclerosis. Aerobic exercise represents a cost-effective, widely available, natural, and self-administered treatment with no adverse side effects that may be the first effective memory treatment for multiple sclerosis patients.

A mathematical model of aging-related and cortisol induced hippocampal dysfunction

PubMed Central

McAuley, Mark T; Kenny, Rose Anne; Kirkwood, Thomas BL; Wilkinson, Darren J; Jones, Janette JL; Miller, Veronica M

2009-01-01

Background The hippocampus is essential for declarative memory synthesis and is a core pathological substrate for Alzheimer's disease (AD), the most common aging-related dementing disease. Acute increases in plasma cortisol are associated with transient hippocampal inhibition and retrograde amnesia, while chronic cortisol elevation is associated with hippocampal atrophy. Thus, cortisol levels could be monitored and managed in older people, to decrease their risk of AD type hippocampal dysfunction. We generated an in silicomodel of the chronic effects of elevated plasma cortisol on hippocampal activity and atrophy, using the systems biology mark-up language (SBML). We further challenged the model with biologically based interventions to ascertain if cortisol associated hippocampal dysfunction could be abrogated. Results The in silicoSBML model reflected the in vivoaging of the hippocampus and increased plasma cortisol and negative feedback to the hypothalamic pituitary axis. Aging induced a 12% decrease in hippocampus activity (HA), increased to 30% by acute and 40% by chronic elevations in cortisol. The biological intervention attenuated the cortisol associated decrease in HA by 2% in the acute cortisol simulation and by 8% in the chronic simulation. Conclusion Both acute and chronic elevations in cortisol secretion increased aging-associated hippocampal atrophy and a loss of HA in the model. We suggest that this first SMBL model, in tandem with in vitroand in vivostudies, may provide a backbone to further frame computational cortisol and brain aging models, which may help predict aging-related brain changes in vulnerable older people. PMID:19320982

Early Adolescent MK-801 Exposure Impairs the Maturation of Ventral Hippocampal Control of Basolateral Amygdala Drive in the Adult Prefrontal Cortex

PubMed Central

Thomases, Daniel R.; Cass, Daryn K.; Meyer, Jacqueline D.; Caballero, Adriana

2014-01-01

The adolescent susceptibility to the onset of psychiatric disorders is only beginning to be understood when factoring in the development of the prefrontal cortex (PFC). The functional maturation of the PFC is dependent upon proper integration of glutamatergic inputs from the ventral hippocampus (vHipp) and the basolateral amygdala (BLA). Here we assessed how transient NMDAR blockade during adolescence alters the functional interaction of vHipp–BLA inputs in regulating PFC plasticity. Local field potential recordings were used to determine changes in long-term depression (LTD) and long-term potentiation (LTP) of PFC responses resulting from vHipp and BLA high-frequency stimulation in adult rats that received repeated injections of saline or the NMDAR antagonist MK-801 from postnatal day 35 (P35) to P40. We found that early adolescent MK-801 exposure elicited an age- and input-specific dysregulation of vHipp–PFC plasticity, characterized by a shift from LTD to LTP without altering the BLA-induced LTP. Data also showed that the vHipp normally resets the LTP state of BLA transmission; however, this inhibitory regulation is absent following early adolescent MK-801 treatment. This deficit was reminiscent of PFC responses seen in drug-naive juveniles. Notably, local prefrontal upregulation of GABAAα1 function completely restored vHipp functionality and its regulation of BLA plasticity in MK-801-treated rats. Thus, NMDAR signaling is critical for the periadolescent acquisition of a GABA-dependent hippocampal control of PFC plasticity, which enables the inhibitory control of the prefrontal output by the vHipp. A dysregulation of this pathway can alter PFC processing of other converging afferents such as those from the BLA. PMID:24990926

Impaired emotional autobiographical memory associated with right amygdalar-hippocampal atrophy in Alzheimer's disease patients.

PubMed

Philippi, Nathalie; Botzung, Anne; Noblet, Vincent; Rousseau, François; Després, Olivier; Cretin, Benjamin; Kremer, Stéphane; Blanc, Frédéric; Manning, Liliann

2015-01-01

We studied the influence of emotions on autobiographical memory (AbM) in patients with Alzheimer's disease (AD), characteristically triggering atrophy in the hippocampus and the amygdala, two crucial structures sustaining memory and emotional processing. Our first aim was to analyze the influence of emotion on AbM in AD patients, on both the proportion and the specificity of emotional memories. Additionally, we sought to determine the relationship of emotional AbM to amygdalar-hippocampal volumes. Eighteen prodromal to mild AD patients and 18 age-matched healthy controls were included. We obtained 30 autobiographical memories per participant using the modified Crovitz test (MCT). Analyses were performed on global scores, rates and specificity scores of the emotional vs. neutral categories of memories. Amygdalar-hippocampal volumes were extracted from 3D T1-weighted MRI scans and tested for correlations with behavioral data. Overall, AD patients displayed a deficit in emotional AbMs as they elicited less emotional memories than the controls, however, the specificity of those memories was preserved. The deficit likely implied retrieval or storage as it was extended in time and without reminiscence bump effect. Global scores and rates of emotional memories, but not the specificity scores, were correlated to right amygdalar and hippocampal volumes, indicating that atrophy in these structures has a central role in the deficit observed. Conversely, emotional memories were more specific than neutral memories in both groups, reflecting an enhancement effect of emotion that could be supported by other brain regions that are spared during the early stages of the disease.

Validity Evidence for the Test of Silent Reading Efficiency and Comprehension (TOSREC)

ERIC Educational Resources Information Center

Johnson, Evelyn S.; Pool, Juli L.; Carter, Deborah R.

2011-01-01

An essential component of a response to intervention (RTI) framework is a screening process that is both accurate and efficient. The purpose of this study was to analyze the validity evidence for the "Test of Silent Reading Efficiency and Comprehension" (TOSREC) to determine its potential for use within a screening process. Participants included…

Stimulation of estradiol biosynthesis by tributyltin in rat hippocampal slices.

PubMed

Munetsuna, Eiji; Hattori, Minoru; Yamazaki, Takeshi

2014-01-01

Hippocampal functions are influenced by steroid hormones, such as testosterone and estradiol. It has been demonstrated that hippocampus-derived steroid hormones play important roles in neuronal protection and synapse formation. Our research groups have demonstrated that estradiol is de novo synthesized in the rat hippocampus. However, the mechanism(s) regulating this synthesis remains unclear. It has been reported that tributyltin, an environmental pollutant, binds to the retinoid X receptor (RXR) and modifies estrogen synthesis in human granulosa-like tumor cells. This compound can penetrate the blood brain barrier, and tends to accumulate in the brain. Based on these facts, we hypothesized that tributyltin could influence the hippocampal estradiol synthesis. A concentration of 0.1 μM tributyltin induced an increase in the mRNA content of P450(17α) and P450arom in hippocampal slices, as determined using real-time PCR. The transcript levels of other steroidogenic enzymes and a steroidogenic acute regulatory protein were not affected. The estradiol level in rat hippocampal slices was subsequently determined using a radioimmunoassay. We found that the estradiol synthesis was stimulated by ∼2-fold following a 48-h treatment with 0.1 μM tributyltin, and this was accompanied by transcriptional activation of P450(17α) and P450arom. Tributyltin stimulated de novo hippocampal estradiol synthesis by modifying the transcription of specific steroidogenic enzymes.

Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing.

PubMed

Neltner, Janna H; Abner, Erin L; Baker, Steven; Schmitt, Frederick A; Kryscio, Richard J; Jicha, Gregory A; Smith, Charles D; Hammack, Eleanor; Kukull, Walter A; Brenowitz, Willa D; Van Eldik, Linda J; Nelson, Peter T

2014-01-01

Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer's Disease Centre, Nun Study, and National Alzheimer's Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case-control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P < 0.001). This enables informative evaluation of anatomical regions outside of the hippocampus. To assess the morphology of brain microvasculature far more rigorously than what is possible using semi-quantitative pathological scoring, we applied digital pathological (Aperio ScanScope) methods on a subsample of frontal cortex sections from hippocampal sclerosis of ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections

Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing

PubMed Central

Neltner, Janna H.; Abner, Erin L.; Baker, Steven; Schmitt, Frederick A.; Kryscio, Richard J.; Jicha, Gregory A.; Smith, Charles D.; Hammack, Eleanor; Kukull, Walter A.; Brenowitz, Willa D.; Van Eldik, Linda J.

2014-01-01

Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer’s Disease Centre, Nun Study, and National Alzheimer’s Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case–control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P < 0.001). This enables informative evaluation of anatomical regions outside of the hippocampus. To assess the morphology of brain microvasculature far more rigorously than what is possible using semi-quantitative pathological scoring, we applied digital pathological (Aperio ScanScope) methods on a subsample of frontal cortex sections from hippocampal sclerosis of ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections

Combined effects of marijuana and nicotine on memory performance and hippocampal volume.

PubMed

Filbey, Francesca M; McQueeny, Tim; Kadamangudi, Shrinath; Bice, Collette; Ketcherside, Ariel

2015-10-15

Combined use of marijuana (MJ) and tobacco is highly prevalent in today's population. Individual use of either substance is linked to structural brain changes and altered cognitive function, especially with consistent reports of hippocampal volume deficits and poorer memory performance. However, the combined effects of MJ and tobacco on hippocampal structure and on learning and memory processes remain unknown. In this study, we examined both the individual and combined effects of MJ and tobacco on hippocampal volumes and memory performance in four groups of adults taken from two larger studies: MJ-only users (n=36), nicotine-only (Nic-only, n=19), combined marijuana and nicotine users (MJ+Nic, n=19) and non-using healthy controls (n=16). Total bilateral hippocampal volumes and memory performance (WMS-III logical memory) were compared across groups controlling for total brain size and recent alcohol use. Results found MJ and MJ+Nic groups had smaller total hippocampal volumes compared to Nic-only and controls. No significant difference between groups was found between immediate and delayed story recall. However, the controls showed a trend for larger hippocampal volumes being associated with better memory scores, while MJ+Nic users showed a unique inversion, whereby smaller hippocampal volume was associated with better memory. Overall, results suggest abnormalities in the brain-behavior relationships underlying memory processes with combined use of marijuana and nicotine use. Further research will need to address these complex interactions between MJ and nicotine. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Educational attainment and hippocampal atrophy in the Alzheimer's disease neuroimaging initiative cohort.

PubMed

Shpanskaya, Katie S; Choudhury, Kingshuk Roy; Hostage, Christopher; Murphy, Kelly R; Petrella, Jeffrey R; Doraiswamy, P Murali

2014-12-01

Subjects with higher cognitive reserve (CR) may be at a lower risk for Alzheimer's disease (AD), but the neural mechanisms underlying this are not known. Hippocampal volume loss is an early event in AD that triggers cognitive decline. Regression analyses of the effects of education on MRI-measured baseline HV in 675 subjects (201 normal, 329 with mild cognitive impairment (MCI), and 146 subjects with mild AD), adjusting for age, gender, APOE ɛ4 status and intracranial volume (ICV). Subjects were derived from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a large US national biomarker study. The association between higher education and larger HV was significant in AD (P=0.014) but not in cognitively normal or MCI subjects. In AD, HV was about 8% larger in a person with 20 years of education relative to someone with 6 years of education. There was also a trend for the interaction between education and APOE ɛ4 to be significant in AD (P=0.056). A potential protective association between higher education and lower hippocampal atrophy in patients with AD appears consistent with prior epidemiologic data linking higher education levels with lower rates of incident dementia. Longitudinal studies are warranted to confirm these findings. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

BOOK REVIEW: ARE YOU AN ADVOCATE, TACIT SUPPORTER, CRITICAL SKEPTIC, OR SILENT SKEPTIC?

EPA Science Inventory

"Silent Sperm," "You're not half the man your grandfather was," "Assault on the Male," "Gender Benders,"-perhaps no other public health concern has given rise to the number of memorable sound bites than has the issue of whether environmental contaminants are causing adverse healt...

Transient slow gamma synchrony underlies hippocampal memory replay

PubMed Central

Carr, Margaret F.; Karlsson, Mattias P.; Frank, Loren M.

2012-01-01

Summary The replay of previously stored memories during hippocampal sharp wave ripples (SWRs) is thought to support both memory retrieval and consolidation in distributed hippocampal-neocortical circuits. Replay events consist of precisely timed sequences of spikes from CA3 and CA1 neurons that are coordinated both within and across hemispheres. The mechanism of this coordination is not understood. Here we show that during SWRs in both awake and quiescent states there are transient increases in slow gamma (20-50Hz) power and synchrony across dorsal CA3 and CA1 networks of both hemispheres. These gamma oscillations entrain CA3 and CA1 spiking. Moreover, during awake SWRs, higher levels of slow gamma synchrony are predictive of higher quality replay of past experiences. Our results indicate that CA3–CA1 gamma synchronization is a central component of awake memory replay and suggest that transient gamma synchronization serves as a clocking mechanism to enable coordinated memory reactivation across the hippocampal network. PMID:22920260

Prevalence of silent vertebral fractures detected by vertebral fracture assessment in young Portuguese men with hyperthyroidism.

PubMed

Barbosa, Ana Paula; Rui Mascarenhas, Mário; Silva, Carlos Francisco; Távora, Isabel; Bicho, Manuel; do Carmo, Isabel; de Oliveira, António Gouveia

2015-02-01

Hyperthyroidism is a risk factor for reduced bone mineral density (BMD) and osteoporotic fractures. Vertebral fracture assessment (VFA) by dual-energy X-ray absorptiometry (DXA) is a radiological method of visualization of the spine, which enables patient comfort and reduced radiation exposure. This study was carried out to evaluate BMD and the prevalence of silent vertebral fractures in young men with hyperthyroidism. We conducted a cross-sectional study in a group of Portuguese men aged up to 50 years and matched in hyperthyroidism (n=24) and control (n=24) groups. A group of 48 Portuguese men aged up to 50 years was divided and matched in hyperthyroidism (n=24) and control (n=24) groups. BMD (g/cm(2)) at L1-L4, hip, radius 33%, and whole body as well as the total body masses (kg) were studied by DXA. VFA was used to detect fractures and those were classified by Genant's semiquantitative method. No patient had previously been treated for hyperthyroidism, osteoporosis, or low bone mass. Adequate statistical tests were used. The mean age, height, and total fat mass were similar in both groups (P≥0.05). The total lean body mass and the mean BMD at lumbar spine, hip, and whole body were significantly decreased in the hyperthyroidism group. In this group, there was also a trend for an increased prevalence of reduced BMD/osteoporosis and osteoporotic vertebral fractures. The results obtained using VFA technology (confirmed by X-ray) suggest that the BMD changes in young men with nontreated hyperthyroidism may lead to the development of osteoporosis and vertebral fractures. This supports the pertinence of using VFA in the routine of osteoporosis assessment to detect silent fractures precociously and consider early treatment. © 2015 European Society of Endocrinology.

Age-dependent long-term structural and functional effects of early life seizures: evidence for a hippocampal critical period influencing plasticity in adulthood

PubMed Central

Meyerand, M.E.; Sutula, T.

2015-01-01

Neural activity promotes circuit formation in developing systems and during critical periods permanently modifies circuit organization and functional properties. These observations suggest that excessive neural activity, as occurs during seizures, might influence developing neural circuitry with long-term outcomes that depend on age at the time of seizures. We systematically examined long-term structural and functional consequences of seizures induced in rats by kainic acid, pentylenetetrazol, and hyperthermia across postnatal ages from birth through postnatal day 90 in adulthood (P90). Magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and electrophysiological methods at ≥P95 following seizures induced from P1 to P90 demonstrated consistent patterns of gross atrophy, microstructural abnormalities in the corpus callosum and hippocampus, and functional alterations in hippocampal circuitry at ≥P95 that were independent of the method of seizure induction and varied systematically as a function of age at the time of seizures. Three distinct epochs were observed in which seizures resulted in distinct long-term structural and functional outcomes at ≥P95. Seizures prior to P20 resulted in DTI abnormalities in corpus callosum and hippocampus in the absence of gross cerebral atrophy, and increased paired pulse inhibition (PPI) in the dentate gyrus at ≥P95. Seizures after P30 induced a different pattern of DTI abnormalities in the fimbria and hippocampus accompanied by gross cerebral atrophy with increases in lateral ventricular volume, as well as increased PPI in the dentate gyrus at ≥P95. In contrast, seizures between P20-P30 did not result in cerebral atrophy or significant imaging abnormalities in the hippocampus or white matter, but irreversibly decreased PPI in the dentate gyrus compared to normal adult controls. These age-specific long-term structural and functional outcomes identify P20-P30 as a potential critical period in hippocampal

The evolving concept of the intrinsic hippocampal theta/gamma oscillator.

PubMed

Cataldi, Mauro; Vigliotti, Chiara

2018-01-01

Three main types of electrical oscillations are recorded from the hippocampus in vivo : theta (θ), gamma (γ) and sharp wave ripples with frequency bands of 4-12, 25-100 and 110-250 Hz, respectively. Theta activity is the more robust of them, and has important physiological roles because it is involved in spatial navigation, memory formation and memory retrieval. Classical lesion studies in vivo have suggested that the hippocampus passively follows the θ  rhythm generated in the septum by neurons that are synaptically connected with hippocampal neurons though septo-hippocampal connections. This view has been questioned since several studies have shown that oscillations in the θ range can be recorded in in vitro hippocampal preparations thus indicating that the hippocampus itself can act as a θ oscillator. In this review, we will describe how the paradigm of the intrinsic θ oscillator has been changing over the years from simple models that have proposed single hippocampal lamellae to contain the θ oscillator to the current models that include some degree of septo-temporal integration.

Genome mining-directed activation of a silent angucycline biosynthetic gene cluster in Streptomyces chattanoogensis.

PubMed

Zhou, Zhenxing; Xu, Qingqing; Bu, Qingting; Guo, Yuanyang; Liu, Shuiping; Liu, Yu; Du, Yiling; Li, Yongquan

2015-02-09

Genomic sequencing of actinomycetes has revealed the presence of numerous gene clusters seemingly capable of natural product biosynthesis, yet most clusters are cryptic under laboratory conditions. Bioinformatics analysis of the completely sequenced genome of Streptomyces chattanoogensis L10 (CGMCC 2644) revealed a silent angucycline biosynthetic gene cluster. The overexpression of a pathway-specific activator gene under the constitutive ermE* promoter successfully triggered the expression of the angucycline biosynthetic genes. Two novel members of the angucycline antibiotic family, chattamycins A and B, were further isolated and elucidated. Biological activity assays demonstrated that chattamycin B possesses good antitumor activities against human cancer cell lines and moderate antibacterial activities. The results presented here provide a feasible method to activate silent angucycline biosynthetic gene clusters to discover potential new drug leads. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A novel non-contrast-enhanced MRA using silent scan for evaluation of brain arteriovenous malformation: A case report and review of literature.

PubMed

Moon, Jin Il; Baek, Hye Jin; Ryu, Kyeong Hwa; Park, Hyun

2017-11-01

Brain arteriovenous malformations (AVMs) are congenital vascular abnormalities involving abnormal connections between arteries and veins. In clinical practice, imaging studies help evaluate feeding arteries, niduses, draining venous systems, and coexisting complications in patients with brain AVM. They also have an impact on decision-making regarding clinical management. We applied a novel non-contrast-enhanced MR angiography (MRA) technique, termed "silent MRA," for evaluating an incidental brain AVM. Here, we describe the clinical case with radiological review and highlight the technical background and clinical usefulness of silent MRA. A 60-year-old woman underwent neuroimaging study including MRA to evaluate intracranial cause of headache. The brain AVM, including its nidus and draining veins, was conspicuously delineated on silent MRA images; these findings correlated well with conventional angiographic findings. The patient did not receive interventional or surgical treatment. The patient is being followed up regularly at the outpatient department. The silent MRA can be a suitable imaging modality for repeated follow-up evaluation for not only brain AVMs but also various intracranial vascular diseases without the use of contrast materials.

Hippocampal Morphology in a Rat Model of Depression: The Effects of Physical Activity

PubMed Central

Sierakowiak, Adam; Mattsson, Anna; Gómez-Galán, Marta; Feminía, Teresa; Graae, Lisette; Aski, Sahar Nikkhou; Damberg, Peter; Lindskog, Mia; Brené, Stefan; Åberg, Elin

2015-01-01

Accumulating in vivo and ex vivo evidences show that humans suffering from depression have decreased hippocampal volume and altered spine density. Moreover, physical activity has an antidepressant effect in humans and in animal models, but to what extent physical activity can affect hippocampal volume and spine numbers in a model for depression is not known. In this study we analyzed whether physical activity affects hippocampal volume and spine density by analyzing a rodent genetic model of depression, Flinders Sensitive Line Rats (FSL), with Magnetic Resonance Imaging (MRI) and ex vivo Golgi staining. We found that physical activity in the form of voluntary wheel running during 5 weeks increased hippocampal volume. Moreover, runners also had larger numbers of thin spines in the dentate gyrus. Our findings support that voluntary wheel running, which is antidepressive in FSL rats, is associated with increased hippocampal volume and spine numbers. PMID:25674191

Hippocampal morphology in a rat model of depression: the effects of physical activity.

PubMed

Sierakowiak, Adam; Mattsson, Anna; Gómez-Galán, Marta; Feminía, Teresa; Graae, Lisette; Aski, Sahar Nikkhou; Damberg, Peter; Lindskog, Mia; Brené, Stefan; Åberg, Elin

2014-01-01

Accumulating in vivo and ex vivo evidences show that humans suffering from depression have decreased hippocampal volume and altered spine density. Moreover, physical activity has an antidepressant effect in humans and in animal models, but to what extent physical activity can affect hippocampal volume and spine numbers in a model for depression is not known. In this study we analyzed whether physical activity affects hippocampal volume and spine density by analyzing a rodent genetic model of depression, Flinders Sensitive Line Rats (FSL), with Magnetic Resonance Imaging (MRI) and ex vivo Golgi staining. We found that physical activity in the form of voluntary wheel running during 5 weeks increased hippocampal volume. Moreover, runners also had larger numbers of thin spines in the dentate gyrus. Our findings support that voluntary wheel running, which is antidepressive in FSL rats, is associated with increased hippocampal volume and spine numbers.

Hippocampal dentation: Structural variation and its association with episodic memory in healthy adults.

PubMed

Fleming Beattie, Julia; Martin, Roy C; Kana, Rajesh K; Deshpande, Hrishikesh; Lee, Seongtaek; Curé, Joel; Ver Hoef, Lawrence

2017-07-01

While the hippocampus has long been identified as a structure integral to memory, the relationship between morphology and function has yet to be fully explained. We present an analysis of hippocampal dentation, a morphological feature previously unexplored in regard to its relationship with episodic memory. "Hippocampal dentation" in this case refers to surface convolutions, primarily present in the CA1/subiculum on the inferior aspect of the hippocampus. Hippocampal dentation was visualized using ultra-high resolution structural MRI and evaluated using a novel visual rating scale. The degree of hippocampal dentation was found to vary considerably across individuals, and was positively associated with verbal memory recall and visual memory recognition in a sample of 22 healthy adults. This study is the first to characterize the variation in hippocampal dentation in a healthy cohort and to demonstrate its association with aspects of episodic memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

Imbalance of incidental encoding across tasks: an explanation for non-memory-related hippocampal activations?

PubMed

Reas, Emilie T; Brewer, James B

2013-11-01

Functional neuroimaging studies have increasingly noted hippocampal activation associated with a variety of cognitive functions--such as decision making, attention, perception, incidental learning, prediction, and working memory--that have little apparent relation to declarative memory. Such findings might be difficult to reconcile with classical hippocampal lesion studies that show remarkable sparing of cognitive functions outside the realm of declarative memory. Even the oft-reported hippocampal activations during confident episodic retrieval are not entirely congruent with evidence that hippocampal lesions reliably impair encoding but inconsistently affect retrieval. Here we explore the conditions under which the hippocampus responds during episodic recall and recognition. Our findings suggest that anterior hippocampal activity may be related to the imbalance of incidental encoding across tasks and conditions rather than due to retrieval per se. Incidental encoding and hippocampal activity may be reduced during conditions where retrieval requires greater attentional engagement. During retrieval, anterior hippocampal activity decreases with increasing search duration and retrieval effort, and this deactivation corresponds with a coincident impaired encoding of the external environment (Israel, Seibert, Black, & Brewer, 2010; Reas & Brewer, 2013; Reas, Gimbel, Hales, & Brewer, 2011). In light of this emerging evidence, we discuss the proposal that some hippocampal activity observed during memory retrieval, or other non-memory conditions, may in fact be attributable to concomitant encoding activity that is regulated by the attentional demands of the principal task. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Neuropsychology, autobiographical memory, and hippocampal volume in "younger" and "older" patients with chronic schizophrenia.

PubMed

Herold, Christina Josefa; Lässer, Marc Montgomery; Schmid, Lena Anna; Seidl, Ulrich; Kong, Li; Fellhauer, Iven; Thomann, Philipp Arthur; Essig, Marco; Schröder, Johannes

2015-01-01

Despite a wide range of studies on neuropsychology in schizophrenia, autobiographical memory (AM) has been scarcely investigated in these patients. Hence, less is known about AM in older patients and hippocampal contribution to autobiographical memories of varying remoteness. Therefore, we investigated hippocampal volume and AM along with important neuropsychological domains in patients with chronic schizophrenia and the respective relationships between these parameters. We compared 25 older patients with chronic schizophrenia to 23 younger patients and an older healthy control group (N = 21) with respect to AM, additional neuropsychological parameters, and hippocampal volume. Personal episodic and semantic memory was investigated using a semi-structured interview. Additional neuropsychological parameters were assessed by using a battery of standard neuropsychological tests. Structural magnetic resonance imaging data were analyzed with an automated region-of-interest procedure. While hippocampal volume reduction and neuropsychological impairment were more pronounced in the older than in the younger patients, both groups showed equivalent reduced AM performance for recent personal episodes. In the patient group, significant correlations between left hippocampal volume and recent autobiographical episodes as well as personal semantic memories arose. Verbal memory and working memory were significantly correlated with right hippocampal volume; executive functions, however, were associated with bilateral hippocampal volumes. These findings underline the complexity of AM and its impairments in the course of schizophrenia in comparison to rather progressive neuropsychological deficits and address the importance of hippocampal contribution.

Specific responses of human hippocampal neurons are associated with better memory.

PubMed

Suthana, Nanthia A; Parikshak, Neelroop N; Ekstrom, Arne D; Ison, Matias J; Knowlton, Barbara J; Bookheimer, Susan Y; Fried, Itzhak

2015-08-18

A population of human hippocampal neurons has shown responses to individual concepts (e.g., Jennifer Aniston) that generalize to different instances of the concept. However, recordings from the rodent hippocampus suggest an important function of these neurons is their ability to discriminate overlapping representations, or pattern separate, a process that may facilitate discrimination of similar events for successful memory. In the current study, we explored whether human hippocampal neurons can also demonstrate the ability to discriminate between overlapping representations and whether this selectivity could be directly related to memory performance. We show that among medial temporal lobe (MTL) neurons, certain populations of neurons are selective for a previously studied (target) image in that they show a significant decrease in firing rate to very similar (lure) images. We found that a greater proportion of these neurons can be found in the hippocampus compared with other MTL regions, and that memory for individual items is correlated to the degree of selectivity of hippocampal neurons responsive to those items. Moreover, a greater proportion of hippocampal neurons showed selective firing for target images in good compared with poor performers, with overall memory performance correlated with hippocampal selectivity. In contrast, selectivity in other MTL regions was not associated with memory performance. These findings show that a substantial proportion of human hippocampal neurons encode specific memories that support the discrimination of overlapping representations. These results also provide previously unidentified evidence consistent with a unique role of the human hippocampus in orthogonalization of representations in declarative memory.

Comparison of the force exerted by hippocampal and DRG growth cones.

PubMed

Amin, Ladan; Ercolini, Erika; Ban, Jelena; Torre, Vincent

2013-01-01

Mechanical properties such as force generation are fundamental for neuronal motility, development and regeneration. We used optical tweezers to compare the force exerted by growth cones (GCs) of neurons from the Peripheral Nervous System (PNS), such as Dorsal Root Ganglia (DRG) neurons, and from the Central Nervous System (CNS) such as hippocampal neurons. Developing GCs from dissociated DRG and hippocampal neurons were obtained from P1-P2 and P10-P12 rats. Comparing their morphology, we observed that the area of GCs of hippocampal neurons was 8-10 µm(2) and did not vary between P1-P2 and P10-P12 rats, but GCs of DRG neurons were larger and their area increased from P1-P2 to P10-P12 by 2-4 times. The force exerted by DRG filopodia was in the order of 1-2 pN and never exceeded 5 pN, while hippocampal filopodia exerted a larger force, often in the order of 5 pN. Hippocampal and DRG lamellipodia exerted lateral forces up to 20 pN, but lamellipodia of DRG neurons could exert a vertical force larger than that of hippocampal neurons. Force-velocity relationships (Fv) in both types of neurons had the same qualitative behaviour, consistent with a common autocatalytic model of force generation. These results indicate that molecular mechanisms of force generation of GC from CNS and PNS neurons are similar but the amplitude of generated force is influenced by their cytoskeletal properties.

Comparison of the Force Exerted by Hippocampal and DRG Growth Cones

PubMed Central

Amin, Ladan; Ercolini, Erika; Ban, Jelena; Torre, Vincent

2013-01-01

Mechanical properties such as force generation are fundamental for neuronal motility, development and regeneration. We used optical tweezers to compare the force exerted by growth cones (GCs) of neurons from the Peripheral Nervous System (PNS), such as Dorsal Root Ganglia (DRG) neurons, and from the Central Nervous System (CNS) such as hippocampal neurons. Developing GCs from dissociated DRG and hippocampal neurons were obtained from P1-P2 and P10-P12 rats. Comparing their morphology, we observed that the area of GCs of hippocampal neurons was 8-10 µm2 and did not vary between P1-P2 and P10-P12 rats, but GCs of DRG neurons were larger and their area increased from P1-P2 to P10-P12 by 2-4 times. The force exerted by DRG filopodia was in the order of 1-2 pN and never exceeded 5 pN, while hippocampal filopodia exerted a larger force, often in the order of 5 pN. Hippocampal and DRG lamellipodia exerted lateral forces up to 20 pN, but lamellipodia of DRG neurons could exert a vertical force larger than that of hippocampal neurons. Force-velocity relationships (Fv) in both types of neurons had the same qualitative behaviour, consistent with a common autocatalytic model of force generation. These results indicate that molecular mechanisms of force generation of GC from CNS and PNS neurons are similar but the amplitude of generated force is influenced by their cytoskeletal properties. PMID:23991169

Mind-Wandering in People with Hippocampal Damage.

PubMed

McCormick, Cornelia; Rosenthal, Clive R; Miller, Thomas D; Maguire, Eleanor A

2018-03-14

Subjective inner experiences, such as mind-wandering, represent the fundaments of human cognition. Although the precise function of mind-wandering is still debated, it is increasingly acknowledged to have influence across cognition on processes such as future planning, creative thinking, and problem-solving and even on depressive rumination and other mental health disorders. Recently, there has been important progress in characterizing mind-wandering and identifying the associated neural networks. Two prominent features of mind-wandering are mental time travel and visuospatial imagery, which are often linked with the hippocampus. People with selective bilateral hippocampal damage cannot vividly recall events from their past, envision their future, or imagine fictitious scenes. This raises the question of whether the hippocampus plays a causal role in mind-wandering and, if so, in what way. Leveraging a unique opportunity to shadow people (all males) with bilateral hippocampal damage for several days, we examined, for the first time, what they thought about spontaneously, without direct task demands. We found that they engaged in as much mind-wandering as control participants. However, whereas controls thought about the past, present, and future, imagining vivid visual scenes, hippocampal damage resulted in thoughts primarily about the present comprising verbally mediated semantic knowledge. These findings expose the hippocampus as a key pillar in the neural architecture of mind-wandering and also reveal its impact beyond episodic memory, placing it at the heart of our mental life. SIGNIFICANCE STATEMENT Humans tend to mind-wander ∼30-50% of their waking time. Two prominent features of this pervasive form of thought are mental time travel and visuospatial imagery, which are often associated with the hippocampus. To examine whether the hippocampus plays a causal role in mind-wandering, we examined the frequency and phenomenology of mind-wandering in patients with

Mind-Wandering in People with Hippocampal Damage

PubMed Central

2018-01-01

Subjective inner experiences, such as mind-wandering, represent the fundaments of human cognition. Although the precise function of mind-wandering is still debated, it is increasingly acknowledged to have influence across cognition on processes such as future planning, creative thinking, and problem-solving and even on depressive rumination and other mental health disorders. Recently, there has been important progress in characterizing mind-wandering and identifying the associated neural networks. Two prominent features of mind-wandering are mental time travel and visuospatial imagery, which are often linked with the hippocampus. People with selective bilateral hippocampal damage cannot vividly recall events from their past, envision their future, or imagine fictitious scenes. This raises the question of whether the hippocampus plays a causal role in mind-wandering and, if so, in what way. Leveraging a unique opportunity to shadow people (all males) with bilateral hippocampal damage for several days, we examined, for the first time, what they thought about spontaneously, without direct task demands. We found that they engaged in as much mind-wandering as control participants. However, whereas controls thought about the past, present, and future, imagining vivid visual scenes, hippocampal damage resulted in thoughts primarily about the present comprising verbally mediated semantic knowledge. These findings expose the hippocampus as a key pillar in the neural architecture of mind-wandering and also reveal its impact beyond episodic memory, placing it at the heart of our mental life. SIGNIFICANCE STATEMENT Humans tend to mind-wander ∼30–50% of their waking time. Two prominent features of this pervasive form of thought are mental time travel and visuospatial imagery, which are often associated with the hippocampus. To examine whether the hippocampus plays a causal role in mind-wandering, we examined the frequency and phenomenology of mind-wandering in patients with

Hippocampal BOLD response during category learning predicts subsequent performance on transfer generalization.

PubMed

Fera, Francesco; Passamonti, Luca; Herzallah, Mohammad M; Myers, Catherine E; Veltri, Pierangelo; Morganti, Giuseppina; Quattrone, Aldo; Gluck, Mark A

2014-07-01

To test a prediction of our previous computational model of cortico-hippocampal interaction (Gluck and Myers [1993, 2001]) for characterizing individual differences in category learning, we studied young healthy subjects using an fMRI-adapted category-learning task that has two phases, an initial phase in which associations are learned through trial-and-error feedback followed by a generalization phase in which previously learned rules can be applied to novel associations (Myers et al. [2003]). As expected by our model, we found a negative correlation between learning-related hippocampal responses and accuracy during transfer, demonstrating that hippocampal adaptation during learning is associated with better behavioral scores during transfer generalization. In addition, we found an inverse relationship between Blood Oxygenation Level Dependent (BOLD) activity in the striatum and that in the hippocampal formation and the orbitofrontal cortex during the initial learning phase. Conversely, activity in the dorsolateral prefrontal cortex, orbitofrontal cortex and parietal lobes dominated over that of the hippocampal formation during the generalization phase. These findings provide evidence in support of theories of the neural substrates of category learning which argue that the hippocampal region plays a critical role during learning for appropriately encoding and representing newly learned information so that that this learning can be successfully applied and generalized to subsequent novel task demands. Copyright © 2013 Wiley Periodicals, Inc.

Prospective and Episodic Memory in Relation to Hippocampal Volume in Adults with Spina Bifida Myelomeningocele

PubMed Central

Treble-Barna, Amery; Juranek, Jenifer; Stuebing, Karla K.; Cirino, Paul T.; Dennis, Maureen; Fletcher, Jack M.

2014-01-01

The present study examined prospective and episodic memory in relation to age, functional independence, and hippocampal volume in younger to middle-aged adults with spina bifida myelomeningocele (SBM) and typically developing (TD) adults. Prospective and episodic memory, as well as hippocampal volume, were reduced in adults with SBM relative to TD adults. Neither memory performance nor hippocampal volume showed greater decrements in older adults. Lower hippocampal volume was associated with reduced prospective memory in adults with SBM, and this relation was specific to the hippocampus and not to a contrast structure, the amygdala. Prospective memory mediated the relation between hippocampal volume and functional independence in adults with SBM. The results add to emerging evidence for reduced memory function in adults with SBM, and provide quantitative evidence for compromised hippocampal macrostructure as a neural correlate of reduced memory in this population. PMID:25068670

Low-intensity daily walking activity is associated with hippocampal volume in older adults.

PubMed

Varma, Vijay R; Chuang, Yi-Fang; Harris, Gregory C; Tan, Erwin J; Carlson, Michelle C

2015-05-01

Hippocampal atrophy is associated with memory impairment and dementia and serves as a key biomarker in the preclinical stages of Alzheimer's disease. Physical activity, one of the most promising behavioral interventions to prevent or delay cognitive decline, has been shown to be associated with hippocampal volume; specifically increased aerobic activity and fitness may have a positive effect on the size of the hippocampus. The majority of older adults, however, are sedentary and have difficulty initiating and maintaining exercise programs. A modestly more active lifestyle may nonetheless be beneficial. This study explored whether greater objectively measured daily walking activity was associated with larger hippocampal volume. We additionally explored whether greater low-intensity walking activity, which may be related to leisure-time physical, functional, and social activities, was associated with larger hippocampal volume independent of exercise and higher-intensity walking activity. Segmentation of hippocampal volumes was performed using Functional Magnetic Resonance Imaging of the Brain's Software Library (FSL), and daily walking activity was assessed using a step activity monitor on 92, nondemented, older adult participants. After controlling for age, education, body mass index, cardiovascular disease risk factors, and the Mini Mental State Exam, we found that a greater amount, duration, and frequency of total daily walking activity were each associated with larger hippocampal volume among older women, but not among men. These relationships were specific to hippocampal volume, compared with the thalamus, used as a control brain region, and remained significant for low-intensity walking activity, independent of moderate- to vigorous-intensity activity and self-reported exercise. This is the first study, to our knowledge, to explore the relationship between objectively measured daily walking activity and hippocampal volume in an older adult population. Findings

Chronic peripheral inflammation, hippocampal neurogenesis, and behavior.

PubMed

Chesnokova, Vera; Pechnick, Robert N; Wawrowsky, Kolja

2016-11-01

Adult hippocampal neurogenesis is involved in memory and learning, and disrupted neurogenesis is implicated in cognitive impairment and mood disorders, including anxiety and depression. Some long-term peripheral illnesses and metabolic disorders, as well as normal aging, create a state of chronic peripheral inflammation. These conditions are associated with behavioral disturbances linked to disrupted adult hippocampal neurogenesis, such as cognitive impairment, deficits in learning and memory, and depression and anxiety. Pro-inflammatory cytokines released in the periphery are involved in peripheral immune system-to-brain communication by activating resident microglia in the brain. Activated microglia reduce neurogenesis by suppressing neuronal stem cell proliferation, increasing apoptosis of neuronal progenitor cells, and decreasing survival of newly developing neurons and their integration into existing neuronal circuits. In this review, we summarize evolving evidence that the state of chronic peripheral inflammation reduces adult hippocampal neurogenesis, which, in turn, produces the behavioral disturbances observed in chronic inflammatory disorders. As there are no data available on neurogenesis in humans with chronic peripheral inflammatory disease, we focus on animal models and, in parallel, consider the evidence of cognitive disturbance and mood disorders in human patients. Copyright © 2016 Elsevier Inc. All rights reserved.

The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner.

PubMed

Clarke, G; Grenham, S; Scully, P; Fitzgerald, P; Moloney, R D; Shanahan, F; Dinan, T G; Cryan, J F

2013-06-01

Bacterial colonisation of the intestine has a major role in the post-natal development and maturation of the immune and endocrine systems. These processes are key factors underpinning central nervous system (CNS) signalling. Regulation of the microbiome-gut-brain axis is essential for maintaining homeostasis, including that of the CNS. However, there is a paucity of data pertaining to the influence of microbiome on the serotonergic system. Germ-free (GF) animals represent an effective preclinical tool to investigate such phenomena. Here we show that male GF animals have a significant elevation in the hippocampal concentration of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid, its main metabolite, compared with conventionally colonised control animals. Moreover, this alteration is sex specific in contrast with the immunological and neuroendocrine effects which are evident in both sexes. Concentrations of tryptophan, the precursor of serotonin, are increased in the plasma of male GF animals, suggesting a humoral route through which the microbiota can influence CNS serotonergic neurotransmission. Interestingly, colonisation of the GF animals post weaning is insufficient to reverse the CNS neurochemical consequences in adulthood of an absent microbiota in early life despite the peripheral availability of tryptophan being restored to baseline values. In addition, reduced anxiety in GF animals is also normalised following restoration of the intestinal microbiota. These results demonstrate that CNS neurotransmission can be profoundly disturbed by the absence of a normal gut microbiota and that this aberrant neurochemical, but not behavioural, profile is resistant to restoration of a normal gut flora in later life.

Spectroscopic imaging of the pilocarpine model of human epilepsy suggests that early NAA reduction predicts epilepsy.

PubMed

Gomes, W A; Lado, F A; de Lanerolle, N C; Takahashi, K; Pan, C; Hetherington, H P

2007-08-01

Reduced hippocampal N-acetyl aspartate (NAA) is commonly observed in patients with advanced, chronic temporal lobe epilepsy (TLE). It is unclear, however, whether an NAA deficit is also present during the clinically quiescent latent period that characterizes early TLE. This question has important implications for the use of MR spectroscopic imaging (MRSI) in the early identification of patients at risk for TLE. To determine whether NAA is diminished during the latent period, we obtained high-resolution (1)H spectroscopic imaging during the latent period of the rat pilocarpine model of human TLE. We used actively detuneable surface reception and volume transmission coils to enhance sensitivity and a semiautomated voxel shifting method to accurately position voxels within the hippocampi. During the latent period, 2 and 7 d following pilocarpine treatment, hippocampal NAA was significantly reduced by 27.5 +/- 6.9% (P < 0.001) and 17.3 +/- 6.9% (P < 0.001) at 2 and 7 d, respectively. Quantitative estimates of neuronal loss at 7 d (2.3 +/- 7.7% reduction; P = 0.58, not significant) demonstrate that the NAA deficit is not due to neuron loss and therefore likely represents metabolic impairment of hippocampal neurons during the latent phase. Therefore, spectroscopic imaging provides an early marker for metabolic dysfunction in this model of TLE.

The Silent Thief: Osteoporosis and Women's Health Care across the Life Span

ERIC Educational Resources Information Center

Munch, Shari; Shapiro, Sarah

2006-01-01

Osteoporosis is a skeletal disease characterized by loss of bone mass and density, which results in an increased risk of fractures. The disease is referred to as the "silent thief," because it is often not until a person falls and breaks a bone that patients and their physicians become aware of weakening bones. An estimated 1.5 million…

Uncovering representations of sleep-associated hippocampal ensemble spike activity

NASA Astrophysics Data System (ADS)