Intermediate Cognitive Phenotypes in Bipolar Disorder

PubMed Central

Langenecker, Scott A.; Saunders, Erika F.H.; Kade, Allison M.; Ransom, Michael T.; McInnis, Melvin G.

2013-01-01

Background Intermediate cognitive phenotypes (ICPs) are measurable and quantifiable states that may be objectively assessed in a standardized method, and can be integrated into association studies, including genetic, biochemical, clinical, and imaging based correlates. The present study used neuropsychological measures as ICPs, with factor scores in executive functioning, attention, memory, fine motor function, and emotion processing, similar to prior work in schizophrenia. Methods Healthy control subjects (HC, n=34) and euthymic (E, n=66), depressed (D, n=43), or hypomanic/mixed (HM, n=13) patients with bipolar disorder (BD) were assessed with neuropsychological tests. These were from eight domains consistent with previous literature; auditory memory, visual memory, processing speed with interference resolution, verbal fluency and processing speed, conceptual reasoning and set-shifting, inhibitory control, emotion processing, and fine motor dexterity. Results Of the eight factor scores, the HC group outperformed the E group in three (Processing Speed with Interference Resolution, Visual Memory, Fine Motor Dexterity), the D group in seven (all except Inhibitory Control), and the HM group in four (Inhibitory Control, Processing Speed with Interference Resolution, Fine Motor Dexterity, and Auditory Memory). Limitations The HM group was relatively small, thus effects of this phase of illness may have been underestimated. Effects of medication could not be fully controlled without a randomized, double-blind, placebo-controlled study. Conclusions Use of the factor scores can assist in determining ICPs for BD and related disorders, and may provide more specific targets for development of new treatments. We highlight strong ICPs (Processing Speed with Interference Resolution, Visual Memory, Fine Motor Dexterity) for further study, consistent with the existing literature. PMID:19800130

Inhibitory and Working Memory Demands of the Day-Night Task in Children

ERIC Educational Resources Information Center

Simpson, Andrew; Riggs, Kevin J.

2005-01-01

Gerstadt, Hong, and Diamond (1994) investigated the development of inhibitory control in children aged 3 1/2 - 7 years using the day-night task. In two studies we build on Gerstadt et al.'s findings with a measure of inhibitory control that can be used throughout childhood. In Study 1 (twenty-four 3 1/2-year-olds and sixteen 5-year-olds) we…

Predictors of early growth in academic achievement: the head-toes-knees-shoulders task

PubMed Central

McClelland, Megan M.; Cameron, Claire E.; Duncan, Robert; Bowles, Ryan P.; Acock, Alan C.; Miao, Alicia; Pratt, Megan E.

2014-01-01

Children's behavioral self-regulation and executive function (EF; including attentional or cognitive flexibility, working memory, and inhibitory control) are strong predictors of academic achievement. The present study examined the psychometric properties of a measure of behavioral self-regulation called the Head-Toes-Knees-Shoulders (HTKS) by assessing construct validity, including relations to EF measures, and predictive validity to academic achievement growth between prekindergarten and kindergarten. In the fall and spring of prekindergarten and kindergarten, 208 children (51% enrolled in Head Start) were assessed on the HTKS, measures of cognitive flexibility, working memory (WM), and inhibitory control, and measures of emergent literacy, mathematics, and vocabulary. For construct validity, the HTKS was significantly related to cognitive flexibility, working memory, and inhibitory control in prekindergarten and kindergarten. For predictive validity in prekindergarten, a random effects model indicated that the HTKS significantly predicted growth in mathematics, whereas a cognitive flexibility task significantly predicted growth in mathematics and vocabulary. In kindergarten, the HTKS was the only measure to significantly predict growth in all academic outcomes. An alternative conservative analytical approach, a fixed effects analysis (FEA) model, also indicated that growth in both the HTKS and measures of EF significantly predicted growth in mathematics over four time points between prekindergarten and kindergarten. Results demonstrate that the HTKS involves cognitive flexibility, working memory, and inhibitory control, and is substantively implicated in early achievement, with the strongest relations found for growth in achievement during kindergarten and associations with emergent mathematics. PMID:25071619

Human Immunodeficiency Virus Type-1 Elite Controllers Maintain Low Co-Expression of Inhibitory Receptors on CD4+ T Cells.

PubMed

Noyan, Kajsa; Nguyen, Son; Betts, Michael R; Sönnerborg, Anders; Buggert, Marcus

2018-01-01

Human immunodeficiency virus type-1 (HIV-1) elite controllers (ELCs) represent a unique population that control viral replication in the absence of antiretroviral therapy (cART). It is well established that expression of multiple inhibitory receptors on CD8+ T cells is associated with HIV-1 disease progression. However, whether reduced co-expression of inhibitory receptors on CD4+ T cells is linked to natural viral control and slow HIV-1 disease progression remains undefined. Here, we report on the expression pattern of numerous measurable inhibitory receptors, associated with T cell exhaustion (programmed cell death-1, CTLA-4, and TIGIT), on different CD4+ T cell memory populations in ELCs and HIV-infected subjects with or without long-term cART. We found that the co-expression pattern of inhibitory receptors was significantly reduced in ELCs compared with HIV-1 cART-treated and viremic subjects, and similar to healthy controls. Markers associated with T cell exhaustion varied among different memory CD4+ T cell subsets and highest levels were found mainly on transitional memory T cells. CD4+ T cells co-expressing all inhibitory markers were positively correlated to T cell activation (CD38+ HLA-DR+) as well as the transcription factors Helios and FoxP3. Finally, clinical parameters such as CD4 count, HIV-1 viral load, and the CD4/CD8 ratio all showed significant associations with CD4+ T cell exhaustion. We demonstrate that ELCs are able to maintain lower levels of CD4+ T cell exhaustion despite years of ongoing viral replication compared with successfully cART-treated subjects. Our findings suggest that ELCs harbor a "healthy" state of inhibitory receptor expression on CD4+ T cells that might play part in maintenance of their control status.

Hippocampal Infusion of Zeta Inhibitory Peptide Impairs Recent, but Not Remote, Recognition Memory in Rats

PubMed Central

Hales, Jena B.; Ocampo, Amber C.; Broadbent, Nicola J.; Clark, Robert E.

2015-01-01

Spatial memory in rodents can be erased following the infusion of zeta inhibitory peptide (ZIP) into the dorsal hippocampus via indwelling guide cannulas. It is believed that ZIP impairs spatial memory by reversing established late-phase long-term potentiation (LTP). However, it is unclear whether other forms of hippocampus-dependent memory, such as recognition memory, are also supported by hippocampal LTP. In the current study, we tested recognition memory in rats following hippocampal ZIP infusion. In order to combat the limited targeting of infusions via cannula, we implemented a stereotaxic approach for infusing ZIP throughout the dorsal, intermediate, and ventral hippocampus. Rats infused with ZIP 3–7 days after training on the novel object recognition task exhibited impaired object recognition memory compared to control rats (those infused with aCSF). In contrast, rats infused with ZIP 1 month after training performed similar to control rats. The ability to form new memories after ZIP infusions remained intact. We suggest that enhanced recognition memory for recent events is supported by hippocampal LTP, which can be reversed by hippocampal ZIP infusion. PMID:26380123

Older Adults Can Suppress Unwanted Memories When Given an Appropriate Strategy

PubMed Central

2015-01-01

Memory suppression refers to the ability to exclude distracting memories from conscious awareness, and this ability can be assessed with the think/no-think paradigm. Recent research with older adults has provided evidence suggesting both intact and deficient memory suppression. The present studies seek to understand the conditions contributing to older adults’ ability to suppress memories voluntarily. We report 2 experiments indicating that the specificity of the think/no-think task instructions contributes to older adults’ suppression success: When older adults receive open-ended instructions that require them to develop a retrieval suppression strategy on their own, they show diminished memory suppression compared with younger adults. Conversely, when older adults receive focused instructions directing them to a strategy thought to better isolate inhibitory control, they show suppression-induced forgetting similar to that exhibited by younger adults. Younger adults demonstrate memory suppression regardless of the specificity of the instructions given, suggesting that the ability to select a successful suppression strategy spontaneously may be compromised in older adults. If so, this deficit may be associated with diminished control over unwanted memories in naturalistic settings if impeded strategy development reduces the successful deployment of inhibitory control. PMID:25602491

The Development of Automatic and Controlled Inhibitory Retrieval Processes in True and False Recall

ERIC Educational Resources Information Center

Knott, Lauren M.; Howe, Mark L.; Wimmer, Marina C.; Dewhurst, Stephen A.

2011-01-01

In three experiments, we investigated the role of automatic and controlled inhibitory retrieval processes in true and false memory development in children and adults. Experiment 1 incorporated a directed forgetting task to examine controlled retrieval inhibition. Experiments 2 and 3 used a part-set cue and retrieval practice task to examine…

Theory of mind and executive function: working-memory capacity and inhibitory control as predictors of false-belief task performance.

PubMed

Mutter, Brigitte; Alcorn, Mark B; Welsh, Marilyn

2006-06-01

This study of the relationship between theory of mind and executive function examined whether on the false-belief task age differences between 3 and 5 ears of age are related to development of working-memory capacity and inhibitory processes. 72 children completed tasks measuring false belief, working memory, and inhibition. Significant age effects were observed for false-belief and working-memory performance, as well as for the false-alarm and perseveration measures of inhibition. A simultaneous multiple linear regression specified the contribution of age, inhibition, and working memory to the prediction of false-belief performance. This model was significant, explaining a total of 36% of the variance. To examine the independent contributions of the working-memory and inhibition variables, after controlling for age, two hierarchical multiple linear regressions were conducted. These multiple regression analyses indicate that working memory and inhibition make small, overlapping contributions to false-belief performance after accounting for age, but that working memory, as measured in this study, is a somewhat better predictor of false-belief understanding than is inhibition.

Age differences in memory control: evidence from updating and retrieval-practice tasks.

PubMed

Lechuga, Maria Teresa; Moreno, Virginia; Pelegrina, Santiago; Gómez-Ariza, Carlos J; Bajo, Maria Teresa

2006-11-01

Some contemporary approaches suggest that inhibitory mechanisms play an important role in cognitive development. In addition, several authors distinguish between intentional and unintentional inhibitory processes in cognition. We report two experiments aimed at exploring possible developmental changes in these two types of inhibitory mechanisms. In Experiment 1, an updating task was used. This task requires that participants intentionally suppress irrelevant information from working memory. In Experiment 2, the retrieval-practice task was used. Retrieval practice of a subset of studied items is thought to involve unintentional inhibitory processes to overcome interference from competing memories. As a result, suppressed items become forgotten in a later memory test. Results of the experiments indicated that younger children (8) were less efficient than older children (12) and adults at intentionally suppressing information (updating task). However, when the task required unintentional inhibition of competing items (retrieval-practice task), this developmental trend was not found and children and adults showed similar levels of retrieval-induced forgetting. The results are discussed in terms of the development of efficient inhibition and the distinction between intentional and unintentional inhibitions.

Rule-Based Category Learning in Children: The Role of Age and Executive Functioning

PubMed Central

Rabi, Rahel; Minda, John Paul

2014-01-01

Rule-based category learning was examined in 4–11 year-olds and adults. Participants were asked to learn a set of novel perceptual categories in a classification learning task. Categorization performance improved with age, with younger children showing the strongest rule-based deficit relative to older children and adults. Model-based analyses provided insight regarding the type of strategy being used to solve the categorization task, demonstrating that the use of the task appropriate strategy increased with age. When children and adults who identified the correct categorization rule were compared, the performance deficit was no longer evident. Executive functions were also measured. While both working memory and inhibitory control were related to rule-based categorization and improved with age, working memory specifically was found to marginally mediate the age-related improvements in categorization. When analyses focused only on the sample of children, results showed that working memory ability and inhibitory control were associated with categorization performance and strategy use. The current findings track changes in categorization performance across childhood, demonstrating at which points performance begins to mature and resemble that of adults. Additionally, findings highlight the potential role that working memory and inhibitory control may play in rule-based category learning. PMID:24489658

Eye Gaze and Aging: Selective and Combined Effects of Working Memory and Inhibitory Control.

PubMed

Crawford, Trevor J; Smith, Eleanor S; Berry, Donna M

2017-01-01

Eye-tracking is increasingly studied as a cognitive and biological marker for the early signs of neuropsychological and psychiatric disorders. However, in order to make further progress, a more comprehensive understanding of the age-related effects on eye-tracking is essential. The antisaccade task requires participants to make saccadic eye movements away from a prepotent stimulus. Speculation on the cause of the observed age-related differences in the antisaccade task largely centers around two sources of cognitive dysfunction: inhibitory control (IC) and working memory (WM). The IC account views cognitive slowing and task errors as a direct result of the decline of inhibitory cognitive mechanisms. An alternative theory considers that a deterioration of WM is the cause of these age-related effects on behavior. The current study assessed IC and WM processes underpinning saccadic eye movements in young and older participants. This was achieved with three experimental conditions that systematically varied the extent to which WM and IC were taxed in the antisaccade task: a memory-guided task was used to explore the effect of increasing the WM load; a Go/No-Go task was used to explore the effect of increasing the inhibitory load; a 'standard' antisaccade task retained the standard WM and inhibitory loads. Saccadic eye movements were also examined in a control condition: the standard prosaccade task where the load of WM and IC were minimal or absent. Saccade latencies, error rates and the spatial accuracy of saccades of older participants were compared to the same measures in healthy young controls across the conditions. The results revealed that aging is associated with changes in both IC and WM. Increasing the inhibitory load was associated with increased reaction times in the older group, while the increased WM load and the inhibitory load contributed to an increase in the antisaccade errors. These results reveal that aging is associated with changes in both IC and WM.

No Evidence for True Training and Transfer Effects after Inhibitory Control Training in Young Healthy Adults

ERIC Educational Resources Information Center

Enge, Sören; Behnke, Alexander; Fleischhauer, Monika; Küttler, Lena; Kliegel, Matthias; Strobel, Alexander

2014-01-01

Recent studies reported that training of working memory may improve performance in the trained function and beyond. Other executive functions, however, have been rarely or not yet systematically examined. The aim of this study was to test the effectiveness of inhibitory control (IC) training to produce true training-related function improvements…

Retrieval of Inhibitory Avoidance Memory Induces Differential Transcription of arc in Striatum, Hippocampus, and Amygdala.

PubMed

González-Salinas, Sofía; Medina, Andrea C; Alvarado-Ortiz, Eduardo; Antaramian, Anaid; Quirarte, Gina L; Prado-Alcalá, Roberto A

2018-07-01

Similar to the hippocampus and amygdala, the dorsal striatum is involved in memory retrieval of inhibitory avoidance, a task commonly used to study memory processes. It has been reported that memory retrieval of fear conditioning regulates gene expression of arc and zif268 in the amygdala and the hippocampus, and it is surprising that only limited effort has been made to study the molecular events caused by retrieval in the striatum. To further explore the involvement of immediate early genes in retrieval, we used real-time PCR to analyze arc and zif268 transcription in dorsal striatum, dorsal hippocampus, and amygdala at different time intervals after retrieval of step-through inhibitory avoidance memory. We found that arc expression in the striatum increased 30 min after retrieval while no changes were observed in zif268 in this region. Expression of arc and zif268 also increased in the dorsal hippocampus but the changes were attributed to context re-exposure. Control procedures indicated that in the amygdala, arc and zif268 expression was not dependent on retrieval. Our data indicate that memory retrieval of inhibitory avoidance induces arc gene expression in the dorsal striatum, caused, very likely, by the instrumental component of the task. Striatal arc expression after retrieval may induce structural and functional changes in the neurons involved in this process. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

The role of cardiac vagal tone and inhibitory control in pre-schoolers' listening comprehension.

PubMed

Scrimin, Sara; Patron, Elisabetta; Florit, Elena; Palomba, Daniela; Mason, Lucia

2017-12-01

This study investigated the role of basal cardiac activity and inhibitory control at the beginning of the school year in predicting oral comprehension at the end of the year in pre-schoolers. Forty-three, 4-year-olds participated in the study. At the beginning of the school year children's electrocardiogram at rest was registered followed by the assessment of inhibitory control as well as verbal working memory and verbal ability. At the end of the year all children were administered a listening comprehension ability measure. A stepwise regression showed a significant effect of basal cardiac vagal tone in predicting listening comprehension together with inhibitory control and verbal ability. These results are among the first to show the predictive role of basal cardiac vagal tone and inhibitory control in pre-schoolers' oral text comprehension, and offer new insight into the association between autonomic regulation of the heart, inhibitory control, and cognitive activity at a young age. © 2017 Wiley Periodicals, Inc.

Brain ageing changes proteoglycan sulfation, rendering perineuronal nets more inhibitory.

PubMed

Foscarin, Simona; Raha-Chowdhury, Ruma; Fawcett, James W; Kwok, Jessica C F

2017-06-28

Chondroitin sulfate (CS) proteoglycans in perineuronal nets (PNNs) from the central nervous system (CNS) are involved in the control of plasticity and memory. Removing PNNs reactivates plasticity and restores memory in models of Alzheimer's disease and ageing. Their actions depend on the glycosaminoglycan (GAG) chains of CS proteoglycans, which are mainly sulfated in the 4 (C4S) or 6 (C6S) positions. While C4S is inhibitory, C6S is more permissive to axon growth, regeneration and plasticity. C6S decreases during critical period closure. We asked whether there is a late change in CS-GAG sulfation associated with memory loss in aged rats. Immunohistochemistry revealed a progressive increase in C4S and decrease in C6S from 3 to 18 months. GAGs extracted from brain PNNs showed a large reduction in C6S at 12 and 18 months, increasing the C4S/C6S ratio. There was no significant change in mRNA levels of the chondroitin sulfotransferases. PNN GAGs were more inhibitory to axon growth than those from the diffuse extracellular matrix. The 18-month PNN GAGs were more inhibitory than 3-month PNN GAGs. We suggest that the change in PNN GAG sulfation in aged brains renders the PNNs more inhibitory, which lead to a decrease in plasticity and adversely affect memory.

Cognitive Functions in Elite and Sub-Elite Youth Soccer Players Aged 13 to 17 Years.

PubMed

Huijgen, Barbara C H; Leemhuis, Sander; Kok, Niels M; Verburgh, Lot; Oosterlaan, Jaap; Elferink-Gemser, Marije T; Visscher, Chris

2015-01-01

Soccer players are required to anticipate and react continuously in a changing, relatively unpredictable situation in the field. Cognitive functions might be important to be successful in soccer. The current study investigated the relationship between cognitive functions and performance level in elite and sub-elite youth soccer players aged 13-17 years. A total of 47 elite youth soccer players (mean age 15.5 years, SD = 0.9) and 41 sub-elite youth soccer players (mean age 15.2 years, SD = 1.2) performed tasks for "higher-level" cognitive functions measuring working memory (i.e., Visual Memory Span), inhibitory control (i.e., Stop-Signal Task), cognitive flexibility (i.e., Trail Making Test), and metacognition (i.e., Delis-Kaplan Executive Function System Design Fluency Test). "Lower-level" cognitive processes, i.e., reaction time and visuo-perceptual abilities, were also measured with the previous tasks. ANOVA's showed that elite players outscored sub-elite players at the "higher-level" cognitive tasks only, especially on metacognition (p < .05). Using stepwise discriminant analysis, 62.5% of subjects was correctly assigned to one of the groups based on their metacognition, inhibitory control and cognitive flexibility performance. Controlling for training hours and academic level, MANCOVA's showed differences in favor of the elite youth soccer players on inhibitory control (p = .001), and cognitive flexibility (p = .042), but not on metacognition (p = .27). No differences were found concerning working memory nor the "lower-level" cognitive processes (p > .05). In conclusion, elite youth soccer players have better inhibitory control, cognitive flexibility, and especially metacognition than their sub-elite counterparts. However, when training hours are taken into account, differences between elite and sub-elite youth soccer players remain apparent on inhibitory control and cognitive flexibility in contrast to metacognition. This highlights the need for longitudinal studies to further investigate the importance of "higher-level" cognitive functions for talent identification, talent development and performance in soccer.

Cognitive Functions in Elite and Sub-Elite Youth Soccer Players Aged 13 to 17 Years

PubMed Central

Huijgen, Barbara C. H.; Leemhuis, Sander; Kok, Niels M.; Verburgh, Lot; Oosterlaan, Jaap; Elferink-Gemser, Marije T.; Visscher, Chris

2015-01-01

Soccer players are required to anticipate and react continuously in a changing, relatively unpredictable situation in the field. Cognitive functions might be important to be successful in soccer. The current study investigated the relationship between cognitive functions and performance level in elite and sub-elite youth soccer players aged 13–17 years. A total of 47 elite youth soccer players (mean age 15.5 years, SD = 0.9) and 41 sub-elite youth soccer players (mean age 15.2 years, SD = 1.2) performed tasks for “higher-level” cognitive functions measuring working memory (i.e., Visual Memory Span), inhibitory control (i.e., Stop-Signal Task), cognitive flexibility (i.e., Trail Making Test), and metacognition (i.e., Delis-Kaplan Executive Function System Design Fluency Test). “Lower-level” cognitive processes, i.e., reaction time and visuo-perceptual abilities, were also measured with the previous tasks. ANOVA’s showed that elite players outscored sub-elite players at the “higher-level” cognitive tasks only, especially on metacognition (p < .05). Using stepwise discriminant analysis, 62.5% of subjects was correctly assigned to one of the groups based on their metacognition, inhibitory control and cognitive flexibility performance. Controlling for training hours and academic level, MANCOVA’s showed differences in favor of the elite youth soccer players on inhibitory control (p = .001), and cognitive flexibility (p = .042), but not on metacognition (p = .27). No differences were found concerning working memory nor the “lower-level” cognitive processes (p > .05). In conclusion, elite youth soccer players have better inhibitory control, cognitive flexibility, and especially metacognition than their sub-elite counterparts. However, when training hours are taken into account, differences between elite and sub-elite youth soccer players remain apparent on inhibitory control and cognitive flexibility in contrast to metacognition. This highlights the need for longitudinal studies to further investigate the importance of “higher-level” cognitive functions for talent identification, talent development and performance in soccer. PMID:26657073

ADHD and retrieval-induced forgetting: evidence for a deficit in the inhibitory control of memory.

PubMed

Storm, Benjamin C; White, Holly A

2010-04-01

Research on retrieval-induced forgetting has shown that the selective retrieval of some information can cause the forgetting of other information. Such forgetting is believed to result from inhibitory processes that function to resolve interference during retrieval. The current study examined whether individuals with ADHD demonstrate normal levels of retrieval-induced forgetting. A total of 40 adults with ADHD and 40 adults without ADHD participated in a standard retrieval-induced forgetting experiment. Critically, half of the items were tested using category cues and the other half of the items were tested using category-plus-one-letter-stem cues. Whereas both ADHD and non-ADHD participants demonstrated retrieval-induced forgetting on the final category-cued recall test, only non-ADHD participants demonstrated retrieval-induced forgetting on the final category-plus-stem-cued recall test. These results suggest that individuals with ADHD do have a deficit in the inhibitory control of memory, but that this deficit may only be apparent when output interference is adequately controlled on the final test.

Individual Differences in Working Memory Capacity Predict Retrieval-Induced Forgetting

ERIC Educational Resources Information Center

Aslan, Alp; Bauml, Karl-Heinz T.

2011-01-01

Selectively retrieving a subset of previously studied information enhances memory for the retrieved information but causes forgetting of related, nonretrieved information. Such retrieval-induced forgetting (RIF) has often been attributed to inhibitory executive-control processes that supposedly suppress the nonretrieved items' memory…

Inhibitory Voluntary Control of Memory: Effect of Stimulus Onset Asynchrony on Reaction Time to Suppressed Memories

ERIC Educational Resources Information Center

Algarabel, Salvador; Luciano, Juan V.; Martinez, Jose L.

2006-01-01

Anderson & Green (2001) have recently shown that using an adaptation of the go-no go task, participants can voluntarily inhibit the retrieval of specific memories. We present three experiments in which we try to determine the degree of automaticity involved, and the role of the previous prime-target relation on the development of this inhibitory…

Early Childhood Predictors of Post-Kindergarten Executive Function: Behavior, Parent Report, and Psychophysiology

ERIC Educational Resources Information Center

Cuevas, Kimberly; Hubble, Morgan; Bell, Martha Ann

2012-01-01

Research Findings: This study examined whether children's executive functions before kindergarten would predict variance in executive functions after kindergarten. We obtained behavioral (working memory task performance), parent-reported (temperament-based inhibitory control), and psychophysiological (working memory-related changes in heart rate…

Aversive Learning and Appetitive Motivation Toggle Feed-Forward Inhibition in the Drosophila Mushroom Body.

PubMed

Perisse, Emmanuel; Owald, David; Barnstedt, Oliver; Talbot, Clifford B; Huetteroth, Wolf; Waddell, Scott

2016-06-01

In Drosophila, negatively reinforcing dopaminergic neurons also provide the inhibitory control of satiety over appetitive memory expression. Here we show that aversive learning causes a persistent depression of the conditioned odor drive to two downstream feed-forward inhibitory GABAergic interneurons of the mushroom body, called MVP2, or mushroom body output neuron (MBON)-γ1pedc>α/β. However, MVP2 neuron output is only essential for expression of short-term aversive memory. Stimulating MVP2 neurons preferentially inhibits the odor-evoked activity of avoidance-directing MBONs and odor-driven avoidance behavior, whereas their inhibition enhances odor avoidance. In contrast, odor-evoked activity of MVP2 neurons is elevated in hungry flies, and their feed-forward inhibition is required for expression of appetitive memory at all times. Moreover, imposing MVP2 activity promotes inappropriate appetitive memory expression in food-satiated flies. Aversive learning and appetitive motivation therefore toggle alternate modes of a common feed-forward inhibitory MVP2 pathway to promote conditioned odor avoidance or approach. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Neural correlates of impaired cognitive control over working memory in schizophrenia.

PubMed

Eich, Teal S; Nee, Derek Evan; Insel, Catherine; Malapani, Chara; Smith, Edward E

2014-07-15

One of the most common deficits in patients with schizophrenia (SZ) is in working memory (WM), which has wide-reaching impacts across cognition. However, previous approaches to studying WM in SZ have used tasks that require multiple cognitive-control processes, making it difficult to determine which specific cognitive and neural processes underlie the WM impairment. We used functional magnetic resonance imaging to investigate component processes of WM in SZ. Eighteen healthy controls (HCs) and 18 patients with SZ performed an item-recognition task that permitted separate neural assessments of 1) WM maintenance, 2) inhibition, and 3) interference control in response to recognition probes. Before inhibitory demands, posterior ventrolateral prefrontal cortex (VLPFC), an area involved in WM maintenance, was activated to a similar degree in both HCs and patients, indicating preserved maintenance operations in SZ. When cued to inhibit items from WM, HCs showed reduced activation in posterior VLPFC, commensurate with appropriately inhibiting items from WM. However, these inhibition-related reductions were absent in patients. When later probed with items that should have been inhibited, patients showed reduced behavioral performance and increased activation in mid-VLPFC, an area implicated in interference control. A mediation analysis indicated that impaired inhibition led to increased reliance on interference control and reduced behavioral performance. In SZ, impaired control over memory, manifested through proactive inhibitory deficits, leads to increased reliance on reactive interference-control processes. The strain on interference-control processes results in reduced behavioral performance. Thus, inhibitory deficits in SZ may underlie widespread impairments in WM and cognition. © 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.

Inhibitory Control and Working Memory in Post-Institutionalized Children

PubMed Central

Merz, Emily C.; McCall, Robert B.; Wright, Amanda J.; Luna, Beatriz

2013-01-01

Inhibitory control and working memory were examined in post-institutionalized (PI) children adopted into United States families from Russian institutions. The PI sample originated from institutions that were less severely depriving than those represented in previous studies and approximated the level of psychosocial deprivation, which is characterized by adequate physical resources but a lack of consistent and responsive caregiving. PI children (N=75; 29 male) ranged in age from 8–17 years (M=12.97; SD=3.03) and were grouped according to whether they were adopted after 14 months or before 9 months. A non-adopted comparison group (N=133; 65 male) ranged in age from 8–17 years (M=12.26; SD=2.75). PI children adopted after 14 months of age displayed poorer performance on the stop-signal and spatial span tasks relative to PI children adopted before 9 months of age after controlling for age at assessment. The two PI groups did not differ in their performance on a spatial self-ordered search task. Older-adopted PI children also showed poorer spatial span task performance compared to non-adopted children, but younger-adopted PI children did not. Task performance was significantly associated with parent-rated hyperactive-impulsive behavior in everyday contexts. These findings suggest that exposure to prolonged early institutional deprivation may be linked with inhibitory control and working memory difficulties years after adoption. PMID:23519375

Efficiency of the Prefrontal Cortex during Working Memory in Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Sheridan, Margaret A.; Hinshaw, Stephen; D'Esposito, Mark

2007-01-01

Objective: Previous research has demonstrated that during task conditions requiring an increase in inhibitory function or working memory, children and adults with attention-deficit/hyperactivity disorder (ADHD) exhibit greater and more varied prefrontal cortical(PFC) activation compared to age-matched control participants. This pattern may reflect…

Sources of Variability in Working Memory in Early Childhood: A Consideration of Age, Temperament, Language, and Brain Electrical Activity

ERIC Educational Resources Information Center

Wolfe, Christy D.; Bell, Martha Ann

2007-01-01

This study investigated age-related differences in working memory and inhibitory control (WMIC) in 3 1/2-, 4-, and 4 1/2-year-olds and how these differences were associated with differences in regulatory aspects of temperament, language comprehension, and brain electrical activity. A series of cognitive control tasks was administered to measure…

Sleep supports inhibitory operant conditioning memory in Aplysia.

PubMed

Vorster, Albrecht P A; Born, Jan

2017-06-01

Sleep supports memory consolidation as shown in mammals and invertebrates such as bees and Drosophila. Here, we show that sleep's memory function is preserved in Aplysia californica with an even simpler nervous system. Animals performed on an inhibitory conditioning task ("learning that a food is inedible") three times, at Training, Retrieval 1, and Retrieval 2, with 17-h intervals between tests. Compared with Wake animals, remaining awake between Training and Retrieval 1, Sleep animals with undisturbed post-training sleep, performed significantly better at Retrieval 1 and 2. Control experiments testing retrieval only after ∼34 h, confirmed the consolidating effect of sleep occurring within 17 h after training. © 2017 Vorster and Born; Published by Cold Spring Harbor Laboratory Press.

Balanced Cortical Microcircuitry for Spatial Working Memory Based on Corrective Feedback Control

PubMed Central

2014-01-01

A hallmark of working memory is the ability to maintain graded representations of both the spatial location and amplitude of a memorized stimulus. Previous work has identified a neural correlate of spatial working memory in the persistent maintenance of spatially specific patterns of neural activity. How such activity is maintained by neocortical circuits remains unknown. Traditional models of working memory maintain analog representations of either the spatial location or the amplitude of a stimulus, but not both. Furthermore, although most previous models require local excitation and lateral inhibition to maintain spatially localized persistent activity stably, the substrate for lateral inhibitory feedback pathways is unclear. Here, we suggest an alternative model for spatial working memory that is capable of maintaining analog representations of both the spatial location and amplitude of a stimulus, and that does not rely on long-range feedback inhibition. The model consists of a functionally columnar network of recurrently connected excitatory and inhibitory neural populations. When excitation and inhibition are balanced in strength but offset in time, drifts in activity trigger spatially specific negative feedback that corrects memory decay. The resulting networks can temporally integrate inputs at any spatial location, are robust against many commonly considered perturbations in network parameters, and, when implemented in a spiking model, generate irregular neural firing characteristic of that observed experimentally during persistent activity. This work suggests balanced excitatory–inhibitory memory circuits implementing corrective negative feedback as a substrate for spatial working memory. PMID:24828633

Are planning, working memory, and inhibition associated with individual differences in preschool ADHD symptoms?

PubMed

Sonuga-Barke, Edmund J S; Dalen, Lindy; Daley, Dave; Remington, Bob

2002-01-01

The association between executive function (EF; planning, working memory, and inhibition) and individual differences in symptoms of attention deficit hyperactivity disorder (ADHD) was explored in a sample of preschool children. One hundred sixty children (between the ages of 3 years, 0 months and 5 years, 6 months), selected so as to oversample high ADHD scorers, performed 3 tasks previously shown to measure planning (Tower of London), working memory (Noisy Book) and inhibition ("Puppet Says..."). EF measures were reliable (kappa > .77) and were correlated with IQ (rs > .38) and age (rs > .59). Once IQ and age were controlled, planning and working memory (r = .41) were correlated. Planning and working memory were not correlated with inhibition (rs < .20). There was no association between ADHD and working memory or planning (rs < .12). There was a significant negative association between ADHD and conduct problems and inhibition (r = -.30 and r = -.25, respectively). Only the link with ADHD persisted after the effects of other factors were controlled for in a multiple regression. Specific deficits in inhibitory control rather than general EF deficits are associated with ADHD in the preschool period. This association is linear in nature, supporting the idea that ADHD is better seen as a continuum rather than a discrete category. This association provides evidence for Barkley's (1997) view that ADHD is underpinned by inhibitory deficits in the preschool period.

Differential roles of resistance to proactive interference and suppression of prepotent responses in overgeneral memory.

PubMed

Comas, Michelle; Valentino, Kristin; Johnson, Anne F; Gibson, Bradley S; Taylor, Courtney

2018-06-12

Overgeneral memory (OGM), difficulty in retrieving specific autobiographical memories, is a robust phenomenon related to the onset and course of depressive and posttraumatic stress disorders. Inhibitory mechanisms are theorized to underlie OGM; however, empirical support for this link is equivocal. The current study examines the differential roles of two aspects of inhibitory control in association with OGM: suppression of prepotent responses and resistance to proactive interference (PI). Only resistance to PI was expected to be negatively related to OGM, whereby individuals with greater ability to resist PI would have reduced OGM. Participants (n = 49) completed a self-report measure of depressive symptoms and engaged in two tasks aimed at assessing resistance to PI and suppression of prepotent responses. Participants also completed a task assessing overgeneral autobiographical memory. As hypothesized, resistance to PI, but not suppression of prepotent responses negatively predicted OGM above and beyond the influence of depressive symptoms. Because a double dissociation was not examined, we cannot address the potential independence of the submechanisms of inhibitory control that we assessed. Results exemplify the differential associations of two components of inhibition and OGM, suggesting that resistance to PI, in particular, may contribute to the development and/or maintenance of OGM and associated depressive disorders. Directions for future research are discussed. Copyright © 2018. Published by Elsevier Ltd.

Anterior cingulate synapses in prefrontal areas 10 and 46 suggest differential influence in cognitive control

PubMed Central

Medalla, M.; Barbas, H.

2011-01-01

Dorsolateral prefrontal areas 46 and 10 are involved in distinct aspects of cognition. Area 46 has a key role in working memory tasks, and frontopolar area 10 is recruited in complex multi-task operations. Both areas are innervated by the anterior cingulate cortex (ACC) a region associated with emotions and memory, but is also important for attentional control through unknown synaptic mechanisms. Here we found that in rhesus monkeys (Macaca mulatta) most axon terminals labeled from tracers injected in ACC area 32 innervated spines of presumed excitatory neurons, but about 20–30% formed mostly large synapses with dendritic shafts of presumed inhibitory neurons in the upper layers (I–IIIa) of dorsolateral areas 10, 46, and 9. Moreover, area 32 terminals targeted preferentially calbindin and, to a lesser extent, calretinin neurons, which are thought to be inhibitory neurons that modulate the gain of task-relevant activity during working memory tasks. Area 46 was distinguished as recipient of more (by ~40%) area 32 synapses on putative inhibitory neurons. Area 10 stood apart as recipient of significantly larger (by ~40% in volume) area 32 terminals on spines of putative excitatory neurons. These synaptic specializations suggest that area 32 has complementary roles, potentially enhancing inhibition in area 46 and strengthening excitation in area 10, which may help direct attention to new tasks while temporarily holding in memory another task. PMID:21123554

Enhancement of Functional Connectivity, Working Memory and Inhibitory Control on Multi-modal Brain MR Imaging with Rifaximin in Cirrhosis: Implications for the Gut-Liver-Brain Axis

PubMed Central

Ahluwalia, Vishwadeep; Wade, James B; Heuman, Douglas M; Hammeke, Thomas A; Sanyal, Arun J; Sterling, Richard K; Stravitz, R. Todd; Luketic, Velimir; Siddiqui, Mohammad S; Puri, Puneet; Fuchs, Michael; Lennon, Micheal J; Kraft, Kenneth A; Gilles, HoChong; White, Melanie B; Noble, Nicole A; Bajaj, Jasmohan S

2014-01-01

Objective Minimal hepatic encephalopathy (MHE) impairs daily functioning in cirrhosis, but its functional brain impact is not completely understood. Aim To evaluate the effect of rifaximin, a gut-specific antibiotic, on the gut-liver-brain axis in MHE. Hypothesis Rifaximin will reduce endotoxemia, enhance cognition, increase activation during working memory(N-back) and reduce activation needed for inhibitory control tasks. Methods Cirrhotics with MHE underwent baseline endotoxin and cognitive testing, then underwent fMRI, diffusion tensor imaging and MR spectroscopy(MRS). On fMRI, two tasks; N-back (outcome: correct responses) and inhibitory control tests(outcomes: lure inhibition) were performed. All procedures were repeated after 8 weeks of rifaximin. Results were compared before/after rifaximin. Results 20 MHE patients (59.7 years) were included; sixteen completed pre/post-rifaximin scanning with 92% medication compliance. Pre-rifaximin patients had cognitive impairment. At trial-end, there was a significantly higher correct 2-back responses, ICT lure inhibitions and reduced endotoxemia(p=0.002). This was accompanied by significantly higher activation from baseline in subcortical structures (thalamus, caudate, insula and hippocampus) and left parietal operculum (LPO) during N-back, decrease in fronto-parietal activation required for inhibiting lures, including LPO during ICT compared to baseline values. Connectivity studies in N-back showed significant shifts in linkages after therapy in fronto-parietal regions with a reduction in fractional anisotropy (FA) but not mean diffusivity (MD), and no change in MRS metabolites at the end of the trial. Conclusion A significant improvement in cognition including working memory and inhibitory control, and fractional anisotropy without effect on MD or MRS, through modulation of fronto-parietal and subcortical activation and connectivity was seen after open-label rifaximin therapy in MHE. PMID:24590688

Enhancement of functional connectivity, working memory and inhibitory control on multi-modal brain MR imaging with Rifaximin in Cirrhosis: implications for the gut-liver-brain axis.

PubMed

Ahluwalia, Vishwadeep; Wade, James B; Heuman, Douglas M; Hammeke, Thomas A; Sanyal, Arun J; Sterling, Richard K; Stravitz, R Todd; Luketic, Velimir; Siddiqui, Mohammad S; Puri, Puneet; Fuchs, Michael; Lennon, Micheal J; Kraft, Kenneth A; Gilles, HoChong; White, Melanie B; Noble, Nicole A; Bajaj, Jasmohan S

2014-12-01

Minimal hepatic encephalopathy (MHE) impairs daily functioning in cirrhosis, but its functional brain impact is not completely understood. To evaluate the effect of rifaximin, a gut-specific antibiotic, on the gut-liver-brain axis in MHE. Rifaximin will reduce endotoxemia, enhance cognition, increase activation during working memory(N-back) and reduce activation needed for inhibitory control tasks. Cirrhotics with MHE underwent baseline endotoxin and cognitive testing, then underwent fMRI, diffusion tensor imaging and MR spectroscopy(MRS). On fMRI, two tasks; N-back (outcome: correct responses) and inhibitory control tests(outcomes: lure inhibition) were performed. All procedures were repeated after 8 weeks of rifaximin. RESULTS were compared before/after rifaximin. 20 MHE patients (59.7 years) were included; sixteen completed pre/post-rifaximin scanning with 92% medication compliance. Pre-rifaximin patients had cognitive impairment. At trial-end, there was a significantly higher correct 2-back responses, ICT lure inhibitions and reduced endotoxemia(p = 0.002). This was accompanied by significantly higher activation from baseline in subcortical structures (thalamus, caudate, insula and hippocampus) and left parietal operculum (LPO) during N-back, decrease in fronto-parietal activation required for inhibiting lures, including LPO during ICT compared to baseline values. Connectivity studies in N-back showed significant shifts in linkages after therapy in fronto-parietal regions with a reduction in fractional anisotropy (FA) but not mean diffusivity (MD), and no change in MRS metabolites at the end of the trial. A significant improvement in cognition including working memory and inhibitory control, and fractional anisotropy without effect on MD or MRS, through modulation of fronto-parietal and subcortical activation and connectivity was seen after open-label rifaximin therapy in MHE.

Memory Inhibition, Aging, and the Executive Deficit Hypothesis

ERIC Educational Resources Information Center

Ortega, Almudena; Gomez-Ariza, Carlos J.; Roman, Patricia; Bajo, M. Teresa

2012-01-01

Although memory inhibition seems to underlie retrieval-induced forgetting (RIF), there is some controversy about the precise nature of this effect. Because normal RIF is observed in people with deficits in executive control (i.e., older adults), some have proposed that an automatic-like inhibitory process is responsible for the effect. On the…

Functional magnetic resonance imaging of working memory and response inhibition in children with mild traumatic brain injury.

PubMed

Krivitzky, Lauren S; Roebuck-Spencer, Tresa M; Roth, Robert M; Blackstone, Kaitlin; Johnson, Chad P; Gioia, Gerard

2011-11-01

The current pilot study examined functional magnetic resonance imaging (fMRI) activation in children with mild traumatic brain injury (mTBI) during tasks of working memory and inhibitory control, both of which are vulnerable to impairment following mTBI. Thirteen children with symptomatic mTBI and a group of controls completed a version of the Tasks of Executive Control (TEC) during fMRI scanning. Both groups showed greater prefrontal activation in response to increased working memory load. Activation patterns did not differ between groups on the working memory aspects of the task, but children with mTBI showed greater activation in the posterior cerebellum with the addition of a demand for inhibitory control. Children with mTBI showed greater impairment on symptom report and "real world" measures of executive functioning, but not on traditional "paper and pencil" tasks. Likewise, cognitive testing did not correlate significantly with imaging results, whereas increased report of post-concussive symptoms were correlated with increased cerebellar activation. Overall, results provide some evidence for the utility of symptom report as an indicator of recovery and the hypothesis that children with mTBI may experience disrupted neural circuitry during recovery. Limitations of the study included a small sample size, wide age range, and lack of in-scanner accuracy data.

Nogo-A regulates spatial learning as well as memory formation and modulates structural plasticity in the adult mouse hippocampus.

PubMed

Zagrebelsky, Marta; Lonnemann, Niklas; Fricke, Steffen; Kellner, Yves; Preuß, Eike; Michaelsen-Preusse, Kristin; Korte, Martin

2017-02-01

Behavioral learning has been shown to involve changes in the function and structure of synaptic connections of the central nervous system (CNS). On the other hand, the neuronal circuitry in the mature brain is characterized by a high degree of stability possibly providing a correlate for long-term storage of information. This observation indicates the requirement for a set of molecules inhibiting plasticity and promoting stability thereby providing temporal and spatial specificity to plastic processes. Indeed, signaling of Nogo-A via its receptors has been shown to play a crucial role in restricting activity-dependent functional and structural plasticity in the adult CNS. However, whether Nogo-A controls learning and memory formation and what are the cellular and molecular mechanisms underlying this function is still unclear. Here we show that Nogo-A signaling controls spatial learning and reference memory formation upon training in the Morris water maze and negatively modulates structural changes at spines in the mouse hippocampus. Learning processes and the correlated structural plasticity have been shown to involve changes in excitatory as well as in inhibitory neuronal connections. We show here that Nogo-A is highly expressed not only in excitatory, but also in inhibitory, Parvalbumin positive neurons in the adult hippocampus. By this means our current and previous data indicate that Nogo-A loss-of-function positively influences spatial learning by priming the neuronal structure to a higher plasticity level. Taken together our results link the role of Nogo-A in negatively regulating plastic processes to a physiological function in controlling learning and memory processes in the mature hippocampus and open the interesting possibility that it might mainly act by controlling the function of the hippocampal inhibitory circuitry. Copyright © 2016 Elsevier Inc. All rights reserved.

Childhood Maltreatment and Its Effect on Neurocognitive Functioning: Timing and Chronicity Matter

PubMed Central

Cowell, Raquel A.; Cicchetti, Dante; Rogosch, Fred A.; Toth, Sheree L.

2015-01-01

Childhood maltreatment represents a complex stressor, with the developmental timing, duration, frequency, and type of maltreatment varying with each child (Barnett, Manly, & Cicchetti, 1993; Cicchetti & Manly, 2001). Multiple brain regions and neural circuits are disrupted by the experience of child maltreatment (Cicchetti & Toth, in press; DeBellis et al., 2002; McCrory & Viding, 2010; Teicher, Anderson, & Polcari, 2012). These neurobiological compromises indicate the impairment of a number of important cognitive functions, including working memory and inhibitory control. The present study extends prior research by examining the effect of childhood maltreatment on neurocognitive functioning based on developmental timing of maltreatment, including onset, chronicity, and recency, in a sample of 3- to 9-year-old nonmaltreated (n = 136) and maltreated children (n = 223). Maltreated children performed more poorly on inhibitory control and working memory tasks than nonmaltreated children. Group differences between maltreated children based on the timing of maltreatment and the chronicity of maltreatment also were evident. Specifically, children who were maltreated during infancy, and children with a chronic history of maltreatment, exhibited significantly poorer inhibitory control and working memory performance than children without a history of maltreatment. The results suggest that maltreatment occurring during infancy, a period of major brain organization, disrupts normative structure and function, and these deficits are further instantiated by the prolonged stress of chronic maltreatment during the early years of life. PMID:25997769

Improving attention control in dysphoria through cognitive training: transfer effects on working memory capacity and filtering efficiency.

PubMed

Owens, Max; Koster, Ernst H W; Derakshan, Nazanin

2013-03-01

Impaired filtering of irrelevant information from working memory is thought to underlie reduced working memory capacity for relevant information in dysphoria. The current study investigated whether training-related gains in working memory performance on the adaptive dual n-back task could result in improved inhibitory function. Efficacy of training was monitored in a change detection paradigm allowing measurement of a sustained event-related potential asymmetry sensitive to working memory capacity and the efficient filtering of irrelevant information. Dysphoric participants in the training group showed training-related gains in working memory that were accompanied by gains in working memory capacity and filtering efficiency compared to an active control group. Results provide important initial evidence that behavioral performance and neural function in dysphoria can be improved by facilitating greater attentional control. Copyright © 2013 Society for Psychophysiological Research.

Balanced cortical microcircuitry for spatial working memory based on corrective feedback control.

PubMed

Lim, Sukbin; Goldman, Mark S

2014-05-14

A hallmark of working memory is the ability to maintain graded representations of both the spatial location and amplitude of a memorized stimulus. Previous work has identified a neural correlate of spatial working memory in the persistent maintenance of spatially specific patterns of neural activity. How such activity is maintained by neocortical circuits remains unknown. Traditional models of working memory maintain analog representations of either the spatial location or the amplitude of a stimulus, but not both. Furthermore, although most previous models require local excitation and lateral inhibition to maintain spatially localized persistent activity stably, the substrate for lateral inhibitory feedback pathways is unclear. Here, we suggest an alternative model for spatial working memory that is capable of maintaining analog representations of both the spatial location and amplitude of a stimulus, and that does not rely on long-range feedback inhibition. The model consists of a functionally columnar network of recurrently connected excitatory and inhibitory neural populations. When excitation and inhibition are balanced in strength but offset in time, drifts in activity trigger spatially specific negative feedback that corrects memory decay. The resulting networks can temporally integrate inputs at any spatial location, are robust against many commonly considered perturbations in network parameters, and, when implemented in a spiking model, generate irregular neural firing characteristic of that observed experimentally during persistent activity. This work suggests balanced excitatory-inhibitory memory circuits implementing corrective negative feedback as a substrate for spatial working memory. Copyright © 2014 the authors 0270-6474/14/346790-17$15.00/0.

Working memory and inhibitory control across the life span: Intrusion errors in the Reading Span Test.

PubMed

Robert, Christelle; Borella, Erika; Fagot, Delphine; Lecerf, Thierry; de Ribaupierre, Anik

2009-04-01

The aim of this study was to examine to what extent inhibitory control and working memory capacity are related across the life span. Intrusion errors committed by children and younger and older adults were investigated in two versions of the Reading Span Test. In Experiment 1, a mixed Reading Span Test with items of various list lengths was administered. Older adults and children recalled fewer correct words and produced more intrusions than did young adults. Also, age-related differences were found in the type of intrusions committed. In Experiment 2, an adaptive Reading Span Test was administered, in which the list length of items was adapted to each individual's working memory capacity. Age groups differed neither on correct recall nor on the rate of intrusions, but they differed on the type of intrusions. Altogether, these findings indicate that the availability of attentional resources influences the efficiency of inhibition across the life span.

Parent-delivered compensatory education for children at risk of educational failure: Improving the academic and self-regulatory skills of a Sure Start preschool sample.

PubMed

Ford, Ruth M; McDougall, Sine J P; Evans, Daphne

2009-11-01

Thirty preschoolers from low-income families participated in a 12-month intervention programme, funded by Sure Start, which engaged them in scaffolded educational activities delivered at home by their mothers. Immediately following the programme, the intervention group outperformed matched controls in tests of academic knowledge, receptive vocabulary, and inhibitory control, but not short-term memory or theory of mind. Teachers' ratings of children's capabilities upon school entry favoured the intervention group, especially in terms of listening, responding, writing, mathematics, and personal/social skills. Superior inhibitory control, short-term memory, and numerical skills were associated with higher ratings whereas theory of mind made a unique, negative contribution to responding. We discuss the implications of these findings for efforts to nurture the development of cognitive self-regulation and school readiness during early childhood.

The origins of repetitive thought in rumination: separating cognitive style from deficits in inhibitory control over memory.

PubMed

Fawcett, Jonathan M; Benoit, Roland G; Gagnepain, Pierre; Salman, Amna; Bartholdy, Savani; Bradley, Caroline; Chan, Daniel K Y; Roche, Ayesha; Brewin, Chris R; Anderson, Michael C

2015-06-01

Rumination is a major contributor to the maintenance of affective disorders and has been linked to memory control deficits. However, ruminators often report intentionally engaging in repetitive thought due to its perceived benefits. Deliberate re-processing may lead to the appearance of a memory control deficit that is better explained as a difference in cognitive style. Ninety-six undergraduate students volunteered to take part in a direct-suppression variant of the Think/No-Think paradigm after which they completed self-report measures of rumination and the degree to which they deliberately re-processed the to-be-suppressed items. We demonstrate a relation between rumination and impaired suppression-induced forgetting. This relation is robust even when controlling for deliberate re-processing of the to-be-suppressed items, a behavior itself related to both rumination and suppression. Therefore, whereas conscious fixation on to-be-suppressed items reduced memory suppression, it did not fully account for the relation between rumination and memory suppression. The current experiment employed a retrospective measure of deliberate re-processing in the context of an unscreened university sample; future research might therefore generalize our findings using an online measure of deliberate re-processing or within a clinical population. We provide evidence that deliberate re-processing accounts for some--but not all--of the relation between rumination and suppression-induced forgetting. The present findings, observed in a paradigm known to engage top-down inhibitory modulation of mnemonic processing, provide the most theoretically focused evidence to date for the existence of a memory control deficit in rumination. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Incidental threat during visuospatial working memory in adolescent anxiety: an emotional memory-guided saccade task.

PubMed

Mueller, Sven C; Shechner, Tomer; Rosen, Dana; Nelson, Eric E; Pine, Daniel S; Ernst, Monique

2015-04-01

Pediatric anxiety disorders are among the most common psychiatric mental illnesses in children and adolescents, and are associated with abnormal cognitive control in emotional, particularly threat, contexts. In a series of studies using eye movement saccade tasks, we reported anxiety-related alterations in the interplay of inhibitory control with incentives, or with emotional distractors. The present study extends these findings to working memory (WM), and queries the interaction of spatial WM with emotional stimuli in pediatric clinical anxiety. Participants were 33 children/adolescents diagnosed with an anxiety disorder, and 22 age-matched healthy comparison youths. Participants completed a novel eye movement task, an affective variant of the memory-guided saccade task. This task assessed the influence of incidental threat on spatial WM processes during high and low cognitive load. Healthy but not anxious children/adolescents showed slowed saccade latencies during incidental threat in low-load but not high-load WM conditions. No other group effects emerged on saccade latency or accuracy. The current data suggest a differential pattern of how emotion interacts with cognitive control in healthy youth relative to anxious youth. These findings extend data from inhibitory processes, reported previously, to spatial WM in pediatric anxiety. © 2015 Wiley Periodicals, Inc.

Inhibition-Induced Forgetting Results from Resource Competition between Response Inhibition and Memory Encoding Processes.

PubMed

Chiu, Yu-Chin; Egner, Tobias

2015-08-26

Response inhibition is a key component of executive control, but its relation to other cognitive processes is not well understood. We recently documented the "inhibition-induced forgetting effect": no-go cues are remembered more poorly than go cues. We attributed this effect to central-resource competition, whereby response inhibition saps attention away from memory encoding. However, this proposal is difficult to test with behavioral means alone. We therefore used fMRI in humans to test two neural predictions of the "common resource hypothesis": (1) brain regions associated with response inhibition should exhibit greater resource demands during encoding of subsequently forgotten than remembered no-go cues; and (2) this higher inhibitory resource demand should lead to memory encoding regions having less resources available during encoding of subsequently forgotten no-go cues. Participants categorized face stimuli by gender in a go/no-go task and, following a delay, performed a surprise recognition memory test for those faces. Replicating previous findings, memory was worse for no-go than for go stimuli. Crucially, forgetting of no-go cues was predicted by high inhibitory resource demand, as quantified by the trial-by-trial ratio of activity in neural "no-go" versus "go" networks. Moreover, this index of inhibitory demand exhibited an inverse trial-by-trial relationship with activity in brain regions responsible for the encoding of no-go cues into memory, notably the ventrolateral prefrontal cortex. This seesaw pattern between the neural resource demand of response inhibition and activity related to memory encoding directly supports the hypothesis that response inhibition temporarily saps attentional resources away from stimulus processing. Recent behavioral experiments showed that inhibiting a motor response to a stimulus (a "no-go cue") impairs subsequent memory for that cue. Here, we used fMRI to test whether this "inhibition-induced forgetting effect" is caused by competition for neural resources between the processes of response inhibition and memory encoding. We found that trial-by-trial variations in neural inhibitory resource demand predicted subsequent forgetting of no-go cues and that higher inhibitory demand was furthermore associated with lower concurrent activation in brain regions responsible for successful memory encoding of no-go cues. Thus, motor inhibition and stimulus encoding appear to compete with each other: when more resources have to be devoted to inhibiting action, less are available for encoding sensory stimuli. Copyright © 2015 the authors 0270-6474/15/3511936-10$15.00/0.

[Comparison between the diagnosis of attention deficit hyperactivity disorder with the DSM-5 and neuropsychological evaluation of the executive functions].

PubMed

Abad-Mas, L; Caloca-Catala, O; Mulas, F; Ruiz-Andres, R

2017-02-24

The attention deficit-hyperactivity disorder (ADHD) has a prevalence among 3-7% in scholar population and it is associated with learning disabilities and executive dysfunctions. To study the relationship between the ADHD diagnostic through DSM-5 criteria and the neuropshychology evaluation of executive functions. The sample of this study consisted in 50 subjects, 12 females and 38 males, with an age between 8 and 10 years old. To evaluate the inhibitory control, we used the Stroop Test and the Continuous Performance Test (CPT), to evaluate intelligence and working memory we use the Wechsler Intelligence Scale WISC-IV, to evaluate attention we used the CPT and Selective Attention Test. There weren't significant differences between both subtypes of ADHD regarding working memory, on the other hand the female group had better abilities in cognitive flexibility task than males and subjects diagnosed with combined ADHD had more difficulties in inhibitory control. We can confirm that the definition of ADHD in DSM-5 isn't enough as them are imprecise. Therefore, the disease definition it's performed by a specific evaluation of attention and inhibitory control mechanisms and its necessary a neuropshychological evaluation of these brain functions.

Executive Functioning Heterogeneity in Pediatric ADHD.

PubMed

Kofler, Michael J; Irwin, Lauren N; Soto, Elia F; Groves, Nicole B; Harmon, Sherelle L; Sarver, Dustin E

2018-04-28

Neurocognitive heterogeneity is increasingly recognized as a valid phenomenon in ADHD, with most estimates suggesting that executive dysfunction is present in only about 33%-50% of these children. However, recent critiques question the veracity of these estimates because our understanding of executive functioning in ADHD is based, in large part, on data from single tasks developed to detect gross neurological impairment rather than the specific executive processes hypothesized to underlie the ADHD phenotype. The current study is the first to comprehensively assess heterogeneity in all three primary executive functions in ADHD using a criterion battery that includes multiple tests per construct (working memory, inhibitory control, set shifting). Children ages 8-13 (M = 10.37, SD = 1.39) with and without ADHD (N = 136; 64 girls; 62% Caucasian/Non-Hispanic) completed a counterbalanced series of executive function tests. Accounting for task unreliability, results indicated significantly improved sensitivity and specificity relative to prior estimates, with 89% of children with ADHD demonstrating objectively-defined impairment on at least one executive function (62% impaired working memory, 27% impaired inhibitory control, 38% impaired set shifting; 54% impaired on one executive function, 35% impaired on two or all three executive functions). Children with working memory deficits showed higher parent- and teacher-reported ADHD inattentive and hyperactive/impulsive symptoms (BF 10  = 5.23 × 10 4 ), and were slightly younger (BF 10  = 11.35) than children without working memory deficits. Children with vs. without set shifting or inhibitory control deficits did not differ on ADHD symptoms, age, gender, IQ, SES, or medication status. Taken together, these findings confirm that ADHD is characterized by neurocognitive heterogeneity, while suggesting that contemporary, cognitively-informed criteria may provide improved precision for identifying a smaller number of neuropsychologically-impaired subtypes than previously described.

Prefrontal-Hippocampal Pathways Underlying Inhibitory Control Over Memory

PubMed Central

Anderson, Michael C.; Bunce, Jamie G.; Barbas, Helen

2016-01-01

A key function of the prefrontal cortex is to support inhibitory control over behavior. It is widely believed that this function extends to stopping cognitive processes as well. Consistent with this, mounting evidence establishes the role of the right lateral prefrontal cortex in a clear case of cognitive control: retrieval suppression. Retrieval suppression refers to the ability to intentionally stop the retrieval process that arises when a reminder to a memory appears. Functional imaging data indicates that retrieval suppression involves top-down modulation of hippocampal activity by the dorsolateral prefrontal cortex, but the anatomical pathways supporting this inhibitory modulation remain unclear. Here we bridge this gap by integrating key findings about retrieval suppression observed through functional imaging with a detailed consideration of relevant anatomical pathways observed in non-human primates. Focusing selectively on the potential role of the anterior cingulate cortex, we develop two hypotheses about the pathways mediating interactions between lateral prefrontal cortex and the medial temporal lobes during suppression, and their cellular targets: the entorhinal gating hypothesis, and thalamo-hippocampal modulation via the nucleus reuniens. We hypothesize that whereas entorhinal gating is well situated to stop retrieval proactively, thalamo-hippocampal modulation may interrupt an ongoing act of retrieval reactively. Isolating the pathways that underlie retrieval suppression holds the potential to advance our understanding of a range of psychiatric disorders characterized by persistent intrusive thoughts. More broadly, an anatomical account of retrieval suppression would provide a key model system for understanding inhibitory control over cognition. PMID:26642918

Role of D2 dopamine receptors of the ventral pallidum in inhibitory avoidance learning.

PubMed

Lénárd, László; Ollmann, Tamás; László, Kristóf; Kovács, Anita; Gálosi, Rita; Kállai, Veronika; Attila, Tóth; Kertes, Erika; Zagoracz, Olga; Karádi, Zoltán; Péczely, László

2017-03-15

In our present experiments, the role of D2 dopamine (DA) receptors of the ventral pallidum (VP) was investigated in one trial step-through inhibitory avoidance paradigm. Animals were shocked 3 times in the conditioning trial, with 0.5mA current for 1s. Subsequently bilateral microinjection of the D2 DA receptor agonist quinpirole was administered into the VP in three doses (0.1μg, 1.0μg or 5.0μg in 0.4μl saline). We also applied the D2 DA receptor antagonist sulpiride (0.4μg in 0.4μl saline) alone or 15min prior to the agonist treatment to elucidate whether the agonist effect was specific for the D2 DA receptors. Control animals received saline. In a supplementary experiment, it was also investigated whether application of the same conditioning method leads to the formation of short-term memory in the experimental animals. In the experiment with the D2 DA receptor agonist, only the 0.1μg quinpirole increased significantly the step-through latency during the test trials: retention was significant compared to the controls even 2 weeks after conditioning. The D2 DA receptor antagonist sulpiride pretreatment proved that the effect was due to the agonist induced activation of the D2 DA receptors of the VP. The supplementary experiment demonstrated that short-term memory is formed after conditioning in the experimental animals, supporting that the agonist enhanced memory consolidation in the first two experiments. Our results show that the activation of the D2 DA receptors in the VP facilitates memory consolidation as well as memory-retention in inhibitory avoidance paradigm. Copyright © 2017 Elsevier B.V. All rights reserved.

Mental Set Shifting in Childhood: The Role of Working Memory and Inhibitory Control

ERIC Educational Resources Information Center

Brocki, Karin C.; Tillman, Carin

2014-01-01

The role of working memory (WM) and inhibition in mental set shifting was examined from an individual difference perspective in children aged 5-14?years (N?=?117). Using the Hearts and Flowers task the rationale of the present study was to directly test the theoretical assumption that mental set shifiting in childhood primarily builds on WM and…

Cue-independent forgetting by intentional suppression - Evidence for inhibition as the mechanism of intentional forgetting.

PubMed

Wang, Yingying; Cao, Zhijun; Zhu, Zijian; Cai, Huaqian; Wu, Yanhong

2015-10-01

People are able to intentionally forget unwanted memories through voluntary suppression, as revealed by the Think/No-think (TNT) paradigm. However, the nature of intentional forgetting is controversial. Findings that forgetting is independent of retrieval cues suggest that inhibitory control underlies intentional forgetting, but this result is also in line with an interference account. To resolve this controversy, we have directly contrasted the cue-independent characteristic of suppression versus interference. A double-cue paradigm was used, in which two different cues were associated with the same target during initial memory formation. Only one cue-target association received further interference/suppression training. In the test phase, when both cues were used to retrieve the target, we found that interference caused memory impairment that was restricted to the trained cue-target association, while suppression induced forgetting that generalized to the independent cue-target association. Therefore, the effect of suppression differs from that of interference. The cue-independent forgetting by voluntary suppression indicates that the target memory itself is inhibited, providing evidence that the underlying mechanism of suppression-induced forgetting is inhibitory control. Copyright © 2015 Elsevier B.V. All rights reserved.

Evidence for selective inhibitory impairment in individuals with autism spectrum disorder.

PubMed

Christ, Shawn E; Kester, Lindsay E; Bodner, Kimberly E; Miles, Judith H

2011-11-01

The social and communicative challenges faced by individuals with autism spectrum disorder (ASD) are often compounded by additional difficulties with executive function. It remains unclear, however, to what the extent individuals with ASD experienced impairment in inhibitory control. The objective of the present study was to assess the three main subtypes of executive inhibitory control within a single ASD sample thus providing new insight into the unique ASD-related pattern of sparing and impairment observed across different aspects of inhibitory control. A sample of 28 children with ASD (mean age = 13.1 years) and a comparison group of 49 neurologically uncompromised children (mean age = 13.3 years) participated. A prepotent response inhibition task, a flanker visual filtering task, and a proactive interference memory task were used to evaluate prepotent response inhibition, resistance to distracter interference, and resistance to proactive interference, respectively. After accounting for individual differences in noninhibition abilities (e.g., processing speed) and overall level of functioning, there was no evidence of group-related differences in inhibitory performance on the prepotent response inhibition test or proactive interference test. ASD-related impairments in inhibitory control were evident, however, on the flanker visual filtering task. Taken together, the present findings indicate that ASD is associated with impairments in some, but not all, aspects of inhibitory control. Individuals with ASD appear to have difficulty ignoring distracting visual information, but prepotent response inhibition and resistance to proactive interference are relatively intact. The current findings also provide support for a multitype model of inhibitory control.

Cognitive self-regulation and social functioning among French children: A longitudinal study from kindergarten to first grade.

PubMed

Hubert, Blandine; Guimard, Philippe; Florin, Agnès

2017-03-01

This study adds to the body of research examining the links between two components of cognitive self-regulation (inhibitory control and verbal working memory) and social functioning (social integration, social problem solving, and prosocial skills) and focuses on children's sex as a moderator of the association between cognitive self-regulation and social functioning. The participants (N = 131) were French schoolchildren followed from kindergarten (Mage = 68.36 months, SD = 3.33 months) through Grade 1. Using hierarchical regression analyses, three major findings were revealed: (1) inhibitory control was a better predictor than verbal working memory of prosocial skills assessed by peers using the sociometric technique as well as by teachers using questionnaires, after controlling for sex, mother's education, and verbal and non-verbal IQ; (2) the prosocial skills assessed by teachers in kindergarten contributed more to explaining the prosocial skills and peer acceptance assessed in Grade 1 than cognitive self-regulation; and (3) sex did not moderate the relationship between cognitive self-regulation and social functioning. These results suggest that developing strong cognitive self-regulation, especially inhibitory control and prosocial skills, in young children schooled in France could be beneficial for their social development. © 2017 The Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

Sleep Supports Inhibitory Operant Conditioning Memory in "Aplysia"

ERIC Educational Resources Information Center

Vorster, Albrecht P. A.; Born, Jan

2017-01-01

Sleep supports memory consolidation as shown in mammals and invertebrates such as bees and "Drosophila." Here, we show that sleep's memory function is preserved in "Aplysia californica" with an even simpler nervous system. Animals performed on an inhibitory conditioning task ("learning that a food is inedible") three…

Proactive interference and concurrent inhibitory processes do not differentially affect item and associative recognition: Implication for the age-related associative memory deficit.

PubMed

Guez, Jonathan; Naveh-Benjamin, Moshe

2016-09-01

Previous studies have suggested an associative deficit hypothesis [Naveh-Benjamin, M. ( 2000 ). Adult age differences in memory performance: Tests of an associative deficit hypothesis. Journal of Experimental Psychology: Learning, Memory, and Cognition, 26, 1170-1187] to explain age-related episodic memory declines. The hypothesis attributes part of the deficient episodic memory performance in older adults to a difficulty in creating and retrieving cohesive episodes. In this article, we further evaluate this hypothesis by testing two alternative processes that potentially mediate associative memory deficits in older adults. Four experiments are presented that assess whether failure of inhibitory processes (proactive interference in Experiments 1 and 2), and concurrent inhibition (in Experiments 3 and 4) are mediating factors in age-related associative deficits. The results suggest that creating conditions that require the operation of inhibitory processes, or that interfere with such processes, cannot simulate associative memory deficit in older adults. Instead, such results support the idea that associative memory deficits reflect a unique binding failure in older adults. This failure seems to be independent of other cognitive processes, including inhibitory and other resource-demanding processes.

Vitamin B6 prevents cognitive impairment in experimental pneumococcal meningitis.

PubMed

Barichello, Tatiana; Generoso, Jaqueline S; Simões, Lutiana R; Ceretta, Renan A; Dominguini, Diogo; Ferrari, Pâmela; Gubert, Carolina; Jornada, Luciano K; Budni, Josiane; Kapczinski, Flávio; Quevedo, João

2014-10-01

Streptococcus pneumoniae is the relevant cause of bacterial meningitis, with a high-mortality rate and long-term neurological sequelae, affecting up to 50% of survivors. Pneumococcal compounds are pro-inflammatory mediators that induce an innate immune response and tryptophan degradation through the kynurenine pathway. Vitamin B6 acts as a cofactor at the active sites of enzymes that catalyze a great number of reactions involved in the metabolism of tryptophan, preventing the accumulation of neurotoxic intermediates. In the present study, we evaluated the effects of vitamin B6 on memory and on brain-derived neurotrophic factor (BDNF) expression in the brain of adult Wistar rats subjected to pneumococcal meningitis. The animals received either 10 µL of artificial cerebral spinal fluid (CSF) or an equivalent volume of S. pneumoniae suspension. The animals were divided into four groups: control, control treated with vitamin B6, meningitis, and meningitis treated with vitamin B6. Ten days after induction, the animals were subjected to behavioral tests: open-field task and step-down inhibitory avoidance task. In the open-field task, there was a significant reduction in both crossing and rearing in the control group, control/B6 group, and meningitis/B6 group compared with the training session, demonstrating habituation memory. However, the meningitis group showed no difference in motor and exploratory activity between training and test sessions, demonstrating memory impairment. In the step-down inhibitory avoidance task, there was a difference between training and test sessions in the control group, control/B6 group, and meningitis/B6 group, demonstrating aversive memory. In the meningitis group, there was no difference between training and test sessions, demonstrating impairment of aversive memory. In the hippocampus, BDNF expression decreased in the meningitis group when compared to the control group; however, adjuvant treatment with vitamin B6 increased BDNF expression in the meningitis group. Thus, vitamin B6 attenuated the memory impairment in animals subjected to pneumococcal meningitis. © 2014 by the Society for Experimental Biology and Medicine.

Temporal Preparation and Inhibitory Deficit in Fibromyalgia Syndrome

ERIC Educational Resources Information Center

Correa, Angel; Miro, Elena; Martinez, M. Pilar; Sanchez, Ana I.; Lupianez, Juan

2011-01-01

Cognitive deficits in fibromyalgia may be specifically related to controlled processes, such as those measured by working memory or executive function tasks. This hypothesis was tested here by measuring controlled temporal preparation (temporal orienting) during a response inhibition (go no-go) task. Temporal orienting effects (faster reaction…

When this means that: the role of working memory and inhibitory control in children's understanding of representations.

PubMed

Astle, Andrea; Kamawar, Deepthi; Vendetti, Corrie; Podjarny, Gal

2013-10-01

We investigated cognitive skills that contribute to 4-year-olds' understanding of representations. In our main task, children used representations on a perspective line drawing to find stickers hidden in a model room. To compare the contributions made by various cognitive skills with children's understanding of different types of representations, we manipulated the resemblance between the representations and their referents. Our results indicate that when representations are iconic (i.e., look like their referents), children have very little difficulty with the task. Controlling for performance on this baseline version of the task, we found that specific cognitive skills are differentially predictive of performance when using arbitrary and conflicting representations (i.e., symbols). When the representation was arbitrarily linked to the sticker, performance was related to phonological and visuospatial working memory. When the representation matched the color of an alternate sticker (thereby conflicting with the desired sticker), performance was related to phonological working memory and inhibitory control. We discuss the role that different cognitive skills play in representational understanding as a function of the nature of the representation-referent relation. Copyright © 2013 Elsevier Inc. All rights reserved.

The inhibitory avoidance discrimination task to investigate accuracy of memory.

PubMed

Atucha, Erika; Roozendaal, Benno

2015-01-01

The present study was aimed at developing a new inhibitory avoidance task, based on training and/or testing rats in multiple contexts, to investigate accuracy of memory. In the first experiment, male Sprague-Dawley rats were given footshock in an inhibitory avoidance apparatus and, 48 h later, retention latencies of each rat were assessed in the training apparatus (Shock box) as well as in a novel, contextually modified, apparatus. Retention latencies in the Shock box were significantly longer than those in the Novel box, indicating accurate memory of the training context. When the noradrenergic stimulant yohimbine (0.3 mg/kg, sc) was administered after the training, 48-h retention latencies in the Shock box, but not Novel box, were increased, indicating that the noradrenergic activation enhanced memory of the training experience without reducing memory accuracy. In the second experiment, rats were trained on an inhibitory avoidance discrimination task: They were first trained in an inhibitory avoidance apparatus without footshock (Non-Shock box), followed 1 min later by footshock training in a contextually modified apparatus (Shock box). Forty-eight-hour retention latencies in the Shock and Non-Shock boxes did not differ from each other but were both significantly longer than those in a Novel box, indicating that rats remembered the two training contexts but did not have episodic-like memory of the association of footshock with the correct training context. When the interval between the two training episodes was increased to 2 min, rats showed accurate memory of the association of footshock with the training context. Yohimbine administered after the training also enhanced rats' ability to remember in which training context they had received actual footshock. These findings indicate that the inhibitory avoidance discrimination task is a novel variant of the well-established inhibitory avoidance task suitable to investigate accuracy of memory.

Post-Training Reversible Disconnection of the Ventral Hippocampal-Basolateral Amygdaloid Circuits Impairs Consolidation of Inhibitory Avoidance Memory in Rats

ERIC Educational Resources Information Center

Wang, Gong-Wu; Liu, Jian; Wang, Xiao-Qin

2017-01-01

The ventral hippocampus (VH) and the basolateral amygdala (BLA) are both crucial in inhibitory avoidance (IA) memory. However, the exact role of the VH-BLA circuit in IA memory consolidation is unclear. This study investigated the effect of post-training reversible disconnection of the VH-BLA circuit in IA memory consolidation. Male Wistar rats…

Executive Functioning Skills Uniquely Predict Chinese Word Reading

ERIC Educational Resources Information Center

Chung, Kevin K. H.; McBride-Chang, Catherine

2011-01-01

Eighty-five Hong Kong Chinese children were tested across both the 2nd and 3rd years of kindergarten (ages 4-5 years) on tasks of inhibitory control, working memory, vocabulary knowledge, phonological awareness, morphological awareness, and word reading. With age, vocabulary knowledge, and metalinguistic skills statistically controlled, the…

Neural mechanisms of motivated forgetting

PubMed Central

Anderson, Michael C.; Hanslmayr, Simon

2014-01-01

Not all memories are equally welcome in awareness. People limit the time they spend thinking about unpleasant experiences, a process that begins during encoding, but that continues when cues later remind someone of the memory. Here, we review the emerging behavioural and neuroimaging evidence that suppressing awareness of an unwelcome memory, at encoding or retrieval, is achieved by inhibitory control processes mediated by the lateral prefrontal cortex. These mechanisms interact with neural structures that represent experiences in memory, disrupting traces that support retention. Thus, mechanisms engaged to regulate momentary awareness introduce lasting biases in which experiences remain accessible. We argue that theories of forgetting that neglect the motivated control of awareness omit a powerful force shaping the retention of our past. PMID:24747000

No Retrieval-Induced Forgetting Using Item-Specific Independent Cues: Evidence against a General Inhibitory Account

ERIC Educational Resources Information Center

Camp, Gino; Pecher, Diane; Schmidt, Henk G.

2007-01-01

Retrieval practice with particular items from memory can impair the recall of related items on a later memory test. This retrieval-induced forgetting effect has been ascribed to inhibitory processes (M. C. Anderson & B. A. Spellman, 1995). A critical finding that distinguishes inhibitory from interference explanations is that forgetting is found…

Resveratrol Supplementation Did Not Improve Cognition in Patients with Schizophrenia: Results from a Randomized Clinical Trial.

PubMed

Zortea, Karine; Franco, Viviane C; Guimarães, Paula; Belmonte-de-Abreu, Paulo S

2016-01-01

Schizophrenia (SZ) is associated with psychotic experiences and cognitive deficits. Therefore, cognitive function is one of the most critical determinants of quality of life in this pathology. Resveratrol has been related to neuroprotective action, but there are no studies evaluating resveratrol in SZ. The objective of this study was to determine the efficacy of resveratrol supplementation on cognition in individuals with SZ. This is a 1-month randomized, double-blind, and controlled trial (NCT 02062190), in which 19 men with diagnosis of SZ, aged 18-65 years, were assigned to a resveratrol supplementation group (200 mg) or placebo group (200 mg), with a 1-month follow-up. Applying a series of cognitive tests assessed neuropsychology performance (Hopkins Verbal Learning Test, Stroop Color and Word Test, and Weschler Adult Intelligence Scale) and Brief Psychiatric Rating Scale assessed psychopathology severity. There were no significant improvement in neuropsychology performance (episodic memory, working memory, attention and concentration capacity, inhibitory control, interference measures, selective attention, and mental flexibility) and psychopathology severity after 1 month of resveratrol supplementation ( P  > 0.05). In conclusion, we have shown that 1 month of a resveratrol supplementation (200 mg/day) did not improve episodic memory, working memory, attention and concentration capacity, inhibitory control, interference measures, selective attention, and mental flexibility as compared with placebo in patients with SZ.

Transcranial Direct Current Stimulation Improves Executive Dysfunctions in ADHD: Implications for Inhibitory Control, Interference Control, Working Memory, and Cognitive Flexibility.

PubMed

Nejati, Vahid; Salehinejad, Mohammad Ali; Nitsche, Michael A; Najian, Asal; Javadi, Amir-Homayoun

2017-09-01

This study examined effects of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) on major executive functions (EFs), including response inhibition, executive control, working memory (WM), and cognitive flexibility/task switching in ADHD. ADHD children received (a) left anodal/right cathodal DLPFC tDCS and (b) sham stimulation in Experiment 1 and (a) left anodal DLPFC/right cathodal OFC tDCS, (b) left cathodal DLPFC/right anodal OFC tDCS, and (c) sham stimulation in Experiment 2. The current intensity was 1 mA for 15 min with a 72-hr interval between sessions. Participants underwent Go/No-Go task, N-back test, Wisconsin Card Sorting Test (WCST), and Stroop task after each tDCS condition. Anodal left DLPFC tDCS most clearly affected executive control functions (e.g., WM, interference inhibition), while cathodal left DLPFC tDCS improved inhibitory control. Cognitive flexibility/task switching benefited from combined DLPFC-OFC, but not DLPFC stimulation alone. Task-specific stimulation protocols can improve EFs in ADHD.

Can't control yourself? Monitor those bad habits.

PubMed

Quinn, Jeffrey M; Pascoe, Anthony; Wood, Wendy; Neal, David T

2010-04-01

What strategies can people use to control unwanted habits? Past work has focused on controlling other kinds of automatic impulses, especially temptations. The nature of habit cuing calls for certain self-control strategies. Because the slow-to-change memory trace of habits is not amenable to change or reinterpretation, successful habit control involves inhibiting the unwanted response when activated in memory. In support, two episode-sampling diary studies demonstrated that bad habits, unlike responses to temptations, were controlled most effectively through spontaneous use of vigilant monitoring (thinking "don't do it," watching carefully for slipups). No other strategy was useful in controlling strong habits, despite that stimulus control was effective at inhibiting responses to temptations. A subsequent experiment showed that vigilant monitoring aids habit control, not by changing the strength of the habit memory trace but by heightening inhibitory, cognitive control processes. The implications of these findings for behavior change interventions are discussed.

Evaluation of a teacher training program to enhance executive functions in preschool children.

PubMed

Walk, Laura M; Evers, Wiebke F; Quante, Sonja; Hille, Katrin

2018-01-01

Executive functions (EFs) play a critical role in cognitive and social development. During preschool years, children show not only rapid improvement in their EFs, but also appear sensitive to developmentally appropriate interventions. EMIL is a training program for German preschool teachers that was developed and implemented to improve the EFs of preschoolers. The aim of the present study was to evaluate its effects on the EFs of children between three and six years old. The teacher training (eight sessions, 28.5 hours) was implemented in four preschools. The EFs of children of the intervention group (n = 72, 32 girls, Mage = 48 months) and the control group of four other matched preschools (n = 61, 27 girls, Mage = 48 months) were tested before, during, and after the intervention using different measures assessing working memory, inhibitory control, and cognitive flexibility. The intervention group showed significant gains on three out of seven EF tests (behavioral inhibition, visual-spatial working memory, and combined EFs) compared to the control group. Post hoc analyses for children with low initial EFs scores revealed that participation in the intervention led to significant gains in inhibitory control, visual-spatial working memory, and phonological working memory as well as a marginally significant difference for combined EFs. However, effect sizes were rather small. The results suggest that teacher training can lead to significant improvements in preschooler's EFs. Although preliminary, the results could contribute to the discussion on how teacher training can facilitate the improvement of EFs in preschool children.

Working memory and executive function: the influence of content and load on the control of attention.

PubMed

Hester, Robert; Garavan, Hugh

2005-03-01

In a series of three experiments, increasing working memory (WM) load was demonstrated to reduce the executive control of attention, measured via task-switching and inhibitory control paradigms. Uniquely, our paradigms allowed comparison of the ability to exert executive control when the stimulus was either part of the currently rehearsed memory set or an unrelated distractor item. The results demonstrated a content-specific effect-insofar as switching attention away from, or exerting inhibitory control over, items currently held in WM was especially difficult-compounded by increasing WM load. This finding supports the attentional control theory that active maintenance of competing task goals is critical to executive function and WM capacity; however, it also suggests that the increased salience provided to the contents of WM through active rehearsal exerts a content-specific influence on attentional control. These findings are discussed in relation to cue-induced ruminations, where active rehearsal of evocative information (e.g., negative thoughts in depression or drug-related thoughts in addiction) in WM typically results from environmental cuing. The present study has demonstrated that when information currently maintained in WM is reencountered, it is harder to exert executive control over it. The difficulty with suppressing the processing of these stimuli presumably reinforces the maintenance of these items in WM, due to the greater level of attention they are afforded, and may help to explain how the cue-induced craving/rumination cycle is perpetuated.

Opposing roles for GABAA and GABAC receptors in short-term memory formation in young chicks.

PubMed

Gibbs, M E; Johnston, G A R

2005-01-01

The inhibitory neurotransmitter GABA has both inhibitory and enhancing effects on short-term memory for a bead discrimination task in the young chick. Low doses of GABA (1-3 pmol/hemisphere) injected into the multimodal association area of the chick forebrain, inhibit strongly reinforced memory, whereas higher doses (30-100 pmol/hemisphere) enhance weakly reinforced memory. The effect of both high and low doses of GABA is clearly on short-term memory in terms of both the time of injection and in the time that the memory loss occurs. We argue on the basis of relative sensitivities to GABA and to selective GABA receptor antagonists that low doses of GABA act at GABAC receptors (EC50 approximately 1 microM) and the higher doses of GABA act via GABAA receptors (EC50 approximately 10 microM). The selective GABAA receptor antagonist bicuculline inhibited strongly reinforced memory in a dose and time dependent manner, whereas the selective GABAC receptor antagonists TPMPA and P4MPA enhanced weakly reinforced in a dose and time dependent manner. Confirmation that different levels of GABA affect different receptor subtypes was demonstrated by the shift in the GABA dose-response curves to the selective antagonists. It is clear that GABA is involved in the control of short-term memory formation and its action, enhancing or inhibiting, depends on the level of GABA released at the time of learning.

A Neuroanatomical Model of Prefrontal Inhibitory Modulation of Memory Retrieval

PubMed Central

Depue, Brendan E.

2012-01-01

Memory of past experience is essential for guiding goal-related behavior. Being able to control accessibility of memory through modulation of retrieval enables humans to flexibly adapt to their environment. Understanding the specific neural pathways of how this control is achieved has largely eluded cognitive neuroscience. Accordingly, in the current paper I review literature that examines the overt control over retrieval in order to reduce accessibility. I first introduce three hypotheses of inhibition of retrieval. These hypotheses involve: i) attending to other stimuli as a form of diversionary attention, ii) inhibiting the specific individual neural representation of the memory, and iii) inhibiting the hippocampus and retrieval process more generally to prevent reactivation of the representation. I then analyze literature taken from the White Bear Suppression, Directed Forgetting and Think/No-Think tasks to provide evidence for these hypotheses. Finally, a neuroanatomical model is developed to indicate three pathways from PFC to the hippocampal complex that support inhibition of memory retrieval. Describing these neural pathways increases our understanding of control over memory in general. PMID:22374224

Frontotemporal Functional Connectivity and Executive Functions Contribute to Episodic Memory Performance

PubMed Central

Blankenship, Tashauna L.; O'Neill, Meagan; Deater-Deckard, Kirby; Diana, Rachel A.; Bell, Martha Ann

2016-01-01

The contributions of hemispheric-specific electrophysiology (electroencephalogram or EEG) and independent executive functions (inhibitory control, working memory, cognitive flexibility) to episodic memory performance were examined using abstract paintings. Right hemisphere frontotemporal functional connectivity during encoding and retrieval, measured via EEG alpha coherence, statistically predicted performance on recency but not recognition judgments for the abstract paintings. Theta coherence, however, did not predict performance. Likewise, cognitive flexibility statistically predicted performance on recency judgments, but not recognition. These findings suggest that recognition and recency operate via separate electrophysiological and executive mechanisms. PMID:27388478

Extinction and recovery of an avoidance memory impaired by scopolamine.

PubMed

Navarro, N M; Krawczyk, M C; Boccia, M M; Blake, M G

2017-03-15

Pre-training administration of scopolamine (SCP) resembles situations of cholinergic dysfunction, leading to memory impairment of mice trained in an inhibitory avoidance task. We suggest here that SCP does not impair memory formation, but acquisition is affected in a way that reduces the strength of the stored memory, thus making this memory less able to control behavior when tested. Hence, a memory trace is stored, but is poorly expressed during the test. Although weakly expressed, this memory shows extinction during successive tests, and can be strengthened by using a reminder. Our results indicate that memories stored under cholinergic dysfunction conditions seem absent or lost, but are in fact present and experience common memory processes, such as extinction, and could be even recovered by using appropriate protocols. Copyright © 2017 Elsevier Inc. All rights reserved.

Detection of an inhibitory cortical gradient underlying peak shift in learning: a neural basis for a false memory.

PubMed

Miasnikov, Alexandre A; Weinberger, Norman M

2012-11-01

Experience often does not produce veridical memory. Understanding false attribution of events constitutes an important problem in memory research. "Peak shift" is a well-characterized, controllable phenomenon in which human and animal subjects that receive reinforcement associated with one sensory stimulus later respond maximally to another stimulus in post-training stimulus generalization tests. Peak shift ordinarily develops in discrimination learning (reinforced CS+, unreinforced CS-) and has long been attributed to the interaction of an excitatory gradient centered on the CS+ and an inhibitory gradient centered on the CS-; the shift is away from the CS-. In contrast, we have obtained peak shifts during single tone frequency training, using stimulation of the cholinergic nucleus basalis (NB) to implant behavioral memory into the rat. As we also recorded cortical activity, we took the opportunity to investigate the possible existence of a neural frequency gradient that could account for behavioral peak shift. Behavioral frequency generalization gradients (FGGs, interruption of ongoing respiration) were determined twice before training while evoked potentials were recorded from the primary auditory cortex (A1), to obtain a baseline gradient of "habituatory" neural decrement. A post-training behavioral FGG obtained 24h after three daily sessions of a single tone paired with NB stimulation (200 trials/day) revealed a peak shift. The peak of the FGG was at a frequency lower than the CS while the cortical inhibitory gradient was at a frequency higher than the CS frequency. Further analysis indicated that the frequency location and magnitude of the gradient could account for the behavioral peak shift. These results provide a neural basis for a systematic case of memory misattribution and may provide an animal model for the study of the neural bases of a type of "false memory". Published by Elsevier Inc.

Inhibition of histone deacetylase 3 via RGFP966 facilitates cortical plasticity underlying unusually accurate auditory associative cue memory for excitatory and inhibitory cue-reward associations.

PubMed

Shang, Andrea; Bylipudi, Sooraz; Bieszczad, Kasia M

2018-05-31

Epigenetic mechanisms are key for regulating long-term memory (LTM) and are known to exert control on memory formation in multiple systems of the adult brain, including the sensory cortex. One epigenetic mechanism is chromatin modification by histone acetylation. Blocking the action of histone de-acetylases (HDACs) that normally negatively regulate LTM by repressing transcription has been shown to enable memory formation. Indeed, HDAC inhibition appears to facilitate memory by altering the dynamics of gene expression events important for memory consolidation. However, less understood are the ways in which molecular-level consolidation processes alter subsequent memory to enhance storage or facilitate retrieval. Here we used a sensory perspective to investigate whether the characteristics of memory formed with HDAC inhibitors are different from naturally-formed memory. One possibility is that HDAC inhibition enables memory to form with greater sensory detail than normal. Because the auditory system undergoes learning-induced remodeling that provides substrates for sound-specific LTM, we aimed to identify behavioral effects of HDAC inhibition on memory for specific sound features using a standard model of auditory associative cue-reward learning, memory, and cortical plasticity. We found that three systemic post-training treatments of an HDAC3-inhibitor (RGPF966, Abcam Inc.) in rats in the early phase of training facilitated auditory discriminative learning, changed auditory cortical tuning, and increased the specificity for acoustic frequency formed in memory of both excitatory (S+) and inhibitory (S-) associations for at least 2 weeks. The findings support that epigenetic mechanisms act on neural and behavioral sensory acuity to increase the precision of associative cue memory, which can be revealed by studying the sensory characteristics of long-term associative memory formation with HDAC inhibitors. Published by Elsevier B.V.

Prelimbic cortex extracellular signal-regulated kinase 1/2 activation is required for memory retrieval of long-term inhibitory avoidance.

PubMed

Luo, Fei; Zheng, Jian; Sun, Xuan; Deng, Wei-Ke; Li, Bao Ming; Liu, Fang

2017-04-15

Neural mechanism underlying memory retrieval has been extensively studied in the hippocampus and amygdala. However, little is known about the role of medial prefrontal cortex in long-term memory retrieval. We evaluate this issue in one-trial step-through inhibitory avoidance (IA) paradigm. Our results showed that, 1) inactivation of mPFC by local infusion of GABA A -receptor agonist muscimol caused severe deficits in retrieval of 1-day and 7-day but had no effects on 2-h inhibitory avoidance memory; 2) the protein level of phosphorylated-ERK1/2 in mPFC were significantly increased following retrieval of 1-day and 7-day IA memory, so did the numbers of phosphorylated-ERK (pERK) and phosphorylated-CREB (pCREB) labeled neurons; 3) intra-mPFC infusion of ERK kinase inhibitor PD98095 significantly reduced phosphorylated ERK1/2 levels and phosphorylated-ERK1/2 and phosphorylated-CREB labeled cells, and severely impaired retrieval of 7-day IA memory when the drugs were administrated 30min prior to test. The present study provides evidence that retrieval of long-lasting memory for inhibitory avoidance requires mPFC and involves the ERK-CREB signaling cascade. Copyright © 2017 Elsevier B.V. All rights reserved.

Impact of sleep on executive functioning in school-age children with Down syndrome.

PubMed

Esbensen, A J; Hoffman, E K

2018-06-01

Sleep problems have an impact on executive functioning in the general population. While children with Down syndrome (DS) are at high risk for sleep problems, the impact of these sleep problems on executive functioning in school-age children with DS is less well documented. Our study examined the relationship between parent-reported and actigraphy-measured sleep duration and sleep quality with parent and teacher reports and neuropsychology assessments of executive functioning among school-age children with DS. Thirty school-age children with DS wore an actigraph watch for a week at home at night. Their parent completed ratings of the child's sleep during that same week. Children completed a neuropsychology assessment of their inhibitory control, ability to shift and working memory. Their parents and teachers completed rating scales to assess these same constructs of executive functioning. Parent reports of restless sleep behaviours on the Children's Sleep Habits Questionnaire (CSHQ), but not actigraph-measured sleep period or efficiency, were predictive of parent reports of concerns with inhibitory control, shifting and working memory, and of teacher reports of inhibitory control. No measure of sleep was predictive of executive functioning as measured by the neuropsychology assessment. The study findings corroborate the preliminary literature that parent-reported sleep problems are related to executive functioning in school-age children with DS, particularly in the area of inhibitory control across home and school. These findings have implications for understanding contributing factors to academic performance and school behaviour in school-age children with DS. © 2018 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Role of sleep continuity and total sleep time in executive function across the adult lifespan.

PubMed

Wilckens, Kristine A; Woo, Sarah G; Kirk, Afton R; Erickson, Kirk I; Wheeler, Mark E

2014-09-01

The importance of sleep for cognition in young adults is well established, but the role of habitual sleep behavior in cognition across the adult life span remains unknown. We examined the relationship between sleep continuity and total sleep time as assessed with a sleep-detection device, and cognitive performance using a battery of tasks in young (n = 59, mean age = 23.05) and older (n = 53, mean age = 62.68) adults. Across age groups, higher sleep continuity was associated with better cognitive performance. In the younger group, higher sleep continuity was associated with better working memory and inhibitory control. In the older group, higher sleep continuity was associated with better inhibitory control, memory recall, and verbal fluency. Very short and very long total sleep time was associated with poorer working memory and verbal fluency, specifically in the younger group. Total sleep time was not associated with cognitive performance in any domains for the older group. These findings reveal that sleep continuity is important for executive function in both young and older adults, but total sleep time may be more important for cognition in young adults. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Indirect and Direct Relationships between Self-Regulation and Academic Achievement during the Nursery/Elementary School Transition of French Students

ERIC Educational Resources Information Center

Hubert, Blandine; Guimard, Philippe; Florin, Agnès; Tracy, Alexis

2015-01-01

Research Findings: Several recent studies carried out in the United States and abroad (i.e., Asia and Europe) have demonstrated that the ability of young children to regulate their behavior (including inhibitory control, working memory, attentional control) significantly predicts their academic achievement. The current study examined the…

Attention-deficit/hyperactivity disorder: the impact of methylphenidate on working memory, inhibition capacity and mental flexibility.

PubMed

Bolfer, Cristiana; Pacheco, Sandra Pasquali; Tsunemi, Miriam Harumi; Carreira, Walter Souza; Casella, Beatriz Borba; Casella, Erasmo Barbante

2017-04-01

To compare children with attention-deficit/hyperactivity disorder (ADHD), before and after the use of methylphenidate, and a control group, using tests of working memory, inhibition capacity and mental flexibility. Neuropsychological tests were administrated to 53 boys, 9-12 years old: the WISC-III digit span backward, and arithmetic; Stroop Color; and Trail Making Tests. The case group included 23 boys with ADHD, who were combined type, treatment-naive, and with normal intelligence without comorbidities. The control group (n = 30) were age and gender matched. After three months on methylphenidate, the ADHD children were retested. The control group was also retested after three months. Before treatment, ADHD children had lower scores than the control group on the tests (p ≤ 0.001) and after methylphenidate had fewer test errors than before (p ≤ 0.001). Methylphenidate treatment improves the working memory, inhibitory control and mental flexibility of ADHD boys.

When stress gets into your head: Socioeconomic risk, executive functions, and maternal sensitivity across childrearing contexts.

PubMed

Sturge-Apple, Melissa L; Jones, Hannah R; Suor, Jennifer H

2017-03-01

Socioeconomic adversity has been targeted as a key upstream mechanism with robust pathogenic effects on maternal caregiving. Although research has demonstrated the negative repercussions of socioeconomic difficulties, little research has documented potential mechanisms underlying this association. Toward increasing understanding, the present study examined how maternal working memory capacity and inhibitory control may mediate associations between socioeconomic risk and change in maternal sensitivity across free-play and discipline caregiving contexts. This study used a longitudinal design, and utilized a socioeconomically diverse sample of 185 mothers and their 3.5-year-old toddlers. Multi-informants and methods were used to assess constructs. Findings revealed that maternal EF mediated associations between socioeconomic risk and parenting sensitivity with specific effects for working memory and baseline sensitivity and inhibitory control and change in sensitivity as childrearing demands increased. Results are interpreted within emerging conceptual frameworks regarding the role of parental neurocognitive functioning and caregiving. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

How do stimulant treatments for ADHD work? Evidence for mediation by improved cognition.

PubMed

Hawk, Larry W; Fosco, Whitney D; Colder, Craig R; Waxmonsky, James G; Pelham, William E; Rosch, Keri S

2018-05-07

Stimulant medications such as methylphenidate (MPH) are the frontline treatment for Attention-Deficit/Hyperactivity Disorder (ADHD). Despite their well-documented efficacy, the mechanisms by which stimulants improve clinical outcomes are not clear. The current study evaluated whether MPH effects on classroom behavior were mediated by improved cognitive functioning. Children with ADHD (n = 82; 9-12 years old) participated in a week-long summer research camp, consisting of cognitive testing, classroom periods, and recreational activities. After a baseline day, participants completed a 3-day randomized, double-blind, placebo-controlled trial of MPH (at doses approximating 0.3 and 0.6 mg/kg of immediate-release MPH dosed TID). Cognitive domains included inhibitory control (Stop Signal Task and prepulse inhibition of startle), attention (Continuous Performance Task and reaction time variability), and working memory (forward and backward spatial span). Clinical outcomes included math seatwork productivity and teacher-rated classroom behavior. A within-subjects path-analytic approach was used to test mediation. MPH-placebo and dose-response contrasts were used to evaluate drug effects. Methylphenidate improved seatwork productivity and teacher ratings (ds = 1.4 and 1.1) and all domains of cognition (ds = 0.3-1.1). Inhibitory control (Stop Signal Task, SST) and working memory backward uniquely mediated the effect of MPH (vs. placebo) on productivity. Only working memory backward mediated the impact of MPH on teacher-rated behavior. The dose-response (0.6 vs. 0.3 mg/kg) effects were more modest for clinical outcomes (ds = 0.4 and 0.2) and cognition (ds = 0-0.3); there was no evidence of cognitive mediation of the clinical dose-response effects. These findings are novel in demonstrating that specific cognitive processes mediate clinical improvement with stimulant treatment for ADHD. They converge with work on ADHD theory, neurobiology, and treatment development in suggesting that inhibitory control and working memory may be mechanisms of stimulant treatment response in ADHD. More work is necessary to evaluate the degree to which these findings generalize to chronic treatment, a broader array of clinical outcomes, and nonstimulant treatments. © 2018 Association for Child and Adolescent Mental Health.

Inhibitory Processes in Young Children and Individual Variation in Short-Term Memory

PubMed Central

Espy, Kimberly Andrews; Bull, Rebecca

2009-01-01

A precise definition of executive control remains elusive, related in part to the variations among executive tasks in the nature of the task demands, which complicate the identification of test-specific versus construct-specific performance. In this study, tasks were chosen that varied in the nature of the stimulus (verbal, nonverbal), response (naming, somatic motor), conflict type (proactive interference, distraction), and inhibitory process (attention control, response suppression) required. Then performance differences were examined in 184 young children (age range = 3 years 6 months to 6 years 1 month), comparing those with high (5 or more digits) and low (3 or fewer digits) spans to determine the dependence on short-term memory. Results indicated that there was communality in inhibitory task demands across instruments, although the specific pattern of task intercorrelations varied in children with high and low spans. Furthermore, only performance on attention control tasks—that is, that require cognitive engagement/disengagement among an internally represented rule or response set that was previously active versus those currently active—differed between children of high and low spans. In contrast, there were differences neither between children with high and low spans on response suppression tasks nor on tasks when considered by type of stimulus, response, or conflict. Individual differences in well-regulated thought may rest in variations in the ability to maintain information in an active, quickly retrievable state that subserve controlling attention in a goal-relevant fashion. PMID:16144432

Individual differences in children's memory and reading comprehension: an investigation of semantic and inhibitory deficits.

PubMed

Cain, Kate

2006-07-01

Three experiments compared the verbal memory skills of children with poor reading comprehension with that of same-age good comprehenders. The aims were to determine if semantic and/or inhibitory deficits explained comprehenders' problems on measures of verbal short-term memory and verbal working memory. In Experiment 1 there were no group differences on word- and number-based measures of short-term storage and no evidence that semantic knowledge mediated word recall. In Experiment 2 poor comprehenders were impaired on word- and number-based assessments of working memory, the greatest deficit found on the word-based task. Error analysis of both word-based tasks revealed that poor comprehenders were more likely to recall items that should have been inhibited than were good comprehenders. Experiment 3 extended this finding: Poor comprehenders were less able to inhibit information that was no longer relevant. Together, these findings suggest that individual differences in inhibitory processing influence the ability to regulate the contents of working memory, which may contribute to the differential memory performance of good and poor comprehenders.

Assessment of executive functioning in binge-eating disorder independent of weight status.

PubMed

Eneva, Kalina T; Arlt, Jean M; Yiu, Angelina; Murray, Susan M; Chen, Eunice Y

2017-08-01

Executive functioning (EF) problems may serve as vulnerability or maintenance factors for Binge-Eating Disorder (BED). However, it is unclear if EF problems observed in BED are related to overweight status or BED status. The current study extends this literature by examining EF in overweight and normal-weight BED compared to weight-matched controls. Participants were normal-weight women with BED (n = 23), overweight BED (n = 32), overweight healthy controls (n = 48), and normal-weight healthy controls (n = 29). The EF battery utilized tests from the National Institutes of Health (NIH) Toolbox and Delis-Kaplan Executive Function System (D-KEFS). After controlling for years of education and minority status, overweight individuals performed more poorly than normal-weight individuals on a task of cognitive flexibility requiring generativity (p < .01), and speed on psychomotor performance tasks (p = .01). Normal-weight and overweight BED performed worse on working memory tasks compared to controls (p = .04). Unexpectedly, normal-weight BED individuals out-performed all other groups on an inhibitory control task (p < .01). No significant differences were found between the four groups on tasks of planning. Regardless of weight status, BED is associated with working memory problems. Replication of the finding that normal-weight BED is associated with enhanced inhibitory control is needed. © 2017 Wiley Periodicals, Inc.

Robust sequential working memory recall in heterogeneous cognitive networks

PubMed Central

Rabinovich, Mikhail I.; Sokolov, Yury; Kozma, Robert

2014-01-01

Psychiatric disorders are often caused by partial heterogeneous disinhibition in cognitive networks, controlling sequential and spatial working memory (SWM). Such dynamic connectivity changes suggest that the normal relationship between the neuronal components within the network deteriorates. As a result, competitive network dynamics is qualitatively altered. This dynamics defines the robust recall of the sequential information from memory and, thus, the SWM capacity. To understand pathological and non-pathological bifurcations of the sequential memory dynamics, here we investigate the model of recurrent inhibitory-excitatory networks with heterogeneous inhibition. We consider the ensemble of units with all-to-all inhibitory connections, in which the connection strengths are monotonically distributed at some interval. Based on computer experiments and studying the Lyapunov exponents, we observed and analyzed the new phenomenon—clustered sequential dynamics. The results are interpreted in the context of the winnerless competition principle. Accordingly, clustered sequential dynamics is represented in the phase space of the model by two weakly interacting quasi-attractors. One of them is similar to the sequential heteroclinic chain—the regular image of SWM, while the other is a quasi-chaotic attractor. Coexistence of these quasi-attractors means that the recall of the normal information sequence is intermittently interrupted by episodes with chaotic dynamics. We indicate potential dynamic ways for augmenting damaged working memory and other cognitive functions. PMID:25452717

Beyond the dual pathway model: evidence for the dissociation of timing, inhibitory, and delay-related impairments in attention-deficit/hyperactivity disorder.

PubMed

Sonuga-Barke, Edmund; Bitsakou, Paraskevi; Thompson, Margaret

2010-04-01

The dual pathway model explains neuro-psychological heterogeneity in Attention Deficit/Hyperactivity Disorder (ADHD) in terms of dissociable cognitive and motivational deficits each affecting some but not other patients. We explore whether deficits in temporal processing might constitute a third dissociable neuropsychological component of ADHD. Nine tasks designed to tap three domains (inhibitory control, delay aversion and temporal processing) were administered to ADHD probands (n=71; ages 6 to 17 years), their siblings (n=71; 65 unaffected by ADHD) and a group of non-ADHD controls (n=50). IQ and working memory were measured. Temporal processing, inhibitory control and delay-related deficits represented independent neuropsychological components. ADHD children differed from controls on all factors. For ADHD patients, the co-occurrence of inhibitory, temporal processing and delay-related deficits was no greater than expected by chance with substantial groups of patients showing only one problem. Domain-specific patterns of familial co-segregation provided evidence for the validity of neuropsychological subgroupings. The current results illustrate the neuropsychological heterogeneity in ADHD and initial support for a triple pathway model. The findings need to be replicated in larger samples.

Retrieval Property of Attractor Network with Synaptic Depression

NASA Astrophysics Data System (ADS)

Matsumoto, Narihisa; Ide, Daisuke; Watanabe, Masataka; Okada, Masato

2007-08-01

Synaptic connections are known to change dynamically. High-frequency presynaptic inputs induce decrease of synaptic weights. This process is known as short-term synaptic depression. The synaptic depression controls a gain for presynaptic inputs. However, it remains a controversial issue what are functional roles of this gain control. We propose a new hypothesis that one of the functional roles is to enlarge basins of attraction. To verify this hypothesis, we employ a binary discrete-time associative memory model which consists of excitatory and inhibitory neurons. It is known that the excitatory-inhibitory balance controls an overall activity of the network. The synaptic depression might incorporate an activity control mechanism. Using a mean-field theory and computer simulations, we find that the synaptic depression enlarges the basins at a small loading rate while the excitatory-inhibitory balance enlarges them at a large loading rate. Furthermore the synaptic depression does not affect the steady state of the network if a threshold is set at an appropriate value. These results suggest that the synaptic depression works in addition to the effect of the excitatory-inhibitory balance, and it might improve an error-correcting ability in cortical circuits.

The Role of Executive Control and Readiness to Change in Problematic Drinkers with Mild to Borderline Intellectual Disability.

PubMed

van Duijvenbode, Neomi; Didden, Robert; Korzilius, Hubert P L M; Engels, Rutger C M E

2017-09-01

Problematic alcohol use is associated with neuropsychological consequences, including cognitive biases. The goal of the study was to explore the moderating role of executive control and readiness to change on the relationship between alcohol use and cognitive biases in light and problematic drinkers with and without mild to borderline intellectual disability (MBID). Participants (N = 112) performed the visual dot probe task to measure the strength of the cognitive biases. Executive control was measured using two computerised tasks for working memory capacity (Corsi block-tapping task) and inhibitory control (Go/No-go task). Readiness to change was measured using the Readiness to Change Questionnaire. No cognitive biases or executive dysfunctions were found in problematic drinkers. Working memory capacity and inhibitory control were impaired among individuals with MBID, irrespective of severity of alcohol use-related problems. Executive control and readiness to change did not moderate the relationship between alcohol use and cognitive biases. The results fail to support the dual-process models of addiction, but results need to be treated with caution given the problematic psychometric qualities of the visual dot probe task. Implementing a neurocognitive assessment and protocols in the treatment of substance use disorders seems premature. © 2016 John Wiley & Sons Ltd.

Development of the updating executive function: From 7-year-olds to young adults.

PubMed

Carriedo, Nuria; Corral, Antonio; Montoro, Pedro R; Herrero, Laura; Rucián, Mercedes

2016-04-01

Updating information in working memory (WM) is a critical executive function responsible both for continuously replacing outdated information with new relevant data and to suppress or inhibit content that is no longer relevant according to task demands. The goal of the present research is twofold: First, we aimed to study updating development in 548 participants of 4 different age ranges--7-, 11-, and 15-year-olds and young adults--using the updating task devised by R. De Beni and P. Palladino (2004), which allows differentiating maintenance and inhibition processes. Second, we attempted to determine the relation between these processes across development as well as the differentiation among different types of inhibition processes tapped by this task. Results showed that there was an improvement of memory performance with age along with an upgrading of inhibitory efficiency. However, whereas in memory performance, a progressive increase was observed until the age of 15 years followed by stabilization, in inhibition, a continuous progressive increase was observed until young adulthood. Importantly, results showed that development of the different inhibitory mechanisms does not progress equally. All the groups committed more errors related to inefficient suppression mechanisms in WM than errors related to control of long-term memory interference. Principal component analysis showed that updating implies different subprocesses: active maintenance/suppression of information in WM and control of proactive interference. Developmental trajectories showed that the maintenance/suppression of information in the WM component continues to develop far beyond adolescence but that proactive interference control is responsible for variations in updating across development. (c) 2016 APA, all rights reserved).

[Learning difficulties in mathematics in children with attention deficit hyperactivity disorder].

PubMed

Miranda-Casas, A; Meliá-de Alba, A; Marco-Taverner, R; Roselló, B; Mulas, F

2006-02-13

Attention deficit hyperactivity disorder (ADHD) and learning difficulties are two diagnostic categories of great social importance and impact, and which are associated in around 25-35% of cases. One explanation offered by researchers to account for this overlap is a deficit in executive functioning (EF). 1) To compare EF and applied mathematical knowledge in children with ADHD, difficulties in learning mathematics (DLM) or ADHD + DLM, and to identify the deficiencies they experience. 2) To verify whether the phenotype hypothesis is fulfilled in the case of the ADHD + DLM condition. The study involved a quasi-experimental 2 x 2 design, with a sample made up of 78 participants (6-13 years old) who were divided into four groups: ADHD (n = 33), DLM (n = 15), ADHD + DLM (n = 15) and a control group (n = 15). Tests aimed at evaluating different cognitive processes as well as applied mathematical knowledge were administered: inhibitory control (go/no go); verbal working (backward digit-recall and counting memory task) and temporal-visual-spatial memory; short-term memory (direct digit-recall); attention (CPT); calculation speed (Canals) and real-life problems. Taking the variables age, gender and intelligence quotient as covariables, results showed that the three groups with problems displayed a deficit of attention and in working memory; the DLM group stood out from the other owing to the presence of a specific deficiency affecting the ability to recall temporal-visual-spatial information. In contrast, deficits in inhibitory control were seen to be specific to ADHD. Finally, findings did not support the phenotype hypothesis, and it was therefore an accumulative profile.

Attenuation of HIV-associated human B cell exhaustion by siRNA downregulation of inhibitory receptors

PubMed Central

Kardava, Lela; Moir, Susan; Wang, Wei; Ho, Jason; Buckner, Clarisa M.; Posada, Jacqueline G.; O’Shea, Marie A.; Roby, Gregg; Chen, Jenny; Sohn, Hae Won; Chun, Tae-Wook; Pierce, Susan K.; Fauci, Anthony S.

2011-01-01

Chronic immune activation in HIV-infected individuals leads to accumulation of exhausted tissue-like memory B cells. Exhausted lymphocytes display increased expression of multiple inhibitory receptors, which may contribute to the inefficiency of HIV-specific antibody responses. Here, we show that downregulation of B cell inhibitory receptors in primary human B cells led to increased tissue-like memory B cell proliferation and responsiveness against HIV. In human B cells, siRNA knockdown of 9 known and putative B cell inhibitory receptors led to enhanced B cell receptor–mediated (BCR-mediated) proliferation of tissue-like memory but not other B cell subpopulations. The strongest effects were observed with the putative inhibitory receptors Fc receptor–like–4 (FCRL4) and sialic acid–binding Ig-like lectin 6 (Siglec-6). Inhibitory receptor downregulation also led to increased levels of HIV-specific antibody-secreting cells and B cell–associated chemokines and cytokines. The absence of known ligands for FCRL4 and Siglec-6 suggests these receptors may regulate BCR signaling through their own constitutive or tonic signaling. Furthermore, the extent of FCLR4 knockdown effects on BCR-mediated proliferation varied depending on the costimulatory ligand, suggesting that inhibitory receptors may engage specific pathways in inhibiting B cell proliferation. These findings on HIV-associated B cell exhaustion define potential targets for reversing the deleterious effect of inhibitory receptors on immune responses against persistent viral infections. PMID:21633172

Predictors of Early Growth in Academic Achievement: The Head-Toes-Knees-Shoulders Task

ERIC Educational Resources Information Center

McClelland, Megan M.; Cameron, Claire E.; Duncan, Robert; Bowles, Ryan P.; Acock, Alan C.; Miao, Alicia; Pratt, Megan E.

2014-01-01

Children's behavioral self-regulation and executive function (EF; including attentional or cognitive flexibility, working memory, and inhibitory control) are strong predictors of academic achievement. The present study examined the psychometric properties of a measure of behavioral self-regulation called the Head-Toes-Knees-Shoulders (HTKS) by…

Executive Function and Mathematics Achievement: Are Effects Construct- and Time-General or Specific?

ERIC Educational Resources Information Center

Duncan, Robert; Nguyen, Tutrang; Miao, Alicia; McClelland, Megan; Bailey, Drew

2016-01-01

Executive function (EF) is considered a set of interrelated cognitive processes, including inhibitory control, working memory, and attentional shifting, that are connected to the development of the prefrontal cortex and contribute to children's problem solving skills and self regulatory behavior (Best & Miller, 2010; Garon, Bryson, &…

Is There a Role for Executive Functions in the Development of Mathematics Ability?

ERIC Educational Resources Information Center

Blair, Clancy; Knipe, Hilary; Gamson, David

2008-01-01

This article examines the role of working memory, attention shifting, and inhibitory control executive cognitive functions in the development of mathematics knowledge and ability in children. It suggests that an examination of the executive cognitive demand of mathematical thinking can complement procedural and conceptual knowledge-based…

Working Memory: Its Role in Dyslexia and Other Specific Learning Difficulties

ERIC Educational Resources Information Center

Jeffries, Sharman; Everatt, John

2004-01-01

This paper reports a study contrasting dyslexic children against a control group of children without special educational needs (SEN) and a group with varied SENs. Children's abilities were compared on tasks assessing phonological processing, visuo-spatial/motor coordination and executive/inhibitory functioning; being targeted for assessment based…

Self-Regulation and Academic Achievement in Elementary School Children

ERIC Educational Resources Information Center

McClelland, Megan M.; Cameron, Claire E.

2011-01-01

Self-regulation is a key construct in children's healthy and adaptive development. In this chapter, the authors situate self-regulation in a theoretical context that describes its underlying components that are most important for early school success: flexible attention, working memory, and inhibitory control. The authors review evidence that…

Medial prefrontal cortex dopamine controls the persistent storage of aversive memories

PubMed Central

Gonzalez, María C.; Kramar, Cecilia P.; Tomaiuolo, Micol; Katche, Cynthia; Weisstaub, Noelia; Cammarota, Martín; Medina, Jorge H.

2014-01-01

Medial prefrontal cortex (mPFC) is essential for initial memory processing and expression but its involvement in persistent memory storage has seldom been studied. Using the hippocampus dependent inhibitory avoidance learning task and the hippocampus-independent conditioned taste aversion paradigm together with specific dopamine receptor agonists and antagonists we found that persistence but not formation of long-term aversive memories requires dopamine D1/D5 receptors activation in mPFC immediately after training and, depending on the task, between 6 and 12 h later. Our results indicate that besides its well-known participation in retrieval and early consolidation, mPFC also modulates the endurance of long-lasting aversive memories regardless of whether formation of the aversive mnemonic trace requires the participation of the hippocampus. PMID:25506318

Retrieval-practice task affects relationship between working memory capacity and retrieval-induced forgetting.

PubMed

Storm, Benjamin C; Bui, Dung C

2016-11-01

Retrieving a subset of items from memory can cause forgetting of other items in memory, a phenomenon referred to as retrieval-induced forgetting (RIF). Individuals who exhibit greater amounts of RIF have been shown to also exhibit superior working memory capacity (WMC) and faster stop-signal reaction times (SSRTs), results which have been interpreted as suggesting that RIF reflects an inhibitory process that is mediated by the processes of executive control. Across four experiments, we sought to further elucidate this issue by manipulating the way in which participants retrieved items during retrieval practice and examining how the resulting effects of forgetting correlated with WMC (Experiments 1-3) and SSRT (Experiment 4). Significant correlations were observed when participants retrieved items from an earlier study phase (within-list retrieval practice), but not when participants generated items from semantic memory (extra-list retrieval practice). These results provide important new insight into the role of executive-control processes in RIF.

Aerobic Capacity and Cognitive Control in Elementary School-Age Children

PubMed Central

Scudder, Mark R.; Lambourne, Kate; Drollette, Eric S.; Herrmann, Stephen; Washburn, Richard; Donnelly, Joseph E.; Hillman, Charles H.

2014-01-01

Purpose The current study examined the relationship between children’s performance on the Progressive Aerobic Cardiovascular Endurance Run (PACER) subtest of the FitnessGram® and aspects of cognitive control that are believed to support academic success. Methods Hierarchical linear regression analyses were conducted on a sample of 2nd and 3rd grade children (n = 397) who completed modified versions of a flanker task and spatial n-back task to assess inhibitory control and working memory, respectively. Results Greater aerobic fitness was significantly related to shorter reaction time and superior accuracy during the flanker task, suggesting better inhibitory control and the facilitation of attention in higher fit children. A similar result was observed for the n-back task such that higher fit children exhibited more accurate target detection and discrimination performance when working memory demands were increased. Conclusion These findings support the positive association between aerobic fitness and multiple aspects of cognitive control in a large sample of children, using a widely implemented and reliable field estimate of aerobic capacity. Importantly, the current results suggest that this relationship is consistent across methods used to assess fitness, which may have important implications for extending this research to more representative samples of children in a variety of experimental contexts. PMID:24743109

Synchronization and long-time memory in neural networks with inhibitory hubs and synaptic plasticity

NASA Astrophysics Data System (ADS)

Bertolotti, Elena; Burioni, Raffaella; di Volo, Matteo; Vezzani, Alessandro

2017-01-01

We investigate the dynamical role of inhibitory and highly connected nodes (hub) in synchronization and input processing of leaky-integrate-and-fire neural networks with short term synaptic plasticity. We take advantage of a heterogeneous mean-field approximation to encode the role of network structure and we tune the fraction of inhibitory neurons fI and their connectivity level to investigate the cooperation between hub features and inhibition. We show that, depending on fI, highly connected inhibitory nodes strongly drive the synchronization properties of the overall network through dynamical transitions from synchronous to asynchronous regimes. Furthermore, a metastable regime with long memory of external inputs emerges for a specific fraction of hub inhibitory neurons, underlining the role of inhibition and connectivity also for input processing in neural networks.

The integrated role of ACh, ERK and mTOR in the mechanisms of hippocampal inhibitory avoidance memory.

PubMed

Giovannini, Maria Grazia; Lana, Daniele; Pepeu, Giancarlo

2015-03-01

The purpose of this review is to summarize the present knowledge on the interplay among the cholinergic system, Extracellular signal-Regulated Kinase (ERK) and Mammalian Target of Rapamycin (mTOR) pathways in the development of short and long term memories during the acquisition and recall of the step-down inhibitory avoidance in the hippocampus. The step-down inhibitory avoidance is a form of associative learning that is acquired in a relatively simple one-trial test through several sensorial inputs. Inhibitory avoidance depends on the integrated activity of hippocampal CA1 and other brain areas. Recall can be performed at different times after acquisition, thus allowing for the study of both short and long term memory. Among the many neurotransmitter systems involved, the cholinergic neurons that originate in the basal forebrain and project to the hippocampus are of crucial importance in inhibitory avoidance processes. Acetylcholine released from cholinergic fibers during acquisition and/or recall of behavioural tasks activates muscarinic and nicotinic acetylcholine receptors and brings about a long-lasting potentiation of the postsynaptic membrane followed by downstream activation of intracellular pathway (ERK, among others) that create conditions favourable for neuronal plasticity. ERK appears to be salient not only in long term memory, but also in the molecular mechanisms underlying short term memory formation in the hippocampus. Since ERK can function as a biochemical coincidence detector in response to extracellular signals in neurons, the activation of ERK-dependent downstream effectors is determined, in part, by the duration of ERK phosphorylation itself. Long term memories require protein synthesis, that in the synapto-dendritic compartment represents a direct mechanism that can produce rapid changes in protein content in response to synaptic activity. mTOR in the brain regulates protein translation in response to neuronal activity, thereby modulating synaptic plasticity and long term memory formation. Some studies demonstrate a complex interplay among the cholinergic system, ERK and mTOR. It has been shown that co-activation of muscarinic acetylcholine receptors and β-adrenergic receptors facilitates the conversion of short term to long term synaptic plasticity through an ERK- and mTOR-dependent mechanism which requires translation initiation. It seems therefore that the complex interplay among the cholinergic system, ERK and mTOR is crucial in the development of new inhibitory avoidance memories in the hippocampus. Copyright © 2015 Elsevier Inc. All rights reserved.

Fear Conditioning Selectively Disrupts Noradrenergic Facilitation of GABAergic Inhibition in the Basolateral Amygdala

PubMed Central

Skelly, M. J.; Ariwodola, O. J.; Weiner, J. L.

2016-01-01

Inappropriate fear memory formation is symptomatic of many psychopathologies, and delineating the neurobiology of non-pathological fear learning may provide critical insight into treating these disorders. Fear memory formation is associated with decreased inhibitory signaling in the basolateral amygdala (BLA), and disrupted noradrenergic signaling may contribute to this decrease. BLA noradrenergic neurotransmission has been implicated in fear memory formation, and distinct adrenoreceptor (AR) subtypes modulate excitatory and inhibitory neurotransmission in this region. For example, α1-ARs promote GABA release from local inhibitory interneurons, while β3-ARs potentiate neurotransmission at lateral paracapsular (LPC) GABAergic synapses. Conversely, β1/2-ARs amplify excitatory signaling at glutamatergic synapses in the BLA. As increased BLA excitability promotes fear memory formation, we hypothesized that fear learning shifts the balanced regional effects of noradrenergic signaling toward excitation. To test this hypothesis, we used the fear-potentiated startle paradigm in combination with whole cell patch clamp electrophysiology to examine the effects of AR activation on BLA synaptic transmission following fear conditioning in male Long-Evans rats. We first demonstrated that inhibitory neurotransmission is decreased at both local and LPC synapses following fear conditioning. We next measured noradrenergic facilitation of BLA inhibitory signaling at local and LPC synapses using α1- and β3-AR agonists (1μM A61603 and 10μM BRL37344), and found that the ability of these agents to facilitate inhibitory neurotransmission is disrupted following fear conditioning. Conversely, we found that fear learning does not disrupt noradrenergic modulation of glutamatergic signaling via a β1/2-AR agonist (1μM isoproterenol). Taken together, these studies suggest that fear learning increases BLA excitability by selectively disrupting the inhibitory effects of noradrenaline. PMID:27720769

Fear conditioning selectively disrupts noradrenergic facilitation of GABAergic inhibition in the basolateral amygdala.

PubMed

Skelly, M J; Ariwodola, O J; Weiner, J L

2017-02-01

Inappropriate fear memory formation is symptomatic of many psychopathologies, and delineating the neurobiology of non-pathological fear learning may provide critical insight into treating these disorders. Fear memory formation is associated with decreased inhibitory signaling in the basolateral amygdala (BLA), and disrupted noradrenergic signaling may contribute to this decrease. BLA noradrenergic neurotransmission has been implicated in fear memory formation, and distinct adrenoreceptor (AR) subtypes modulate excitatory and inhibitory neurotransmission in this region. For example, α1-ARs promote GABA release from local inhibitory interneurons, while β3-ARs potentiate neurotransmission at lateral paracapsular (LPC) GABAergic synapses. Conversely, β1/2-ARs amplify excitatory signaling at glutamatergic synapses in the BLA. As increased BLA excitability promotes fear memory formation, we hypothesized that fear learning shifts the balanced regional effects of noradrenergic signaling toward excitation. To test this hypothesis, we used the fear-potentiated startle paradigm in combination with whole cell patch clamp electrophysiology to examine the effects of AR activation on BLA synaptic transmission following fear conditioning in male Long-Evans rats. We first demonstrated that inhibitory neurotransmission is decreased at both local and LPC synapses following fear conditioning. We next measured noradrenergic facilitation of BLA inhibitory signaling at local and LPC synapses using α1-and β3-AR agonists (1 μM A61603 and 10 μM BRL37344), and found that the ability of these agents to facilitate inhibitory neurotransmission is disrupted following fear conditioning. Conversely, we found that fear learning does not disrupt noradrenergic modulation of glutamatergic signaling via a β1/2-AR agonist (1 μM isoproterenol). Taken together, these studies suggest that fear learning increases BLA excitability by selectively disrupting the inhibitory effects of noradrenaline. Copyright © 2016 Elsevier Ltd. All rights reserved.

Control of Excitation/Inhibition Balance in a Hippocampal Circuit by Calcium Sensor Protein Regulation of Presynaptic Calcium Channels.

PubMed

Nanou, Evanthia; Lee, Amy; Catterall, William A

2018-05-02

Activity-dependent regulation controls the balance of synaptic excitation to inhibition in neural circuits, and disruption of this regulation impairs learning and memory and causes many neurological disorders. The molecular mechanisms underlying short-term synaptic plasticity are incompletely understood, and their role in inhibitory synapses remains uncertain. Here we show that regulation of voltage-gated calcium (Ca 2+ ) channel type 2.1 (Ca V 2.1) by neuronal Ca 2+ sensor (CaS) proteins controls synaptic plasticity and excitation/inhibition balance in a hippocampal circuit. Prevention of CaS protein regulation by introducing the IM-AA mutation in Ca V 2.1 channels in male and female mice impairs short-term synaptic facilitation at excitatory synapses of CA3 pyramidal neurons onto parvalbumin (PV)-expressing basket cells. In sharp contrast, the IM-AA mutation abolishes rapid synaptic depression in the inhibitory synapses of PV basket cells onto CA1 pyramidal neurons. These results show that CaS protein regulation of facilitation and inactivation of Ca V 2.1 channels controls the direction of short-term plasticity at these two synapses. Deletion of the CaS protein CaBP1/caldendrin also blocks rapid depression at PV-CA1 synapses, implicating its upregulation of inactivation of Ca V 2.1 channels in control of short-term synaptic plasticity at this inhibitory synapse. Studies of local-circuit function revealed reduced inhibition of CA1 pyramidal neurons by the disynaptic pathway from CA3 pyramidal cells via PV basket cells and greatly increased excitation/inhibition ratio of the direct excitatory input versus indirect inhibitory input from CA3 pyramidal neurons to CA1 pyramidal neurons. This striking defect in local-circuit function may contribute to the dramatic impairment of spatial learning and memory in IM-AA mice. SIGNIFICANCE STATEMENT Many forms of short-term synaptic plasticity in neuronal circuits rely on regulation of presynaptic voltage-gated Ca 2+ (Ca V ) channels. Regulation of Ca V 2.1 channels by neuronal calcium sensor (CaS) proteins controls short-term synaptic plasticity. Here we demonstrate a direct link between regulation of Ca V 2.1 channels and short-term synaptic plasticity in native hippocampal excitatory and inhibitory synapses. We also identify CaBP1/caldendrin as the calcium sensor interacting with Ca V 2.1 channels to mediate rapid synaptic depression in the inhibitory hippocampal synapses of parvalbumin-expressing basket cells to CA1 pyramidal cells. Disruption of this regulation causes altered short-term plasticity and impaired balance of hippocampal excitatory to inhibitory circuits. Copyright © 2018 the authors 0270-6474/18/384430-11$15.00/0.

Bidirectional control of spike timing by GABA(A) receptor-mediated inhibition during theta oscillation in CA1 pyramidal neurons.

PubMed

Kwag, Jeehyun; Paulsen, Ole

2009-08-26

Precisely controlled spike times relative to theta-frequency network oscillations play an important role in hippocampal memory processing. Here we study how inhibitory synaptic input during theta oscillation contributes to the control of spike timing. Using whole-cell patch-clamp recordings from CA1 pyramidal cells in vitro with dynamic clamp to simulate theta-frequency oscillation (5 Hz), we show that gamma-aminobutyric acid-A (GABA(A)) receptor-mediated inhibitory postsynaptic potentials (IPSPs) can not only delay but also advance the postsynaptic spike depending on the timing of the inhibition relative to the oscillation. Spike time advancement with IPSP was abolished by the h-channel blocker ZD7288 (10 microM), suggesting that IPSPs can interact with intrinsic membrane conductances to yield bidirectional control of spike timing.

Counterfactual Thinking and False Belief: The Role of Executive Function

ERIC Educational Resources Information Center

Drayton, Stefane; Turley-Ames, Kandi J.; Guajardo, Nicole R.

2011-01-01

The purpose of the current study was to examine further the relationship between counterfactual thinking and false belief (FB) as examined by Guajardo and Turley-Ames ("Cognitive Development, 19" (2004) 53-80). More specifically, the current research examined the importance of working memory and inhibitory control in understanding the relationship…

A Computational Account of Children's Analogical Reasoning: Balancing Inhibitory Control in Working Memory and Relational Representation

ERIC Educational Resources Information Center

Morrison, Robert G.; Doumas, Leonidas A. A.; Richland, Lindsey E.

2011-01-01

Theories accounting for the development of analogical reasoning tend to emphasize either the centrality of relational knowledge accretion or changes in information processing capability. Simulations in LISA (Hummel & Holyoak, 1997, 2003), a neurally inspired computer model of analogical reasoning, allow us to explore how these factors may…

Children's Self-Regulation in the Context of Participatory Pedagogy in Early Childhood Education

ERIC Educational Resources Information Center

Kangas, Jonna; Ojala, Mikko; Venninen, Tuulikki

2015-01-01

Research Findings: Research has shown that self-regulation can support child development in the areas of children's attentional flexibility, working memory, and inhibitory control for excluding impulsive responses. How this is actually related in everyday pedagogical early childhood education (ECE) activities has rarely been studied in detail. In…

Individual differences in experiencing intrusive memories: the role of the ability to resist proactive interference.

PubMed

Verwoerd, Johan; Wessel, Ineke; de Jong, Peter J

2009-06-01

This study explored whether a relatively poor ability to resist or inhibit interference from irrelevant information in working memory is associated with experiencing undesirable intrusive memories. Non-selected participants (N=91) completed a self-report measure of intrusive memories, and carried out experimental tasks intended to measure two different types of inhibition: resistance to proactive interference and response inhibition (i.e., the ability to prevent automatically triggered responses). The results showed a significant relationship between inhibition at the cognitive level (i.e., resistance to proactive interference) and the frequency of intrusive memories (especially in the group of female participants) whereas no such relationship with measures of response inhibition emerged. These findings are consistent with the idea that deficient inhibitory control reflects a vulnerability factor for experiencing intrusive memories. Implications for research investigating risk factors for the development of posttraumatic stress disorder (PTSD) are discussed.

Deciphering the role of CA1 inhibitory circuits in sharp wave-ripple complexes.

PubMed

Cutsuridis, Vassilis; Taxidis, Jiannis

2013-01-01

Sharp wave-ripples (SWRs) are population oscillatory patterns in hippocampal LFPs during deep sleep and immobility, involved in the replay of memories acquired during wakefulness. SWRs have been extensively studied, but their exact generation mechanism is still unknown. A computational model has suggested that fast perisomatic inhibition may generate the high frequency ripples (~200 Hz). Another model showed how replay of memories can be controlled by various classes of inhibitory interneurons targeting specific parts of pyramidal cells (PC) and firing at particular SWR phases. Optogenetic studies revealed new roles for interneuronal classes and rich dynamic interplays between them, shedding new light in their potential role in SWRs. Here, we integrate these findings in a conceptual model of how dendritic and somatic inhibition may collectively contribute to the SWR generation. We suggest that sharp wave excitation and basket cell (BC) recurrent inhibition synchronises BC spiking in ripple frequencies. This rhythm is imposed on bistratified cells which prevent pyramidal bursting. Axo-axonic and stratum lacunosum/moleculare interneurons are silenced by inhibitory inputs originating in the medial septum. PCs receiving rippling inhibition in both dendritic and perisomatic areas and excitation in their apical dendrites, exhibit sparse ripple phase-locked spiking.

Training on Working Memory and Inhibitory Control in Young Adults

PubMed Central

Maraver, Maria J.; Bajo, M. Teresa; Gomez-Ariza, Carlos J.

2016-01-01

Different types of interventions have focused on trying to improve Executive Functions (EFs) due to their essential role in human cognition and behavior regulation. Although EFs are thought to be diverse, most training studies have targeted cognitive processes related to working memory (WM), and fewer have focused on training other control mechanisms, such as inhibitory control (IC). In the present study, we aimed to investigate the differential impact of training WM and IC as compared with control conditions performing non-executive control activities. Young adults were divided into two training (WM/IC) and two (active/passive) control conditions. Over six sessions, the training groups engaged in three different computer-based adaptive activities (WM or IC), whereas the active control group completed a program with low control-demanding activities that mainly involved processing speed. In addition, motivation and engagement were monitored through the training. The WM-training activities required maintenance, updating and memory search processes, while those from the IC group engaged response inhibition and interference control. All participants were pre- and post-tested in criterion tasks (n-back and Stroop), near transfer measures of WM (Operation Span) and IC (Stop-Signal). Non-trained far transfer outcome measures included an abstract reasoning test (Raven’s Advanced Progressive Matrices) and a well-validated experimental task (AX-CPT) that provides indices of cognitive flexibility considering proactive/reactive control. Training results revealed that strongly motivated participants reached higher levels of training improvements. Regarding transfer effects, results showed specific patterns of near transfer effects depending on the type of training. Interestingly, it was only the IC training group that showed far transfer to reasoning. Finally, all trained participants showed a shift toward a more proactive mode of cognitive control, highlighting a general effect of training on cognitive flexibility. The present results reveal specific and general modulations of executive control mechanisms after brief training intervention targeting either WM or IC. PMID:27917117

Effects of ethanolic extract and naphthoquinones obtained from the bulbs of Cipura paludosa on short-term and long-term memory: involvement of adenosine A₁ and A₂A receptors.

PubMed

Lucena, Greice M R S; Matheus, Filipe C; Ferreira, Vania M; Tessele, Priscila B; Azevedo, Mariangela S; Cechinel-Filho, Valdir; Prediger, Rui D

2013-04-01

Previous studies from our group have indicated important biological properties of the ethanolic extract and isolated compounds from the bulbs of Cipura paludosa (Iridaceae), a native plant widely distributed in northern Brazil, including antioxidant, neuroprotective and anti-nociceptive activities. In the present study, the effects of the ethanolic extract and its two naphthoquinones (eleutherine and isoeleutherine) on the short- and long-term memory of adult rodents were assessed in social recognition and inhibitory avoidance tasks. Acute pre-training oral administration of the ethanolic extract improved the short-term social memory in rats as well as facilitated the step-down inhibitory avoidance short- and long-term memory in mice. Moreover, the co-administration of 'non-effective' doses of the extract of Cipura paludosa and the adenosine receptor antagonists caffeine (non-selective), DPCPX (adenosine A1 receptor antagonist) and ZM241385 (adenosine A2A receptor antagonist) improved the social recognition memory of rats. In the inhibitory avoidance task, the co-administration of sub-effective doses of the extract with caffeine or ZM241385, but not with DPCPX, improved the short- and long-term memory of mice. Finally, the acute oral administration of eleutherine and isoeleutherine facilitated the inhibitory avoidance short- and long-term memory in mice. These results demonstrate for the first time the cognitive-enhancing properties of the extract and isolated compounds from the bulbs of Cipura paludosa in rodents and suggest a possible involvement of adenosine A1 and A2A receptors in these effects. © 2012 The Authors Basic & Clinical Pharmacology & Toxicology © 2012 Nordic Pharmacological Society.

Speech-in-speech perception and executive function involvement

PubMed Central

Perrone-Bertolotti, Marcela; Tassin, Maxime

2017-01-01

This present study investigated the link between speech-in-speech perception capacities and four executive function components: response suppression, inhibitory control, switching and working memory. We constructed a cross-modal semantic priming paradigm using a written target word and a spoken prime word, implemented in one of two concurrent auditory sentences (cocktail party situation). The prime and target were semantically related or unrelated. Participants had to perform a lexical decision task on visual target words and simultaneously listen to only one of two pronounced sentences. The attention of the participant was manipulated: The prime was in the pronounced sentence listened to by the participant or in the ignored one. In addition, we evaluate the executive function abilities of participants (switching cost, inhibitory-control cost and response-suppression cost) and their working memory span. Correlation analyses were performed between the executive and priming measurements. Our results showed a significant interaction effect between attention and semantic priming. We observed a significant priming effect in the attended but not in the ignored condition. Only priming effects obtained in the ignored condition were significantly correlated with some of the executive measurements. However, no correlation between priming effects and working memory capacity was found. Overall, these results confirm, first, the role of attention for semantic priming effect and, second, the implication of executive functions in speech-in-noise understanding capacities. PMID:28708830

Behavioral Self-Regulation and Executive Function Both Predict Visuomotor Skills and Early Academic Achievement

ERIC Educational Resources Information Center

Becker, Derek R.; Miao, Alicia; Duncan, Robert; McClelland, Megan M.

2014-01-01

The present study explored direct and interactive effects between behavioral self-regulation (SR) and two measures of executive function (EF, inhibitory control and working memory), with a fine motor measure tapping visuomotor skills (VMS) in a sample of 127 prekindergarten and kindergarten children. It also examined the relative contribution of…

Validating the Electric Maze Task as a Measure of Planning

ERIC Educational Resources Information Center

Sheppard, Kelly W.; Cheatham, Carol L.

2017-01-01

The Electric Maze Task (EMT) is a novel planning task designed to allow flexible testing of planning abilities across a broad age range and to incorporate manipulations to test underlying planning abilities, such as working-memory and inhibitory control skills. The EMT was tested in a group of 63 typically developing 7- to 12-year-olds.…

Executive Function in Preschool-Age Children: Integrating Measurement, Neurodevelopment, and Translational Research

ERIC Educational Resources Information Center

Griffin, James A., Ed.; McCardle, Peggy, Ed.; Freund, Lisa, Ed.

2016-01-01

A primary aim of the neuropsychological revolution has been the mapping of what has come to be known as executive function (EF). This term encompasses a range of mental processes such as working memory, inhibitory control, and cognitive flexibility that, together, regulate our social behavior, and our emotional and cognitive well-being. In this…

Working memory predicts children's analogical reasoning.

PubMed

Simms, Nina K; Frausel, Rebecca R; Richland, Lindsey E

2018-02-01

Analogical reasoning is the cognitive skill of drawing relationships between representations, often between prior knowledge and new representations, that allows for bootstrapping cognitive and language development. Analogical reasoning proficiency develops substantially during childhood, although the mechanisms underlying this development have been debated, with developing cognitive resources as one proposed mechanism. We explored the role of executive function (EF) in supporting children's analogical reasoning development, with the goal of determining whether predicted aspects of EF were related to analogical development at the level of individual differences. We assessed 5- to 11-year-old children's working memory, inhibitory control, and cognitive flexibility using measures from the National Institutes of Health Toolbox Cognition battery. Individual differences in children's working memory best predicted performance on an analogical mapping task, even when controlling for age, suggesting a fundamental interrelationship between analogical reasoning and working memory development. These findings underscore the need to consider cognitive capacities in comprehensive theories of children's reasoning development. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of co-morbid attention-deficit and hyperactivity disorder on cognitive function in male children with Tourette syndrome: A controlled study.

PubMed

Termine, Cristiano; Luoni, Chiara; Fontolan, Stefania; Selvini, Claudia; Perego, Livia; Pavone, Francesca; Rossi, Giorgio; Balottin, Umberto; Cavanna, Andrea E

2016-09-30

Tourette syndrome (TS) and attention-deficit and hyperactivity disorder (ADHD) are co-morbid neurodevelopmental conditions affecting more commonly male patients. We set out to determine the impact of co-morbid ADHD on cognitive function in male children with TS by conducting a controlled study. Participants included four matched groups of unmedicated children (age range 6-15 years): TS (n=13), TS+ADHD (n=8), ADHD (n=39), healthy controls (n=66). Following clinical assessment, each participant completed a battery of tests from the Wechsler Intelligence Scale for Children-III, the Italian Battery for ADHD, the Tower of London test, the Corsi test, and the Digit Span test. All patient groups reported significantly lower scores than healthy controls across the neuropsychological tests involving executive functions. The TS+ADHD group was the most severely affected, followed by the ADHD group and the TS group, particularly in the tests assessing planning ability, inhibitory function, working memory and visual attention, but not auditory attention. Problems in executive functions are more common in patients with neurodevelopmental disorders than controls. Deficits in planning ability, inhibitory function, working memory and visual attention reported by children with TS appear to be more strongly related to the presence of co-morbid ADHD symptoms than core TS symptoms. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A Positive Autoregulatory BDNF Feedback Loop via C/EBPβ Mediates Hippocampal Memory Consolidation

PubMed Central

Bambah-Mukku, Dhananjay; Travaglia, Alessio; Chen, Dillon Y.; Pollonini, Gabriella

2014-01-01

Little is known about the temporal progression and regulation of the mechanisms underlying memory consolidation. Brain-derived-neurotrophic-factor (BDNF) has been shown to mediate the maintenance of memory consolidation, but the mechanisms of this regulation remain unclear. Using inhibitory avoidance (IA) in rats, here we show that a hippocampal BDNF-positive autoregulatory feedback loop via CCAAT-enhancer binding protein β (C/EBPβ) is necessary to mediate memory consolidation. At training, a very rapid, learning-induced requirement of BDNF accompanied by rapid de novo translation controls the induction of a persistent activation of cAMP-response element binding-protein (CREB) and C/EBPβ expression. The latter, in turn, controls an increase in expression of bdnf exon IV transcripts and BDNF protein, both of which are necessary and, together with the initial BDNF requirement, mediate memory consolidation. The autoregulatory loop terminates by 48 h after training with decreased C/EBPβ and pCREB and increased methyl-CpG binding protein-2, histone-deacetylase-2, and switch-independent-3a binding at the bdnf exon IV promoter. PMID:25209292

Experienced stress produces inhibitory deficits in old adults' Flanker task performance: First evidence for lifetime stress effects beyond memory.

PubMed

Marshall, Amanda C; Cooper, Nicholas R; Geeraert, Nicolas

2016-01-01

Studies regarding aged individuals' performance on the Flanker task differ with respect to reporting impaired or intact executive control. Past work has explained this discrepancy by hypothesising that elderly individuals use increased top-down control mechanisms advantageous to Flanker performance. This study investigated this mechanism, focussing on cumulative experienced stress as a factor that may impact on its execution, thereby leading to impaired performance. Thirty elderly and thirty young participants completed a version of the Flanker task paired with electroencephalographic recordings of the alpha frequency, whose increased synchronisation indexes inhibitory processes. Among high stress elderly individuals, findings revealed a general slowing of reaction times for congruent and incongruent stimuli, which correlated with alpha desynchronisation for both stimulus categories. Results found high performing (low stress) elderly revealed neither a behavioural nor electrophysiological difference compared to young participants. Therefore, rather than impacting on top-down compensatory mechanisms, findings indicate that stress may affect elderly participants' inhibitory control in attentional and sensorimotor domains. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Parallel Regulation of Memory and Emotion Supports the Suppression of Intrusive Memories

PubMed Central

Anderson, Michael C.

2017-01-01

Intrusive memories often take the form of distressing images that emerge into a person's awareness, unbidden. A fundamental goal of clinical neuroscience is to understand the mechanisms allowing people to control these memory intrusions and reduce their emotional impact. Mnemonic control engages a right frontoparietal network that interrupts episodic retrieval by modulating hippocampal activity; less is known, however, about how this mechanism contributes to affect regulation. Here we report evidence in humans (males and females) that stopping episodic retrieval to suppress an unpleasant image triggers parallel inhibition of mnemonic and emotional content. Using fMRI, we found that regulation of both mnemonic and emotional content was driven by a shared frontoparietal inhibitory network and was predicted by a common profile of medial temporal lobe downregulation involving the anterior hippocampus and the amygdala. Critically, effective connectivity analysis confirmed that reduced amygdala activity was not merely an indirect consequence of hippocampal suppression; rather, both the hippocampus and the amygdala were targeted by a top-down inhibitory control signal originating from the dorsolateral prefrontal cortex. This negative coupling was greater when unwanted memories intruded into awareness and needed to be purged. Together, these findings support the broad principle that retrieval suppression is achieved by regulating hippocampal processes in tandem with domain-specific brain regions involved in reinstating specific content, in an activity-dependent fashion. SIGNIFICANCE STATEMENT Upsetting events sometimes trigger intrusive images that cause distress and that may contribute to psychiatric disorders. People often respond to intrusions by suppressing their retrieval, excluding them from awareness. Here we examined whether suppressing aversive images might also alter emotional responses to them, and the mechanisms underlying such changes. We found that the better people were at suppressing intrusions, the more it reduced their emotional responses to suppressed images. These dual effects on memory and emotion originated from a common right prefrontal cortical mechanism that downregulated the hippocampus and amygdala in parallel. Thus, suppressing intrusions affected emotional content. Importantly, participants who did not suppress intrusions well showed increased negative affect, suggesting that suppression deficits render people vulnerable to psychiatric disorders. PMID:28559378

Role of state-dependent learning in the cognitive effects of caffeine in mice.

PubMed

Sanday, Leandro; Zanin, Karina A; Patti, Camilla L; Fernandes-Santos, Luciano; Oliveira, Larissa C; Longo, Beatriz M; Andersen, Monica L; Tufik, Sergio; Frussa-Filho, Roberto

2013-08-01

Caffeine is the most widely used psychoactive substance in the world and it is generally believed that it promotes beneficial effects on cognitive performance. However, there is also evidence suggesting that caffeine has inhibitory effects on learning and memory. Considering that caffeine may have anxiogenic effects, thus changing the emotional state of the subjects, state-dependent learning may play a role in caffeine-induced cognitive alterations. Mice were administered 20 mg/kg caffeine before training and/or before testing both in the plus-maze discriminative avoidance task (an animal model that concomitantly evaluates learning, memory, anxiety-like behaviour and general activity) and in the inhibitory avoidance task, a classic paradigm for evaluating memory in rodents. Pre-training caffeine administration did not modify learning, but produced an anxiogenic effect and impaired memory retention. While pre-test administration of caffeine did not modify retrieval on its own, the pre-test administration counteracted the memory deficit induced by the pre-training caffeine injection in both the plus-maze discriminative and inhibitory avoidance tasks. Our data demonstrate that caffeine-induced memory deficits are critically related to state-dependent learning, reinforcing the importance of considering the participation of state-dependency on the interpretation of the cognitive effects of caffeine. The possible participation of caffeine-induced anxiety alterations in state-dependent memory deficits is discussed.

Executive Functions in Children Who Experience Bullying Situations

PubMed Central

Medeiros, Wandersonia; Torro-Alves, Nelson; Malloy-Diniz, Leandro F.; Minervino, Carla M.

2016-01-01

Bullying is characterized by intentional, repetitive, and persistent aggressive behavior that causes damage to the victim. Many studies investigate the social and emotional aspects related to bullying, but few assess the cognitive aspects it involves. Studies with aggressive individuals indicate impairment in executive functioning and decision-making. The objective of this study was to assess hot and cold executive functions in children who experience bullying. A total of 60 children between 10 and 11 years of age were included in the study. They were divided into four groups: aggressors (bullies), victims, bully-victims, and control. Tests for decision-making, inhibitory control, working memory, and cognitive flexibility were used. The bully group made more unfavorable choices on the Iowa Gambling Task, which may indicate difficulties in the decision-making process. The victim group took longer to complete the Trail Making Test (Part B) than aggressors, suggesting lower cognitive flexibility in victims. The hypothesis that aggressors would have lower performance in other executive functions such as inhibitory control, working memory, and cognitive flexibility has not been confirmed. This study indicates that bullies have an impairment of hot executive functions whereas victims have a comparatively lower performance in cold executive functions. In addition to social and cultural variables, neurocognitive and emotional factors seem to influence the behavior of children in bullying situations. PMID:27616998

The Neuropsychology of Amphetamine and Opiate Dependence: Implications for Treatment

PubMed Central

Sahakian, Barbara J

2013-01-01

Chronic use of amphetamines and/or opiates has been associated with a wide range of cognitive deficits, involving domains of attention, inhibitory control, planning, decision-making, learning and memory. Although both amphetamine and opiate users show marked impairment in various aspects of cognitive function, the impairment profile is distinctly different according to the substance of abuse. In light of evidence showing that cognitive impairment in drug users has a negative impact on treatment engagement and efficacy, we review substance-specific deficits on executive and memory function, and discuss possibilities to address these during treatment intervention. PMID:17690986

The development of inhibitory control in preschool children: effects of "executive skills" training.

PubMed

Dowsett, S M; Livesey, D J

2000-03-01

As one of several processes involved in the executive functioning of the cognitive system, inhibitory control plays a significant role in determining how various mental processes work together in the successful performance of a task. Studies of response inhibition have shown that although 3-year-old children have the cognitive capacity to learn the rules required for response control, indicated by the correct verbal response, developmental constraints prevent them from withholding the correct response (Bell & Livesey, 1985; Livesey & Morgan, 1991). Some argue that these abulic dissociations are relative to children's ability to reflect on the rules required for response control (Zelazo, Reznick, & Pinon, 1995). The current study showed that repeated exposure to tasks facilitating the acquisition of increasingly complex rule structures could improve inhibitory control (as measured by a go/no-go discrimination learning task), even in children aged 3 years. These tasks included a variant of Diamond and Boyer's (1989) modified version of the Wisconsin Card Sort Task and a simplification of the change paradigm (Logan & Burkell, 1986). It is argued that experience with these tasks increased the acquisition of complex rules by placing demands on executive processes. This includes response control and other executive functions, such as representational flexibility, the ability to maintain information in working memory, the selective control of attention, and proficiency at error correction. The role of experiential variables in the development of inhibitory control is discussed in terms of the interaction between neural development and appropriate executive task experience in the early years. Copyright 2000 John Wiley & Sons, Inc.

Divided attention reduces resistance to distraction at encoding but not retrieval.

PubMed

Weeks, Jennifer C; Hasher, Lynn

2017-08-01

Older adults show implicit memory for previously seen distraction, an effect attributed to poor attentional control. It is unclear whether this effect results from lack of control over encoding during the distraction task, lack of retrieval constraint during the test task, or both. In the present study, we simulated poor distraction control in young adults using divided attention at encoding, at retrieval, at both times, or not at all. The encoding task was a 1-back task on pictures with distracting superimposed letter strings, some of which were words. The retrieval task was a word fragment completion task testing implicit memory for the distracting words. Attention was divided using an auditory odd digit detection task. Dividing attention at encoding, but not at retrieval, resulted in significant priming for distraction, which suggests that control over encoding processes is a primary determinant of distraction transfer in populations with low inhibitory control (e.g. older adults).

Age-Related Changes in Antisaccade Task Performance: Inhibitory Control or Working-Memory Engagement?

ERIC Educational Resources Information Center

Eenshuistra, R.M.; Ridderinkhof, K.R.; Molen, M.W.v.d.

2004-01-01

In antisaccade tasks, subjects are required to generate a saccade in the direction opposite to the location of a sudden-onset target stimulus. Compared to young adults, older adults tend to make more reflex-like eye movements towards the target, and/or show longer saccadic onset latencies on correct direct antisaccades. To better understand the…

Executive Function Skills, Early Mathematics, and Vocabulary in Head Start Preschool Children

ERIC Educational Resources Information Center

Harvey, Hattie A.; Miller, Gloria E.

2017-01-01

Research Findings: The contribution of 3 executive function skills (shifting, inhibitory control, and working memory) and their relation to early mathematical skills was investigated with preschoolers attending 6 Head Start centers. Ninety-two children ranging in age from 3 years, 1 month, to 4 years, 11 months, who were native English or Spanish…

Different Executive Functions Support Different Kinds of Cognitive Flexibility: Evidence from 2-, 3-, and 4-Year-Olds

ERIC Educational Resources Information Center

Blakey, Emma; Visser, Ingmar; Carroll, Daniel J.

2016-01-01

Improvements in cognitive flexibility during the preschool years have been linked to developments in both working memory and inhibitory control, though the precise contribution of each remains unclear. In the current study, one hundred and twenty 2-, 3-, and 4-year-olds completed two rule-switching tasks. In one version, children switched rules in…

Cognitive and Personality Components Underlying Spoken Idiom Comprehension in Context. An Exploratory Study.

PubMed

Cacciari, Cristina; Corrardini, Paola; Ferlazzo, Fabio

2018-01-01

In this exploratory study, we investigated whether and to what extent individual differences in cognitive and personality variables are associated with spoken idiom comprehension in context. Language unimpaired participants were enrolled in a cross-modal lexical decision study in which semantically ambiguous Italian idioms (i.e., strings with both a literal and an idiomatic interpretation as, for instance, break the ice ), predictable or unpredictable before the string offset, were embedded in idiom-biasing contexts. To explore the contributions of different cognitive and personality components, participants also completed a series of tests respectively assessing general speed, inhibitory control, short-term and working memory, cognitive flexibility, crystallized and fluid intelligence, and personality. Stepwise regression analyses revealed that online idiom comprehension was associated with the participants' working memory, inhibitory control and crystallized verbal intelligence, an association modulated by idiom type. Also personality-related variables (State Anxiety and Openness to Experience) were associated with idiom comprehension, although in marginally significant ways. These results contribute to the renewed interest on how individual variability modulates language comprehension, and for the first time document contributions of individual variability on lexicalized, high frequency multi-word expressions as idioms adding new knowledge to the existing evidence on metaphor and sarcasm.

Enhancement of Inhibitory Avoidance and Conditioned Taste Aversion Memory with Insular Cortex Infusions of 8-Br-cAMP: Involvement of the Basolateral Amygdala

ERIC Educational Resources Information Center

Miranda, Maria I.; McGaugh, James L.

2004-01-01

There is considerable evidence that in rats, the insular cortex (IC) and amygdala are involved in the learning and memory of aversively motivated tasks. The present experiments examined the effects of 8-Br-cAMP, an analog of cAMP, and oxotremorine, a muscarinic agonist, infused into the IC after inhibitory avoidance (IA) training and during the…

Tonic Inhibitory Control of Dentate Gyrus Granule Cells by α5-Containing GABAA Receptors Reduces Memory Interference.

PubMed

Engin, Elif; Zarnowska, Ewa D; Benke, Dietmar; Tsvetkov, Evgeny; Sigal, Maksim; Keist, Ruth; Bolshakov, Vadim Y; Pearce, Robert A; Rudolph, Uwe

2015-10-07

Interference between similar or overlapping memories formed at different times poses an important challenge on the hippocampal declarative memory system. Difficulties in managing interference are at the core of disabling cognitive deficits in neuropsychiatric disorders. Computational models have suggested that, in the normal brain, the sparse activation of the dentate gyrus granule cells maintained by tonic inhibitory control enables pattern separation, an orthogonalization process that allows distinct representations of memories despite interference. To test this mechanistic hypothesis, we generated mice with significantly reduced expression of the α5-containing GABAA (α5-GABAARs) receptors selectively in the granule cells of the dentate gyrus (α5DGKO mice). α5DGKO mice had reduced tonic inhibition of the granule cells without any change in fast phasic inhibition and showed increased activation in the dentate gyrus when presented with novel stimuli. α5DGKO mice showed impairments in cognitive tasks characterized by high interference, without any deficiencies in low-interference tasks, suggesting specific impairment of pattern separation. Reduction of fast phasic inhibition in the dentate gyrus through granule cell-selective knock-out of α2-GABAARs or the knock-out of the α5-GABAARs in the downstream CA3 area did not detract from pattern separation abilities, which confirms the anatomical and molecular specificity of the findings. In addition to lending empirical support to computational hypotheses, our findings have implications for the treatment of interference-related cognitive symptoms in neuropsychiatric disorders, particularly considering the availability of pharmacological agents selectively targeting α5-GABAARs. Interference between similar memories poses a significant limitation on the hippocampal declarative memory system, and impaired interference management is a cognitive symptom in many disorders. Thus, understanding mechanisms of successful interference management or processes that can lead to interference-related memory problems has high theoretical and translational importance. This study provides empirical evidence that tonic inhibition in the dentate gyrus (DG), which maintains sparseness of neuronal activation in the DG, is essential for management of interference. The specificity of findings to tonic, but not faster, more transient types of neuronal inhibition and to the DG, but not the neighboring brain areas, is presented through control experiments. Thus, the findings link interference management to a specific mechanism, proposed previously by computational models. Copyright © 2015 the authors 0270-6474/15/3513699-15$15.00/0.

Alpha Oscillations Are Causally Linked to Inhibitory Abilities in Ageing.

PubMed

Borghini, Giulia; Candini, Michela; Filannino, Cristina; Hussain, Masud; Walsh, Vincent; Romei, Vincenzo; Zokaei, Nahid; Cappelletti, Marinella

2018-05-02

Aging adults typically show reduced ability to ignore task-irrelevant information, an essential skill for optimal performance in many cognitive operations, including those requiring working memory (WM) resources. In a first experiment, young and elderly human participants of both genders performed an established WM paradigm probing inhibitory abilities by means of valid, invalid, and neutral retro-cues. Elderly participants showed an overall cost, especially in performing invalid trials, whereas younger participants' general performance was comparatively higher, as expected.Inhibitory abilities have been linked to alpha brain oscillations but it is yet unknown whether in aging these oscillations (also typically impoverished) and inhibitory abilities are causally linked. To probe this possible causal link in aging, we compared in a second experiment parietal alpha-transcranial alternating current stimulation (tACS) with either no stimulation (Sham) or with two control stimulation frequencies (theta- and gamma-tACS) in the elderly group while performing the same WM paradigm. Alpha- (but not theta- or gamma-) tACS selectively and significantly improved performance (now comparable to younger adults' performance in the first experiment), particularly for invalid cues where initially elderly showed the highest costs. Alpha oscillations are therefore causally linked to inhibitory abilities and frequency-tuned alpha-tACS interventions can selectively change these abilities in the elderly. SIGNIFICANCE STATEMENT Ignoring task-irrelevant information, an ability associated to rhythmic brain activity in the alpha frequency band, is fundamental for optimal performance. Indeed, impoverished inhibitory abilities contribute to age-related decline in cognitive functions like working memory (WM), the capacity to briefly hold information in mind. Whether in aging adults alpha oscillations and inhibitory abilities are causally linked is yet unknown. We experimentally manipulated frequency-tuned brain activity using transcranial alternating current stimulation (tACS), combined with a retro-cue paradigm assessing WM and inhibition. We found that alpha-tACS induced a significant improvement in target responses and misbinding errors, two indexes of inhibition. We concluded that in aging alpha oscillations are causally linked to inhibitory abilities, and that despite being impoverished, these abilities are still malleable. Copyright © 2018 the authors 0270-6474/18/384419-12$15.00/0.

The neural correlates of impaired inhibitory control in anxiety.

PubMed

Ansari, Tahereh L; Derakshan, Nazanin

2011-04-01

According to Attentional Control Theory (Eysenck et al., 2007) anxiety impairs the inhibition function of working memory by increasing the influence of stimulus-driven processes over efficient top-down control. We investigated the neural correlates of impaired inhibitory control in anxiety using an antisaccade task. Low- and high-anxious participants performed anti- and prosaccade tasks and electrophysiological activity was recorded. Consistent with previous research high-anxious individuals had longer antisaccade latencies in response to the to-be-inhibited target, compared with low-anxious individuals. Central to our predictions, high-anxious individuals showed lower ERP activity, at frontocentral and central recording sites, than low anxious individuals, in the period immediately prior to onset of the to-be-inhibited target on correct antisaccade trials. Our findings indicate that anxiety interferes with the efficient recruitment of top-down mechanisms required for the suppression of prepotent responses. Implications are discussed within current models of attentional control in anxiety (Bishop, 2009; Eysenck et al., 2007). Copyright © 2011 Elsevier Ltd. All rights reserved.

Disinhibition, an emerging pharmacology of learning and memory.

PubMed

Möhler, Hanns; Rudolph, Uwe

2017-01-01

Learning and memory are dependent on interactive excitatory and inhibitory mechanisms. In this review, we discuss a mechanism called disinhibition, which is the release of an inhibitory constraint that effectively results in an increased activity in the target neurons (for example, principal or projection neurons). We focus on discussing the role of disinhibition in learning and memory at a basic level and in disease models with cognitive deficits and highlight a strategy to reverse cognitive deficits caused by excess inhibition, through disinhibition of α5-containing GABA A receptors mediating tonic inhibition in the hippocampus, based on subtype-selective negative allosteric modulators as a novel class of drugs.

Living in the moment: Effects of time perspective and emotional valence of episodic thinking on delay discounting

PubMed Central

Lin, Henry; Epstein, Leonard H.

2014-01-01

Excessive delay discounting (DD) has been related to various maladaptive behaviors, and may stem from a myopic focus on immediate gratification. Neuroimaging studies have shown that episodic future thinking (EFT) – vivid mental simulation of future experiences – may reduce DD by promoting consideration of delayed outcomes. However, the EFT manipulations in these experiments may have induced positive affect, which could independently enhance executive functions that facilitate self-regulation. To clarify the mechanism of this effect, 87 participants were randomized to visualize neutral- or positive-valenced events expected to occur in the present or in the future while completing a standardized DD questionnaire. Working memory capacity, inhibitory control, the genotypes of 3 functional dopaminergic polymorphisms (DRD1 rs686, DRD2 rs1800497 and COMT rs4680), as well as an additive dopamine genetic risk score were assessed as potential moderators. The results indicate that EFT reduces DD primarily by shifting the time perspective of intertemporal decision-making, and that this effect is moderated by working memory capacity. In addition, positive episodic thinking may independently attenuate the protective effects of high working memory capacity, high inhibitory control, and lower dopamine genetic risk scores on DD. The current findings dovetail with previous research to suggest that the time perspective and emotional valence of episodic thinking may dynamically shape intertemporal choice, perhaps in part by transiently modulating executive function and dopaminergic neurotransmission. PMID:24512061

Effects of tennis play on executive function in 6-11-year-old children: a 12-month longitudinal study.

PubMed

Ishihara, Toru; Mizuno, Masao

2018-06-01

The present study aimed to assess the effects of 12 months of frequent tennis play on executive functions and the relationships of daily moderate-to-vigorous physical activity (MVPA), physical competence, and enjoyment of playing tennis to executive functions in children. Thirty-two children (6-11 years old) who had regularly played tennis (once a week; mean = 3 years, range = 0-6 years) before the study were enrolled in a 12-month intervention. Participants were allocated into two groups: low-dose (maintain current frequency of tennis play, N = 19) or high-dose (increased frequency of tennis play to four times per week, N = 13). Participants' MVPA, physical competence, enjoyment of playing tennis, and executive functions (i.e. inhibitory control, working memory, and cognitive flexibility) were evaluated before and after this intervention. The high-dose group demonstrated a greater improvement in working memory than the low-dose group, while there was no group difference in MVPA, physical competence, and enjoyment of playing tennis. Changes in MVPA were associated with improvements in cognitive flexibility. Changes in physical competence were associated with improvements in working memory and cognitive flexibility. Changes in the enjoyment of playing tennis were associated with improvements in inhibitory control. The current findings suggest that replacement of MVPA with sports activity, such as tennis enhances executive functions development, and suggest that sports programmes that seek to build competence and enjoyment might help support the development of executive functions in children.

GABAergic contributions to gating, timing, and phase precession of hippocampal neuronal activity during theta oscillations.

PubMed

Cutsuridis, Vassilis; Hasselmo, Michael

2012-07-01

Successful spatial exploration requires gating, storage, and retrieval of spatial memories in the correct order. The hippocampus is known to play an important role in the temporal organization of spatial information. Temporally ordered spatial memories are encoded and retrieved by the firing rate and phase of hippocampal pyramidal cells and inhibitory interneurons with respect to ongoing network theta oscillations paced by intra- and extrahippocampal areas. Much is known about the anatomical, physiological, and molecular characteristics as well as the connectivity and synaptic properties of various cell types in the hippocampal microcircuits, but how these detailed properties of individual neurons give rise to temporal organization of spatial memories remains unclear. We present a model of the hippocampal CA1 microcircuit based on observed biophysical properties of pyramidal cells and six types of inhibitory interneurons: axo-axonic, basket, bistratistified, neurogliaform, ivy, and oriens lacunosum-moleculare cells. The model simulates a virtual rat running on a linear track. Excitatory transient inputs come from the entorhinal cortex (EC) and the CA3 Schaffer collaterals and impinge on both the pyramidal cells and inhibitory interneurons, whereas inhibitory inputs from the medial septum impinge only on the inhibitory interneurons. Dopamine operates as a gate-keeper modulating the spatial memory flow to the PC distal dendrites in a frequency-dependent manner. A mechanism for spike-timing-dependent plasticity in distal and proximal PC dendrites consisting of three calcium detectors, which responds to the instantaneous calcium level and its time course in the dendrite, is used to model the plasticity effects. The model simulates the timing of firing of different hippocampal cell types relative to theta oscillations, and proposes functional roles for the different classes of the hippocampal and septal inhibitory interneurons in the correct ordering of spatial memories as well as in the generation and maintenance of theta phase precession of pyramidal cells (place cells) in CA1. The model leads to a number of experimentally testable predictions that may lead to a better understanding of the biophysical computations in the hippocampus and medial septum. Copyright © 2011 Wiley Periodicals, Inc.

mTORC1 controls long-term memory retrieval.

PubMed

Pereyra, Magdalena; Katche, Cynthia; de Landeta, Ana Belén; Medina, Jorge H

2018-06-08

Understanding how stored information emerges is a main question in the neurobiology of memory that is now increasingly gaining attention. However, molecular events underlying this memory stage, including involvement of protein synthesis, are not well defined. Mammalian target of rapamycin complex 1 (mTORC1), a central regulator of protein synthesis, has been implicated in synaptic plasticity and is required for memory formation. Using inhibitory avoidance (IA), we evaluated the role of mTORC1 in memory retrieval. Infusion of a selective mTORC1 inhibitor, rapamycin, into the dorsal hippocampus 15 or 40 min but not 3 h before testing at 24 h reversibly disrupted memory expression even in animals that had already expressed IA memory. Emetine, a general protein synthesis inhibitor, provoked a similar impairment. mTORC1 inhibition did not interfere with short-term memory retrieval. When infused before test at 7 or 14 but not at 28 days after training, rapamycin impaired memory expression. mTORC1 blockade in retrosplenial cortex, another structure required for IA memory, also impaired memory retention. In addition, pretest intrahippocampal rapamycin infusion impaired object location memory retrieval. Our results support the idea that ongoing protein synthesis mediated by activation of mTORC1 pathway is necessary for long but not for short term memory.

Moderate-to-Vigorous Physical Activity, Indices of Cognitive Control, and Academic Achievement in Preadolescents.

PubMed

Pindus, Dominika M; Drollette, Eric S; Scudder, Mark R; Khan, Naiman A; Raine, Lauren B; Sherar, Lauren B; Esliger, Dale W; Kramer, Arthur F; Hillman, Charles H

2016-06-01

To assess whether preadolescents' objectively measured moderate-to-vigorous physical activity (MVPA) is associated with cognitive control and academic achievement, independent of aerobic fitness. A sample of 74 children (Meanage = 8.64 years, SD = .58, 46% girls) were included in the analyses. Daily MVPA (min/d) was measured over 7 days using ActiGraph wGT3X+ accelerometer. Aerobic fitness was measured using a maximal graded exercise test and expressed as maximal oxygen uptake (mL*kg(-1)*min(-1)). Inhibitory control was measured with a modified Eriksen flanker task (reaction time and accuracy), and working memory with an Operation Span Task (accuracy scores). Academic achievement (in reading, mathematics, and spelling) was expressed as standardized scores on the Kaufman Test of Educational Achievement. The relationships were assessed using hierarchical regression models adjusting for aerobic fitness and other covariates. No significant associations were found between MVPA and inhibition, working memory, or academic achievement. Aerobic fitness was positively associated with inhibitory control (P = .02) and spelling (P = .04) but not with other cognitive or academic variables (all P > .05). Aerobic fitness, rather than daily MVPA, is positively associated with childhood ability to manage perceptual interference and spelling. Further research into the associations between objectively measured MVPA and cognitive and academic outcomes in children while controlling for important covariates is needed. Copyright © 2016 Elsevier Inc. All rights reserved.

Post-training reversible disconnection of the ventral hippocampal-basolateral amygdaloid circuits impairs consolidation of inhibitory avoidance memory in rats.

PubMed

Wang, Gong-Wu; Liu, Jian; Wang, Xiao-Qin

2017-11-01

The ventral hippocampus (VH) and the basolateral amygdala (BLA) are both crucial in inhibitory avoidance (IA) memory. However, the exact role of the VH-BLA circuit in IA memory consolidation is unclear. This study investigated the effect of post-training reversible disconnection of the VH-BLA circuit in IA memory consolidation. Male Wistar rats with implanted guide cannulae were trained with a one-trial IA task, then received immediate intracerebral injections of muscimol or saline, and were tested 24 h later. Muscimol injection into the bilateral BLA, or the unilateral VH and contralateral BLA, but not the unilateral VH and ipsilateral BLA, significantly decreased the retention latencies (versus saline treatment). The results suggest that the VH-BLA circuit could be an important circuit to modulate consolidation of IA memory in rats. © 2017 Wang et al.; Published by Cold Spring Harbor Laboratory Press.

Alcohol and behavioral control: cognitive and neural mechanisms.

PubMed

Vogel-Sprott, M; Easdon, C; Fillmore, M; Finn, P; Justus, A

2001-01-01

This article represents the proceedings of a symposium at the 2000 RSA Meeting in Denver, Colorado. The organizer/chair was Muriel Vogel-Sprott. The presentations were (1) Alcohol-induced impairment of inhibitory control: Some commonalities with attention deficit hyperactivity disorder, by Mark Fillmore; (2) Neural interactions that underlie response inhibition under alcohol: A functional magnetic resonance imaging investigation, by Craig Easdon; (3) Intentional control of behavior under alcohol, by Muriel Vogel-Sprott; and (4) Working memory and the disinhibiting effects of alcohol on passive avoidance learning, by Alicia Justius and Peter Finn.

Factor Structure and Heritability of Endophenotypes in Schizophrenia: Findings from the Consortium on the Genetics of Schizophrenia (COGS-1)

PubMed Central

Seidman, Larry J.; Hellemann, Gerhard; Nuechterlein, Keith H.; Greenwood, Tiffany A.; Braff, David L.; Cadenhead, Kristin S.; Calkins, Monica E.; Freedman, Robert; Gur, Raquel E.; Gur, Ruben C.; Lazzeroni, Laura C.; Light, Gregory A.; Olincy, Ann; Radant, Allen D.; Siever, Larry J.; Silverman, Jeremy M.; Sprock, Joyce; Stone, William S.; Sugar, Catherine; Swerdlow, Neal R.; Tsuang, Debby W.; Tsuang, Ming T.; Turetsky, Bruce I.; Green, Michael F.

2018-01-01

Background Although many endophenotypes for schizophrenia have been studied individually, few studies have examined the extent to which common neurocognitive and neurophysiological measures reflect shared versus unique endophenotypic factors. It may be possible to distill individual endophenotypes into composite measures that reflect dissociable, genetically informative elements. Methods The first phase of the Consortium on the Genetics of Schizophrenia (COGS-1) is a multisite family study that collected neurocognitive and neurophysiological data between 2003–2008. For these analyses, participants included schizophrenia probands (n=83), their nonpsychotic siblings (n=151), and community comparison subjects (n=209) with complete data on a battery of 12 neurocognitive tests (assessing domains of working memory, declarative memory, vigilance, spatial ability, abstract reasoning, facial emotion processing, and motor speed) and 3 neurophysiological tasks reflecting inhibitory processing (P50 gating, prepulse inhibition and antisaccade tasks). Factor analyses were conducted on the measures for each subject group and across the entire sample. Heritability analyses of factors were performed using SOLAR. Results Analyses yielded 5 distinct factors: 1) Episodic Memory, 2) Working Memory, 3) Perceptual Vigilance, 4) Visual Abstraction, and 5) Inhibitory Processing. Neurophysiological measures had low associations with these factors. The factor structure of endophenotypes was largely comparable across probands, siblings and controls. Significant heritability estimates for the factors ranged from 22% (Episodic Memory) to 39% (Visual Abstraction). Conclusions Neurocognitive measures reflect a meaningful amount of shared variance whereas the neurophysiological measures reflect largely unique contributions as endophenotypes for schizophrenia. Composite endophenotype measures may inform our neurobiological and genetic understanding of schizophrenia. PMID:25682549

Factor structure and heritability of endophenotypes in schizophrenia: findings from the Consortium on the Genetics of Schizophrenia (COGS-1).

PubMed

Seidman, Larry J; Hellemann, Gerhard; Nuechterlein, Keith H; Greenwood, Tiffany A; Braff, David L; Cadenhead, Kristin S; Calkins, Monica E; Freedman, Robert; Gur, Raquel E; Gur, Ruben C; Lazzeroni, Laura C; Light, Gregory A; Olincy, Ann; Radant, Allen D; Siever, Larry J; Silverman, Jeremy M; Sprock, Joyce; Stone, William S; Sugar, Catherine; Swerdlow, Neal R; Tsuang, Debby W; Tsuang, Ming T; Turetsky, Bruce I; Green, Michael F

2015-04-01

Although many endophenotypes for schizophrenia have been studied individually, few studies have examined the extent to which common neurocognitive and neurophysiological measures reflect shared versus unique endophenotypic factors. It may be possible to distill individual endophenotypes into composite measures that reflect dissociable, genetically informative elements. The first phase of the Consortium on the Genetics of Schizophrenia (COGS-1) is a multisite family study that collected neurocognitive and neurophysiological data between 2003 and 2008. For these analyses, participants included schizophrenia probands (n=83), their nonpsychotic siblings (n=151), and community comparison subjects (n=209) with complete data on a battery of 12 neurocognitive tests (assessing domains of working memory, declarative memory, vigilance, spatial ability, abstract reasoning, facial emotion processing, and motor speed) and 3 neurophysiological tasks reflecting inhibitory processing (P50 gating, prepulse inhibition and antisaccade tasks). Factor analyses were conducted on the measures for each subject group and across the entire sample. Heritability analyses of factors were performed using SOLAR. Analyses yielded 5 distinct factors: 1) Episodic Memory, 2) Working Memory, 3) Perceptual Vigilance, 4) Visual Abstraction, and 5) Inhibitory Processing. Neurophysiological measures had low associations with these factors. The factor structure of endophenotypes was largely comparable across probands, siblings and controls. Significant heritability estimates for the factors ranged from 22% (Episodic Memory) to 39% (Visual Abstraction). Neurocognitive measures reflect a meaningful amount of shared variance whereas the neurophysiological measures reflect largely unique contributions as endophenotypes for schizophrenia. Composite endophenotype measures may inform our neurobiological and genetic understanding of schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.

The role of inhibition for working memory processes: ERP evidence from a short-term storage task.

PubMed

Getzmann, Stephan; Wascher, Edmund; Schneider, Daniel

2018-05-01

Human working memory is the central unit for short-term storage of information. In addition to the selection and adequate storage of relevant information, the suppression of irrelevant stimuli from the environment seems to be of importance for working memory processes. To learn more about the interplay of information uptake and inhibition of irrelevant information, the present study used ERP measures and a short-term storage and retrieval task, in which pairs of either numbers or letters had to be compared. Random sequences of four stimuli (two numbers and two letters) were presented, with either the numbers or the letters being relevant for comparison. The analysis of ERPs to each of the four stimuli indicated more pronounced P2 and P3b amplitudes for relevant than irrelevant stimuli. In contrast, the N2 (reflecting inhibitory control) was only elicited by irrelevant stimuli. Moreover, the N2 amplitude of the second irrelevant stimulus was associated with behavioral performance, indicating the importance of inhibition of task-irrelevant stimuli for working memory processes. In sum, the findings demonstrate the role of cognitive control mechanisms for protecting relevant contents in working memory against irrelevant information. © 2017 Society for Psychophysiological Research.

Early Life Manipulations Alter Learning and Memory in Rats

PubMed Central

Kosten, Therese A; Kim, Jeansok J; Lee, Hongjoo J.

2012-01-01

Much research shows early life manipulations have enduring behavioral, neural, and hormonal effects. However, findings of learning and memory performance vary widely across studies. We reviewed studies in which pre-weaning rat pups were exposed to stressors and tested on learning and memory tasks in adulthood. Tasks were classified as aversive conditioning, inhibitory learning, or spatial/relational memory. Variables of duration, type, and timing of neonatal manipulation and sex and strain of animals were examined to determine if any predict enhanced or impaired performance. Brief separations enhanced and prolonged separations impaired performance on spatial/relational tasks. Performance was impaired in aversive conditioning and enhanced in inhibitory learning tasks regardless of manipulation duration. Opposing effects on performance for spatial/relational memory also depended upon timing of manipulation. Enhanced performance was likely if the manipulation occurred during postnatal week 3 but performance was impaired if it was confined to the first two postnatal weeks. Thus, the relationship between early life experiences and adulthood learning and memory performance is multifaceted and decidedly task-dependent. PMID:22819985

[Do practices of learning activities improve the cognitive functioning of healthy elderly adults? From the viewpoint of a transfer effect].

PubMed

Yoshida, Hajime; Sun, Qin; Tsuchida, Noriaki; Ohkawa, Ichiro

2014-06-01

The present study examined influences of reading aloud and performing simple calculation on the cognitive functioning of healthy elderly adults, based on the findings that these tasks activated the prefrontal lobe. The elderly adults' memory and inhibitory functions were assesed by Short-Term memory, CST, Stroop, and SRC tasks, before and after intervention for 18 months. The study found that the learning group had significant improvement from the pre- to the post-test for the short-term memory, STM, CST, and Stroop tasks. On the other hand, there was significant decline over the 18 months in the control group which was given only the assessment tasks. These results are discussed in terms of the effectiveness of cognitive training.

Intra-Amygdala Injections of CREB Antisense Impair Inhibitory Avoidance Memory: Role of Norepinephrine and Acetylcholine

ERIC Educational Resources Information Center

Canal, Clinton E.; Chang, Qing; Gold, Paul E.

2008-01-01

Infusions of CREB antisense into the amygdala prior to training impair memory for aversive tasks, suggesting that the antisense may interfere with CRE-mediated gene transcription and protein synthesis important for the formation of new memories within the amygdala. However, the amygdala also appears to modulate memory formation in distributed…

No retrieval-induced forgetting using item-specific independent cues: evidence against a general inhibitory account.

PubMed

Camp, Gino; Pecher, Diane; Schmidt, Henk G

2007-09-01

Retrieval practice with particular items from memory can impair the recall of related items on a later memory test. This retrieval-induced forgetting effect has been ascribed to inhibitory processes (M. C. Anderson & B. A. Spellman, 1995). A critical finding that distinguishes inhibitory from interference explanations is that forgetting is found with independent (or extralist) cues. In 4 experiments, the authors tested whether the forgetting effect is cue-independent. Forgetting was investigated for both studied and unstudied semantically related items. Retrieval-induced forgetting was not found using item-specific independent cues for either studied or unstudied items. However, forgetting was found for both item types when studied categories were used as cues. These results are not in line with a general inhibitory account, because this account predicts retrieval-induced forgetting with independent cues. Interference and context-specific inhibition are discussed as possible explanations for the data. 2007 APA

Short-term memory for pictures seen once or twice.

PubMed

Martini, Paolo; Maljkovic, Vera

2009-06-01

The present study is concerned with the effects of exposure time, repetition, spacing and lag on old/new recognition memory for generic visual scenes presented in a RSVP paradigm. Early memory studies with verbal material found that knowledge of total exposure time at study is sufficient to accurately predict memory performance at test (the Total Time Hypothesis), irrespective of number of repetitions, spacing or lag. However, other studies have disputed such simple dependence of memory strength on total study time, demonstrating super-additive facilitatory effects of spacing and lag, as well as inhibitory effects, such as the Ranschburg effect, Repetition Blindness and the Attentional Blink. In the experimental conditions of the present study we find no evidence of either facilitatory or inhibitory effects: recognition memory for pictures in RSVP supports the Total Time Hypothesis. The data are consistent with an Unequal-Variance Signal Detection Theory model of memory that assumes the average strength and the variance of the familiarity of pictures both increase with total study time. The main conclusion is that the growth of visual scene familiarity with temporal exposure and repetition is a stochastically independent process.

[Executive dysfunction in attention deficit hyperactivity disorder in childhood].

PubMed

Romero-Ayuso, D M; Maestú, F; González-Marqués, J; Romo-Barrientos, C; Andrade, J M

The principal problem of ADHD is the difficulty to execute inhibitory control. The inhibition is an executive function that is develop during childhood. To know if other executive functions shower a lower performance in ADHD versus control group and these were different between ADHD-I and ADHD-C. Fifty three children, between 7 to 10 years old, participated and were assess with EMIC and Simon task. The results showed similar profile in working memory and verbal span. In contrast, ADHD-C showed lower performance in Simon task and more impulsively. On an other hand, ADHD-I showed lower performance in memory working tasks and planning. These results suggest differences in the executive profile between ADHD-I and ADHD-C and these support the hypothesis of Barkley about the necessity to differ both clinical subtypes.

Plasticity of inhibitory processes and associated far-transfer effects in older adults.

PubMed

Ji, Yang; Wang, Jun; Chen, Tianyong; Du, Xin; Zhan, Yi

2016-08-01

Inhibition deficit plays a crucial part in cognitive aging; however, few studies have systematically investigated the plasticity of various inhibitory processes among older adults. We studied the plasticity of 3 inhibitory processes (access, deletion, and restraint) and the extent of far transfer of inhibition training to other general cognitive abilities. Thirty-six participants (aged 60 years and above, M = 70.06, SD = 5.53) were randomly assigned to an adaptive training group that received 12 sessions of training covering 3 inhibitory processes or an active control group that received 4 sessions of mental health lectures. Participants in both groups completed pre- and posttest assessments, in which behavioral and electrophysiological measures were used to evaluate potential transfer effects. Direct training gains were observed for trained tasks of all inhibitory processes, but near-transfer effects were only found within untrained tasks associated with deletion at a composite score level. Furthermore, far-transfer effects were demonstrated for fluid intelligence (Gf) but not for working memory or other general cognitive abilities. Near transfer to deletion and far transfer to Gf persisted at a 3-month follow-up assessment session. We discussed differences in plasticity between the 3 inhibitory processes as well as their possible associations with far transfer to Gf. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

The effects of aging on the working memory processes of multimodal information.

PubMed

Solesio-Jofre, Elena; López-Frutos, José María; Cashdollar, Nathan; Aurtenetxe, Sara; de Ramón, Ignacio; Maestú, Fernando

2017-05-01

Normal aging is associated with deficits in working memory processes. However, the majority of research has focused on storage or inhibitory processes using unimodal paradigms, without addressing their relationships using different sensory modalities. Hence, we pursued two objectives. First, was to examine the effects of aging on storage and inhibitory processes. Second, was to evaluate aging effects on multisensory integration of visual and auditory stimuli. To this end, young and older participants performed a multimodal task for visual and auditory pairs of stimuli with increasing memory load at encoding and interference during retention. Our results showed an age-related increased vulnerability to interrupting and distracting interference reflecting inhibitory deficits related to the off-line reactivation and on-line suppression of relevant and irrelevant information, respectively. Storage capacity was impaired with increasing task demands in both age groups. Additionally, older adults showed a deficit in multisensory integration, with poorer performance for new visual compared to new auditory information.

Antibody recognizing 4-sulfated chondroitin sulfate proteoglycans restores memory in tauopathy-induced neurodegeneration.

PubMed

Yang, Sujeong; Hilton, Sam; Alves, João Nuno; Saksida, Lisa M; Bussey, Timothy; Matthews, Russell T; Kitagawa, Hiroshi; Spillantini, Maria Grazia; Kwok, Jessica C F; Fawcett, James W

2017-11-01

Chondroitin sulfate proteoglycans (CSPGs) are the main active component of perineuronal nets (PNNs). Digestion of the glycosaminoglycan chains of CSPGs with chondroitinase ABC or transgenic attenuation of PNNs leads to prolongation of object recognition memory and activation of various forms of plasticity in the adult central nervous system. The inhibitory properties of the CSPGs depend on the pattern of sulfation of their glycosaminoglycans, with chondroitin 4-sulfate (C4S) being the most inhibitory form. In this study, we tested a number of candidates for functional blocking of C4S, leading to selection of an antibody, Cat316, which specifically recognizes C4S and blocks its inhibitory effects on axon growth. It also partly blocks binding of semaphorin 3A to PNNs and attenuates PNN formation. We asked whether injection of Cat316 into the perirhinal cortex would have the same effects on memory as chondroitinase ABC treatment. We found that masking C4S with the Cat316 antibody extended long-term object recognition memory in normal wild-type mice to 24 hours, similarly to chondroitinase or transgenic PNN attenuation. We then tested Cat316 for restoration of memory in a neurodegeneration model. Mice expressing tau with the P301S mutation showed profound loss of object recognition memory at 4 months of age. Injection of Cat316 into the perirhinal cortex normalized object recognition at 3 hours in P301S mice. These data indicate that Cat316 binding to C4S in the extracellular matrix can restore plasticity and memory in the same way as chondroitinase ABC digestion. Our results suggest that antibodies to C4S could be a useful therapeutic to restore memory function in neurodegenerative disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

Working memory training in old age: an examination of transfer and maintenance effects.

PubMed

Borella, Erika; Carretti, Barbara; Zanoni, Giulia; Zavagnin, Michela; De Beni, Rossana

2013-06-01

The present study examined the efficacy of a verbal working memory (WM) training program in old-old individuals (over 75 years of age). Thirty-six adults aged 75-87 took part in the study: 18 were randomly assigned to receive training and the remainder served as active controls. Specific training gains in a verbal WM task (criterion task), and transfer effects on measures of visuospatial WM, short-term memory, inhibition, processing speed, and fluid intelligence were examined. The trained old-old adults performed better than the controls in the criterion task, and this benefit persisted after 8 months; they also showed an increase in the efficiency of inhibitory mechanisms at follow-up compared with pretest. The results of this study suggest that the present WM training program produces benefits maintained over time even in old-old adults. These findings confirm that there is still room for plasticity in the basic mechanisms of cognition in advance old age.

Children's memory distortions following social contact with a co-witness: disentangling social and cognitive mechanisms.

PubMed

Bright-Paul, Alexandra; Jarrold, Christopher; Wright, Daniel B; Guillaume, Stephanie

2012-01-01

This study examined whether recalling an event with a co-witness influences children's recall. Individual 3-5-year-olds (n = 48) watched a film with a co-witness. Unbeknown to participants, the co-witness was watching an alternative version of the film. Afterwards both the co-witness and the participant answered questions about the film together (public recall), and the degree to which children conformed to the co-witness's alternative version of events was measured. Subsequently participants were questioned again individually (private recall). Children also completed false belief and inhibitory control tasks. By separating errors made in public and private, the results indicated that both social conformity (32% of errors) and memory distortion (68% of errors) played a role in co-witness influence. Inhibitory control predicted the likelihood of retracting errors in private, but only for children who failed (r = .66) rather than passed false belief tasks (r = -.10). The results suggest that children with a theory of mind conform in the company of the co-witness to avoid social embarrassment, while those a poor theory of mind conform on the basis of an inability to inhibit the co-witness's response. The findings contribute to our understanding of the motivations responsible for co-witness conformity across early childhood.

Cognitive and Personality Components Underlying Spoken Idiom Comprehension in Context. An Exploratory Study

PubMed Central

Cacciari, Cristina; Corrardini, Paola; Ferlazzo, Fabio

2018-01-01

In this exploratory study, we investigated whether and to what extent individual differences in cognitive and personality variables are associated with spoken idiom comprehension in context. Language unimpaired participants were enrolled in a cross-modal lexical decision study in which semantically ambiguous Italian idioms (i.e., strings with both a literal and an idiomatic interpretation as, for instance, break the ice), predictable or unpredictable before the string offset, were embedded in idiom-biasing contexts. To explore the contributions of different cognitive and personality components, participants also completed a series of tests respectively assessing general speed, inhibitory control, short-term and working memory, cognitive flexibility, crystallized and fluid intelligence, and personality. Stepwise regression analyses revealed that online idiom comprehension was associated with the participants' working memory, inhibitory control and crystallized verbal intelligence, an association modulated by idiom type. Also personality-related variables (State Anxiety and Openness to Experience) were associated with idiom comprehension, although in marginally significant ways. These results contribute to the renewed interest on how individual variability modulates language comprehension, and for the first time document contributions of individual variability on lexicalized, high frequency multi-word expressions as idioms adding new knowledge to the existing evidence on metaphor and sarcasm. PMID:29765350

Inhibitory ryanodine prevents ryanodine receptor-mediated Ca²⁺ release without affecting endoplasmic reticulum Ca²⁺ content in primary hippocampal neurons.

PubMed

Adasme, Tatiana; Paula-Lima, Andrea; Hidalgo, Cecilia

2015-02-27

Ryanodine is a cell permeant plant alkaloid that binds selectively and with high affinity to ryanodine receptor (RyR) Ca(2+) release channels. Sub-micromolar ryanodine concentrations activate RyR channels while micromolar concentrations are inhibitory. Several reports indicate that neuronal synaptic plasticity, learning and memory require RyR-mediated Ca(2+)-release, which is essential for muscle contraction. The use of micromolar (inhibitory) ryanodine represents a common strategy to suppress RyR activity in neuronal cells: however, micromolar ryanodine promotes RyR-mediated Ca(2+) release and endoplasmic reticulum Ca(2+) depletion in muscle cells. Information is lacking in this regard in neuronal cells; hence, we examined here if addition of inhibitory ryanodine elicited Ca(2+) release in primary hippocampal neurons, and if prolonged incubation of primary hippocampal cultures with inhibitory ryanodine affected neuronal ER calcium content. Our results indicate that inhibitory ryanodine does not cause Ca(2+) release from the ER in primary hippocampal neurons, even though ryanodine diffusion should produce initially low intracellular concentrations, within the RyR activation range. Moreover, neurons treated for 1 h with inhibitory ryanodine had comparable Ca(2+) levels as control neurons. These combined findings imply that prolonged incubation with inhibitory ryanodine, which effectively abolishes RyR-mediated Ca(2+) release, preserves ER Ca(2+) levels and thus constitutes a sound strategy to suppress neuronal RyR function. Copyright © 2015 Elsevier Inc. All rights reserved.

Hippocampal place cell and inhibitory neuron activity in disrupted-in-schizophrenia-1 mutant mice: implications for working memory deficits

PubMed Central

Mesbah-Oskui, Lia; Georgiou, John; Roder, John C

2015-01-01

Background: Despite the prevalence of working memory deficits in schizophrenia, the neuronal mechanisms mediating these deficits are not fully understood. Importantly, deficits in spatial working memory are identified in numerous mouse models that exhibit schizophrenia-like endophenotypes. The hippocampus is one of the major brain regions that actively encodes spatial location, possessing pyramidal neurons, commonly referred to as ‘place cells’, that fire in a location-specific manner. This study tests the hypothesis that mice with a schizophrenia-like endophenotype exhibit impaired encoding of spatial location in the hippocampus. Aims: To characterize hippocampal place cell activity in mice that exhibit a schizophrenia-like endophenotype. Methods: We recorded CA1 place cell activity in six control mice and six mice that carry a point mutation in the disrupted-in-schizophrenia-1 gene (Disc1-L100P) and have previously been shown to exhibit deficits in spatial working memory. Results: The spatial specificity and stability of Disc1-L100P place cells were similar to wild-type place cells. Importantly, however, Disc1-L100P place cells exhibited a higher propensity to increase their firing rate in a single, large location of the environment, rather than multiple smaller locations, indicating a generalization in their spatial selectivity. Alterations in the signaling and numbers of CA1 putative inhibitory interneurons and decreased hippocampal theta (5–12 Hz) power were also identified in the Disc1-L100P mice. Conclusions: The generalized spatial selectivity of Disc1-L100P place cells suggests a simplification of the ensemble place codes that encode individual locations and subserve spatial working memory. Moreover, these results suggest that deficient working memory in schizophrenia results from an impaired ability to uniquely code the individual components of a memory sequence. PMID:27280123

Hilar GABAergic Interneuron Activity Controls Spatial Learning and Memory Retrieval

PubMed Central

Andrews-Zwilling, Yaisa; Gillespie, Anna K.; Kravitz, Alexxai V.; Nelson, Alexandra B.; Devidze, Nino; Lo, Iris; Yoon, Seo Yeon; Bien-Ly, Nga; Ring, Karen; Zwilling, Daniel; Potter, Gregory B.; Rubenstein, John L. R.; Kreitzer, Anatol C.; Huang, Yadong

2012-01-01

Background Although extensive research has demonstrated the importance of excitatory granule neurons in the dentate gyrus of the hippocampus in normal learning and memory and in the pathogenesis of amnesia in Alzheimer's disease (AD), the role of hilar GABAergic inhibitory interneurons, which control the granule neuron activity, remains unclear. Methodology and Principal Findings We explored the function of hilar GABAergic interneurons in spatial learning and memory by inhibiting their activity through Cre-dependent viral expression of enhanced halorhodopsin (eNpHR3.0)—a light-driven chloride pump. Hilar GABAergic interneuron-specific expression of eNpHR3.0 was achieved by bilaterally injecting adeno-associated virus containing a double-floxed inverted open-reading frame encoding eNpHR3.0 into the hilus of the dentate gyrus of mice expressing Cre recombinase under the control of an enhancer specific for GABAergic interneurons. In vitro and in vivo illumination with a yellow laser elicited inhibition of hilar GABAergic interneurons and consequent activation of dentate granule neurons, without affecting pyramidal neurons in the CA3 and CA1 regions of the hippocampus. We found that optogenetic inhibition of hilar GABAergic interneuron activity impaired spatial learning and memory retrieval, without affecting memory retention, as determined in the Morris water maze test. Importantly, optogenetic inhibition of hilar GABAergic interneuron activity did not alter short-term working memory, motor coordination, or exploratory activity. Conclusions and Significance Our findings establish a critical role for hilar GABAergic interneuron activity in controlling spatial learning and memory retrieval and provide evidence for the potential contribution of GABAergic interneuron impairment to the pathogenesis of amnesia in AD. PMID:22792368

Deficits in oculomotor performance in pediatric epilepsy

PubMed Central

Asato, Miya R.; Nawarawong, Natalie; Hermann, Bruce; Crumrine, Patricia; Luna, Beatriz

2010-01-01

Summary Purpose Given evidence of limitations in neuropsychological performance in epilepsy, we probed the integrity of components of cognition, including speed of processing, response inhibition, and spatial working memory supporting executive function in pediatric epilepsy patients and matched controls. Methods A total of 44 pairs of controls and medically treated pediatric epilepsy patients with no known brain pathology completed cognitive oculomotor tasks, computerized neuropsychological testing, and psychiatric assessment. Results Patients showed slower reaction time to initiate a saccadic response compared to controls but had intact saccade accuracy. Cognitively driven responses including response inhibition were impaired in the patient group. Patients had increased incidence of comorbid psychopathology but comorbidity did not predict worse functioning compared to patients with no ADHD. Epilepsy type and medication status were not predictive of outcome. More complex neuropsychological performance was impaired in tasks requiring visual memory and sequential processing which was correlated with inhibitory control and antisaccade accuracy. Discussion Pediatric epilepsy may be associated with vulnerabilities that specifically undermine speed of processing and response inhibition but not working memory and may underlie known neuropsychological performance limitations. This particular profile of abnormalities may be associated with seizure-mediated compromises in brain maturation early in development. PMID:21087246

Executive function, approach sensitivity, and emotional decision making as influences on risk behaviors in young adults.

PubMed

Patrick, Megan E; Blair, Clancy; Maggs, Jennifer L

2008-05-01

Relations among executive function, behavioral approach sensitivity, emotional decision making, and risk behaviors (alcohol use, drug use, and delinquent behavior) were examined in single female college students (N = 72). Hierarchical multiple regressions indicated a significant Approach Sensitivity x Working Memory interaction in which higher levels of alcohol use were associated with the combination of greater approach tendency and better working memory. This Approach Sensitivity x Working Memory interaction was also marginally significant for drug use and delinquency. Poor emotional decision making, as measured by a gambling task, was also associated with higher levels of alcohol use, but only for individuals low in inhibitory control. Findings point to the complexity of relations among aspects of self-regulation and personality and provide much needed data on neuropsychological correlates of risk behaviors in a nonclinical population.

Can task-switching training enhance executive control functioning in children with attention deficit/-hyperactivity disorder?

PubMed

Kray, Jutta; Karbach, Julia; Haenig, Susann; Freitag, Christine

2011-01-01

The key cognitive impairments of children with attention deficit/-hyperactivity disorder (ADHD) include executive control functions such as inhibitory control, task-switching, and working memory (WM). In this training study we examined whether task-switching training leads to improvements in these functions. Twenty children with combined type ADHD and stable methylphenidate medication performed a single-task and a task-switching training in a crossover training design. The children were randomly assigned to one of two groups. One group started with the single-task training and then performed the task-switching training and the other group vice versa. The effectiveness of the task-switching training was measured as performance improvements (relative to the single-task training) on a structurally similar but new switching task and on other executive control tasks measuring inhibitory control and verbal WM as well as on fluid intelligence (reasoning). The children in both groups showed improvements in task-switching, that is, a reduction of switching costs, but not in performing the single-tasks across four training sessions. Moreover, the task-switching training lead to selective enhancements in task-switching performance, that is, the reduction of task-switching costs was found to be larger after task-switching than after single-task training. Similar selective improvements were observed for inhibitory control and verbal WM, but not for reasoning. Results of this study suggest that task-switching training is an effective cognitive intervention that helps to enhance executive control functioning in children with ADHD.

Can Task-Switching Training Enhance Executive Control Functioning in Children with Attention Deficit/-Hyperactivity Disorder?

PubMed Central

Kray, Jutta; Karbach, Julia; Haenig, Susann; Freitag, Christine

2012-01-01

The key cognitive impairments of children with attention deficit/-hyperactivity disorder (ADHD) include executive control functions such as inhibitory control, task-switching, and working memory (WM). In this training study we examined whether task-switching training leads to improvements in these functions. Twenty children with combined type ADHD and stable methylphenidate medication performed a single-task and a task-switching training in a crossover training design. The children were randomly assigned to one of two groups. One group started with the single-task training and then performed the task-switching training and the other group vice versa. The effectiveness of the task-switching training was measured as performance improvements (relative to the single-task training) on a structurally similar but new switching task and on other executive control tasks measuring inhibitory control and verbal WM as well as on fluid intelligence (reasoning). The children in both groups showed improvements in task-switching, that is, a reduction of switching costs, but not in performing the single-tasks across four training sessions. Moreover, the task-switching training lead to selective enhancements in task-switching performance, that is, the reduction of task-switching costs was found to be larger after task-switching than after single-task training. Similar selective improvements were observed for inhibitory control and verbal WM, but not for reasoning. Results of this study suggest that task-switching training is an effective cognitive intervention that helps to enhance executive control functioning in children with ADHD. PMID:22291628

Rapid Neocortical Dynamics: Cellular and Network Mechanisms

PubMed Central

Haider, Bilal; McCormick, David A.

2011-01-01

The highly interconnected local and large-scale networks of the neocortical sheet rapidly and dynamically modulate their functional connectivity according to behavioral demands. This basic operating principle of the neocortex is mediated by the continuously changing flow of excitatory and inhibitory synaptic barrages that not only control participation of neurons in networks but also define the networks themselves. The rapid control of neuronal responsiveness via synaptic bombardment is a fundamental property of cortical dynamics that may provide the basis of diverse behaviors, including sensory perception, motor integration, working memory, and attention. PMID:19409263

Quiescence of Memory CD8(+) T Cells Is Mediated by Regulatory T Cells through Inhibitory Receptor CTLA-4.

PubMed

Kalia, Vandana; Penny, Laura Anne; Yuzefpolskiy, Yevgeniy; Baumann, Florian Martin; Sarkar, Surojit

2015-06-16

Immune memory cells are poised to rapidly expand and elaborate effector functions upon reinfection yet exist in a functionally quiescent state. The paradigm is that memory T cells remain inactive due to lack of T cell receptor (TCR) stimuli. Here, we report that regulatory T (Treg) cells orchestrate memory T cell quiescence by suppressing effector and proliferation programs through inhibitory receptor, cytotoxic-T-lymphocyte-associated protein-4 (CTLA-4). Loss of Treg cells resulted in activation of genome-wide transcriptional programs characteristic of effector T cells and drove transitioning as well as established memory CD8(+) T cells toward terminally differentiated KLRG-1(hi)IL-7Rα(lo)GzmB(hi) phenotype, with compromised metabolic fitness, longevity, polyfunctionality, and protective efficacy. CTLA-4 functionally replaced Treg cells in trans to rescue memory T cell defects and restore homeostasis. These studies present the CTLA-4-CD28-CD80/CD86 axis as a potential target to accelerate vaccine-induced immunity and improve T cell memory quality in current cancer immunotherapies proposing transient Treg cell ablation. Copyright © 2015 Elsevier Inc. All rights reserved.

Searching for memories, Sudoku, implicit check bits, and the iterative use of not-always-correct rapid neural computation.

PubMed

Hopfield, J J

2008-05-01

The algorithms that simple feedback neural circuits representing a brain area can rapidly carry out are often adequate to solve easy problems but for more difficult problems can return incorrect answers. A new excitatory-inhibitory circuit model of associative memory displays the common human problem of failing to rapidly find a memory when only a small clue is present. The memory model and a related computational network for solving Sudoku puzzles produce answers that contain implicit check bits in the representation of information across neurons, allowing a rapid evaluation of whether the putative answer is correct or incorrect through a computation related to visual pop-out. This fact may account for our strong psychological feeling of right or wrong when we retrieve a nominal memory from a minimal clue. This information allows more difficult computations or memory retrievals to be done in a serial fashion by using the fast but limited capabilities of a computational module multiple times. The mathematics of the excitatory-inhibitory circuits for associative memory and for Sudoku, both of which are understood in terms of energy or Lyapunov functions, is described in detail.

Distinct sets of FGF receptors sculpt excitatory and inhibitory synaptogenesis.

PubMed

Dabrowski, Ania; Terauchi, Akiko; Strong, Cameron; Umemori, Hisashi

2015-05-15

Neurons in the brain must establish a balanced network of excitatory and inhibitory synapses during development for the brain to function properly. An imbalance between these synapses underlies various neurological and psychiatric disorders. The formation of excitatory and inhibitory synapses requires precise molecular control. In the hippocampus, the structure crucial for learning and memory, fibroblast growth factor 22 (FGF22) and FGF7 specifically promote excitatory or inhibitory synapse formation, respectively. Knockout of either Fgf gene leads to excitatory-inhibitory imbalance in the mouse hippocampus and manifests in an altered susceptibility to epileptic seizures, underscoring the importance of FGF-dependent synapse formation. However, the receptors and signaling mechanisms by which FGF22 and FGF7 induce excitatory and inhibitory synapse differentiation are unknown. Here, we show that distinct sets of overlapping FGF receptors (FGFRs), FGFR2b and FGFR1b, mediate excitatory or inhibitory presynaptic differentiation in response to FGF22 and FGF7. Excitatory presynaptic differentiation is impaired in Fgfr2b and Fgfr1b mutant mice; however, inhibitory presynaptic defects are only found in Fgfr2b mutants. FGFR2b and FGFR1b are required for an excitatory presynaptic response to FGF22, whereas only FGFR2b is required for an inhibitory presynaptic response to FGF7. We further find that FGFRs are required in the presynaptic neuron to respond to FGF22, and that FRS2 and PI3K, but not PLCγ, mediate FGF22-dependent presynaptic differentiation. Our results reveal the specific receptors and signaling pathways that mediate FGF-dependent presynaptic differentiation, and thereby provide a mechanistic understanding of precise excitatory and inhibitory synapse formation in the mammalian brain. © 2015. Published by The Company of Biologists Ltd.

Cognitive Deficits in Calsyntenin-2-deficient Mice Associated with Reduced GABAergic Transmission

PubMed Central

Lipina, Tatiana V; Prasad, Tuhina; Yokomaku, Daisaku; Luo, Lin; Connor, Steven A; Kawabe, Hiroshi; Wang, Yu Tian; Brose, Nils; Roder, John C; Craig, Ann Marie

2016-01-01

Calsyntenin-2 has an evolutionarily conserved role in cognition. In a human genome-wide screen, the CLSTN2 locus was associated with verbal episodic memory, and expression of human calsyntenin-2 rescues the associative learning defect in orthologous Caenorhabditis elegans mutants. Other calsyntenins promote synapse development, calsyntenin-1 selectively of excitatory synapses and calsyntenin-3 of excitatory and inhibitory synapses. We found that targeted deletion of calsyntenin-2 in mice results in a selective reduction in functional inhibitory synapses. Reduced inhibitory transmission was associated with a selective reduction of parvalbumin interneurons in hippocampus and cortex. Clstn2−/− mice showed normal behavior in elevated plus maze, forced swim test, and novel object recognition assays. However, Clstn2−/− mice were hyperactive in the open field and showed deficits in spatial learning and memory in the Morris water maze and Barnes maze. These results confirm a function for calsyntenin-2 in cognitive performance and indicate an underlying mechanism that involves parvalbumin interneurons and aberrant inhibitory transmission. PMID:26171716

Belief-bias reasoning in non-clinical delusion-prone individuals.

PubMed

Anandakumar, T; Connaughton, E; Coltheart, M; Langdon, R

2017-03-01

It has been proposed that people with delusions have difficulty inhibiting beliefs (i.e., "doxastic inhibition") so as to reason about them as if they might not be true. We used a continuity approach to test this proposal in non-clinical adults scoring high and low in psychometrically assessed delusion-proneness. High delusion-prone individuals were expected to show greater difficulty than low delusion-prone individuals on "conflict" items of a "belief-bias" reasoning task (i.e. when required to reason logically about statements that conflicted with reality), but not on "non-conflict" items. Twenty high delusion-prone and twenty low delusion-prone participants (according to the Peters et al. Delusions Inventory) completed a belief-bias reasoning task and tests of IQ, working memory and general inhibition (Excluded Letter Fluency, Stroop and Hayling Sentence Completion). High delusion-prone individuals showed greater difficulty than low delusion-prone individuals on the Stroop and Excluded Letter Fluency tests of inhibition, but no greater difficulty on the conflict versus non-conflict items of the belief-bias task. They did, however, make significantly more errors overall on the belief-bias task, despite controlling for IQ, working memory and general inhibitory control. The study had a relatively small sample size and used non-clinical participants to test a theory of cognitive processing in individuals with clinically diagnosed delusions. Results failed to support a role for doxastic inhibitory failure in non-clinical delusion-prone individuals. These individuals did, however, show difficulty with conditional reasoning about statements that may or may not conflict with reality, independent of any general cognitive or inhibitory deficits. Copyright © 2016 Elsevier Ltd. All rights reserved.

Belief-bias reasoning in non-clinical delusion-prone individuals.

PubMed

Anandakumar, T; Connaughton, E; Coltheart, M; Langdon, R

2017-09-01

It has been proposed that people with delusions have difficulty inhibiting beliefs (i.e., "doxastic inhibition") so as to reason about them as if they might not be true. We used a continuity approach to test this proposal in non-clinical adults scoring high and low in psychometrically assessed delusion-proneness. High delusion-prone individuals were expected to show greater difficulty than low delusion-prone individuals on "conflict" items of a "belief-bias" reasoning task (i.e. when required to reason logically about statements that conflicted with reality), but not on "non-conflict" items. Twenty high delusion-prone and twenty low delusion-prone participants (according to the Peters et al. Delusions Inventory) completed a belief-bias reasoning task and tests of IQ, working memory and general inhibition (Excluded Letter Fluency, Stroop and Hayling Sentence Completion). High delusion-prone individuals showed greater difficulty than low delusion-prone individuals on the Stroop and Excluded Letter Fluency tests of inhibition, but no greater difficulty on the conflict versus non-conflict items of the belief-bias task. They did, however, make significantly more errors overall on the belief-bias task, despite controlling for IQ, working memory and general inhibitory control. The study had a relatively small sample size and used non-clinical participants to test a theory of cognitive processing in individuals with clinically diagnosed delusions. Results failed to support a role for doxastic inhibitory failure in non-clinical delusion-prone individuals. These individuals did, however, show difficulty with conditional reasoning about statements that may or may not conflict with reality, independent of any general cognitive or inhibitory deficits. Copyright © 2016 Elsevier Ltd. All rights reserved.

The effect of inhibitory signals on the priming of drug-hapten-specific T-cells that express distinct Vβ receptors

PubMed Central

Gibson, Andrew; Faulkner, Lee; Lichtenfels, Maike; Ogese, Monday; Al-Attar, Zaid; Alfirevic, Ana; Esser, Philipp R.; Martin, Stefan F.; Pirmohamed, Munir; Park, B. Kevin; Naisbitt, Dean J.

2017-01-01

Drug hypersensitivity involves the activation of T-cells in an HLA allele-restricted manner. Since the majority of individuals who carry HLA risk alleles do not develop hypersensitivity, other parameters must control development of the drug-specific T-cell response. Thus, we have utilized a T-cell priming assay and nitroso sulfamethoxazole (SMX-NO) as a model antigen to investigate (1) the activation of specific T-cell receptor (TCR)Vβ subtypes, (2) the impact of PD-1, CTLA4 and TIM-3 co-inhibitory signalling on activation of naïve and memory T-cells and (3) the ability of Tregs to prevent responses. An expansion of the TCR repertoire was observed for nine different Vβ subtypes, while spectratyping revealed that SMX-NO-specific T-cell responses are controlled by public TCRs present in all individuals alongside private TCR repertoires specific to each individual. We proceeded to evaluate the extent to which the activation of these TCR Vβ-restricted antigen-specific T-cell responses is governed by regulatory signals. Blockade of PDL-1/CTLA4 signalling dampened activation of SMX-NO-specific naïve and memory T-cells, while blockade of TIM-3 produced no effect. PD-1, CTLA4, and TIM-3 displayed discrete expression profiles during drug-induced T-cell activation and expression of each receptor was enhanced on dividing T-cells. As these receptors are also expressed on Tregs, Treg-mediated suppression of SMX-NO-induced T-cell activation was investigated. Tregs significantly dampened the priming of T-cells. In conclusion, our findings demonstrate that distinct TCR Vβ subtypes, dysregulation of co-inhibitory signalling pathways and dysfunctional Tregs may influence predisposition to hypersensitivity. PMID:28687658

Aqueous Extract of Black Maca (Lepidium meyenii) on Memory Impairment Induced by Ovariectomy in Mice

PubMed Central

Rubio, Julio; Qiong, Wang; Liu, Xinmin; Jiang, Zhen; Dang, Haixia; Chen, Shi-Lin; Gonzales, Gustavo F.

2011-01-01

The present study aims to test two different doses of aqueous extract of black maca on learning and memory in ovariectomized (OVX) mice and their relation with malonalehyde (MDA), acetylcholinesterase (Ache) and monoamine oxidase (MAO) brain levels. Female mice were divided into five groups: (i) naive (control), (ii) sham, (iii) OVX mice and OVX mice treated with (iv) 0.50 g kg−1 and (v) 2.00 g kg−1 black maca. Mice were orally treated with distilled water or black maca during 35 days starting 7 days after surgery. Memory and learning were assessed using the water Morris maze (from day 23–27) and the step-down avoidance test (days 34 and 35). At the end of each treatment, mice were sacrificed by decapitation and brains were dissected out for MDA, Ache and MAO determinations. Black maca (0.5 and 2.0 g/kg) increased step-down latency when compared to OVX control mice. Black maca decreased MDA and Ache levels in OVX mice; whereas, no differences were observed in MAO levels. Finally, black maca improved experimental memory impairment induced by ovariectomy, due in part, by its antioxidant and Ache inhibitory activities. PMID:18955369

Aqueous Extract of Black Maca (Lepidium meyenii) on Memory Impairment Induced by Ovariectomy in Mice.

PubMed

Rubio, Julio; Qiong, Wang; Liu, Xinmin; Jiang, Zhen; Dang, Haixia; Chen, Shi-Lin; Gonzales, Gustavo F

2011-01-01

The present study aims to test two different doses of aqueous extract of black maca on learning and memory in ovariectomized (OVX) mice and their relation with malonalehyde (MDA), acetylcholinesterase (Ache) and monoamine oxidase (MAO) brain levels. Female mice were divided into five groups: (i) naive (control), (ii) sham, (iii) OVX mice and OVX mice treated with (iv) 0.50 g kg(-1) and (v) 2.00 g kg(-1) black maca. Mice were orally treated with distilled water or black maca during 35 days starting 7 days after surgery. Memory and learning were assessed using the water Morris maze (from day 23-27) and the step-down avoidance test (days 34 and 35). At the end of each treatment, mice were sacrificed by decapitation and brains were dissected out for MDA, Ache and MAO determinations. Black maca (0.5 and 2.0 g/kg) increased step-down latency when compared to OVX control mice. Black maca decreased MDA and Ache levels in OVX mice; whereas, no differences were observed in MAO levels. Finally, black maca improved experimental memory impairment induced by ovariectomy, due in part, by its antioxidant and Ache inhibitory activities.

Number Conservation is Related to Children’s Prefrontal Inhibitory Control: An fMRI Study of a Piagetian Task

PubMed Central

Simon, Grégory; Rossi, Sandrine; Cassotti, Mathieu; Pineau, Arlette; Houdé, Olivier

2012-01-01

Although young children can accurately determine that two rows contain the same number of coins when they are placed in a one-to-one correspondence, children younger than 7 years of age erroneously think that the longer row contains more coins when the coins in one of the rows are spread apart. To demonstrate that prefrontal inhibitory control is necessary to succeed at this task (Piaget’s conservation-of-number task), we studied the relationship between the percentage of BOLD signal changes in the brain areas activated in this developmental task and behavioral performance on a Stroop task and a Backward Digit Span task. The level of activation in the right insula/inferior frontal gyrus was selectively related to inhibitory control efficiency (i.e., the Stroop task), whereas the activation in the left intraparietal sulcus (IPS) was selectively related to the ability to manipulate numerical information in working memory (i.e., the Backward Digit Span task). Taken together, the results indicate that to acquire number conservation, children’s brains must not only activate the reversibility of cognitive operations (supported by the IPS) but also inhibit a misleading length-equal-number strategy (supported by the right insula/inferior frontal gyrus). PMID:22815825

Transcranial Direct Current Stimulation in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder (ADHD): A Pilot Study.

PubMed

Bandeira, Igor Dórea; Guimarães, Rachel Silvany Quadros; Jagersbacher, João Gabriel; Barretto, Thiago Lima; de Jesus-Silva, Jéssica Regina; Santos, Samantha Nunes; Argollo, Nayara; Lucena, Rita

2016-06-01

Studies investigating the possible benefits of transcranial direct current stimulation on left dorsolateral prefrontal cortex in children and adolescents with attention-deficit hyperactivity disorder (ADHD) have not been performed. This study assesses the effect of transcranial direct current stimulation in children and adolescents with ADHD on neuropsychological tests of visual attention, visual and verbal working memory, and inhibitory control. An auto-matched clinical trial was performed involving transcranial direct current stimulation in children and adolescents with ADHD, using SNAP-IV and subtests Vocabulary and Cubes of the Wechsler Intelligence Scale for Children III (WISC-III). Subjects were assessed before and after transcranial direct current stimulation sessions with the Digit Span subtest of the WISC-III, inhibitory control subtest of the NEPSY-II, Corsi cubes, and the Visual Attention Test (TAVIS-3). There were 9 individuals with ADHD according to Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria. There was statistically significant difference in some aspects of TAVIS-3 tests and the inhibitory control subtest of NEPSY-II. Transcranial direct current stimulation can be related to a more efficient processing speed, improved detection of stimuli, and improved ability to switch between an ongoing activity and a new one. © The Author(s) 2016.

Sesquiterpenes and a monoterpenoid with acetylcholinesterase (AchE) inhibitory activity from Valeriana officinalis var. latiofolia in vitro and in vivo.

PubMed

Chen, Heng-Wen; He, Xuan-Hui; Yuan, Rong; Wei, Ben-Jun; Chen, Zhong; Dong, Jun-Xing; Wang, Jie

2016-04-01

Acetylcholinesterase Inhibitor (AchEI) is the most extensive in all anti-dementia drugs. The extracts and isolated compounds from the Valeriana genus have shown anti-dementia bioactivity. Four new sesquiterpenoids (1-4) and a new monoterpenoid (5) were isolated from the root of Valeriana officinalis var. latiofolia. The acetylcholinesterase (AchE) inhibitory activity of isolates was evaluated by modified Ellman method in vitro. Learning and memory ability of compound 4 on mice was evaluated by the Morris water maze. The contents of acetylcholine (Ach), acetylcholine transferase (ChAT) and AchE in mice brains were determined by colorimetry. The results showed IC50 of compound 4 was 0.161 μM in vitro. Compared with the normal group, the learning and memory ability of mice and the contents of Ach and ChAT decreased in model group mice (P<0.01), while the AchE increased (P<0.01). Compared with the model group, Ach and ChAT in the positive control group, the high-dose group and the medium-dose group increased (P<0.01), while the AchE decreased (P<0.01). Compound 4 can improve the learning and memory abilities of APPswe/PSΔE9 double-transgenic mice, and the mechanism may be related to the regulation of the relative enzyme in the cholinergic system. Copyright © 2016 Elsevier B.V. All rights reserved.

RGS7/Gβ5/R7BP complex regulates synaptic plasticity and memory by modulating hippocampal GABABR-GIRK signaling

PubMed Central

Ostrovskaya, Olga; Xie, Keqiang; Masuho, Ikuo; Fajardo-Serrano, Ana; Lujan, Rafael; Wickman, Kevin; Martemyanov, Kirill A

2014-01-01

In the hippocampus, the inhibitory neurotransmitter GABA shapes the activity of the output pyramidal neurons and plays important role in cognition. Most of its inhibitory effects are mediated by signaling from GABAB receptor to the G protein-gated Inwardly-rectifying K+ (GIRK) channels. Here, we show that RGS7, in cooperation with its binding partner R7BP, regulates GABABR-GIRK signaling in hippocampal pyramidal neurons. Deletion of RGS7 in mice dramatically sensitizes GIRK responses to GABAB receptor stimulation and markedly slows channel deactivation kinetics. Enhanced activity of this signaling pathway leads to decreased neuronal excitability and selective disruption of inhibitory forms of synaptic plasticity. As a result, mice lacking RGS7 exhibit deficits in learning and memory. We further report that RGS7 is selectively modulated by its membrane anchoring subunit R7BP, which sets the dynamic range of GIRK responses. Together, these results demonstrate a novel role of RGS7 in hippocampal synaptic plasticity and memory formation. DOI: http://dx.doi.org/10.7554/eLife.02053.001 PMID:24755289

Influence of Response Prepotency Strength, General Working Memory Resources, and Specific Working Memory Load on the Ability to Inhibit Predominant Responses: A Comparison of Young and Elderly Participants

ERIC Educational Resources Information Center

Grandjean, Julien; Collette, Fabienne

2011-01-01

One conception of inhibitory functioning suggests that the ability to successfully inhibit a predominant response depends mainly on the strength of that response, the general functioning of working memory processes, and the working memory demand of the task (Roberts, Hager, & Heron, 1994). The proposal that inhibition and functional working memory…

Source Monitoring and False Memories in Children: Relation to Certainty and Executive Functioning.

ERIC Educational Resources Information Center

Ruffman, Ted; Rustin, Charlotte; Garnham, Wendy; Parkin, Alan J.

2001-01-01

Examined source monitoring and false memories in 6-, 8-, and 10-year-olds related to their memory of information presented by videotape and/or audiotape. Found that certainty rating revealed deficits in children's understanding of when they had erred on source questions and when they had made false alarms. Inhibitory ability accounted for unique…

Interaction of Inhibitory and Facilitatory Effects of Conditioning Trials on Long-Term Memory Formation

ERIC Educational Resources Information Center

Hosono, Shouhei; Matsumoto, Yukihisa; Mizunami, Makoto

2016-01-01

Animals learn through experience and consolidate the memories into long-time storage. Conditioning parameters to induce protein synthesis-dependent long-term memory (LTM) have been the subject of extensive studies in many animals. Here we found a case in which a conditioning trial inhibits or facilitates LTM formation depending on the intervals…

The Roles of MAPK Cascades in Synaptic Plasticity and Memory in "Aplysia": Facilitatory Effects and Inhibitory Constraints

ERIC Educational Resources Information Center

Sharma, Shiv K.; Carew, Thomas J.

2004-01-01

Synaptic plasticity is thought to contribute to memory formation. Serotonin-induced facilitation of sensory-motor (SN-MN) synapses in "Aplysia" is an extensively studied cellular analog of memory for sensitization. Serotonin, a modulatory neurotransmitter, is released in the CNS during sensitization training, and induces three temporally and…

Complex-learning Induced Modifications in Synaptic Inhibition: Mechanisms and Functional Significance.

PubMed

Reuveni, Iris; Lin, Longnian; Barkai, Edi

2018-06-15

Following training in a difficult olfactory-discrimination (OD) task rats acquire the capability to perform the task easily, with little effort. This new acquired skill, of 'learning how to learn' is termed 'rule learning'. At the single-cell level, rule learning is manifested in long-term enhancement of intrinsic neuronal excitability of piriform cortex (PC) pyramidal neurons, and in excitatory synaptic connections between these neurons to maintain cortical stability, such long-lasting increase in excitability must be accompanied by paralleled increase in inhibitory processes that would prevent hyper-excitable activation. In this review we describe the cellular and molecular mechanisms underlying complex-learning-induced long-lasting modifications in GABA A -receptors and GABA B -receptor-mediated synaptic inhibition. Subsequently we discuss how such modifications support the induction and preservation of long-term memories in the in the mammalian brain. Based on experimental results, computational analysis and modeling, we propose that rule learning is maintained by doubling the strength of synaptic inputs, excitatory as well as inhibitory, in a sub-group of neurons. This enhanced synaptic transmission, which occurs in all (or almost all) synaptic inputs onto these neurons, activates specific stored memories. At the molecular level, such rule-learning-relevant synaptic strengthening is mediated by doubling the conductance of synaptic channels, but not their numbers. This post synaptic process is controlled by a whole-cell mechanism via particular second messenger systems. This whole-cell mechanism enables memory amplification when required and memory extinction when not relevant. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Atypical Neural Activity during Inhibitory Processing in Substance-Naïve Youth Who Later Experience Alcohol-Induced Blackouts

PubMed Central

Wetherill, Reagan R.; Castro, Norma; Squeglia, Lindsay M.; Tapert, Susan F.

2012-01-01

BACKGROUND Alcohol-induced blackouts are associated with the development of alcohol abuse and dependence, so it is important to consider potential neurobiological risk factors for experiencing this problem prior to the onset of substance use. This study examines whether neural activity during inhibitory processing might be atypical in substance-naïve youth who later experience alcohol-induced blackouts. METHODS We examined inhibitory processing during fMRI with a go/no-go task that requires withholding a prepotent response in substance-naïve youth who would later transition into heavy drinking (n=40) and youth who remain abstinent (n=20). After approximately 5 years of annual follow-up assessments, youth were classified as nondrinkers (n=20), and heavy drinking youth were classified as having experienced an alcohol-induced blackout (blackout+; n=20) or not (blackout−; n=20). Groups were matched on demographic variables, and youth who experienced blackouts were matched on follow-up substance use. RESULTS Prior to initiating substance use, blackout+ youth showed greater activation during inhibitory processing than nondrinkers and blackout− youth in frontal and cerebellar brain regions. Mean activation during correct inhibitory responses relative to go responses in the left and right middle frontal gyri at baseline predicted future blackout experience, after controlling for follow-up externalizing behaviors and lifetime alcohol consumption. CONCLUSIONS Substance-naïve adolescents who later experience alcohol-induced blackouts show increased neural effort during inhibitory processing, as compared to adolescents who go on to drink at similar levels but do not experience blackouts and healthy, nondrinking controls, suggesting a neurobiological vulnerability to alcohol-induced memory impairments. PMID:23021773

DNA methylation mediates neural processing after odor learning in the honeybee

PubMed Central

Biergans, Stephanie D.; Claudianos, Charles; Reinhard, Judith; Galizia, C. Giovanni

2017-01-01

DNA methyltransferases (Dnmts) - epigenetic writers catalyzing the transfer of methyl-groups to cytosine (DNA methylation) – regulate different aspects of memory formation in many animal species. In honeybees, Dnmt activity is required to adjust the specificity of olfactory reward memories and bees’ relearning capability. The physiological relevance of Dnmt-mediated DNA methylation in neural networks, however, remains unknown. Here, we investigated how Dnmt activity impacts neuroplasticity in the bees’ primary olfactory center, the antennal lobe (AL) an equivalent of the vertebrate olfactory bulb. The AL is crucial for odor discrimination, an indispensable process in forming specific odor memories. Using pharmacological inhibition, we demonstrate that Dnmt activity influences neural network properties during memory formation in vivo. We show that Dnmt activity promotes fast odor pattern separation in trained bees. Furthermore, Dnmt activity during memory formation increases both the number of responding glomeruli and the response magnitude to a novel odor. These data suggest that Dnmt activity is necessary for a form of homoeostatic network control which might involve inhibitory interneurons in the AL network. PMID:28240742

A role for neuronal piRNAs in the epigenetic control of memory-related synaptic plasticity.

PubMed

Rajasethupathy, Priyamvada; Antonov, Igor; Sheridan, Robert; Frey, Sebastian; Sander, Chris; Tuschl, Thomas; Kandel, Eric R

2012-04-27

Small RNA-mediated gene regulation during development causes long-lasting changes in cellular phenotypes. To determine whether small RNAs of the adult brain can regulate memory storage, a process that requires stable and long-lasting changes in the functional state of neurons, we generated small RNA libraries from the Aplysia CNS. In these libraries, we discovered an unexpectedly abundant expression of a 28 nucleotide sized class of piRNAs in brain, which had been thought to be germline specific. These piRNAs have unique biogenesis patterns, predominant nuclear localization, and robust sensitivity to serotonin, a modulatory transmitter that is important for memory. We find that the Piwi/piRNA complex facilitates serotonin-dependent methylation of a conserved CpG island in the promoter of CREB2, the major inhibitory constraint of memory in Aplysia, leading to enhanced long-term synaptic facilitation. These findings provide a small RNA-mediated gene regulatory mechanism for establishing stable long-term changes in neurons for the persistence of memory. Copyright © 2012 Elsevier Inc. All rights reserved.

Integrating impairments in reaction time and executive function using a diffusion model framework

PubMed Central

Karalunas, Sarah L.; Huang-Pollock, Cynthia L.

2013-01-01

Using Ratcliff’s diffusion model and ex-Gaussian decomposition, we directly evaluate the role individual differences in reaction time (RT) distribution components play in the prediction of inhibitory control and working memory (WM) capacity in children with and without ADHD. Children with (n=92, x̄ age= 10.2 years, 67% male) and without ADHD (n=62, x̄ age=10.6 years, 46% male) completed four tasks of WM and a stop signal reaction time (SSRT) task. Children with ADHD had smaller WM capacities and less efficient inhibitory control. Diffusion model analyses revealed that children with ADHD had slower drift rates (v) and faster non-decision times (Ter), but there were no group differences in boundary separations (a). Similarly, using an ex-Gaussian approach, children with ADHD had larger τ values than non-ADHD controls, but did not differ in µ or σ distribution components. Drift rate mediated the association between ADHD status and performance on both inhibitory control and WM capacity. τ also mediated the ADHD-executive function impairment associations; however, models were a poorer fit to the data. Impaired performance on RT and executive functioning tasks has long been associated with childhood ADHD. Both are believed to be important cognitive mechanisms to the disorder. We demonstrate here that drift rate, or the speed at which information accumulates towards a decision, is able to explain both. PMID:23334775

Integrated plasticity at inhibitory and excitatory synapses in the cerebellar circuit.

PubMed

Mapelli, Lisa; Pagani, Martina; Garrido, Jesus A; D'Angelo, Egidio

2015-01-01

The way long-term potentiation (LTP) and depression (LTD) are integrated within the different synapses of brain neuronal circuits is poorly understood. In order to progress beyond the identification of specific molecular mechanisms, a system in which multiple forms of plasticity can be correlated with large-scale neural processing is required. In this paper we take as an example the cerebellar network, in which extensive investigations have revealed LTP and LTD at several excitatory and inhibitory synapses. Cerebellar LTP and LTD occur in all three main cerebellar subcircuits (granular layer, molecular layer, deep cerebellar nuclei) and correspondingly regulate the function of their three main neurons: granule cells (GrCs), Purkinje cells (PCs) and deep cerebellar nuclear (DCN) cells. All these neurons, in addition to be excited, are reached by feed-forward and feed-back inhibitory connections, in which LTP and LTD may either operate synergistically or homeostatically in order to control information flow through the circuit. Although the investigation of individual synaptic plasticities in vitro is essential to prove their existence and mechanisms, it is insufficient to generate a coherent view of their impact on network functioning in vivo. Recent computational models and cell-specific genetic mutations in mice are shedding light on how plasticity at multiple excitatory and inhibitory synapses might regulate neuronal activities in the cerebellar circuit and contribute to learning and memory and behavioral control.

Strategic value-directed learning and memory in Alzheimer's disease and behavioural-variant frontotemporal dementia.

PubMed

Wong, Stephanie; Irish, Muireann; Savage, Greg; Hodges, John R; Piguet, Olivier; Hornberger, Michael

2018-02-12

In healthy adults, the ability to prioritize learning of highly valued information is supported by executive functions and enhances subsequent memory retrieval for this information. In Alzheimer's disease (AD) and behavioural-variant frontotemporal dementia (bvFTD), marked deficits are evident in learning and memory, presenting in the context of executive dysfunction. It is unclear whether these patients show a typical memory bias for higher valued stimuli. We administered a value-directed word-list learning task to AD (n = 10) and bvFTD (n = 21) patients and age-matched healthy controls (n = 22). Each word was assigned a low, medium or high point value, and participants were instructed to maximize the number of points earned across three learning trials. Participants' memory for the words was assessed on a delayed recall trial, followed by a recognition test for the words and corresponding point values. Relative to controls, both patient groups showed poorer overall learning, delayed recall and recognition. Despite these impairments, patients with AD preferentially recalled high-value words on learning trials and showed significant value-directed enhancement of recognition memory for the words and points. Conversely, bvFTD patients did not prioritize recall of high-value words during learning trials, and this reduced selectivity was related to inhibitory dysfunction. Nonetheless, bvFTD patients showed value-directed enhancement of recognition memory for the point values, suggesting a mismatch between memory of high-value information and the ability to apply this in a motivationally salient context. Our findings demonstrate that value-directed enhancement of memory may persist to some degree in patients with dementia, despite pronounced deficits in learning and memory. © 2018 The British Psychological Society.

Origin and fate of lymphocytic choriomeningitis virus-specific CD8+ T cells coexpressing the inhibitory NK cell receptor Ly49G2.

PubMed

Peacock, Craig D; Welsh, Raymond M

2004-07-01

CD8+ T cells that coexpress the inhibitory NK cell receptor, Ly49G2 (G2), are present in immunologically naive C57BL/6 mice but display Ags found on memory T cells. To assess how G2+CD8+ cells relate to bona fide memory cells, we examined the origin and fate of lymphocytic choriomeningitis virus (LCMV)-induced G2+CD8+ cells. During early (day 4) acute LCMV infection, both G2+ and G2-CD8+ T cell subsets underwent an attrition in number and displayed an activation (CD69(high)1B11(high)CD62L(low)) phenotype. By day 8, both subsets synthesized IFN-gamma in response to immunodominant LCMV peptides, though the expansion of G2+ cells was less than that of G2- cells. Adoptive transfer experiments with purified G2- or G2+CD8+ cells from naive mice indicated that the LCMV-specific G2+ subset was derived from a pre-existing G2+ population and not generated from G2- cells responding to LCMV infection. Their participation in the LCMV-specific T cell response increased with age, reflecting an increase in the size of the pre-existing G2+ pool. Following establishment of stable LCMV memory, the proportion of CD8+ cells coexpressing G2 was reduced in comparison to naive controls, presumably due to displacement by G2- LCMV-specific memory cells. LCMV-specific G2+ cells were present in the memory pool, but at low frequencies, and they did not exhibit the typical phenotypic changes of reactivation during secondary challenge. We suggest that G2+CD8+ cells represent a cell lineage distinct from bona fide memory T cells, but that they can participate in an acute virus-specific T cell response.

Aversive and non-aversive memory impairment in the mucopolysaccharidosis II mouse model.

PubMed

Azambuja, Amanda Stapenhorst; Correa, Lilian; Gabiatti, Bernardo Pappi; Martins, Giselle Renata; de Oliveira Franco, Álvaro; Ribeiro, Maria Flávia Marques; Baldo, Guilherme

2018-02-01

Hunter syndrome (MPS II, OMIM 309900) is a lysosomal storage disorder due to deficient iduronate sulphatase activity. Patients present multiple cognitive alterations, and the aim of this work was to verify if MPS II mice also present some progressive cognitive alterations. For that, MPS II mice from 2 to 6 months of age were submitted to repeated open field and inhibitory avoidance tests to evaluate memory parameters. MPS II mice presented impaired memory at 6 months evaluated by open field test. They also performed poorly in the inhibitory avoidance test from 4 months. We conclude that MPS II mice develop cognitive alterations as the disease progresses. These tests can be used in the future to study the efficacy of therapeutic approaches in the central nervous system.

Effects of Trace Amine-associated Receptor 1 Agonists on the Expression, Reconsolidation, and Extinction of Cocaine Reward Memory.

PubMed

Liu, Jian-Feng; Thorn, David A; Zhang, Yanan; Li, Jun-Xu

2016-07-01

As a modulator of dopaminergic system, trace amine-associated receptor 1 has been shown to play a critical role in regulating the rewarding properties of additive drugs. It has been demonstrated that activation of trace amine-associated receptor 1 decreased the abuse-related behaviors of cocaine in rats. However, the role of trace amine-associated receptor 1 in specific stages of cocaine reward memory is still unclear. Here, using a cocaine-induced conditioned place preference model, we tested the effects of a selective trace amine-associated receptor 1 agonist RO5166017 on the expression, reconsolidation, and extinction of cocaine reward memory. We found that RO5166017 inhibited the expression but not retention of cocaine-induced conditioned place preference. RO5166017 had no effect on the reconsolidation of cocaine reward memory. Pretreatment with RO5166017 before extinction hindered the formation of extinction long-term memory. RO5166017 did not affect the movement during the conditioned place preference test, indicating the inhibitory effect of RO5166017 on the expression of cocaine-induced conditioned place preference was not caused by locomotion inhibition. Using a cocaine i.v. self-administration model, we found that the combined trace amine-associated receptor 1 partial agonist RO5263397 with extinction had no effect on the following cue- and drug-induced reinstatement of cocaine-seeking behavior. Repeated administration of the trace amine-associated receptor 1 agonist during extinction showed a continually inhibitory effect on the expression of cocaine reward memory both in cocaine-induced conditioned place preference and cocaine self-administration models. Taken together, these results indicate that activation of trace amine-associated receptor 1 specifically inhibited the expression of cocaine reward memory. The inhibitory effect of trace amine-associated receptor 1 agonists on cocaine reward memory suggests that trace amine-associated receptor 1 agonists could be a promising agent to prevent cocaine relapse. © The Author 2016. Published by Oxford University Press on behalf of CINP.

Effects of cortisol on the memory bias for emotional words? A study in patients with depression and healthy participants using the Directed Forgetting task.

PubMed

Kuehl, Linn K; Wolf, Oliver T; Driessen, Martin; Schlosser, Nicole; Fernando, Silvia Carvalho; Wingenfeld, Katja

2017-09-01

Mood congruent alterations in information processing such as an impaired memory bias for emotional information and impaired inhibitory functions are prominent features of a major depressive disorder (MDD). Furthermore, in MDD patients hypothalamic-pituitary-adrenal axis dysfunctions are frequently found. Impairing effects of stress or cortisol administration on memory retrieval as well as impairing stress effects on cognitive inhibition are well documented in healthy participants. In MDD patients, no effect of acute cortisol administration on memory retrieval was found. The current study investigated the effect of acute cortisol administration on memory bias in MDD patients (N = 55) and healthy controls (N = 63) using the Directed Forgetting (DF) task with positive, negative and neutral words in a placebo controlled, double blind design. After oral administration of 10 mg hydrocortisone/placebo, the item method of the DF task was conducted. Memory performance was tested with a free recall test. Cortisol was not found to have an effect on the results of the DF task. Interestingly, there was significant impact of valence: both groups showed the highest DF score for positive words and remembered significantly more positive words that were supposed to be remembered and significantly more negative words that were supposed to be forgotten. In general, healthy participants remembered more words than the depressed patients. Still, the depressed patients were able to inhibit intentionally irrelevant information at a comparable level as the healthy controls. These results demonstrate the importance to distinguish in experimental designs between different cognitive domains such as inhibition and memory in our study. Copyright © 2017 Elsevier Ltd. All rights reserved.

Control of working memory: effects of attention training on target recognition and distractor salience in an auditory selection task.

PubMed

Melara, Robert D; Tong, Yunxia; Rao, Aparna

2012-01-09

Behavioral and electrophysiological measures of target and distractor processing were examined in an auditory selective attention task before and after three weeks of distractor suppression training. Behaviorally, training improved target recognition and led to less conservative and more rapid responding. Training also effectively shortened the temporal distance between distractors and targets needed to achieve a fixed level of target sensitivity. The effects of training on event-related potentials were restricted to the distracting stimulus: earlier N1 latency, enhanced P2 amplitude, and weakened P3 amplitude. Nevertheless, as distractor P2 amplitude increased, so too did target P3 amplitude, connecting experience-dependent changes in distractor processing with greater distinctiveness of targets in working memory. We consider the effects of attention training on the processing priorities, representational noise, and inhibitory processes operating in working memory. Copyright © 2011 Elsevier B.V. All rights reserved.

High Working Memory Capacity Predicts Less Retrieval Induced Forgetting

PubMed Central

Mall, Jonathan T.; Morey, Candice C.

2013-01-01

Background Working Memory Capacity (WMC) is thought to be related to executive control and focused memory search abilities. These two hypotheses make contrasting predictions regarding the effects of retrieval on forgetting. Executive control during memory retrieval is believed to lead to retrieval induced forgetting (RIFO) because inhibition of competing memory traces during retrieval renders them temporarily less accessible. According to this suggestion, superior executive control should increase RIFO. Alternatively, superior focused search abilities could diminish RIFO, because delimiting the search set reduces the amount of competition between traces and thus the need for inhibition. Some evidence suggests that high WMC is related to more RIFO, which is inconsistent with the focused search hypothesis. Methodology/Principal Findings Using the RIFO paradigm, we created distinct and overlapping categories to manipulate the amount of competition between them. This overlap increased competition between some categories while exclusive use of weak exemplars ensured negligible effects of output interference and integration. Low WMC individuals exhibited RIFO within and between overlapping categories, indicating the effect of resolving competition during retrieval. High WMC individuals only exhibited between-category RIFO, suggesting they experienced reduced competition resolution demands. Low WMC Individuals exhibited the strongest RIFO and no retrieval benefits when interference resolution demands were high. Conclusions/Significance Our findings qualify the inhibitory explanation for RIFO by incorporating the focused search hypothesis for materials that are likely to pose extraordinary challenges at retrieval. The results highlight the importance of considering individual differences in retrieval-induced effects and qualify existing models of these effects. PMID:23326359

High working memory capacity predicts less retrieval induced forgetting.

PubMed

Mall, Jonathan T; Morey, Candice C

2013-01-01

Working Memory Capacity (WMC) is thought to be related to executive control and focused memory search abilities. These two hypotheses make contrasting predictions regarding the effects of retrieval on forgetting. Executive control during memory retrieval is believed to lead to retrieval induced forgetting (RIFO) because inhibition of competing memory traces during retrieval renders them temporarily less accessible. According to this suggestion, superior executive control should increase RIFO. Alternatively, superior focused search abilities could diminish RIFO, because delimiting the search set reduces the amount of competition between traces and thus the need for inhibition. Some evidence suggests that high WMC is related to more RIFO, which is inconsistent with the focused search hypothesis. Using the RIFO paradigm, we created distinct and overlapping categories to manipulate the amount of competition between them. This overlap increased competition between some categories while exclusive use of weak exemplars ensured negligible effects of output interference and integration. Low WMC individuals exhibited RIFO within and between overlapping categories, indicating the effect of resolving competition during retrieval. High WMC individuals only exhibited between-category RIFO, suggesting they experienced reduced competition resolution demands. Low WMC Individuals exhibited the strongest RIFO and no retrieval benefits when interference resolution demands were high. Our findings qualify the inhibitory explanation for RIFO by incorporating the focused search hypothesis for materials that are likely to pose extraordinary challenges at retrieval. The results highlight the importance of considering individual differences in retrieval-induced effects and qualify existing models of these effects.

The relationship of working memory, inhibition, and response variability in child psychopathology.

PubMed

Verté, Sylvie; Geurts, Hilde M; Roeyers, Herbert; Oosterlaan, Jaap; Sergeant, Joseph A

2006-02-15

The aim of this study was to investigate the relationship between working memory and inhibition in children with attention deficit hyperactivity disorder (ADHD), high-functioning autism (HFA), and Tourette syndrome (TS), compared to normally developing children. Furthermore, the contribution of variation in processing speed on working memory and inhibition was investigated in these childhood psychopathologies. Four groups of children are reported in this study: 65 children with ADHD, 66 children with HFA, 24 children with TS, and 82 normal control children. All children were in the age range of 6-13 years. The relationship between working memory and inhibition was similar in children with ADHD, HFA, TS, and normally developing children. The relationship between both domains did not alter significantly for any of the groups, when variation in processing speed was taken into account. More symptoms of hyperactivity/impulsivity are related to a poorer inhibitory process and greater response variability. More symptoms of autism are related to a poorer working memory process. The current study showed that working memory, inhibition, and response variability, are distinct, but related cognitive domains in children with developmental psychopathologies. Research with experimental manipulations is needed to tackle the exact relationship between these cognitive domains.

Chronic Cannabinoid Administration in Vivo Compromises Extinction of Fear Memory

ERIC Educational Resources Information Center

Lin, Hui-Ching; Mao, Sheng-Chun; Chen, Po-See; Gean, Po-Wu

2008-01-01

Endocannabinoids are critically involved in the extinction of fear memory. Here we examined the effects of repeated cannabinoid administration on the extinction of fear memory in rats and on inhibitory synaptic transmission in medial prefrontal cortex (mPFC) slices. Rats were treated with the CB1 receptor agonist WIN55212-2 (WIN 10 mg/kg, i.p.)…

Memory-influencing intra-basolateral amygdala drug infusions modulate expression of Arc protein in the hippocampus.

PubMed

McIntyre, Christa K; Miyashita, Teiko; Setlow, Barry; Marjon, Kristopher D; Steward, Oswald; Guzowski, John F; McGaugh, James L

2005-07-26

Activation of beta-adrenoceptors in the basolateral complex of the amygdala (BLA) modulates memory storage processes and long-term potentiation in downstream targets of BLA efferents, including the hippocampus. Here, we show that this activation also increases hippocampal levels of activity-regulated cytoskeletal protein (Arc), an immediate-early gene (also termed Arg 3.1) implicated in hippocampal synaptic plasticity and memory consolidation processes. Infusions of the beta-adrenoreceptor agonist, clenbuterol, into the BLA immediately after training on an inhibitory avoidance task enhanced memory tested 48 h later. The same dose of clenbuterol significantly increased Arc protein levels in the dorsal hippocampus. Additionally, posttraining intra-BLA infusions of a memory-impairing dose of lidocaine significantly reduced Arc protein levels in the dorsal hippocampus. Increases in Arc protein levels were not accompanied by increases in Arc mRNA, suggesting that amygdala modulation of Arc protein and synaptic plasticity in efferent brain regions occurs at a posttranscriptional level. Finally, infusions of Arc antisense oligodeoxynucleotides into the dorsal hippocampus impaired performance of an inhibitory avoidance task, indicating that the changes in Arc protein expression are related to the observed changes in memory performance.

Memory-influencing intra-basolateral amygdala drug infusions modulate expression of Arc protein in the hippocampus

PubMed Central

McIntyre, Christa K.; Miyashita, Teiko; Setlow, Barry; Marjon, Kristopher D.; Steward, Oswald; Guzowski, John F.; McGaugh, James L.

2005-01-01

Activation of β-adrenoceptors in the basolateral complex of the amygdala (BLA) modulates memory storage processes and long-term potentiation in downstream targets of BLA efferents, including the hippocampus. Here, we show that this activation also increases hippocampal levels of activity-regulated cytoskeletal protein (Arc), an immediate-early gene (also termed Arg 3.1) implicated in hippocampal synaptic plasticity and memory consolidation processes. Infusions of the β-adrenoreceptor agonist, clenbuterol, into the BLA immediately after training on an inhibitory avoidance task enhanced memory tested 48 h later. The same dose of clenbuterol significantly increased Arc protein levels in the dorsal hippocampus. Additionally, posttraining intra-BLA infusions of a memory-impairing dose of lidocaine significantly reduced Arc protein levels in the dorsal hippocampus. Increases in Arc protein levels were not accompanied by increases in Arc mRNA, suggesting that amygdala modulation of Arc protein and synaptic plasticity in efferent brain regions occurs at a posttranscriptional level. Finally, infusions of Arc antisense oligodeoxynucleotides into the dorsal hippocampus impaired performance of an inhibitory avoidance task, indicating that the changes in Arc protein expression are related to the observed changes in memory performance. PMID:16020527

Neuropsychological alterations in mercury intoxication persist several years after exposure

PubMed Central

Zachi, Elaine Cristina; Taub, Anita; Faria, Marcília de Araújo Medrado; Ventura, Dora Fix

2008-01-01

Elemental mercury is a liquid toxic metal widely used in industry. Occupational exposure occurs mainly via inhalation. Previously, neuropsychological assessment detected deficits in former workers of a fluorescent lamp plant who had been exposed to elemental mercury vapor and were away from exposure for several years at the time of examination. Objectives The purpose of this work was to reexamine these functions after 18 months in order to evaluate their progression. Methods Thirteen participants completed tests of attention, inhibitory control, verbal/visual memory, psychomotor speed, verbal fluency, visuomotor ability, executive function, semantic knowledge, and depression and anxiety inventories on 2 separate occasions. Results At baseline, the former workers indicated slower psychomotor and information processing speed, verbal spontaneous recall memory impairment, and increased depression and anxiety symptoms compared to controls (P<0.05). Paired comparisons of neuropsychological functioning within the exposed group at baseline and 1.5 years later showed poorer immediate memory performance (P<0.05). There were no differences on other measures. Conclusions Although the literature show signs of recovery of functions, the neuropsychological effects related to mercury exposure are found to persist for many years. PMID:29213549

Neuropsychological alterations in mercury intoxication persist several years after exposure.

PubMed

Zachi, Elaine Cristina; Taub, Anita; Faria, Marcília de Araújo Medrado; Ventura, Dora Fix

2008-01-01

Elemental mercury is a liquid toxic metal widely used in industry. Occupational exposure occurs mainly via inhalation. Previously, neuropsychological assessment detected deficits in former workers of a fluorescent lamp plant who had been exposed to elemental mercury vapor and were away from exposure for several years at the time of examination. The purpose of this work was to reexamine these functions after 18 months in order to evaluate their progression. Thirteen participants completed tests of attention, inhibitory control, verbal/visual memory, psychomotor speed, verbal fluency, visuomotor ability, executive function, semantic knowledge, and depression and anxiety inventories on 2 separate occasions. At baseline, the former workers indicated slower psychomotor and information processing speed, verbal spontaneous recall memory impairment, and increased depression and anxiety symptoms compared to controls (P<0.05). Paired comparisons of neuropsychological functioning within the exposed group at baseline and 1.5 years later showed poorer immediate memory performance (P<0.05). There were no differences on other measures. Although the literature show signs of recovery of functions, the neuropsychological effects related to mercury exposure are found to persist for many years.

Relationship between sports experience and executive function in 6-12-year-old children: independence from physical fitness and moderation by gender.

PubMed

Ishihara, Toru; Sugasawa, Shigemi; Matsuda, Yusuke; Mizuno, Masao

2018-05-01

The purpose of this study was to evaluate the relationship between sports experience (i.e., tennis experience) and executive function in children while controlling for physical activity and physical fitness. Sixty-eight participants (6-12 years old, 34 males and 34 females) were enrolled in regular tennis lessons (mean = 2.4 years, range = 0.1-7.3 years) prior to the study. Executive functions, including inhibitory control (the Stroop Color-Word Test), working memory (the 2-back Task), and cognitive flexibility (the Local-global Task) were evaluated. Participants' levels of daily physical activity, ranging from moderate to vigorous, were evaluated using triaxial accelerometers. The total score for physical fitness was assessed using the Tennis Field Test. Hierarchical multiple regression analyses revealed interaction effects between gender and tennis experience on participants' reaction time (RT) on the switch cost of the Local-global Task after controlling for age, BMI, gender, physical activity, physical fitness, and tennis experience. Longer tennis experience was associated with shorter switch cost in males but not in females. Higher scores on physical fitness were positively associated with lower interference scores on the Stroop Color-Word Test, RT on the 2-back Task, and RT in the switching condition of the Local-global Task, after controlling for age, BMI, gender, and physical activity. In conclusion, all three foundational components of executive function (i.e., inhibitory control, working memory, and cognitive flexibility) were more strongly related to physical fitness than to physical activity in males and females, whereas greater cognitive flexibility was related to tennis experience only in the males. © 2017 John Wiley & Sons Ltd.

Prevention of Memory Impairment and Neurotrophic Factors Increased by Lithium in Wistar Rats Submitted to Pneumococcal Meningitis Model

PubMed Central

Simões, Lutiana R.; Abreu, Roberta R. E. S.; Goularte, Jéssica A.; Collodel, Allan; Giridharan, Vijayasree Vayalanellore

2017-01-01

The aim of this study was to investigate the effects of lithium on brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glial cell line-derived neurotrophic factor (GDNF) expression in the hippocampus and on memory in experimental pneumococcal meningitis. The mood-stabilizer lithium is known as a neuroprotective agent with many effects on the brain. In this study, animals received either artificial cerebrospinal fluid or Streptococcus pneumoniae suspension at a concentration of 5 × 109 CFU/mL. Eighteen hours after induction, all animals received ceftriaxone. The animals received saline or lithium (47.5 mg/kg) or tamoxifen (1 mg/kg) as adjuvant treatment, and they were separated into six groups: control/saline, control/lithium, control/tamoxifen, meningitis/saline, meningitis/lithium, and meningitis/tamoxifen. Ten days after meningitis induction, animals were subjected to open-field habituation and the step-down inhibitory avoidance tasks. Immediately after these tasks, the animals were killed and their hippocampus was removed to evaluate the expression of BDNF, NGF, and GDNF. In the meningitis group, treatment with lithium and tamoxifen resulted in improvement in memory. Meningitis group showed decreased expression of BDNF and GDNF in the hippocampus while lithium reestablished the neurotrophin expression. Lithium was able to prevent memory impairment and reestablishes hippocampal neurotrophin expression in experimental pneumococcal meningitis. PMID:29200666

The Specific Role of Inhibition in Reading Comprehension in Good and Poor Comprehenders

ERIC Educational Resources Information Center

Borella, Erika; Carretti, Barbara; Pelegrina, Santiago

2010-01-01

Difficulties in inhibitory processes have been shown to characterize the performance of poor comprehenders. However, the inhibitory inefficiency of poor comprehenders is most often assessed by their resistance to proactive interference, that is, the ability to suppress off-goal task information from working memory (WM). In two studies tasks…

Diversity in Long-Term Synaptic Plasticity at Inhibitory Synapses of Striatal Spiny Neurons

ERIC Educational Resources Information Center

Rueda-Orozco, Pavel E.; Mendoza, Ernesto; Hernandez, Ricardo; Aceves, Jose J.; Ibanez-Sandoval, Osvaldo; Galarraga, Elvira; Bargas, Jose

2009-01-01

Procedural memories and habits are posited to be stored in the basal ganglia, whose intrinsic circuitries possess important inhibitory connections arising from striatal spiny neurons. However, no information about long-term plasticity at these synapses is available. Therefore, this work describes a novel postsynaptically dependent long-term…

Amnesia of Inhibitory Avoidance by Scopolamine Is Overcome by Previous Openfield Exposure

ERIC Educational Resources Information Center

Colettis, Natalia C.; Snitcofsky, Marina; Kornisiuk, Edgar E.; Gonzalez, Emilio N.; Quillfeldt, Jorge A.; Jerusalinsky, Diana A.

2014-01-01

The muscarinic cholinergic receptor (MAChR) blockade with scopolamine either extended or restricted to the hippocampus, before or after training in inhibitory avoidance (IA) caused anterograde or retrograde amnesia, respectively, in the rat, because there was no long-term memory (LTM) expression. Adult Wistar rats previously exposed to one or two…

Gamma Rhythm Simulations in Alzheimer's Disease

NASA Astrophysics Data System (ADS)

Montgomery, Samuel; Perez, Carlos; Ullah, Ghanim

The different neural rhythms that occur during the sleep-wake cycle regulate the brain's multiple functions. Memory acquisition occurs during fast gamma rhythms during consciousness, while slow oscillations mediate memory consolidation and erasure during sleep. At the neural network level, these rhythms are generated by the finely timed activity within excitatory and inhibitory neurons. In Alzheimer's Disease (AD) the function of inhibitory neurons is compromised due to an increase in amyloid beta (A β) leading to elevated sodium leakage from extracellular space in the hippocampus. Using a Hodgkin-Huxley formalism, heightened sodium leakage current into inhibitory neurons is observed to compromise functionality. Using a simple two neuron system it was observed that as the conductance of the sodium leakage current is increased in inhibitory neurons there is a significant decrease in spiking frequency regarding the membrane potential. This triggers a significant increase in excitatory spiking leading to aberrant network behavior similar to that seen in AD patients. The next step is to extend this model to a larger neuronal system with varying synaptic densities and conductance strengths as well as deterministic and stochastic drives.

Attenuated sensitivity to neuroactive steroids in γ-aminobutyrate type A receptor delta subunit knockout mice

PubMed Central

Mihalek, Robert M.; Banerjee, Pradeep K.; Korpi, Esa R.; Quinlan, Joseph J.; Firestone, Leonard L.; Mi, Zhi-Ping; Lagenaur, Carl; Tretter, Verena; Sieghart, Werner; Anagnostaras, Stephan G.; Sage, Jennifer R.; Fanselow, Michael S.; Guidotti, Alessandro; Spigelman, Igor; Li, Zhiwei; DeLorey, Timothy M.; Olsen, Richard W.; Homanics, Gregg E.

1999-01-01

γ-Aminobutyric acid (GABA) type A receptors mediate fast inhibitory synaptic transmission and have been implicated in responses to sedative/hypnotic agents (including neuroactive steroids), anxiety, and learning and memory. Using gene targeting technology, we generated a strain of mice deficient in the δ subunit of the GABA type A receptors. In vivo testing of various behavioral responses revealed a strikingly selective attenuation of responses to neuroactive steroids, but not to other modulatory drugs. Electrophysiological recordings from hippocampal slices revealed a significantly faster miniature inhibitory postsynaptic current decay time in null mice, with no change in miniature inhibitory postsynaptic current amplitude or frequency. Learning and memory assessed with fear conditioning were normal. These results begin to illuminate the novel contributions of the δ subunit to GABA pharmacology and sedative/hypnotic responses and behavior and provide insights into the physiology of neurosteroids. PMID:10536021

Anisomycin Infused into the Hippocampus Fails to Block "Reconsolidation" but Impairs Extinction: The Role of Re-Exposure Duration

ERIC Educational Resources Information Center

McGaugh, James L.; Steward, Oswald; Power, Ann E.; Berlau, Daniel J.

2006-01-01

Recent studies have reported new evidence consistent with the hypothesis that reactivating a memory by re-exposure to a training context destabilizes the memory and induces "reconsolidation." In the present experiments, rats' memory for inhibitory avoidance (IA) training was tested 6 h (Test 1), 2 d (Test 2), and 6 d (Test 3) after training. On…

Learning by heart-the relationship between resting vagal tone and metacognitive judgments: a pilot study.

PubMed

Meessen, Judith; Sütterlin, Stefan; Gauggel, Siegfried; Forkmann, Thomas

2018-05-23

Metacognitive awareness and resting vagally mediated heart rate variability (HRV) as a physiological trait marker of cognitive inhibitory control capacities are both associated with better well-being and seem to share a common neural basis. Executive functioning which is considered a prerequisite for delivering prospective metacognitive judgments has been found to be correlated with HRV. This pilot study addresses the question, whether metacognitive awareness and resting vagally mediated HRV are positively associated. A sample of 20 healthy participants was analyzed that completed a typical Judgment of Learning task after an electrocardiogram had been recorded. The root-mean-squares of successive differences were used to calculate vagally mediated HRV. Metacognitive awareness was measured by comparing the judgments of learning with the actual memory performance, yielding a deviation score. HRV was found to be positively correlated with metacognitive awareness. Results suggest that metacognitive abilities might relate to physiological trait markers of cognitive inhibitory control capacities. Further experimental studies are needed to investigate causal relations.

Disrupted hippocampal sharp‐wave ripple‐associated spike dynamics in a transgenic mouse model of dementia

PubMed Central

Witton, Jonathan; Staniaszek, Lydia E.; Bartsch, Ullrich; Randall, Andrew D.; Jones, Matthew W.

2015-01-01

Key points High frequency (100–250 Hz) neuronal oscillations in the hippocampus, known as sharp‐wave ripples (SWRs), synchronise the firing behaviour of groups of neurons and play a key role in memory consolidation.Learning and memory are severely compromised in dementias such as Alzheimer's disease; however, the effects of dementia‐related pathology on SWRs are unknown.The frequency and temporal structure of SWRs was disrupted in a transgenic mouse model of tauopathy (one of the major hallmarks of several dementias).Excitatory pyramidal neurons were more likely to fire action potentials in a phase‐locked manner during SWRs in the mouse model of tauopathy; conversely, inhibitory interneurons were less likely to fire phase‐locked spikes during SWRs.These findings indicate there is reduced inhibitory control of hippocampal network events and point to a novel mechanism which may underlie the cognitive impairments in this model of dementia. Abstract Neurons within the CA1 region of the hippocampus are co‐activated during high frequency (100–250 Hz) sharp‐wave ripple (SWR) activity in a manner that probably drives synaptic plasticity and promotes memory consolidation. In this study we have used a transgenic mouse model of dementia (rTg4510 mice), which overexpresses a mutant form of tau protein, to examine the effects of tauopathy on hippocampal SWRs and associated neuronal firing. Tetrodes were used to record simultaneous extracellular action potentials and local field potentials from the dorsal CA1 pyramidal cell layer of 7‐ to 8‐month‐old wild‐type and rTg4510 mice at rest in their home cage. At this age point these mice exhibit neurofibrillary tangles, neurodegeneration and cognitive deficits. Epochs of sleep or quiet restfulness were characterised by minimal locomotor activity and a low theta/delta ratio in the local field potential power spectrum. SWRs detected off‐line were significantly lower in amplitude and had an altered temporal structure in rTg4510 mice. Nevertheless, the average frequency profile and duration of the SWRs were relatively unaltered. Putative interneurons displayed significantly less temporal and phase locking to SWRs in rTg4510 mice, whilst putative pyramidal neurons showed increased temporal and phase locking to SWRs. These findings indicate there is reduced inhibitory control of hippocampal network events and point to a novel mechanism which may contribute to impairments in memory consolidation in this model of dementia. PMID:25480798

Disrupted hippocampal sharp-wave ripple-associated spike dynamics in a transgenic mouse model of dementia.

PubMed

Witton, Jonathan; Staniaszek, Lydia E; Bartsch, Ullrich; Randall, Andrew D; Jones, Matthew W; Brown, Jonathan T

2016-08-15

High frequency (100-250 Hz) neuronal oscillations in the hippocampus, known as sharp-wave ripples (SWRs), synchronise the firing behaviour of groups of neurons and play a key role in memory consolidation. Learning and memory are severely compromised in dementias such as Alzheimer's disease; however, the effects of dementia-related pathology on SWRs are unknown. The frequency and temporal structure of SWRs was disrupted in a transgenic mouse model of tauopathy (one of the major hallmarks of several dementias). Excitatory pyramidal neurons were more likely to fire action potentials in a phase-locked manner during SWRs in the mouse model of tauopathy; conversely, inhibitory interneurons were less likely to fire phase-locked spikes during SWRs. These findings indicate there is reduced inhibitory control of hippocampal network events and point to a novel mechanism which may underlie the cognitive impairments in this model of dementia. Neurons within the CA1 region of the hippocampus are co-activated during high frequency (100-250 Hz) sharp-wave ripple (SWR) activity in a manner that probably drives synaptic plasticity and promotes memory consolidation. In this study we have used a transgenic mouse model of dementia (rTg4510 mice), which overexpresses a mutant form of tau protein, to examine the effects of tauopathy on hippocampal SWRs and associated neuronal firing. Tetrodes were used to record simultaneous extracellular action potentials and local field potentials from the dorsal CA1 pyramidal cell layer of 7- to 8-month-old wild-type and rTg4510 mice at rest in their home cage. At this age point these mice exhibit neurofibrillary tangles, neurodegeneration and cognitive deficits. Epochs of sleep or quiet restfulness were characterised by minimal locomotor activity and a low theta/delta ratio in the local field potential power spectrum. SWRs detected off-line were significantly lower in amplitude and had an altered temporal structure in rTg4510 mice. Nevertheless, the average frequency profile and duration of the SWRs were relatively unaltered. Putative interneurons displayed significantly less temporal and phase locking to SWRs in rTg4510 mice, whilst putative pyramidal neurons showed increased temporal and phase locking to SWRs. These findings indicate there is reduced inhibitory control of hippocampal network events and point to a novel mechanism which may contribute to impairments in memory consolidation in this model of dementia. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Memory Retrieval Has a Dynamic Influence on the Maintenance Mechanisms That Are Sensitive to ζ-Inhibitory Peptide (ZIP).

PubMed

Levitan, David; Fortis-Santiago, Yaihara; Figueroa, Joshua A; Reid, Emily E; Yoshida, Takashi; Barry, Nicholas C; Russo, Abigail; Katz, Donald B

2016-10-12

In neuroscientists' attempts to understand the long-term storage of memory, topics of particular importance and interest are the cellular and system mechanisms of maintenance (e.g., those sensitive to ζ-inhibitory peptide, ZIP) and those induced by memory retrieval (i.e., reconsolidation). Much is known about each of these processes in isolation, but less is known concerning how they interact. It is known that ZIP sensitivity and memory retrieval share at least some molecular targets (e.g., recycling α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, AMPA, receptors to the plasma membrane); conversely, the fact that sensitivity to ZIP emerges only after consolidation ends suggests that consolidation (and by extension reconsolidation) and maintenance might be mutually exclusive processes, the onset of one canceling the other. Here, we use conditioned taste aversion (CTA) in rats, a cortically dependent learning paradigm, to test this hypothesis. First, we demonstrate that ZIP infusions into gustatory cortex begin interfering with CTA memory 43-45 h after memory acquisition-after consolidation ends. Next, we show that a retrieval trial administered after this time point interrupts the ability of ZIP to induce amnesia and that ZIP's ability to induce amnesia is reengaged only 45 h after retrieval. This pattern of results suggests that memory retrieval and ZIP-sensitive maintenance mechanisms are mutually exclusive and that the progression from one to the other are similar after acquisition and retrieval. They also reveal concrete differences between ZIP-sensitive mechanisms induced by acquisition and retrieval: the latency with which ZIP-sensitive mechanisms are expressed differ for the two processes. Memory retrieval and the molecular mechanisms that are sensitive to ζ-inhibitory peptide (ZIP) are the few manipulations that have been shown to effect memory maintenance. Although much is known about their effect on maintenance separately, it is unknown how they interact. Here, we describe a model for the interaction between memory retrieval and ZIP-sensitive mechanisms, showing that retrieval trials briefly (i.e., for 45 h) interrupt these mechanisms. ZIP sensitivity emerges across a similar time window after memory acquisition and retrieval; the maintenance mechanisms that follow acquisition and retrieval differ, however, in the latency with which the impact of ZIP is expressed. Copyright © 2016 the authors 0270-6474/16/3610654-09$15.00/0.

Aging accelerates memory extinction and impairs memory restoration in Drosophila.

PubMed

Chen, Nannan; Guo, Aike; Li, Yan

2015-05-15

Age-related memory impairment (AMI) is a phenomenon observed from invertebrates to human. Memory extinction is proposed to be an active inhibitory modification of memory, however, whether extinction is affected in aging animals remains to be elucidated. Employing a modified paradigm for studying memory extinction in fruit flies, we found that only the stable, but not the labile memory component was suppressed by extinction, thus effectively resulting in higher memory loss in aging flies. Strikingly, young flies were able to fully restore the stable memory component 3 h post extinction, while aging flies failed to do so. In conclusion, our findings reveal that both accelerated extinction and impaired restoration contribute to memory impairment in aging animals. Copyright © 2015 Elsevier Inc. All rights reserved.

Integrating impairments in reaction time and executive function using a diffusion model framework.

PubMed

Karalunas, Sarah L; Huang-Pollock, Cynthia L

2013-07-01

Using Ratcliff's diffusion model and ex-Gaussian decomposition, we directly evaluate the role individual differences in reaction time (RT) distribution components play in the prediction of inhibitory control and working memory (WM) capacity in children with and without ADHD. Children with (n = 91, [Formula: see text] age = 10.2 years, 67 % male) and without ADHD (n = 62, [Formula: see text] age = 10.6 years, 46 % male) completed four tasks of WM and a stop signal reaction time (SSRT) task. Children with ADHD had smaller WM capacities and less efficient inhibitory control. Diffusion model analyses revealed that children with ADHD had slower drift rates (v) and faster non-decision times (Ter), but there were no group differences in boundary separations (a). Similarly, using an ex-Gaussian approach, children with ADHD had larger τ values than non-ADHD controls, but did not differ in μ or σ distribution components. Drift rate mediated the association between ADHD status and performance on both inhibitory control and WM capacity. τ also mediated the ADHD-executive function impairment associations; however, models were a poorer fit to the data. Impaired performance on RT and executive functioning tasks has long been associated with childhood ADHD. Both are believed to be important cognitive mechanisms to the disorder. We demonstrate here that drift rate, or the speed at which information accumulates towards a decision, is able to explain both.

Cognitive and Emotional Factors in Children with Mathematical Learning Disabilities

ERIC Educational Resources Information Center

Passolunghi, Maria Chiara

2011-01-01

Emotional and cognitive factors were examined in 18 children with mathematical learning disabilities (MLD), compared with 18 normally achieving children, matched for chronological age, school level, gender and verbal IQ. Working memory, short-term memory, inhibitory processes, speed of processing and level of anxiety in mathematics were assessed…

Retrieval Does Not Induce Reconsolidation of Inhibitory Avoidance Memory

ERIC Educational Resources Information Center

Medina, Jorge H.; Izquierdo, Ivan; Cammarota, Martin; Bevilaqua, Lia R. M.

2004-01-01

It has been suggested that retrieval during a nonreinforced test induces reconsolidation instead of extinction of the mnemonic trace. Reconsolidation would preserve the original memory from the labilization induced by its nonreinforced recall through a hitherto uncharacterized mechanism requiring protein synthesis. Given the importance that such a…

Computational Model of a Positive BDNF Feedback Loop in Hippocampal Neurons Following Inhibitory Avoidance Training

ERIC Educational Resources Information Center

Zhang, Yili; Smolen, Paul; Alberini, Cristina M.; Baxter, Douglas A.; Byrne, John H.

2016-01-01

Inhibitory avoidance (IA) training in rodents initiates a molecular cascade within hippocampal neurons. This cascade contributes to the transition of short- to long-term memory (i.e., consolidation). Here, a differential equation-based model was developed to describe a positive feedback loop within this molecular cascade. The feedback loop begins…

A neural network model of memory and higher cognitive functions.

PubMed

Vogel, David D

2005-01-01

I first describe a neural network model of associative memory in a small region of the brain. The model depends, unconventionally, on disinhibition of inhibitory links between excitatory neurons rather than long-term potentiation (LTP) of excitatory projections. The model may be shown to have advantages over traditional neural network models both in terms of information storage capacity and biological plausibility. The learning and recall algorithms are independent of network architecture, and require no thresholds or finely graded synaptic strengths. Several copies of this local network are then connected by means of many, weak, reciprocal, excitatory projections that allow one region to control the recall of information in another to produce behaviors analogous to serial memory, classical and operant conditioning, secondary reinforcement, refabrication of memory, and fabrication of possible future events. The network distinguishes between perceived and recalled events, and can predicate its response on the absence as well as the presence of particular stimuli. Some of these behaviors are achieved in ways that seem to provide instances of self-awareness and imagination, suggesting that consciousness may emerge as an epiphenomenon in simple brains.

A systematic review of neuropsychological studies involving young binge drinkers.

PubMed

Carbia, Carina; López-Caneda, Eduardo; Corral, Montserrat; Cadaveira, Fernando

2018-07-01

Binge drinking (BD) is a public health concern with serious implications for brain development. This review is the first in which neuropsychological studies of healthy young BDs are synthesized following PRISMA guidelines. We conducted a literature search in PsycINFO, Web of Science, and PubMed. Articles were screened using strict inclusion criteria. Two authors independently assessed the methodological quality. Of the 27 studies included, 14 (52%) were of intermediate quality, 7 (26%) of poor quality and 6 (22%) of high quality. BD is associated with deficits in verbal memory and executive functions, principally poor inhibitory control. Tentatively, BD may be related to deficits in cognitive flexibility and monitoring of information in working memory. Further studies are needed to determine potential impairments in prospective memory and decision-making. BDs do not seem to show difficulties in planning, short-term memory, attention, processing speed or visuospatial construction. The evidence does not seem to support greater vulnerability in females. Future longitudinal studies should identify the characteristics of extreme trajectories, explore recovery deficits and design intervention programs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Motivation, working memory, and decision making: a cognitive-motivational theory of personality vulnerability to alcoholism.

PubMed

Finn, Peter R

2002-09-01

This article presents a cognitive-motivational theory (CMT) of the mechanisms associated with three basic dimensions of personality vulnerability to alcoholism, impulsivity/novelty seeking, harm avoidance, and excitement seeking. CMT describes the interrelationships between activity in basic motivational systems and attentional, decision-making and working memory processes as the mechanisms associated with variation in each personality trait. Impulsivity/novelty seeking reflects activity in both appetitive and inhibitory motivational systems, greater attention to reward cues, and increased emotional reactivity to reward and frustration. Harm avoidance reflects individual differences in fearfulness and activity in specific inhibitory systems. Excitement seeking reflects the need to engage in appetitive behaviors in less predictable environments to experience positive affect. CMT also describes the impact of working memory and the specific motivational processes underlying each trait dimension on the dynamics of decision making from the perspective of decision field theory.

Autobiographical memory conjunction errors in younger and older adults: Evidence for a role of inhibitory ability

PubMed Central

Devitt, Aleea L.; Tippett, Lynette; Schacter, Daniel L.; Addis, Donna Rose

2016-01-01

Because of its reconstructive nature, autobiographical memory (AM) is subject to a range of distortions. One distortion involves the erroneous incorporation of features from one episodic memory into another, forming what are known as memory conjunction errors. Healthy aging has been associated with an enhanced susceptibility to conjunction errors for laboratory stimuli, yet it is unclear whether these findings translate to the autobiographical domain. We investigated the impact of aging on vulnerability to AM conjunction errors, and explored potential cognitive processes underlying the formation of these errors. An imagination recombination paradigm was used to elicit AM conjunction errors in young and older adults. Participants also completed a battery of neuropsychological tests targeting relational memory and inhibition ability. Consistent with findings using laboratory stimuli, older adults were more susceptible to AM conjunction errors than younger adults. However, older adults were not differentially vulnerable to the inflating effects of imagination. Individual variation in AM conjunction error vulnerability was attributable to inhibitory capacity. An inability to suppress the cumulative familiarity of individual AM details appears to contribute to the heightened formation of AM conjunction errors with age. PMID:27929343

Randomized controlled trial of maternal omega-3 long-chain PUFA supplementation during pregnancy and early childhood development of attention, working memory, and inhibitory control.

PubMed

Gould, Jacqueline F; Makrides, Maria; Colombo, John; Smithers, Lisa G

2014-04-01

Docosahexaenoic acid (DHA) accumulates in the hippocampus and frontal lobes of the fetal brain during the last trimester of pregnancy. These areas of the brain contribute to attention and working memory and inhibitory control (WMIC). We evaluated the effect of maternal omega-3 (n-3) long-chain polyunsaturated fatty acid supplementation in pregnancy on child attention and WMIC. A total of 185 term-born children of mothers who were randomly allocated to consume 800 mg DHA/d (treatment) or a placebo (control) from ∼20 wk of gestation until birth were assessed with multiple measures of attention and WMIC at a mean (± SD) of 27 ± 2 mo. Primary outcomes were the average time it took to be distracted when playing with a toy (distractibility) and the accuracy of remembering a new hiding location while inhibiting a learned response to search in the previous location (WMIC). Assessments were completed by 81 children in the treatment group (mean ± SD age: 835 ± 50.4 d) and 77 children in the control group (839 ± 65.6 d). There was no effect of supplementation on primary outcomes [distractibility mean difference: -0.2 s (95% CI: -0.7, 0.4 s); WMIC mean difference: 8.9 mm (95% CI: -10.6, 28.3 mm)]. There was no difference between DHA-supplemented and control groups except that treatment-group children looked away from the toys fewer times than controls when presented with multiple toys competing for attention but less accurately remembered a repeated hiding location. These secondary effects were not consistent with any other outcomes and may have been a result of chance. Cord plasma DHA was not consistently associated with attention and WMIC. Maternal DHA supplementation during pregnancy does not enhance attention or WMIC in term-born preschoolers. The DHA for Maternal and Infant Outcomes trial was registered at www.anzctr.org.au as ACTRN1260500056906.

Musical training, bilingualism, and executive function: working memory and inhibitory control.

PubMed

D'Souza, Annalise A; Moradzadeh, Linda; Wiseheart, Melody

2018-01-01

The current study investigated whether long-term experience in music or a second language is associated with enhanced cognitive functioning. Early studies suggested the possibility of a cognitive advantage from musical training and bilingualism but have failed to be replicated by recent findings. Further, each form of expertise has been independently investigated leaving it unclear whether any benefits are specifically caused by each skill or are a result of skill learning in general. To assess whether cognitive benefits from training exist, and how unique they are to each training domain, the current study compared musicians and bilinguals to each other, plus to individuals who had expertise in both skills, or neither. Young adults ( n = 153) were categorized into one of four groups: monolingual musician; bilingual musician; bilingual non-musician; and monolingual non-musician. Multiple tasks per cognitive ability were used to examine the coherency of any training effects. Results revealed that musically trained individuals, but not bilinguals, had enhanced working memory. Neither skill had enhanced inhibitory control. The findings confirm previous associations between musicians and improved cognition and extend existing evidence to show that benefits are narrower than expected but can be uniquely attributed to music compared to another specialized auditory skill domain. The null bilingual effect despite a music effect in the same group of individuals challenges the proposition that young adults are at a performance ceiling and adds to increasing evidence on the lack of a bilingual advantage on cognition.

Conceptualizing and Measuring Working Memory and its Relationship to Aphasia

PubMed Central

Wright, Heather Harris; Fergadiotis, Gerasimos

2011-01-01

Background General agreement exists in the literature that individuals with aphasia can exhibit a working memory deficit that contributes to their language processing impairments. Though conceptualized within different working memory frameworks, researchers have suggested that individuals with aphasia have limited working memory capacity, impaired attention-control processes as well as impaired inhibitory mechanisms. However, across studies investigating working memory ability in individuals with aphasia, different measures have been used to quantify their working memory ability and identify the relationship between working memory and language performance. Aims The primary objectives of this article are to (1) review current working memory theoretical frameworks, (2) review tasks used to measure working memory, and (3) discuss findings from studies that have investigated working memory as they relate to language processing in aphasia. Main Contribution Though findings have been consistent across studies investigating working memory ability in individuals with aphasia, discussion of how working memory is conceptualized and defined is often missing, as is discussion of results within a theoretical framework. This is critical, as working memory is conceptualized differently across the different theoretical frameworks. They differ in explaining what limits capacity and the source of individual differences as well as how information is encoded, maintained, and retrieved. When test methods are considered within a theoretical framework, specific hypotheses can be tested and stronger conclusions that are less susceptible to different interpretations can be made. Conclusions Working memory ability has been investigated in numerous studies with individuals with aphasia. To better understand the underlying cognitive constructs that contribute to the language deficits exhibited by individuals with aphasia, future investigations should operationally define the cognitive constructs of interest and discuss findings within theoretical frameworks. PMID:22639480

Transgenic Mice Expressing an Inhibitory Truncated Form of p300 Exhibit Long-Term Memory Deficits

ERIC Educational Resources Information Center

Oliveira, Ana M. M.; Wood, Marcelo A.; McDonough, Conor B.; Abel, Ted

2007-01-01

The formation of many forms of long-term memory requires several molecular mechanisms including regulation of gene expression. The mechanisms directing transcription require not only activation of individual transcription factors but also recruitment of transcriptional coactivators. CBP and p300 are transcriptional coactivators that interact with…

A New Role for Attentional Corticopetal Acetylcholine in Cortical Memory Dynamics

NASA Astrophysics Data System (ADS)

Fujii, Hiroshi; Kanamaru, Takashi; Aihara, Kazuyuki; Tsuda, Ichiro

2011-09-01

Although the role of corticopetal acetylcholine (ACh) in higher cognitive functions is increasingly recognized, the questions as (1) how ACh works in attention(s), memory dynamics and cortical state transitions, and also (2) why and how loss of ACh is involved in dysfunctions such as visual hallucinations in dementia with Lewy bodies and deficit of attention(s), are not well understood. From the perspective of a dynamical systems viewpoint, we hypothesize that transient ACh released under top-down attention serves to temporarily invoke attractor-like memories, while a background level of ACh reverses this process returning the dynamical nature of the memory structure back to attractor ruins (quasi-attractors). In fact, transient ACh loosens inhibitions of py ramidal neurons (PYRs) by P V+ fas t spiking (FS) i nterneurons, while a baseline ACh recovers inhibitory actions of P V+ FS. Attentional A Ch thus dynamically modifies brain's connectivity. Th e core of this process is in the depression of GABAergic inhibitory currents in PYRs due to muscarinic (probably M2 subtype) presyn aptic effects on GABAergic synapses of PV+ FS neurons

Habitual exercise is associated with cognitive control and cognitive reappraisal success.

PubMed

Giles, Grace E; Cantelon, Julie A; Eddy, Marianna D; Brunyé, Tad T; Urry, Heather L; Mahoney, Caroline R; Kanarek, Robin B

2017-12-01

Habitual exercise is associated with enhanced domain-general cognitive control, such as inhibitory control, selective attention, and working memory, all of which rely on the frontal cortex. However, whether regular exercise is associated with more specific aspects of cognitive control, such as the cognitive control of emotion, remains relatively unexplored. The present study employed a correlational design to determine whether level of habitual exercise was related to performance on the Stroop test measuring selective attention and response inhibition, the cognitive reappraisal task measuring cognitive reappraisal success, and associated changes in prefrontal cortex (PFC) oxygenation using functional near-infrared spectroscopy. 74 individuals (24 men, 50 women, age 18-32 years) participated. Higher habitual physical activity was associated with lower Stroop interference (indicating greater inhibitory control) and enhanced cognitive reappraisal success. Higher habitual exercise was also associated with lower oxygenated hemoglobin (O 2 Hb) in the PFC in response to emotional information. However, NIRS data indicated that exercise was not associated with cognitive control-associated O 2 Hb in the PFC. Behaviorally, the findings support and extend the previous findings that habitual exercise relates to more successful cognitive control of neutral information and cognitive reappraisal of emotional information. Future research should explore whether habitual exercise exerts causal benefits to cognitive control and PFC oxygenation, as well as isolate specific cognitive control processes sensitive to change through habitual exercise.

The Role of Muscarinic and Nicotinic Cholinergic Neurotransmission in Aversive Conditioning: Comparing Pavlovian Fear Conditioning and Inhibitory Avoidance

ERIC Educational Resources Information Center

Tinsley, Matthew R.; Quinn, Jennifer J.; Fanselow, Michael S.

2004-01-01

Aversive conditioning is an ideal model for studying cholinergic effects on the processes of learning and memory for several reasons. First, deficits produced by selective lesions of the anatomical structures shown to be critical for Pavlovian fear conditioning and inhibitory avoidance (such as the amygdala and hippocampus) resemble those deficits…

A Disorder of Executive Function and Its Role in Language Processing

PubMed Central

Martin, Randi C.; Allen, Corinne M.

2014-01-01

R. Martin and colleagues have proposed separate stores for the maintenance of phonological and semantic information in short-term memory. Evidence from patients with aphasia has shown that damage to these separable buffers has specific consequences for language comprehension and production, suggesting an interdependence between language and memory systems. This article discusses recent research on aphasic patients with limited-capacity short-term memories (STMs) and reviews evidence suggesting that deficits in retaining semantic information in STM may be caused by a disorder in the executive control process of inhibition, specific to verbal representations. In contrast, a phonological STM deficit may be due to overly rapid decay. In semantic STM deficits, it is hypothesized that the inhibitory deficit produces difficulty inhibiting irrelevant verbal representations, which may lead to excessive interference. In turn, the excessive interference associated with semantic STM deficits has implications for single-word and sentence processing, and it may be the source of the reduced STM capacity shown by these patients. PMID:18720317

The Swedish Hayling task, and its relation to working memory, verbal ability, and speech-recognition-in-noise.

PubMed

Stenbäck, Victoria; Hällgren, Mathias; Lyxell, Björn; Larsby, Birgitta

2015-06-01

Cognitive functions and speech-recognition-in-noise were evaluated with a cognitive test battery, assessing response inhibition using the Hayling task, working memory capacity (WMC) and verbal information processing, and an auditory test of speech recognition. The cognitive tests were performed in silence whereas the speech recognition task was presented in noise. Thirty young normally-hearing individuals participated in the study. The aim of the study was to investigate one executive function, response inhibition, and whether it is related to individual working memory capacity (WMC), and how speech-recognition-in-noise relates to WMC and inhibitory control. The results showed a significant difference between initiation and response inhibition, suggesting that the Hayling task taps cognitive activity responsible for executive control. Our findings also suggest that high verbal ability was associated with better performance in the Hayling task. We also present findings suggesting that individuals who perform well on tasks involving response inhibition, and WMC, also perform well on a speech-in-noise task. Our findings indicate that capacity to resist semantic interference can be used to predict performance on speech-in-noise tasks. © 2015 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

[Analysis of intrusion errors in free recall].

PubMed

Diesfeldt, H F A

2017-06-01

Extra-list intrusion errors during five trials of the eight-word list-learning task of the Amsterdam Dementia Screening Test (ADST) were investigated in 823 consecutive psychogeriatric patients (87.1% suffering from major neurocognitive disorder). Almost half of the participants (45.9%) produced one or more intrusion errors on the verbal recall test. Correct responses were lower when subjects made intrusion errors, but learning slopes did not differ between subjects who committed intrusion errors and those who did not so. Bivariate regression analyses revealed that participants who committed intrusion errors were more deficient on measures of eight-word recognition memory, delayed visual recognition and tests of executive control (the Behavioral Dyscontrol Scale and the ADST-Graphical Sequences as measures of response inhibition). Using hierarchical multiple regression, only free recall and delayed visual recognition retained an independent effect in the association with intrusion errors, such that deficient scores on tests of episodic memory were sufficient to explain the occurrence of intrusion errors. Measures of inhibitory control did not add significantly to the explanation of intrusion errors in free recall, which makes insufficient strength of memory traces rather than a primary deficit in inhibition the preferred account for intrusion errors in free recall.

Involvement of hippocampal cAMP/cAMP-dependent protein kinase signaling pathways in a late memory consolidation phase of aversively motivated learning in rats

PubMed Central

Bernabeu, Ramon; Bevilaqua, Lia; Ardenghi, Patricia; Bromberg, Elke; Schmitz, Paulo; Bianchin, Marino; Izquierdo, Ivan; Medina, Jorge H.

1997-01-01

cAMP/cAMP-dependent protein kinase (PKA) signaling pathway has been recently proposed to participate in both the late phase of long term potentiation in the hippocampus and in the late, protein synthesis-dependent phase of memory formation. Here we report that a late memory consolidation phase of an inhibitory avoidance learning is regulated by an hippocampal cAMP signaling pathway that is activated, at least in part, by D1/D5 receptors. Bilateral infusion of SKF 38393 (7.5 μg/side), a D1/D5 receptor agonist, into the CA1 region of the dorsal hippocampus, enhanced retention of a step-down inhibitory avoidance when given 3 or 6 h, but not immediately (0 h) or 9 h, after training. In contrast, full retrograde amnesia was obtained when SCH 23390 (0.5 μg/side), a D1/D5 receptor antagonist, was infused into the hippocampus 3 or 6 h after training. Intrahippocampal infusion of 8Br-cAMP (1.25 μg/side), or forskolin (0.5 μg/side), an activator of adenylyl cyclase, enhanced memory when given 3 or 6 h after training. KT5720 (0.5 μg/side), a specific inhibitor of PKA, hindered memory consolidation when given immediately or 3 or 6 h posttraining. Rats submitted to the avoidance task showed learning-specific increases in hippocampal 3H-SCH 23390 binding and in the endogenous levels of cAMP 3 and 6 h after training. In addition, PKA activity and P-CREB (phosphorylated form of cAMP responsive element binding protein) immunoreactivity increased in the hippocampus immediately and 3 and 6 h after training. Together, these findings suggest that the late phase of memory consolidation of an inhibitory avoidance is modulated cAMP/PKA signaling pathways in the hippocampus. PMID:9192688

The hippocampus, medial prefrontal cortex, and selective memory retrieval: evidence from a rodent model of the retrieval-induced forgetting effect.

PubMed

Wu, Jade Q; Peters, Greg J; Rittner, Pedro; Cleland, Thomas A; Smith, David M

2014-09-01

Inhibition is an important component of many cognitive functions, including memory. For example, the retrieval-induced forgetting (RIF) effect occurs when extra practice with some items from a study list inhibits the retrieval of the nonpracticed items relative to a baseline condition that does not involve extra practice. Although counterintuitive, the RIF phenomenon may be important for resolving interference by inhibiting potentially competing retrieval targets. Neuroimaging studies suggest that the hippocampus and prefrontal cortex are involved in the RIF effect, but controlled lesion studies have not yet been performed. We developed a rodent model of the RIF training procedure and trained control rats and rats with temporary inactivation of the hippocampus or medial prefrontal cortex (mPFC). Rats were trained on a list of odor cues, presented in cups of digging medium with a buried reward, followed by additional practice trials with a subset of the cues. We then tested the rats' memories for the cues and their association with reward by presenting them with unbaited cups containing the test odorants and measuring how long they persisted in digging. Control rats exhibited a robust RIF effect in which memory for the nonpracticed odors was significantly inhibited. Thus, extra practice with some odor cues inhibited memory for the others, relative to a baseline condition that involved an identical amount of training. Inactivation of either the hippocampus or the mPFC blocked the RIF effect. We also constructed a computational model of a representational learning circuit to simulate the RIF effect. We show in this model that "sideband suppression" of similar memory representations can reproduce the RIF effect and that alteration of the suppression parameters and learning rate can reproduce the lesion effects seen in our rats. Our results suggest that the RIF effect is widespread and that inhibitory processes are an important feature of memory function. © 2014 Wiley Periodicals, Inc.

Conjugated linoleic acid-enriched butter improved memory and up-regulated phospholipase A2 encoding-genes in rat brain tissue.

PubMed

Gama, Marco A S; Raposo, Nádia R B; Mury, Fábio B; Lopes, Fernando C F; Dias-Neto, Emmanuel; Talib, Leda L; Gattaz, Wagner F

2015-10-01

Reduced phospholipase A2 (PLA2) activity has been reported in blood cells and in postmortem brains of patients with Alzheimer disease (AD), and there is evidence that conjugated linoleic acid (CLA) modulates the activity of PLA2 groups in non-brain tissues. As CLA isomers were shown to be actively incorporated and metabolized in the brains of rats, we hypothesized that feeding a diet naturally enriched in CLA would affect the activity and expression of Pla 2 -encoding genes in rat brain tissue, with possible implications for memory. To test this hypothesis, Wistar rats were trained for the inhibitory avoidance task and fed a commercial diet (control) or experimental diets containing either low CLA- or CLA-enriched butter for 4 weeks. After this period, the rats were tested for memory retrieval and killed for tissue collection. Hippocampal expression of 19 Pla 2 genes was evaluated by qPCR, and activities of PLA2 groups (cPLA2, iPLA2, and sPLA2) were determined by radioenzymatic assay. Rats fed the high CLA diet had increased hippocampal mRNA levels for specific PLA2 isoforms (iPla 2 g6γ; cPla 2 g4a, sPla 2 g3, sPla 2 g1b, and sPla 2 g12a) and higher enzymatic activity of all PLA2 groups as compared to those fed the control and the low CLA diet. The increment in PLA2 activities correlated significantly with memory enhancement, as assessed by increased latency in the step-down inhibitory avoidance task after 4 weeks of treatment (rs = 0.69 for iPLA2, P < 0.001; rs = 0.81 for cPLA2, P < 0.001; and rs = 0.69 for sPLA2, P < 0.001). In face of the previous reports showing reduced PLA2 activity in AD brains, the present findings suggest that dairy products enriched in cis-9, trans-11 CLA may be useful in the treatment of this disease.

Impact of oral supplementation of Glutamate and GABA on memory performance and neurochemical profile in hippocampus of rats.

PubMed

Tabassum, Saiqa; Ahmad, Saara; Madiha, Syeda; Khaliq, Saima; Shahzad, Sidrah; Batool, Zehra; Haider, Saida

2017-05-01

Glutamate (GLU) and gamma-amino butyric acid (GABA) are essential amino acids (AA) for brain function serving as excitatory and inhibitory neurotransmitter respectively. Their tablets are available in market for improving gut function and muscle performance. Despite of having a major role during memory formation and processing, effects of these tablets on brain functioning like learning and memory have not been investigated. Therefore, present study is aimed to investigate the effects of orally supplemented GLU and GABA on learning and memory performance and further to monitor related effects of these orally supplemented GLU and GABA on brain levels of these AA. Three groups of rats were supplemented orally with drinking water (control group) or suspension of tablets of GABA and Glutamate, respectively for four weeks. Cognitive performance was determined using behavioral tests (Novel object recognition test, Morris water maze, Passive avoidance test) measuring recognition, spatial reference and aversive memory. Levels of GLU, GABA and acetylcholine (ACh) were estimated in rat hippocampus. Results showed that chronic oral administration of GLU and GABA tablets has a significant impact on brain function and can alter GLU and GABA content in rat hippocampus. Compared to GABA, GLU supplementation specifically enhances memory performance via increasing ACh. Thus, GLU can be suggested as a useful supplement for improving learning and memory performance and neurochemical status of brain and in future could be effective in the treatment of neurological disorders affecting learning and memory performance.

B cell expression of the inhibitory Fc gamma receptor is unchanged in early MS.

PubMed

Comabella, Manuel; Montalban, Xavier; Kakalacheva, Kristina; Osman, Deeqa; Nimmerjahn, Falk; Tintoré, Mar; Lünemann, Jan D

2010-06-01

Expression of the inhibitory Fcgamma receptor IIB (FcgammaRIIB) has emerged as a late checkpoint during peripheral B cell development which prevents autoreactive memory B lymphocytes from becoming long-lived plasma cells. Decreased expression of FcgammaRIIB or non-functional FcgammaRIIB variants are associated with the development of autoimmune tissue inflammation. We determined the expression profile of FcgammaRIIB in peripheral blood cells in treatment-naïve patients with early MS. Twenty-five patients with clinically isolated syndrome (CIS) who converted to clinically definite MS (CDMS) and 25 demographically matched healthy donors were included in the study. Frequencies of peripheral blood monocytes and B cell subsets as well as FcgammaRIIB expression profile was determined by flow cytometry. FcgammaRIIB expression levels were higher in B cells compared to monocytes (p<0.0001) and higher in memory B cells compared to their naïve counterparts (p<0.0001). However, FcgammaRIIB expression in naïve and memory B cells as well as monocytes was unchanged in patients with early MS at onset of symptoms as well as after conversion to CDMS compared to controls. No significant correlations were found between FcgammaRIIB expression levels and brain MRI-derived metrics or EDSS progression during follow-up. These data indicate that FcgammaRIIB expression, a critical late B cell differentiation checkpoint preventing the occurrence of autoreactive long-lived plasma cells, is not impaired in treatment-naïve patients with MS, at least in the early phases of the disease. Copyright 2010 Elsevier B.V. All rights reserved.

A double dissociation of dorsal and ventral hippocampal function on a learning and memory task mediated by the dorso-lateral striatum.

PubMed

McDonald, Robert J; Jones, Jana; Richards, Blake; Hong, Nancy S

2006-09-01

The objectives of this research were to further delineate the neural circuits subserving proposed memory-based behavioural subsystems in the hippocampal formation. These studies were guided by anatomical evidence showing a topographical organization of the hippocampal formation. Briefly, perpendicular to the medial/lateral entorhinal cortex division there is a second system of parallel circuits that separates the dorsal and ventral hippocampus. Recent work from this laboratory has provided evidence that the hippocampus incidentally encodes a context-specific inhibitory association during acquisition of a visual discrimination task. One question that emerges from this dataset is whether the dorsal or ventral hippocampus makes a unique contribution to this newly described function. Rats with neurotoxic lesions of the dorsal or ventral hippocampus were assessed on the acquisition of the visual discrimination task. Following asymptotic performance they were given reversal training in either the same or a different context from the original training. The results showed that the context-specific inhibition effect is mediated by a circuit that includes the ventral but not the dorsal hippocampus. Results from a control procedure showed that rats with either dorso-lateral striatum damage or dorsal hippocampal lesions were impaired on a tactile/spatial discrimination. Taken together, the results represent a double dissociation of learning and memory function between the ventral and dorsal hippocampus. The formation of an incidental inhibitory association was dependent on ventral but not dorsal hippocampal circuitry, and the opposite dependence was found for the spatial component of a tactile/spatial discrimination.

Cognitive biases in binge eating disorder: the hijacking of decision making.

PubMed

Voon, Valerie

2015-12-01

Binge eating disorder (BED) is the most common of eating disorders and is characterized by excessive, out-of-control, rapid food intake. This review focuses on cognitive impairments in BED, which represent an endophenotype that mediates brain function and behavior. Here we focus on reviewing impulsivity, compulsivity, attentional biases to food cues, and executive function. Behavioral regulation in BED appears to be influenced by the context of motivationally salient food cues and the degree of obesity. Deficits in delay discounting and risk taking under ambiguity are impaired in obesity irrespective of BED status. However, in BED subjects with milder obesity, greater risk seeking under explicit probabilistic risk is observed to monetary rewards, whereas this shifts to risk aversion and enhanced delay discounting in more severe obesity. Relative to non-BED obese subjects, BED is characterized by enhanced behavioral inflexibility or compulsivity across multiple domains, with subjects selecting the same choices despite change in relevance (set shifting), being no longer rewarding (habit formation), or irrespective of outcome (perseveration). The context of food cues was associated with multiple attentional and early and late inhibitory impairments and enhanced memory bias, although BED patients also have generalized cognitive interference in working memory. These findings may help explain the phenotype of binge eating. Motivationally salient food cues provoke attentional and memory biases along with impairing response inhibitory processes. Those with BED are also more susceptible to cognitive interference and have impaired decisional impulsivity, with the tendency to inflexibly stick with the same choices irrespective of changes in context. These findings suggest critical cognitive domains that may guide therapeutic interventions.

Acute Modafinil Effects on Attention and Inhibitory Control in Methamphetamine-Dependent Humans*

PubMed Central

Dean, Andy C.; Sevak, Rajkumar J.; Monterosso, John R.; Hellemann, Gerhard; Sugar, Catherine A.; London, Edythe D.

2011-01-01

Objective: Individuals who are methamphetamine dependent exhibit higher rates of cognitive dysfunction than healthy people who do not use methamphetamine, and this dysfunction may have a negative effect on the success of behavioral treatments for the disorder. Therefore, a medication that improves cognition, such as modafinil (Provigil), may serve as a useful adjunct to behavioral treatments for methamphetamine dependence. Although cognitive-enhancing effects of modafinil have been reported in several populations, little is known about the effects of modafinil in methamphetamine-dependent individuals. We thus sought to evaluate the effects of modafinil on the cognitive performance of methamphetamine-dependent and healthy individuals. Method: Seventeen healthy subjects and 24 methamphetamine-dependent subjects participated in this randomized, double-blind, placebo-controlled, crossover study. Effects of modafinil (200 mg, single oral dose) were assessed on participants’ performance on tests of inhibitory control, working memory, and processing speed/attention. Results: Across subjects, modafinil improved performance on a test of sustained attention, with no significant improvement on any other cognitive tests. However, within the methamphetamine-dependent group only, participants with a high baseline frequency of methamphetamine use demonstrated a greater effect of modafinil on tests of inhibitory control and processing speed than those participants with low baseline use of methamphetamine. Conclusions: Although modafinil produced limited effects across all participants, methamphetamine-dependent participants with a high baseline use of methamphetamine demonstrated significant cognitive improvement on modafinil relative to those with low baseline methamphetamine use. These results add to the findings from a clinical trial that suggested that modafinil may be particularly useful in methamphetamine-dependent subjects who use the drug frequently. PMID:22051208

Mathematics Anxiety, Working Memory, and Mathematics Performance in Secondary-School Children.

PubMed

Passolunghi, Maria C; Caviola, Sara; De Agostini, Ruggero; Perin, Chiara; Mammarella, Irene C

2016-01-01

Mathematics anxiety (MA) has been defined as "a feeling of tension and anxiety that interferes with the manipulation of numbers and the solving of math problems in a wide variety of ordinary life and academic situations." Previous studies have suggested that a notable proportion of children in primary and secondary school suffer from MA, which is negatively correlated with calculation skills. The processing efficiency and attentional control theories suggest that working memory (WM) also plays an important part in such anxious feelings. The present study aimed to analyze the academic achievement and cognitive profiles of students with high math anxiety (HMA) and low math anxiety (LMA). Specifically, 32 students with HMA and 34 with LMA matched for age, gender, generalized anxiety, and vocabulary attending sixth to eighth grades were selected from a larger sample. The two groups were tested on reading decoding, reading comprehension, mathematics achievement, and on verbal short-term memory and WM. Our findings showed that HMA students were weak in several measures of mathematics achievement, but not in reading and writing skills, and that students with HMA reported lower scores on short-term memory and WM performances (with associated difficulties in inhibiting irrelevant information) than children with LMA. In addition, a logistic regression showed that weaknesses in inhibitory control and fact retrieval were the strongest variables for classifying children as having HMA or LMA.

Mathematics Anxiety, Working Memory, and Mathematics Performance in Secondary-School Children

PubMed Central

Passolunghi, Maria C.; Caviola, Sara; De Agostini, Ruggero; Perin, Chiara; Mammarella, Irene C.

2016-01-01

Mathematics anxiety (MA) has been defined as “a feeling of tension and anxiety that interferes with the manipulation of numbers and the solving of math problems in a wide variety of ordinary life and academic situations.” Previous studies have suggested that a notable proportion of children in primary and secondary school suffer from MA, which is negatively correlated with calculation skills. The processing efficiency and attentional control theories suggest that working memory (WM) also plays an important part in such anxious feelings. The present study aimed to analyze the academic achievement and cognitive profiles of students with high math anxiety (HMA) and low math anxiety (LMA). Specifically, 32 students with HMA and 34 with LMA matched for age, gender, generalized anxiety, and vocabulary attending sixth to eighth grades were selected from a larger sample. The two groups were tested on reading decoding, reading comprehension, mathematics achievement, and on verbal short-term memory and WM. Our findings showed that HMA students were weak in several measures of mathematics achievement, but not in reading and writing skills, and that students with HMA reported lower scores on short-term memory and WM performances (with associated difficulties in inhibiting irrelevant information) than children with LMA. In addition, a logistic regression showed that weaknesses in inhibitory control and fact retrieval were the strongest variables for classifying children as having HMA or LMA. PMID:26869951

On the Status of Cue Independence as a Criterion for Memory Inhibition: Evidence against the Covert Blocking Hypothesis

ERIC Educational Resources Information Center

Weller, Peter D.; Anderson, Michael C.; Gómez-Ariza, Carlos J.; Bajo, M. Teresa

2013-01-01

Retrieving memories can impair recall of other related traces. Items affected by this retrieval-induced forgetting (RIF) are often less accessible when tested with independent probes, a characteristic known as cue independence. Cue independence has been interpreted as evidence for inhibitory mechanisms that suppress competing items during…

Selective Memories: Infants' Encoding Is Enhanced in Selection via Suppression

ERIC Educational Resources Information Center

Markant, Julie; Amso, Dima

2013-01-01

The present study examined the hypothesis that inhibitory visual selection mechanisms play a vital role in memory by limiting distractor interference during item encoding. In Experiment 1a we used a modified spatial cueing task in which 9-month-old infants encoded multiple category exemplars in the contexts of an attention orienting mechanism…

Behaviorally activated mRNA expression profiles produce signatures of learning and enhanced inhibition in aged rats with preserved memory.

PubMed

Haberman, Rebecca P; Colantuoni, Carlo; Koh, Ming Teng; Gallagher, Michela

2013-01-01

Aging is often associated with cognitive decline, but many elderly individuals maintain a high level of function throughout life. Here we studied outbred rats, which also exhibit individual differences across a spectrum of outcomes that includes both preserved and impaired spatial memory. Previous work in this model identified the CA3 subfield of the hippocampus as a region critically affected by age and integral to differing cognitive outcomes. Earlier microarray profiling revealed distinct gene expression profiles in the CA3 region, under basal conditions, for aged rats with intact memory and those with impairment. Because prominent age-related deficits within the CA3 occur during neural encoding of new information, here we used microarray analysis to gain a broad perspective of the aged CA3 transcriptome under activated conditions. Behaviorally-induced CA3 expression profiles differentiated aged rats with intact memory from those with impaired memory. In the activated profile, we observed substantial numbers of genes (greater than 1000) exhibiting increased expression in aged unimpaired rats relative to aged impaired, including many involved in synaptic plasticity and memory mechanisms. This unimpaired aged profile also overlapped significantly with a learning induced gene profile previously acquired in young adults. Alongside the increased transcripts common to both young learning and aged rats with preserved memory, many transcripts behaviorally-activated in the current study had previously been identified as repressed in the aged unimpaired phenotype in basal expression. A further distinct feature of the activated profile of aged rats with intact memory is the increased expression of an ensemble of genes involved in inhibitory synapse function, which could control the phenotype of neural hyperexcitability found in the CA3 region of aged impaired rats. These data support the conclusion that aged subjects with preserved memory recruit adaptive mechanisms to retain tight control over excitability under both basal and activated conditions.

Cognitive Effects of Androgen Deprivation Therapy in Men With Advanced Prostate Cancer.

PubMed

Gunlusoy, Bulent; Ceylan, Yasin; Koskderelioglu, Aslı; Gedizlioglu, Muhtesem; Degirmenci, Tansu; Ortan, Pınar; Kozacioglu, Zafer

2017-05-01

To evaluate the prostate cancer effects of androgen deprivation therapy (ADT) by using a systematic set of methods to calculate specific cognitive functions in men with locally advanced or metastatic prostate cancer. From April 2014 to February 2016, a prospective, comparative study was done to evaluate the cognitive effects of hormone therapy. Group 1 consisted of 78 patients with locally advanced or metastatic prostate cancer who received complete ADT treatment continuously for 12 months and group 2 (control group) consisted of 78 patients who underwent radical prostatectomy without any additional treatment. The Montreal Cognitive Assessment (MoCA) test and the Frontal Assessment Battery (FAB) test with Turkish language version were used to evaluate multiple domains of cognitive function. Post-treatment results of both tests revealed that patients in group 1 achieved lower mean total scores than group 2. In MoCA test, the deficits were especially prominent in the areas of language ability and short-term memory capacity (P < .05 and P < .05). No significant differences could be identified between groups in respect to attention, executive functions, visuospatial abilities, abstract thinking, calculating abilities, and orientation. In FAB test, the deficits were especially prominent in the areas of mental flexibility and inhibitory control (P < .05 and P < .05). No significant differences could be identified between groups in conceptualization, motor series, conflicting instructions, and environmental autonomy. ADT affects cognitive functions such as language ability, short-term memory capacity, mental flexibility, and inhibitory control. Urologists should keep in mind these side effects and inform the patients and their families for the early symptoms of cognitive dysfunction. Copyright © 2017 Elsevier Inc. All rights reserved.

Time and interference: Effects on working memory.

PubMed

Botto, Marta; Palladino, Paola

2016-05-01

This study tested predictions from the time-based resource-sharing (TBRS) model with a classical verbal working memory (WM) task, where target and non-target information interfere strongly with each other. Different predictions can be formulated according to the dominant perspectives (TBRS and interference hypothesis) on the role of inhibitory control in WM task performance. Here, we aimed to trace the activation of irrelevant information, examining priming effects in a lexical decision task immediately following WM recall. Results indicate the roles of both time and interference constraints in determining task performance. In particular, the role of time available seemed crucial at the highest WM loads (i.e., 3 and 4 memoranda). These were also associated with a higher activation of no-longer-relevant information but, in this case, independently from time available for processing. © 2015 The British Psychological Society.

CB1 receptors in the formation of the different phases of memory-related processes in the inhibitory avoidance test in mice.

PubMed

Kruk-Slomka, Marta; Biala, Grażyna

2016-03-15

The endocannabinoid system, through the cannabinoid type 1 (CB1) and 2 (CB2) receptors modulates many physiological functions, including different aspects of memory-related processes. The aim of the present experiments was to explore the role of the endocannabinoid system, through CB1 receptors in the different stages of short-term (acquisition, retention and retrieval) and long-term (acquisition, consolidation and retrieval) memory-related responses, using the inhibitory avoidance (IA) test in mice. Our results revealed that an acute injection of oleamide (10 and 20mg/kg), a CB1 receptor agonist, impairs the short-term or/and long-term acquisition, retention/consolidation, retrieval memory and learning processes in the IA test in mice. In turn, in this test an acute injection of AM 251 (1 and 3mg/kg), a CB1 receptor antagonist, improves the short-term or/and long-term memory stages, described above. Moreover, this memory impairment induced by effective dose of oleamide (20mg/kg) is reversed by non-effective dose of AM 251 (0.25mg/kg) in the IA task, which proves the selectivity of oleamide to CB1 receptors and confirms that the CB1 receptor-related mechanism is one of the possible mechanisms, responsible for memory and learning responses. Obtained results provide clear evidence that the endocannabinoid system, through CB1 receptors, participates in the different stages of short- and long-term memory-related behavior. This knowledge may open in the future new possibilities for the development of CB-based therapies, especially for memory impairment human disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

Age Differences in Selective Memory of Goal-Relevant Stimuli Under Threat.

PubMed

Durbin, Kelly A; Clewett, David; Huang, Ringo; Mather, Mara

2018-02-01

When faced with threat, people often selectively focus on and remember the most pertinent information while simultaneously ignoring any irrelevant information. Filtering distractors under arousal requires inhibitory mechanisms, which take time to recruit and often decline in older age. Despite the adaptive nature of this ability, relatively little research has examined how both threat and time spent preparing these inhibitory mechanisms affect selective memory for goal-relevant information across the life span. In this study, 32 younger and 31 older adults were asked to encode task-relevant scenes, while ignoring transparent task-irrelevant objects superimposed onto them. Threat levels were increased on some trials by threatening participants with monetary deductions if they later forgot scenes that followed threat cues. We also varied the time between threat induction and a to-be-encoded scene (i.e., 2 s, 4 s, 6 s) to determine whether both threat and timing effects on memory selectivity differ by age. We found that age differences in memory selectivity only emerged after participants spent a long time (i.e., 6 s) preparing for selective encoding. Critically, this time-dependent age difference occurred under threatening, but not neutral, conditions. Under threat, longer preparation time led to enhanced memory for task-relevant scenes and greater memory suppression of task-irrelevant objects in younger adults. In contrast, increased preparation time after threat induction had no effect on older adults' scene memory and actually worsened memory suppression of task-irrelevant objects. These findings suggest that increased time to prepare top-down encoding processes benefits younger, but not older, adults' selective memory for goal-relevant information under threat. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Cognitive Dysfunction, Affective States, and Vulnerability to Nicotine Addiction: A Multifactorial Perspective

PubMed Central

Besson, Morgane; Forget, Benoît

2016-01-01

Although smoking prevalence has declined in recent years, certain subpopulations continue to smoke at disproportionately high rates and show resistance to cessation treatments. Individuals showing cognitive and affective impairments, including emotional distress and deficits in attention, memory, and inhibitory control, particularly in the context of psychiatric conditions, such as attention-deficit hyperactivity disorder, schizophrenia, and mood disorders, are at higher risk for tobacco addiction. Nicotine has been shown to improve cognitive and emotional processing in some conditions, including during tobacco abstinence. Self-medication of cognitive deficits or negative affect has been proposed to underlie high rates of tobacco smoking among people with psychiatric disorders. However, pre-existing cognitive and mood disorders may also influence the development and maintenance of nicotine dependence, by biasing nicotine-induced alterations in information processing and associative learning, decision-making, and inhibitory control. Here, we discuss the potential forms of contribution of cognitive and affective deficits to nicotine addiction-related processes, by reviewing major clinical and preclinical studies investigating either the procognitive and therapeutic action of nicotine or the putative primary role of cognitive and emotional impairments in addiction-like features. PMID:27708591

Intrahippocampal administration of an antibody against the HNK-1 carbohydrate impairs memory consolidation in an inhibitory learning task in mice.

PubMed

Strekalova, T; Wotjak, C T; Schachner, M

2001-06-01

Many cell adhesion molecules express the HNK-1 carbohydrate involved in formation and functioning of synapses. To assess its role in learning, we injected the monoclonal HNK-1 antibody or nonimmune IgG into the hippocampus of C57BL/6J mice 1 h after training in a step-down avoidance task. In animals treated with the HNK-1 antibody, latencies of step down in a recall session 48 h after injection did not change compared to training values and were significantly shorter versus IgG-treated controls, which acquired the task normally. Similar differences between the two treatments were also observed after a stronger training protocol in a step-down avoidance paradigm. The HNK-1 antibody was effective only when injected 1 h, but not 48 h after training, thus affecting memory consolidation but not memory recall itself. The HNK-1 antibody impaired memory also in tenascin-R knock-out mice, indicating that extracellular matrix molecule tenascin-R, one of the carriers of the HNK-1epitope in the hippocampus, does not mediate the function of the HNK-1 carbohydrate in this task. Our observations show that the HNK-1 carbohydrate is critically involved in memory consolidation in hippocampus-dependent learning in mammals. Copyright 2001 Academic Press.

Conflict Inhibitory Control Facilitates Pretense Quality in Young Preschoolers

PubMed Central

Van Reet, Jennifer

2013-01-01

The present research explores the role of inhibitory control in young preschoolers’ pretense ability using an ego depletion paradigm. In Experiment 1 (N = 56), children’s pretense ability was assessed either before or after participating in conflict inhibitory control or control tasks, and in Experiment 2 (N = 36), pretense ability was measured after children engaged in either conflict or delay inhibitory control tasks. In both experiments, pretense scores were significantly higher only after engaging in conflict inhibitory control tasks. Further, pretense scores were positively correlated with inhibitory control scores when conflict inhibitory control was not experienced first. This pattern of results suggests that inhibitory control may underlie pretense, and conflict inhibitory control can boost the quality of children’s subsequent pretending. PMID:26074736

Development of memory CD8+ T cells and their recall responses during blood-stage infection with Plasmodium berghei ANKA.

PubMed

Miyakoda, Mana; Kimura, Daisuke; Honma, Kiri; Kimura, Kazumi; Yuda, Masao; Yui, Katsuyuki

2012-11-01

Conditions required for establishing protective immune memory vary depending on the infecting microbe. Although the memory immune response against malaria infection is generally thought to be relatively slow to develop and can be lost rapidly, experimental evidence is insufficient. In this report, we investigated the generation, maintenance, and recall responses of Ag-specific memory CD8(+) T cells using Plasmodium berghei ANKA expressing OVA (PbA-OVA) as a model system. Mice were transferred with OVA-specific CD8(+) T (OT-I) cells and infected with PbA-OVA or control Listeria monocytogenes expressing OVA (LM-OVA). Central memory type OT-I cells were maintained for >2 mo postinfection and recovery from PbA-OVA. Memory OT-I cells produced IFN-γ as well as TNF-α upon activation and were protective against challenge with a tumor expressing OVA, indicating that functional memory CD8(+) T cells can be generated and maintained postinfection with P. berghei ANKA. Cotransfer of memory OT-I cells with naive OT-I cells to mice followed by infection with PbA-OVA or LM-OVA revealed that clonal expansion of memory OT-I cells was limited during PbA-OVA infection compared with expansion of naive OT-I cells, whereas it was more rapid during LM-OVA infection. The expression of inhibitory receptors programmed cell death-1 and LAG-3 was higher in memory-derived OT-I cells than naive-derived OT-I cells during infection with PbA-OVA. These results suggest that memory CD8(+) T cells can be established postinfection with P. berghei ANKA, but their recall responses during reinfection are more profoundly inhibited than responses of naive CD8(+) T cells.

Compensation or inhibitory failure? Testing hypotheses of age-related right frontal lobe involvement in verbal memory ability using structural and diffusion MRI

PubMed Central

Cox, Simon R.; Bastin, Mark E.; Ferguson, Karen J.; Allerhand, Mike; Royle, Natalie A.; Maniega, Susanna Muñoz; Starr, John M.; MacLullich, Alasdair M.J.; Wardlaw, Joanna M.; Deary, Ian J.; MacPherson, Sarah E.

2015-01-01

Functional neuroimaging studies report increased right prefrontal cortex (PFC) involvement during verbal memory tasks amongst low-scoring older individuals, compared to younger controls and their higher-scoring contemporaries. Some propose that this reflects inefficient use of neural resources through failure of the left PFC to inhibit non-task-related right PFC activity, via the anterior corpus callosum (CC). For others, it indicates partial compensation – that is, the right PFC cannot completely supplement the failing neural network, but contributes positively to performance. We propose that combining structural and diffusion brain MRI can be used to test predictions from these theories which have arisen from fMRI studies. We test these hypotheses in immediate and delayed verbal memory ability amongst 90 healthy older adults of mean age 73 years. Right hippocampus and left dorsolateral prefrontal cortex (DLPFC) volumes, and fractional anisotropy (FA) in the splenium made unique contributions to verbal memory ability in the whole group. There was no significant effect of anterior callosal white matter integrity on performance. Rather, segmented linear regression indicated that right DLPFC volume was a significantly stronger positive predictor of verbal memory for lower-scorers than higher-scorers, supporting a compensatory explanation for the differential involvement of the right frontal lobe in verbal memory tasks in older age. PMID:25241394

Context-Dependent Encoding of Fear and Extinction Memories in a Large-Scale Network Model of the Basal Amygdala

PubMed Central

Vlachos, Ioannis; Herry, Cyril; Lüthi, Andreas; Aertsen, Ad; Kumar, Arvind

2011-01-01

The basal nucleus of the amygdala (BA) is involved in the formation of context-dependent conditioned fear and extinction memories. To understand the underlying neural mechanisms we developed a large-scale neuron network model of the BA, composed of excitatory and inhibitory leaky-integrate-and-fire neurons. Excitatory BA neurons received conditioned stimulus (CS)-related input from the adjacent lateral nucleus (LA) and contextual input from the hippocampus or medial prefrontal cortex (mPFC). We implemented a plasticity mechanism according to which CS and contextual synapses were potentiated if CS and contextual inputs temporally coincided on the afferents of the excitatory neurons. Our simulations revealed a differential recruitment of two distinct subpopulations of BA neurons during conditioning and extinction, mimicking the activation of experimentally observed cell populations. We propose that these two subgroups encode contextual specificity of fear and extinction memories, respectively. Mutual competition between them, mediated by feedback inhibition and driven by contextual inputs, regulates the activity in the central amygdala (CEA) thereby controlling amygdala output and fear behavior. The model makes multiple testable predictions that may advance our understanding of fear and extinction memories. PMID:21437238

[Effect of electromagnetic radiation on discharge activity of neurons in the hippocampus CA1 in rats].

PubMed

Tong, Jun; Chen, Su; Liu, Xiang-Ming; Hao, Dong-Mei

2013-09-01

In order to explore effect of electromagnetic radiation on learning and memory ability of hippocampus neuron in rats, the changes in discharge patterns and overall electrical activity of hippocampus neuron after electromagnetic radiation were observed. Rat neurons discharge was recorded with glass electrode extracellular recording technology and a polygraph respectively. Radiation frequency of electromagnetic wave was 900 MHZ and the power was 10 W/m2. In glass electrode extracellular recording, the rats were separately irradiated for 10, 20, 30, 40, 50 and 60 min, every points repeated 10 times and updated interval of 1h, observing the changes in neuron discharge and spontaneous discharge patterns after electromagnetic radiation. In polygraph recording experiments, irradiation group rats for five days a week, 6 hours per day, repeatedly for 10 weeks, memory electrical changes in control group and irradiation group rats when they were feeding were repeatedly monitored by the implanted electrodes, observing the changes in peak electric digits and the largest amplitude in hippocampal CA1 area, and taking some electromagnetic radiation sampling sequence for correlation analysis. (1) Electromagnetic radiation had an inhibitory role on discharge frequency of the hippocampus CA1 region neurons. After electromagnetic radiation, discharge frequency of the hippocampus CA1 region neurons was reduced, but the changes in scale was not obvious. (2) Electromagnetic radiation might change the spontaneous discharge patterns of hippocampus CA1 region neurons, which made the explosive discharge pattern increased obviously. (3) Peak potential total number within 5 min in irradiation group was significantly reduced, the largest amplitude was less than that of control group. (4) Using mathematical method to make the correlation analysis of the electromagnetic radiation sampling sequence, that of irradiation group was less than that of control group, indicating that there was a tending to be inhibitory connection between neurons in irradiation group after electromagnetic radiation. Electromagnetic radiation may cause structure and function changes of transfer synaptic in global, make hippocampal CA1 area neurons change in the overall discharge characteristic and discharge patterns, thus lead to decrease in the ability of learning and memory.

From brain synapses to systems for learning and memory: Object recognition, spatial navigation, timed conditioning, and movement control.

PubMed

Grossberg, Stephen

2015-09-24

This article provides an overview of neural models of synaptic learning and memory whose expression in adaptive behavior depends critically on the circuits and systems in which the synapses are embedded. It reviews Adaptive Resonance Theory, or ART, models that use excitatory matching and match-based learning to achieve fast category learning and whose learned memories are dynamically stabilized by top-down expectations, attentional focusing, and memory search. ART clarifies mechanistic relationships between consciousness, learning, expectation, attention, resonance, and synchrony. ART models are embedded in ARTSCAN architectures that unify processes of invariant object category learning, recognition, spatial and object attention, predictive remapping, and eye movement search, and that clarify how conscious object vision and recognition may fail during perceptual crowding and parietal neglect. The generality of learned categories depends upon a vigilance process that is regulated by acetylcholine via the nucleus basalis. Vigilance can get stuck at too high or too low values, thereby causing learning problems in autism and medial temporal amnesia. Similar synaptic learning laws support qualitatively different behaviors: Invariant object category learning in the inferotemporal cortex; learning of grid cells and place cells in the entorhinal and hippocampal cortices during spatial navigation; and learning of time cells in the entorhinal-hippocampal system during adaptively timed conditioning, including trace conditioning. Spatial and temporal processes through the medial and lateral entorhinal-hippocampal system seem to be carried out with homologous circuit designs. Variations of a shared laminar neocortical circuit design have modeled 3D vision, speech perception, and cognitive working memory and learning. A complementary kind of inhibitory matching and mismatch learning controls movement. This article is part of a Special Issue entitled SI: Brain and Memory. Copyright © 2014 Elsevier B.V. All rights reserved.

Enhancement of fear memory by retrieval through reconsolidation

PubMed Central

Fukushima, Hotaka; Zhang, Yue; Archbold, Georgia; Ishikawa, Rie; Nader, Karim; Kida, Satoshi

2014-01-01

Memory retrieval is considered to have roles in memory enhancement. Recently, memory reconsolidation was suggested to reinforce or integrate new information into reactivated memory. Here, we show that reactivated inhibitory avoidance (IA) memory is enhanced through reconsolidation under conditions in which memory extinction is not induced. This memory enhancement is mediated by neurons in the amygdala, hippocampus, and medial prefrontal cortex (mPFC) through the simultaneous activation of calcineurin-induced proteasome-dependent protein degradation and cAMP responsive element binding protein-mediated gene expression. Interestingly, the amygdala is required for memory reconsolidation and enhancement, whereas the hippocampus and mPFC are required for only memory enhancement. Furthermore, memory enhancement triggered by retrieval utilizes distinct mechanisms to strengthen IA memory by additional learning that depends only on the amygdala. Our findings indicate that reconsolidation functions to strengthen the original memory and show the dynamic nature of reactivated memory through protein degradation and gene expression in multiple brain regions. DOI: http://dx.doi.org/10.7554/eLife.02736.001 PMID:24963141

Olfactory Interference during Inhibitory Backward Pairing in Honey Bees

PubMed Central

Dacher, Matthieu; Smith, Brian H.

2008-01-01

Background Restrained worker honey bees are a valuable model for studying the behavioral and neural bases of olfactory plasticity. The proboscis extension response (PER; the proboscis is the mouthpart of honey bees) is released in response to sucrose stimulation. If sucrose stimulation is preceded one or a few times by an odor (forward pairing), the bee will form a memory for this association, and subsequent presentations of the odor alone are sufficient to elicit the PER. However, backward pairing between the two stimuli (sucrose, then odor) has not been studied to any great extent in bees, although the vertebrate literature indicates that it elicits a form of inhibitory plasticity. Methodology/Principal Findings If hungry bees are fed with sucrose, they will release a long lasting PER; however, this PER can be interrupted if an odor is presented 15 seconds (but not 7 or 30 seconds) after the sucrose (backward pairing). We refer to this previously unreported process as olfactory interference. Bees receiving this 15 second backward pairing show reduced performance after a subsequent single forward pairing (excitatory conditioning) trial. Analysis of the results supported a relationship between olfactory interference and a form of backward pairing-induced inhibitory learning/memory. Injecting the drug cimetidine into the deutocerebrum impaired olfactory interference. Conclusions/Significance Olfactory interference depends on the associative link between odor and PER, rather than between odor and sucrose. Furthermore, pairing an odor with sucrose can lead either to association of this odor to PER or to the inhibition of PER by this odor. Olfactory interference may provide insight into processes that gate how excitatory and inhibitory memories for odor-PER associations are formed. PMID:18946512

Neural and psychological mechanisms underlying compulsive drug seeking habits and drug memories – indications for novel treatments of addiction*

PubMed Central

Everitt, Barry J

2014-01-01

This review discusses the evidence for the hypothesis that the development of drug addiction can be understood in terms of interactions between Pavlovian and instrumental learning and memory mechanisms in the brain that underlie the seeking and taking of drugs. It is argued that these behaviours initially are goal-directed, but increasingly become elicited as stimulus–response habits by drug-associated conditioned stimuli that are established by Pavlovian conditioning. It is further argued that compulsive drug use emerges as the result of a loss of prefrontal cortical inhibitory control over drug seeking habits. Data are reviewed that indicate these transitions from use to abuse to addiction depend upon shifts from ventral to dorsal striatal control over behaviour, mediated in part by serial connectivity between the striatum and midbrain dopamine systems. Only some individuals lose control over their drug use, and the importance of behavioural impulsivity as a vulnerability trait predicting stimulant abuse and addiction in animals and humans, together with consideration of an emerging neuroendophenotype for addiction are discussed. Finally, the potential for developing treatments for addiction is considered in light of the neuropsychological advances that are reviewed, including the possibility of targeting drug memory reconsolidation and extinction to reduce Pavlovian influences on drug seeking as a means of promoting abstinence and preventing relapse. PMID:24935353

Improved Digit Span in Children after a 6-Week Intervention of Playing a Musical Instrument: An Exploratory Randomized Controlled Trial

PubMed Central

Guo, Xia; Ohsawa, Chie; Suzuki, Akiko; Sekiyama, Kaoru

2018-01-01

Previous studies have reported that music training not only improves children's musical skills, but also enhances their cognitive functions. However, there is a disagreement about what domain(s) might be affected. Moreover, effects of short-term (

Improved Digit Span in Children after a 6-Week Intervention of Playing a Musical Instrument: An Exploratory Randomized Controlled Trial.

PubMed

Guo, Xia; Ohsawa, Chie; Suzuki, Akiko; Sekiyama, Kaoru

2017-01-01

Previous studies have reported that music training not only improves children's musical skills, but also enhances their cognitive functions. However, there is a disagreement about what domain(s) might be affected. Moreover, effects of short-term (

Gastrodia elata Bl. Attenuated learning deficits induced by forced-swimming stress in the inhibitory avoidance task and Morris water maze.

PubMed

Chen, Pei-Ju; Liang, Keng-Chen; Lin, Hui-Chen; Hsieh, Ching-Liang; Su, Kuan-Pin; Hung, Mei-Chu; Sheen, Lee-Yan

2011-06-01

This study adopted the forced-swimming paradigm to induce depressive symptoms in rats and evaluated the effects on learning and memory processing. Furthermore, the effects of the water extract of Gastrodia elata Bl., a well-known Chinese traditional medicine, on amnesia in rats subjected to the forced-swimming procedure were studied. Rats were subjected to the forced-swimming procedure, and the inhibitory avoidance task and Morris water maze were used to assess learning and memory performance. The acquisition of the two tasks was mostly impaired after the 15-minute forced-swimming procedure. Administration of the water extract of G. elata Bl. for 21 consecutive days at a dosage of 0.5 or 1.0 g/kg of body weight significantly improved retention in the inhibitory avoidance test, and the lower dose showed a better effect than the higher one and the antidepressant fluoxetine (18 mg/kg of body weight). In the Morris water maze, the lower dose of the water extract of G. elata Bl. significantly improved retention by shortening escape latency in the first test session and increasing the time in searching the target zone during the probe test. These findings suggest that water extracts of G. elata Bl. ameliorate the learning and memory deficits induced by forced swimming.

Evidence for the involvement of extinction-associated inhibitory learning in the forced swimming test.

PubMed

Campus, P; Colelli, V; Orsini, C; Sarra, D; Cabib, S

2015-02-01

The forced swimming test (FST) remains one of the most used tools for screening antidepressants in rodent models. Nonetheless, the nature of immobility, its main behavioral measure, is still a matter of debate. The present study took advantage of our recent finding that mice of the inbred DBA/2J strain require a functioning left dorsolateral striatum (DLS) to consolidate long-term memory of FST to test whether immobility is the outcome of stress-related learning. Infusion of the GABA-A agonist muscimol in the left DLS immediately after a single experience of FST prevented and infusion in the left or the right amygdala impaired recall of the acquired levels of immobility in a probe test performed 24h later. Post-training left DLS infusion of muscimol, at a dose capable of preventing retention of FST-induced immobility, did not influence 24h retention of inhibitory avoidance training or of the escape response acquired in a water T-maze. However, this same treatment prevented 24h retention of the extinction training of the consolidated escape response. These results indicate that a left DLS-centered memory system selectively mediates memory consolidation of FST and of escape extinction and support the hypothesis that immobility is the result of extinction-like inhibitory learning involving all available escape responses due to the inescapable/unavoidable nature of FST experience. Copyright © 2014 Elsevier B.V. All rights reserved.

Short-term memory impairment after isoflurane in mice is prevented by the α5 γ-aminobutyric acid type A receptor inverse agonist L-655,708.

PubMed

Saab, Bechara J; Maclean, Ashley J B; Kanisek, Marijana; Zurek, Agnieszka A; Martin, Loren J; Roder, John C; Orser, Beverley A

2010-11-01

Memory blockade is an essential component of the anesthetic state. However, postanesthesia memory deficits represent an undesirable and poorly understood adverse effect. Inhibitory α5 subunit-containing γ-aminobutyric acid subtype A receptors (α5GABAA) are known to play a critical role in memory processes and are highly sensitive to positive modulation by anesthetics. We postulated that inhibiting the activity of α5GABAA receptors during isoflurane anesthesia would prevent memory deficits in the early postanesthesia period. Mice were pretreated with L-655,708, an α5GABAA receptor-selective inverse agonist, or vehicle. They were then exposed to isoflurane for 1 h (1.3%, or 1 minimum alveolar concentration, or air-oxygen control). Then, either 1 or 24 h later, mice were conditioned in fear-associated contextual and cued learning paradigms. In addition, the effect of L-655,708 on the immobilizing dose of isoflurane was studied. Motor coordination, sedation, anxiety, and the concentration of isoflurane in the brain at 5 min, 1 h, and 24 h after isoflurane were also examined. Motor and sensory function recovered within minutes after termination of isoflurane administration. In contrast, a robust deficit in contextual fear memory persisted for at least 24 h. The α5GABAA receptor inverse agonist, L-655,708, completely prevented memory deficits without changing the immobilizing dose of isoflurane. Trace concentrations of isoflurane were measured in the brain 24 h after treatment. Memory deficits occurred long after the sedative, analgesic, and anxiolytic effects of isoflurane subsided. L-655,708 prevented memory deficit, suggesting that an isoflurane interaction at α5GABAA receptors contributes to memory impairment during the early postanesthesia period.

Sildenafil, a selective phosphodiesterase type 5 inhibitor, enhances memory reconsolidation of an inhibitory avoidance task in mice.

PubMed

Boccia, M M; Blake, M G; Krawczyk, M C; Baratti, C M

2011-07-07

Intracellular levels of the second messengers cAMP and cGMP are maintained through a balance between production, carried out by adenyl cyclase (AC) and guanylyl cyclase (GC), and degradation, carried out by phosphodiesterases (PDEs). Recently, PDEs have gained increased attention as potential new targets for cognition enhancement, with particular reference to phosphodiesterase type 5 (PDE5A). It is accepted that once consolidation is completed memory becomes permanent, but it has also been suggested that reactivation (memory retrieval) of the original memory makes it sensitive to the same treatments that affect memory consolidation when given after training. This new period of sensitivity coined the term reconsolidation. Sildenafil (1, 3, and 10mg/kg, ip), a cGMP-PDE5 inhibitor, facilitated retention performance of a one-trial step-through inhibitory avoidance task, when administered to CF-1 male mice immediately after retrieval. The effects of sildenafil (1mg/kg, ip) were time-dependent, long-lasting and inversely correlated with memory age. The administration of sildenafil (1mg/kg, ip) 30 min prior to the 2nd retention test did not affect retention of mice given post-retrieval injections of either vehicle or sildenafil (1mg/kg, ip). Finally, an enhancement of retention was also observed in CF-1 female mice receiving sildenafil (1mg/kg, ip) immediately, but not 180 min after retrieval. In the present paper we reported for the first time that systemic administration of sildenafil after memory reactivation enhances retention performance of the original learning. Our results indirectly point out cGMP, a component of the NO/cGMP/PKG pathway, as a necessary factor for memory reconsolidation. Copyright © 2011 Elsevier B.V. All rights reserved.

Cytokine-Induced Memory-Like Differentiation Enhances Unlicensed Natural Killer Cell Antileukemia and FcγRIIIa-Triggered Responses.

PubMed

Wagner, Julia A; Berrien-Elliott, Melissa M; Rosario, Maximillian; Leong, Jeffrey W; Jewell, Brea A; Schappe, Timothy; Abdel-Latif, Sara; Fehniger, Todd A

2017-03-01

Cytokine-induced memory-like natural killer (NK) cells differentiate after short-term preactivation with IL-12, IL-15, and IL-18 and display enhanced effector function in response to cytokines or tumor targets for weeks after the initial preactivation. Conventional NK cell function depends on a licensing signal, classically delivered by an inhibitory receptor engaging its cognate MHC class I ligand. How licensing status integrates with cytokine-induced memory-like NK cell responses is unknown. We investigated this interaction using killer cell immunoglobulin-like receptor- and HLA-genotyped primary human NK cells. Memory-like differentiation resulted in enhanced IFN-γ production triggered by leukemia targets or FcγRIIIa ligation within licensed NK cells, which exhibited the highest functionality of the NK cell subsets interrogated. IFN-γ production by unlicensed memory-like NK cells was also enhanced to a level comparable with that of licensed control NK cells. Mechanistically, differences in responses to FcγRIIIa-based triggering were not explained by alterations in key signaling intermediates, indicating that the underlying biology of memory-like NK cells is distinct from that of adaptive NK cells in human cytomegalovirus-positive individuals. Additionally, memory-like NK cells responded robustly to cytokine receptor restimulation with no impact of licensing status. These results demonstrate that both licensed and unlicensed memory-like NK cell populations have enhanced functionality, which may be translated to improve leukemia immunotherapy. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Do Children with Better Inhibitory Control Donate More? Differentiating between Early and Middle Childhood and Cool and Hot Inhibitory Control.

PubMed

Hao, Jian

2017-01-01

Inhibitory control may play an important part in prosocial behavior, such as donating behavior. However, it is not clear at what developmental stage inhibitory control becomes associated with donating behavior and which aspects of inhibitory control are related to donating behavior during development in early to middle childhood. The present study aimed to clarify these issues with two experiments. In Experiment 1, 103 3- to 5-year-old preschoolers completed cool (Stroop-like) and hot (delay of gratification) inhibitory control tasks and a donating task. The results indicated that there were no relationships between cool or hot inhibitory control and donating behavior in the whole group and each age group of the preschoolers. In Experiment 2, 140 elementary school children in Grades 2, 4, and 6 completed cool (Stroop-like) and hot (delay of gratification) inhibitory control tasks and a donating task. The results showed that inhibitory control was positively associated with donating behavior in the whole group. Cool and hot inhibitory control respectively predicted donating behavior in the second and sixth graders. Therefore, the present study reveals that donating behavior increasingly relies on specific inhibitory control, i.e., hot inhibitory control as children grow in middle childhood.

Amnesia of inhibitory avoidance by scopolamine is overcome by previous open-field exposure

PubMed Central

Colettis, Natalia C.; Snitcofsky, Marina; Kornisiuk, Edgar E.; Gonzalez, Emilio N.; Quillfeldt, Jorge A.

2014-01-01

The muscarinic cholinergic receptor (MAChR) blockade with scopolamine either extended or restricted to the hippocampus, before or after training in inhibitory avoidance (IA) caused anterograde or retrograde amnesia, respectively, in the rat, because there was no long-term memory (LTM) expression. Adult Wistar rats previously exposed to one or two open-field (OF) sessions of 3 min each (habituated), behaved as control animals after a weak though over-threshold training in IA. However, after OF exposure, IA LTM was formed and expressed in spite of an extensive or restricted to the hippocampus MAChR blockade. It was reported that during and after OF exposure and reexposure there was an increase in both hippocampal and cortical ACh release that would contribute to “prime the substrate,” e.g., by lowering the synaptic threshold for plasticity, leading to LTM consolidation. In the frame of the “synaptic tagging and capture” hypothesis, plasticity-related proteins synthesized during/after the previous OF could facilitate synaptic plasticity for IA in the same structure. However, IA anterograde amnesia by hippocampal protein synthesis inhibition with anisomycin was also prevented by two OF exposures, strongly suggesting that there would be alternative interpretations for the role of protein synthesis in memory formation and that another structure could also be involved in this “OF effect.” PMID:25322799

BTLA interaction with HVEM expressed on CD8(+) T cells promotes survival and memory generation in response to a bacterial infection.

PubMed

Steinberg, Marcos W; Huang, Yujun; Wang-Zhu, Yiran; Ware, Carl F; Cheroutre, Hilde; Kronenberg, Mitchell

2013-01-01

The B and T lymphocyte attenuator (BTLA) is an Ig super family member that binds to the herpes virus entry mediator (HVEM), a TNF receptor super family (TNFRSF) member. Engagement of BTLA by HVEM triggers inhibitory signals, although recent evidence indicates that BTLA also may act as an activating ligand for HVEM. In this study, we reveal a novel role for the BTLA-HVEM pathway in promoting the survival of activated CD8(+) T cells in the response to an oral microbial infection. Our data show that both BTLA- and HVEM-deficient mice infected with Listeria monocytogenes had significantly reduced numbers of primary effector and memory CD8(+) T cells, despite normal proliferation and expansion compared to controls. In addition, blockade of the BTLA-HVEM interaction early in the response led to significantly reduced numbers of antigen-specific CD8(+) T cells. HVEM expression on the CD8(+) T cells as well as BTLA expression on a cell type other than CD8(+) T lymphocytes, was required. Collectively, our data demonstrate that the function of the BTLA-HVEM pathway is not limited to inhibitory signaling in T lymphocytes, and instead, that BTLA can provide crucial, HVEM-dependent signals that promote survival of antigen activated CD8(+) T cell during bacterial infection.

The specific role of inhibition in reading comprehension in good and poor comprehenders.

PubMed

Borella, Erika; Carretti, Barbara; Pelegrina, Santiago

2010-01-01

Difficulties in inhibitory processes have been shown to characterize the performance of poor comprehenders. However, the inhibitory inefficiency of poor comprehenders is most often assessed by their resistance to proactive interference, that is, the ability to suppress off-goal task information from working memory (WM). In two studies tasks assessing resistance to proactive interference (intrusion errors), response to distracters (Text With Distracters task) and prepotent response inhibition (Stroop and Hayling tests), along with WM measures, were administered to children aged 10 to 11, both good and poor comprehenders. The aim of the study was to specifically determine whether general or specific inhibitory factors affect poor comprehenders' reading difficulties. Results showed that poor comprehenders, compared to good ones, are impaired in WM tasks and in inhibitory tasks that assess resistance to proactive interference. This suggests that reading comprehension difficulties of poor comprehenders are related to specific inhibitory problems.

Systemic Sclerosis Patients Present Alterations in the Expression of Molecules Involved in B-Cell Regulation

PubMed Central

Soto, Lilian; Ferrier, Ashley; Aravena, Octavio; Fonseca, Elianet; Berendsen, Jorge; Biere, Andrea; Bueno, Daniel; Ramos, Verónica; Aguillón, Juan Carlos; Catalán, Diego

2015-01-01

The activation threshold of B cells is tightly regulated by an array of inhibitory and activator receptors in such a way that disturbances in their expression can lead to the appearance of autoimmunity. The aim of this study was to evaluate the expression of activating and inhibitory molecules involved in the modulation of B cell functions in transitional, naive, and memory B-cell subpopulations from systemic sclerosis patients. To achieve this, blood samples were drawn from 31 systemic sclerosis patients and 53 healthy individuals. Surface expression of CD86, MHC II, CD19, CD21, CD40, CD22, Siglec 10, CD35, and FcγRIIB was determined by flow cytometry. IL-10 production was evaluated by intracellular flow cytometry from isolated B cells. Soluble IL-6 and IL-10 levels were measured by ELISA from supernatants of stimulated B cells. Systemic sclerosis patients exhibit an increased frequency of transitional and naive B cells related to memory B cells compared with healthy controls. Transitional and naive B cells from patients express higher levels of CD86 and FcγRIIB than healthy donors. Also, B cells from patients show high expression of CD19 and CD40, whereas memory cells from systemic sclerosis patients show reduced expression of CD35. CD19 and CD35 expression levels associate with different autoantibody profiles. IL-10+ B cells and secreted levels of IL-10 were markedly reduced in patients. In conclusion, systemic sclerosis patients show alterations in the expression of molecules involved in B-cell regulation. These abnormalities may be determinant in the B-cell hyperactivation observed in systemic sclerosis. PMID:26483788

The addicted human brain viewed in the light of imaging studies: brain circuits and treatment strategies.

PubMed

Volkow, Nora D; Fowler, Joanna S; Wang, Gene-Jack

2004-01-01

Imaging studies have provided evidence of how the human brain changes as an individual becomes addicted. Here, we integrate the findings from imaging studies to propose a model of drug addiction. The process of addiction is initiated in part by the fast and high increases in DA induced by drugs of abuse. We hypothesize that this supraphysiological effect of drugs trigger a series of adaptations in neuronal circuits involved in saliency/reward, motivation/drive, memory/conditioning, and control/disinhibition, resulting in an enhanced (and long lasting) saliency value for the drug and its associated cues at the expense of decreased sensitivity for salient events of everyday life (including natural reinforcers). Although acute drug intake increases DA neurotransmission, chronic drug consumption results in a marked decrease in DA activity, associated with, among others, dysregulation of the orbitofrontal cortex (region involved with salience attribution) and cingulate gyrus (region involved with inhibitory control). The ensuing increase in motivational drive for the drug, strengthened by conditioned responses and the decrease in inhibitory control favors emergence of compulsive drug taking. This view of how drugs of abuse affect the brain suggests strategies for intervention, which might include: (a) those that will decrease the reward value of the drug of choice; (b) interventions to increase the saliency value of non-drug reinforcers; (c) approaches to weaken conditioned drug behaviors; and (d) methods to strengthen frontal inhibitory and executive control. Though this model focuses mostly on findings from PET studies of the brain DA system it is evident that other neurotransmitters are involved and that a better understanding of their roles in addiction would expand the options for therapeutic targets.

Enhancement of Inhibitory Avoidance and Conditioned Taste Aversion Memory With Insular Cortex Infusions of 8-Br-cAMP: Involvement of the Basolateral Amygdala

PubMed Central

Miranda, María I.; McGaugh, James L.

2004-01-01

There is considerable evidence that in rats, the insular cortex (IC) and amygdala are involved in the learning and memory of aversively motivated tasks. The present experiments examined the effects of 8-Br-cAMP, an analog of cAMP, and oxotremorine, a muscarinic agonist, infused into the IC after inhibitory avoidance (IA) training and during the acquisition/consolidation of conditioned taste aversion (CTA). Posttraining infusion into the IC of 0.3 μg oxotremorine and 1.25 μg 8-Br-cAMP enhanced IA retention. Infusions of 8-Br-cAMP, but not oxotremorine, into the IC enhanced taste aversion. The experiments also examined whether noradrenergic activity in the basolateral amygdala (BLA) is critical in enabling the enhancement of CTA and IA memory induced by drug infusions administered into the IC. For both CTA and IA, ipsilateral infusions of β-adrenergic antagonist propranolol administered into the BLA blocked the retention-enhancing effect of 8-Br-cAMP or oxotremorine infused into the IC. These results indicate that the IC is involved in the consolidation of memory for both IA and CTA, and this effect requires intact noradrenergic activity into the BLA. These findings provide additional evidence that the BLA interacts with other brain regions, including sensory cortex, in modulating memory consolidation. PMID:15169861

The BACHD Rat Model of Huntington Disease Shows Signs of Fronto-Striatal Dysfunction in Two Operant Conditioning Tests of Short-Term Memory.

PubMed

Clemensson, Erik Karl Håkan; Clemensson, Laura Emily; Riess, Olaf; Nguyen, Huu Phuc

2017-01-01

The BACHD rat is a recently developed transgenic animal model of Huntington disease, a progressive neurodegenerative disorder characterized by extensive loss of striatal neurons. Cognitive impairments are common among patients, and characterization of similar deficits in animal models of the disease is therefore of interest. The present study assessed the BACHD rats' performance in the delayed alternation and the delayed non-matching to position test, two Skinner box-based tests of short-term memory function. The transgenic rats showed impaired performance in both tests, indicating general problems with handling basic aspects of the tests, while short-term memory appeared to be intact. Similar phenotypes have been found in rats with fronto-striatal lesions, suggesting that Huntington disease-related neuropathology might be present in the BACHD rats. Further analyses indicated that the performance deficit in the delayed alternation test might be due to impaired inhibitory control, which has also been implicated in Huntington disease patients. The study ultimately suggests that the BACHD rats might suffer from neuropathology and cognitive impairments reminiscent of those of Huntington disease patients.

Requirement of NF-kappa B Activation in Different Mice Brain Areas during Long-Term Memory Consolidation in Two Contextual One-Trial Tasks with Opposing Valences

PubMed Central

Salles, Angeles; Krawczyk, Maria del C.; Blake, Mariano; Romano, Arturo; Boccia, Mariano M.; Freudenthal, Ramiro

2017-01-01

NF-kappa B is a transcription factor whose activation has been shown to be necessary for long-term memory consolidation in several species. NF-kappa B is activated and translocates to the nucleus of cells in a specific temporal window during consolidation. Our work focuses on a one trial learning tasks associated to the inhibitory avoidance (IA) setting. Mice were trained either receiving or not a footshock when entering a dark compartment (aversive vs. appetitive learning). Regardless of training condition (appetitive or aversive), latencies to step-through during testing were significantly different to those measured during training. Additionally, these testing latencies were also different from those of a control group that only received a shock unrelated to context. Moreover, nuclear NF-kappa B DNA-binding activity was augmented in the aversive and the appetitive tasks when compared with control and naïve animals. NF-kappa B inhibition by Sulfasalazine injected either in the Hippocampus, Amygdala or Nucleus accumbens immediately after training was able to impair retention in both training versions. Our results suggest that NF-kappa B is a critical molecular step, in different brain areas on memory consolidation. This was the case for both the IA task and also the modified version of the same task where the footshock was omitted during training. This work aims to further investigate how appetitive and aversive memories are consolidated. PMID:28439227

Indomethacin counteracts the effects of chronic social defeat stress on emotional but not recognition memory in mice.

PubMed

Duque, Aránzazu; Vinader-Caerols, Concepción; Monleón, Santiago

2017-01-01

We have previously observed the impairing effects of chronic social defeat stress (CSDS) on emotional memory in mice. Given the relation between stress and inflammatory processes, we sought to study the effectiveness of the anti-inflammatory indomethacin in reversing the detrimental effects of CSDS on emotional memory in mice. The effects of CSDS and indomethacin on recognition memory were also evaluated. Male CD1 mice were randomly divided into four groups: non-stressed + saline (NS+SAL); non-stressed + indomethacin (NS+IND); stressed + saline (S+SAL); and stressed + indomethacin (S+IND). Stressed animals were exposed to a daily 10 min agonistic confrontation (CSDS) for 20 days. All subjects were treated daily with saline or indomethacin (10 mg/kg, i.p.). 24 h after the CSDS period, all the mice were evaluated in a social interaction test to distinguish between those that were resilient or susceptible to social stress. All subjects (n = 10-12 per group) were then evaluated in inhibitory avoidance (IA), novel object recognition (NOR), elevated plus maze and hot plate tests. As in control animals (NS+SAL group), IA learning was observed in the resilient groups, as well as in the susceptible mice treated with indomethacin (S+IND group). Recognition memory was observed in the non-stressed and the resilient mice, but not in the susceptible animals. Also, stressed mice exhibited higher anxiety levels. No significant differences were observed in locomotor activity or analgesia. In conclusion, CSDS induces anxiety in post-pubertal mice and impairs emotional and recognition memory in the susceptible subjects. The effects of CSDS on emotional memory, but not on recognition memory and anxiety, are reversed by indomethacin. Moreover, memory impairment is not secondary to the effects of CSDS on locomotor activity, emotionality or pain sensitivity.

Indomethacin counteracts the effects of chronic social defeat stress on emotional but not recognition memory in mice

PubMed Central

Duque, Aránzazu; Vinader-Caerols, Concepción

2017-01-01

We have previously observed the impairing effects of chronic social defeat stress (CSDS) on emotional memory in mice. Given the relation between stress and inflammatory processes, we sought to study the effectiveness of the anti-inflammatory indomethacin in reversing the detrimental effects of CSDS on emotional memory in mice. The effects of CSDS and indomethacin on recognition memory were also evaluated. Male CD1 mice were randomly divided into four groups: non-stressed + saline (NS+SAL); non-stressed + indomethacin (NS+IND); stressed + saline (S+SAL); and stressed + indomethacin (S+IND). Stressed animals were exposed to a daily 10 min agonistic confrontation (CSDS) for 20 days. All subjects were treated daily with saline or indomethacin (10 mg/kg, i.p.). 24 h after the CSDS period, all the mice were evaluated in a social interaction test to distinguish between those that were resilient or susceptible to social stress. All subjects (n = 10–12 per group) were then evaluated in inhibitory avoidance (IA), novel object recognition (NOR), elevated plus maze and hot plate tests. As in control animals (NS+SAL group), IA learning was observed in the resilient groups, as well as in the susceptible mice treated with indomethacin (S+IND group). Recognition memory was observed in the non-stressed and the resilient mice, but not in the susceptible animals. Also, stressed mice exhibited higher anxiety levels. No significant differences were observed in locomotor activity or analgesia. In conclusion, CSDS induces anxiety in post-pubertal mice and impairs emotional and recognition memory in the susceptible subjects. The effects of CSDS on emotional memory, but not on recognition memory and anxiety, are reversed by indomethacin. Moreover, memory impairment is not secondary to the effects of CSDS on locomotor activity, emotionality or pain sensitivity. PMID:28278165

Protein kinase M ζ and the maintenance of long-term memory.

PubMed

Zhang, Yang; Zong, Wei; Zhang, Lei; Ma, Yuanye; Wang, Jianhong

2016-10-01

Although various molecules have been found to mediate the processes of memory acquisition and consolidation, the molecular mechanism to maintain memory still remains elusive. In recent years, a molecular pathway focusing on protein kinase Mζ (PKMζ) has become of interest to researchers because of its potential role in long-term memory maintenance. PKMζ is an isoform of protein kinase C (PKC) and has a related structure that influences its function in maintaining memory. Considerable evidence has been gathered on PKMζ activity, including loss of function studies using PKMζ inhibitors, such as PKMζ inhibitory peptide (ZIP), suggesting PKMζ plays an important role in long-term memory maintenance. This review provides an overview of the role of PKMζ in long-term memory and outlines the molecular structure of PKMζ, the molecular mechanism of PKMζ in long-term memory maintenance and future directions of PKMζ research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Adenosine A(2A) receptors are necessary and sufficient to trigger memory impairment in adult mice.

PubMed

Pagnussat, N; Almeida, A S; Marques, D M; Nunes, F; Chenet, G C; Botton, P H S; Mioranzza, S; Loss, C M; Cunha, R A; Porciúncula, L O

2015-08-01

Caffeine (a non-selective adenosine receptor antagonist) prevents memory deficits in aging and Alzheimer's disease, an effect mimicked by adenosine A2 A receptor, but not A1 receptor, antagonists. Hence, we investigated the effects of adenosine receptor agonists and antagonists on memory performance and scopolamine-induced memory impairment in mice. We determined whether A2 A receptors are necessary for the emergence of memory impairments induced by scopolamine and whether A2 A receptor activation triggers memory deficits in naïve mice, using three tests to assess short-term memory, namely the object recognition task, inhibitory avoidance and modified Y-maze. Scopolamine (1.0 mg·kg(-1) , i.p.) impaired short-term memory performance in all three tests and this scopolamine-induced amnesia was prevented by the A2 A receptor antagonist (SCH 58261, 0.1-1.0 mg·kg(-1) , i.p.) and by the A1 receptor antagonist (DPCPX, 0.2-5.0 mg·kg(-1) , i.p.), except in the modified Y-maze where only SCH58261 was effective. Both antagonists were devoid of effects on memory or locomotion in naïve rats. Notably, the activation of A2 A receptors with CGS 21680 (0.1-0.5 mg·kg(-1) , i.p.) before the training session was sufficient to trigger memory impairment in the three tests in naïve mice, and this effect was prevented by SCH 58261 (1.0 mg·kg(-1) , i.p.). Furthermore, i.c.v. administration of CGS 21680 (50 nmol) also impaired recognition memory in the object recognition task. These results show that A2 A receptors are necessary and sufficient to trigger memory impairment and further suggest that A1 receptors might also be selectively engaged to control the cholinergic-driven memory impairment. © 2015 The British Pharmacological Society.

Self-restraint spillover: Inhibitory control disrupts appetite regulation among ruminators.

PubMed

Schlinkert, Caroline; Koole, Sander L

2017-10-23

People can use inhibitory control to temporarily inhibit their personal preferences to achieve their long-term goals. According to the ego fixation model (Koole et al., 2014), ruminators have difficulties relaxing inhibitory control, leading them to continue inhibiting their personal needs, even when this is no longer required by the situation. Inhibitory control may thus disrupt healthy appetite regulation among ruminators. Among 324 Dutch undergraduate students (218 women; M age  = 21.5), different inhibitory control states were manipulated by varying whether or not participants exerted inhibitory control (Study 1) or priming high versus low inhibitory control (Study 2). All participants then performed a food-tasting task. Healthy appetite regulation was defined as a positive correlation between level of food deprivation and preference for high-calorie foods. For taste ratings, the interaction between inhibitory control and rumination was significant in each study: Inhibitory control disrupted healthy appetite regulation in taste preferences among ruminators, but not among non-ruminators. For eating behavior, the same interaction effect was significant when the two studies were combined. Inhibitory control disrupts healthy appetite regulation among ruminators. These findings suggest the need for caution in interventions that rely on inhibitory control, especially among samples with compulsive thought tendencies. © 2017 Wiley Periodicals, Inc.

The neural substrates of memory suppression: a FMRI exploration of directed forgetting.

PubMed

Bastin, Christine; Feyers, Dorothée; Majerus, Steve; Balteau, Evelyne; Degueldre, Christian; Luxen, André; Maquet, Pierre; Salmon, Eric; Collette, Fabienne

2012-01-01

The directed forgetting paradigm is frequently used to determine the ability to voluntarily suppress information. However, little is known about brain areas associated with information to forget. The present study used functional magnetic resonance imaging to determine brain activity during the encoding and retrieval phases of an item-method directed forgetting recognition task with neutral verbal material in order to apprehend all processing stages that information to forget and to remember undergoes. We hypothesized that regions supporting few selective processes, namely recollection and familiarity memory processes, working memory, inhibitory and selection processes should be differentially activated during the processing of to-be-remembered and to-be-forgotten items. Successful encoding and retrieval of items to remember engaged the entorhinal cortex, the hippocampus, the anterior medial prefrontal cortex, the left inferior parietal cortex, the posterior cingulate cortex and the precuneus; this set of regions is well known to support deep and associative encoding and retrieval processes in episodic memory. For items to forget, encoding was associated with higher activation in the right middle frontal and posterior parietal cortex, regions known to intervene in attentional control. Items to forget but nevertheless correctly recognized at retrieval yielded activation in the dorsomedial thalamus, associated with familiarity-based memory processes and in the posterior intraparietal sulcus and the anterior cingulate cortex, involved in attentional processes.

The hippocampo-amygdala control of contextual fear expression is affected in a model of intellectual disability.

PubMed

Zhang, Chun-Lei; Houbaert, Xander; Lepleux, Marilyn; Deshors, Melissa; Normand, Elisabeth; Gambino, Frédéric; Herzog, Etienne; Humeau, Yann

2015-11-01

The process of learning mainly depends on the ability to store new information, while the ability to retrieve this information and express appropriate behaviors are also crucial for the adaptation of individuals to environmental cues. Thereby, all three components contribute to the cognitive fitness of an individual. While a lack of behavioral adaptation is a recurrent trait of intellectually disabled patients, discriminating between memory formation, memory retrieval or behavioral expression deficits is not easy to establish. Here, we report some deficits in contextual fear behavior in knockout mice for the intellectual disability gene Il1rapl1. Functional in vivo experiments revealed that the lack of conditioned response resulted from a local inhibitory to excitatory (I/E) imbalance in basolateral amygdala (BLA) consecutive to a loss of excitatory drive onto BLA principal cells by caudal hippocampus axonal projections. A normalization of the fear behavior was obtained in adult mutant mice following opsin-based in vivo synaptic priming of hippocampo-BLA synapses in adult il1rapl1 knockout mice, indicating that synaptic efficacy at hippocampo-BLA projections is crucial for contextual fear memory expression. Importantly, because this restoration was obtained after the learning phase, our results suggest that some of the genetically encoded cognitive deficits in humans may originate from a lack of restitution of genuinely formed memories rather than an exclusive inability to store new memories.

Optogenetic dissection of medial prefrontal cortex circuitry

PubMed Central

Riga, Danai; Matos, Mariana R.; Glas, Annet; Smit, August B.; Spijker, Sabine; Van den Oever, Michel C.

2014-01-01

The medial prefrontal cortex (mPFC) is critically involved in numerous cognitive functions, including attention, inhibitory control, habit formation, working memory and long-term memory. Moreover, through its dense interconnectivity with subcortical regions (e.g., thalamus, striatum, amygdala and hippocampus), the mPFC is thought to exert top-down executive control over the processing of aversive and appetitive stimuli. Because the mPFC has been implicated in the processing of a wide range of cognitive and emotional stimuli, it is thought to function as a central hub in the brain circuitry mediating symptoms of psychiatric disorders. New optogenetics technology enables anatomical and functional dissection of mPFC circuitry with unprecedented spatial and temporal resolution. This provides important novel insights in the contribution of specific neuronal subpopulations and their connectivity to mPFC function in health and disease states. In this review, we present the current knowledge obtained with optogenetic methods concerning mPFC function and dysfunction and integrate this with findings from traditional intervention approaches used to investigate the mPFC circuitry in animal models of cognitive processing and psychiatric disorders. PMID:25538574

Optogenetic dissection of medial prefrontal cortex circuitry.

PubMed

Riga, Danai; Matos, Mariana R; Glas, Annet; Smit, August B; Spijker, Sabine; Van den Oever, Michel C

2014-01-01

The medial prefrontal cortex (mPFC) is critically involved in numerous cognitive functions, including attention, inhibitory control, habit formation, working memory and long-term memory. Moreover, through its dense interconnectivity with subcortical regions (e.g., thalamus, striatum, amygdala and hippocampus), the mPFC is thought to exert top-down executive control over the processing of aversive and appetitive stimuli. Because the mPFC has been implicated in the processing of a wide range of cognitive and emotional stimuli, it is thought to function as a central hub in the brain circuitry mediating symptoms of psychiatric disorders. New optogenetics technology enables anatomical and functional dissection of mPFC circuitry with unprecedented spatial and temporal resolution. This provides important novel insights in the contribution of specific neuronal subpopulations and their connectivity to mPFC function in health and disease states. In this review, we present the current knowledge obtained with optogenetic methods concerning mPFC function and dysfunction and integrate this with findings from traditional intervention approaches used to investigate the mPFC circuitry in animal models of cognitive processing and psychiatric disorders.

Effect of Preschool Working Memory, Language, and Narrative Abilities on Inferential Comprehension at School-Age in Children with Spina Bifida Myelomeningocele and Typically Developing Children

PubMed Central

Pike, Meredith; Swank, Paul; Taylor, Heather; Landry, Susan; Barnes, Marcia A.

2014-01-01

Children with spina bifida myelomeningocele (SBM) are more likely to display a pattern of good-decoding/poor comprehension than their neurologically intact peers. The goals of the current study were to (1) examine the cognitive origins of one of the component skills of comprehension, bridging inferences, from a developmental perspective and (2) to test the effects of those relations on reading comprehension achievement. Data from a sample of children with SBM and a control group (n = 78) who participated in a longitudinal study were taken from age 36-month and 9.5-year time points. A multiple mediation model provided evidence that three preschool cognitive abilities (working memory/inhibitory control, oral comprehension, narrative recall), could partially explain the relation between group and bridging inference skill. A second mediation model supported that each of the 36-month abilities had an indirect effect on reading comprehension through bridging inference skill. Findings contribute to an understanding of both typical and atypical comprehension development, blending theories from the developmental, cognitive, and neuropsychological literature. PMID:23388065

Effect of preschool working memory, language, and narrative abilities on inferential comprehension at school-age in children with spina bifida myelomeningocele and typically developing children.

PubMed

Pike, Meredith; Swank, Paul; Taylor, Heather; Landry, Susan; Barnes, Marcia A

2013-04-01

Children with spina bifida myelomeningocele (SBM) are more likely to display a pattern of good-decoding/poor comprehension than their neurologically intact peers. The goals of the current study were to (1) examine the cognitive origins of one of the component skills of comprehension, bridging inferences, from a developmental perspective and (2) to test the effects of those relations on reading comprehension achievement. Data from a sample of children with SBM and a control group (n = 78) who participated in a longitudinal study were taken from age 36-month and 9.5-year time points. A multiple mediation model provided evidence that three preschool cognitive abilities (working memory/inhibitory control, oral comprehension, narrative recall), could partially explain the relation between group and bridging inference skill. A second mediation model supported that each of the 36-month abilities had an indirect effect on reading comprehension through bridging inference skill. Findings contribute to an understanding of both typical and atypical comprehension development, blending theories from the developmental, cognitive, and neuropsychological literature.

A systematic review of the relationship between eating, weight and inhibitory control using the stop signal task.

PubMed

Bartholdy, Savani; Dalton, Bethan; O'Daly, Owen G; Campbell, Iain C; Schmidt, Ulrike

2016-05-01

Altered inhibitory control (response inhibition, reward-based inhibition, cognitive inhibition, reversal learning) has been implicated in eating disorders (EDs) and obesity. It is unclear, however, how different types of inhibitory control contribute to eating and weight-control behaviours. This review evaluates the relationship between one aspect of inhibitory control (a reactive component of motor response inhibition measured by the stop signal task) and eating/weight in clinical and non-clinical populations. Sixty-two studies from 58 journal articles were included. Restrained eaters had diminished reactive inhibitory control compared to unrestrained eaters, and showed greatest benefit to their eating behaviour from manipulations of inhibitory control. Obese individuals may show less reactive inhibitory control but only in the context of food-specific inhibition or after executive resources are depleted. Of the limited studies in EDs, the majority found no impairment in reactive inhibitory control, although findings are inconsistent. Thus, altered reactive inhibitory control is related to some maladaptive eating behaviours, and hence may provide a therapeutic target for behavioural manipulations and/or neuromodulation. However, other types of inhibitory control may also contribute. Methodological and theoretical considerations are discussed. Copyright © 2016. Published by Elsevier Ltd.

Dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory memory tasks in mice.

PubMed

Vignisse, Julie; Steinbusch, Harry W M; Bolkunov, Alexei; Nunes, Joao; Santos, Ana Isabel; Grandfils, Christian; Bachurin, Sergei; Strekalova, Tatyana

2011-03-30

Pre-clinical and clinical studies on dimebon (dimebolin or latrepirdine) have demonstrated its use as a cognitive enhancer. Here, we show that dimebon administered to 3-month-old C57BL6N mice 15 min prior to training in both appetitive and inhibitory learning tasks via repeated (0.1 mg/kg) and acute (0.5 mg/kg) i.p. injections, respectively, increases memory scores. Acute treatment with dimebon was found to enhance inhibitory learning, as also shown in the step-down avoidance paradigm in 7-month-old mice. Bolus administration of dimebon did not affect the animals' locomotion, exploration or anxiety-like behaviour, with the exception of exploratory behaviour in older mice in the novel cage test. In a model of appetitive learning, a spatial version of the Y-maze, dimebon increased the rate of correct choices and decreased the latency of accessing a water reward after water deprivation, and increased the duration of drinking behaviour during training/testing procedures. Repeated treatment with dimebon did not alter the behaviours in other tests or water consumption. Acute treatment of water-deprived and non-water-deprived mice with dimebon also did not affect their water intake. Our data suggest that dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory tasks in mice. Copyright © 2011 Elsevier B.V. All rights reserved.

Potential roles of cholinergic modulation in the neural coding of location and movement speed

PubMed Central

Dannenberg, Holger; Hinman, James R.; Hasselmo, Michael E.

2016-01-01

Behavioral data suggest that cholinergic modulation may play a role in certain aspects of spatial memory, and neurophysiological data demonstrate neurons that fire in response to spatial dimensions, including grid cells and place cells that respond on the basis of location and running speed. These neurons show firing responses that depend upon the visual configuration of the environment, due to coding in visually-responsive regions of the neocortex. This review focuses on the physiological effects of acetylcholine that may influence the sensory coding of spatial dimensions relevant to behavior. In particular, the local circuit effects of acetylcholine within the cortex regulate the influence of sensory input relative to internal memory representations, via presynaptic inhibition of excitatory and inhibitory synaptic transmission, and the modulation of intrinsic currents in cortical excitatory and inhibitory neurons. In addition, circuit effects of acetylcholine regulate the dynamics of cortical circuits including oscillations at theta and gamma frequencies. These effects of acetylcholine on local circuits and network dynamics could underlie the role of acetylcholine in coding of spatial information for the performance of spatial memory tasks. PMID:27677935

The EEG as an index of neuromodulator balance in memory and mental illness.

PubMed

Vakalopoulos, Costa

2014-01-01

There is a strong correlation between signature EEG frequency patterns and the relative levels of distinct neuromodulators. These associations become particularly evident during the sleep-wake cycle. The monoamine-acetylcholine balance hypothesis is a theory of neurophysiological markers of the EEG and a detailed description of the findings that support this proposal are presented in this paper. According to this model alpha rhythm reflects the relative predominance of cholinergic muscarinic signals and delta rhythm that of monoaminergic receptor effects. Both high voltage synchronized rhythms are likely mediated by inhibitory Gαi/o-mediated transduction of inhibitory interneurons. Cognitively, alpha and delta EEG measures are proposed to indicate automatic and flexible strategies, respectively. Sleep is associated with marked changes in relative neuromodulator levels corresponding to EEG markers of distinct stages. Sleep studies on memory consolidation present some of the strongest evidence yet for the respective roles of monoaminergic and cholinergic projections in declarative and non-declarative memory processes, a key theoretical premise for understanding the data. Affective dysregulation is reflected in altered EEG patterns during sleep.

Memory retrieval and the passage of time: from reconsolidation and strengthening to extinction

PubMed Central

Inda, Maria Carmen; Muravieva, Elizaveta V.; Alberini, Cristina M.

2011-01-01

An established memory can be made transiently labile if retrieved or reactivated. Over time, it becomes again resistant to disruption and this process that renders the memory stable is termed reconsolidation. The reasons why a memory becomes labile after retrieval and reconsolidates still remains debated. Here, using inhibitory avoidance (IA) learning in rats, we provide evidence that retrievals of a young memory, which are accompanied by its reconsolidation, result in memory strengthening and contribute to its overall consolidation. This function associated to reconsolidation is temporally limited. With the passage of time, the stored memory undergoes important changes, as revealed by the behavioral outcomes of its retrieval. Over time, without explicit retrievals, memory first strengthens and becomes refractory to both retrieval-dependent interference and strengthening. At later times, the same retrievals that lead to reconsolidation of a young memory extinguish an older memory. We conclude that the storage of information is very dynamic and that its temporal evolution regulates behavioral outcomes. These results are important for potential clinical applications. PMID:21289172

Memory Effects of Benzodiazepines: Memory Stages and Types Versus Binding-Site Subtypes

PubMed Central

Savić, Miroslav M.; Obradović, Dragan I.; Ugrešić, Nenad D.; Bokonjić, Dubravko R.

2005-01-01

Benzodiazepines are well established as inhibitory modulators of memory processing. This effect is especially prominent when applied before the acquisition phase of a memory task. This minireview concentrates on the putative subtype selectivity of the acquisition-impairing action of benzodiazepines. Namely, recent genetic studies and standard behavioral tests employing subtype-selective ligands pointed to the predominant involvement of two subtypes of benzodiazepine binding sites in memory modulation. Explicit memory learning seems to be affected through the GABAA receptors containing the α1 and α1 subunits, whereas the effects on procedural memory can be mainly mediated by the α1 subunit. The pervading involvement of the α1 subunit in memory modulation is not at all unexpected because this subunit is the major subtype, present in 60% of all GABAA receptors. On the other hand, the role of α5 subunits, mainly expressed in the hippocampus, in modulating distinct forms of memory gives promise of selective pharmacological coping with certain memory deficit states. PMID:16444900

Interactions of nitric oxide with α2 -adrenoceptors within the locus coeruleus underlie the facilitation of inhibitory avoidance memory by agmatine.

PubMed

Shelkar, Gajanan P; Gakare, Sukanya G; Chakraborty, Suwarna; Dravid, Shashank M; Ugale, Rajesh R

2016-09-01

Agmatine, a putative neurotransmitter, plays a vital role in learning and memory. Although it is considered an endogenous ligand of imidazoline receptors, agmatine exhibits high affinity for α-adrenoceptors, NOS and NMDA receptors. These substrates within the locus coeruleus (LC) are critically involved in learning and memory processes. The hippocampus and LC of male Wistar rat were stereotaxically cannulated for injection. Effects of agmatine, given i.p. or intra-LC, on acquisition, consolidation and retrieval of inhibitory avoidance (IA) memory were measured. The NO donor S-nitrosoglutathione, non-specific (L-NAME) and specific NOS inhibitors (L-NIL, 7-NI, L-NIO), the α2 -adrenoceptor antagonist (yohimbine) or the corresponding agonist (clonidine) were injected intra-LC before agmatine. Intra-hippocampal injections of the NMDA antagonist, MK-801 (dizocilpine), were used to modify the memory enhancing effects of agmatine, SNG and yohimbine. Expression of tyrosine hydroxylase (TH) and eNOS in the LC was assessed immunohistochemically. Agmatine (intra-LC or i.p.) facilitated memory retrieval in the IA test. S-nitrosoglutathione potentiated, while L-NAME and L-NIO decreased, these effects of agmatine. L-NIL and 7-NI did not alter the effects of agmatine. Yohimbine potentiated, whereas clonidine attenuated, effects of agmatine within the LC. The effects of agmatine, S-nitrosoglutathione and yohimbine were blocked by intra-hippocampal MK-801. Agmatine increased the population of TH- and eNOS-immunoreactive elements in the LC. The facilitation of memory retrieval in the IA test by agmatine is probably mediated by interactions between eNOS, NO and noradrenergic pathways in the LC. © 2016 The British Pharmacological Society.

Interactions of nitric oxide with α2‐adrenoceptors within the locus coeruleus underlie the facilitation of inhibitory avoidance memory by agmatine

PubMed Central

Shelkar, Gajanan P; Gakare, Sukanya G; Chakraborty, Suwarna; Dravid, Shashank M

2016-01-01

Background and Purpose Agmatine, a putative neurotransmitter, plays a vital role in learning and memory. Although it is considered an endogenous ligand of imidazoline receptors, agmatine exhibits high affinity for α‐adrenoceptors, NOS and NMDA receptors. These substrates within the locus coeruleus (LC) are critically involved in learning and memory processes. Experimental Approach The hippocampus and LC of male Wistar rat were stereotaxically cannulated for injection. Effects of agmatine, given i.p. or intra‐LC, on acquisition, consolidation and retrieval of inhibitory avoidance (IA) memory were measured. The NO donor S‐nitrosoglutathione, non‐specific (L‐NAME) and specific NOS inhibitors (L‐NIL, 7‐NI, L‐NIO), the α2‐adrenoceptor antagonist (yohimbine) or the corresponding agonist (clonidine) were injected intra‐LC before agmatine. Intra‐hippocampal injections of the NMDA antagonist, MK‐801 (dizocilpine), were used to modify the memory enhancing effects of agmatine, SNG and yohimbine. Expression of tyrosine hydroxylase (TH) and eNOS in the LC was assessed immunohistochemically. Key Results Agmatine (intra‐LC or i.p.) facilitated memory retrieval in the IA test. S‐nitrosoglutathione potentiated, while L‐NAME and L‐NIO decreased, these effects of agmatine. L‐NIL and 7‐NI did not alter the effects of agmatine. Yohimbine potentiated, whereas clonidine attenuated, effects of agmatine within the LC. The effects of agmatine, S‐nitrosoglutathione and yohimbine were blocked by intra‐hippocampal MK‐801. Agmatine increased the population of TH‐ and eNOS‐immunoreactive elements in the LC. Conclusions and Implications The facilitation of memory retrieval in the IA test by agmatine is probably mediated by interactions between eNOS, NO and noradrenergic pathways in the LC. PMID:27273730

Memories of Reward and Nonreward Regulate the Extinction and Reacquisition of both Excitatory and Inhibitory Associations

ERIC Educational Resources Information Center

Capaldi, E. J.; Martins, Ana P. G.; Altman, Meaghan

2009-01-01

arrow]US associations also survived The memories of the unconditioned stimulus (US) and its absence (No US), symbolized as S[superscript R] and S[superscript N], respectively, may be retrieved on US or No US trials giving rise to four types of associations, S[superscript R][right arrow]US, S[superscript R][right arrow]No US, S[superscript N][right…

The irrelevant speech effect and working memory load.

PubMed

Gisselgård, Jens; Petersson, Karl Magnus; Ingvar, Martin

2004-07-01

Irrelevant speech impairs the immediate serial recall of visually presented material. Previously, we have shown that the irrelevant speech effect (ISE) was associated with a relative decrease of regional blood flow in cortical regions subserving the verbal working memory, in particular the superior temporal cortex. In this extension of the previous study, the working memory load was increased and an increased activity as a response to irrelevant speech was noted in the dorsolateral prefrontal cortex. We suggest that the two studies together provide some basic insights as to the nature of the irrelevant speech effect. Firstly, no area in the brain can be ascribed as the single locus of the irrelevant speech effect. Instead, the functional neuroanatomical substrate to the effect can be characterized in terms of changes in networks of functionally interrelated areas. Secondly, the areas that are sensitive to the irrelevant speech effect are also generically activated by the verbal working memory task itself. Finally, the impact of irrelevant speech and related brain activity depends on working memory load as indicated by the differences between the present and the previous study. From a brain perspective, the irrelevant speech effect may represent a complex phenomenon that is a composite of several underlying mechanisms, which depending on the working memory load, include top-down inhibition as well as recruitment of compensatory support and control processes. We suggest that, in the low-load condition, a selection process by an inhibitory top-down modulation is sufficient, whereas in the high-load condition, at or above working memory span, auxiliary adaptive cognitive resources are recruited as compensation. Copyright 2004 Elsevier Inc.

Working memory and executive functions in transient global amnesia.

PubMed

Quinette, Peggy; Guillery, Bérengère; Desgranges, Béatrice; de la Sayette, Vincent; Viader, Fausto; Eustache, Francis

2003-09-01

Transient global amnesia (TGA) is usually considered to produce a profound impairment of long-term episodic memory, while at the same time sparing working memory. However, this neuropsychological dissociation has rarely been examined in detail. While a few studies have assessed some components of working memory in TGA, the results that have been obtained are far from conclusive. To clarify this issue, we carried out a comprehensive investigation of working memory in 10 patients during a TGA attack. In the first study, we report the results from three patients examined with a battery of neuropsychological tests designed to assess each of the three subcomponents of Baddeley's model of working memory. In a second study, seven different patients underwent neuropsychological investigations that focused specifically on the central executive system, using a protocol derived from a study by Miyake and colleagues. Our findings showed that subcomponents of working memory, such as the phonological loop and visuo-spatial sketch pad, were spared in TGA patients. Specific executive functions that entailed inhibitory control, dual task performance, updating and shifting mechanisms were also found to be normal. However, we found significantly impaired performance for the Brown-Peterson test, and that TGA patients were significantly impaired in the recollection of their episodic memories. They also made reduced numbers of 'remember' compared with 'know' judgments in the episodic memory test several days after TGA. On the basis of our findings, it would appear that the episodic memory deficit during TGA is not related to elementary aspects of executive functioning. Our data also highlight the nature of the cognitive mechanisms involved in the Brown-Peterson task, which may well depend on long-term memory (such as the process of semantic encoding). Lastly, the selective deficit in recollective episodic memories observed in TGA may be principally related to medial temporal lobe abnormalities that have been reported in this syndrome.

The anticancer estrogen receptor antagonist tamoxifen impairs consolidation of inhibitory avoidance memory through estrogen receptor alpha.

PubMed

Lichtenfels, Martina; Dornelles, Arethuza da Silva; Petry, Fernanda Dos Santos; Blank, Martina; de Farias, Caroline Brunetto; Roesler, Rafael; Schwartsmann, Gilberto

2017-11-01

Over two-thirds of women with breast cancer have positive tumors for hormone receptors, and these patients undergo treatment with endocrine therapy, tamoxifen being the most widely used agent. Despite being very effective in breast cancer treatment, tamoxifen is associated with side effects that include cognitive impairments. However, the specific aspects and mechanisms underlying these impairments remain to be characterized. Here, we have investigated the effects of tamoxifen and interaction with estrogen receptors on formation of memory for inhibitory avoidance conditioning in female rats. In the first experiment, Wistar female rats received a single oral dose of tamoxifen (1, 3, or 10 mg/kg) or saline by gavage immediately after training and were tested for memory consolidation 24 h after training. In the second experiment, rats received a single dose of 1 mg/kg tamoxifen or saline by gavage 3 h after training and were tested 24 h after training for memory consolidation. In the third experiment, rats received a subcutaneous injection with estrogen receptor α agonist or estrogen receptor beta agonist 30 min before the training. After training, rats received a single oral dose of tamoxifen 1 mg/kg or saline and were tested 24 h after training. In the fourth experiment, rats were trained and tested 24 h later. Immediately after test, rats received a single dose of tamoxifen (1 mg/kg) or saline by gavage and were given four additional daily test trials followed by a re-instatement. Tamoxifen at 1 mg/kg impaired memory consolidation when given immediately after training and the estrogen receptor alpha agonist improved the tamoxifen-related memory impairment. Moreover, tamoxifen impairs memory consolidation of the test. These findings indicate that estrogen receptors regulate the early phase of memory consolidation and the effects of tamoxifen on memory consolidation.

Inattentive behaviour is associated with poor working memory and slow processing speed in very pre-term children in middle childhood.

PubMed

Mulder, Hanna; Pitchford, Nicola J; Marlow, Neil

2011-03-01

BACKGROUND. Problem behaviour is common following pre-term birth, but the underlying nature of these difficulties is not well known. AIMS. We sought to establish the mechanisms underpinning behavioural difficulties in very pre-term (VPT) children in middle childhood by comparing their performance to that of term born peers on tasks of working memory, inhibition, and processing speed, and relating these to parent and teacher assessments of their behaviour. Particular focus was given to inattention and overactive/impulsive behaviour, as these behaviours have been associated with different neuropsychological problems in term children. SAMPLES. A group of VPT children (gestational age < 31 weeks, N= 56) aged 9-10 years and term controls (N= 22) participated in the study. METHOD. Children were assessed with measures of working memory, inhibition, and processing speed. Parents and teachers reported behavioural problems using the Strengths and Difficulties Questionnaire and two additional scales measuring overactive/impulsive behaviour and inattention. RESULTS. Results revealed increased rates of problem behaviour in VPT compared to term children for parent-rated total difficulties, hyperactivity, emotional problems, peer problems, prosocial behaviour, overactive/impulsive behaviour, and parent- and teacher-rated inattention. Processing speed and working memory, but not inhibition, were significantly related to inattentive and overactive/impulsive behaviour. CONCLUSIONS. The increased rates of inattention and overactive/impulsive behaviour in VPT children may be explained by impairment in processing speed and working memory. Expected links between overactive/impulsive behaviour and inhibitory control were not identified, suggesting the nature of such difficulties may be different in VPT compared to term children. © 2010 The British Psychological Society.

Resistance Exercise Reduces Seizure Occurrence, Attenuates Memory Deficits and Restores BDNF Signaling in Rats with Chronic Epilepsy.

PubMed

de Almeida, Alexandre Aparecido; Gomes da Silva, Sérgio; Lopim, Glauber Menezes; Vannucci Campos, Diego; Fernandes, Jansen; Cabral, Francisco Romero; Arida, Ricardo Mario

2017-04-01

Epilepsy is a disease characterized by recurrent, unprovoked seizures. Cognitive impairment is an important comorbidity of chronic epilepsy. Human and animal model studies of epilepsy have shown that aerobic exercise induces beneficial structural and functional changes and reduces the number of seizures. However, little is yet understood about the effects of resistance exercise on epilepsy. We evaluated the effects of a resistance exercise program on the number of seizures, long-term memory and expression/activation of signaling proteins in rats with epilepsy. The number of seizures was quantified by video-monitoring and long-term memory was assessed by an inhibitory avoidance test. Using western blotting, multiplex and enzyme-linked immunosorbent assays, we determined the effects of a 4-week resistance exercise program on IGF-1 and BDNF levels and ERK, CREB, mTOR activation in the hippocampus of rats with epilepsy. Rats with epilepsy submitted to resistance exercise showed a decrease in the number of seizures compared to non-exercised epileptic rats. Memory deficits were attenuated by resistance exercise. Rats with epilepsy showed an increase in IGF-1 levels which were restored to control levels by resistance exercise. BDNF levels and ERK and mTOR activation were decreased in rats with epilepsy and resistance exercise restored these to control levels. In conclusion, resistance exercise reduced seizure occurrence and mitigated memory deficits in rats with epilepsy. These resistance exercise-induced beneficial effects can be related to changes in IGF-1 and BDNF levels and its signaling protein activation. Our findings indicate that the resistance exercise might be included as complementary therapeutic strategy for epilepsy treatment.

Benefits of regular aerobic exercise for executive functioning in healthy populations.

PubMed

Guiney, Hayley; Machado, Liana

2013-02-01

Research suggests that regular aerobic exercise has the potential to improve executive functioning, even in healthy populations. The purpose of this review is to elucidate which components of executive functioning benefit from such exercise in healthy populations. In light of the developmental time course of executive functions, we consider separately children, young adults, and older adults. Data to date from studies of aging provide strong evidence of exercise-linked benefits related to task switching, selective attention, inhibition of prepotent responses, and working memory capacity; furthermore, cross-sectional fitness data suggest that working memory updating could potentially benefit as well. In young adults, working memory updating is the main executive function shown to benefit from regular exercise, but cross-sectional data further suggest that task-switching and post error performance may also benefit. In children, working memory capacity has been shown to benefit, and cross-sectional data suggest potential benefits for selective attention and inhibitory control. Although more research investigating exercise-related benefits for specific components of executive functioning is clearly needed in young adults and children, when considered across the age groups, ample evidence indicates that regular engagement in aerobic exercise can provide a simple means for healthy people to optimize a range of executive functions.

Feeling happy and thinking about food. Counteractive effects of mood and memory on food consumption.

PubMed

Collins, Rebecca; Stafford, Lorenzo D

2015-01-01

Separate lines of research have demonstrated the role of mood and memory in the amount of food we consume. However, no work has examined these factors in a single study and given their combined effects beyond food research, this would seem important. In this study, the interactive effect of these factors was investigated. Unrestrained female participants (n = 64) were randomly assigned to either a positive or neutral mood induction, and were subject to a lunch cue (recalling their previously eaten meal) or no lunch cue, followed by a snack taste/intake test. We found that in line with prediction that food intake was lower in the lunch cue versus no cue condition and in contrast, food intake was higher in the positive versus neutral mood condition. We also found that more food was consumed in the lunch cue/positive mood compared to lunch cue/neutral mood condition. This suggests that positive mood places additional demands on attentional resources and thereby reduces the inhibitory effect of memory on food consumption. These findings confirm that memory cue and positive mood exert opposing effects on food consumption and highlight the importance of both factors in weight control interventions. Copyright © 2014 Elsevier Ltd. All rights reserved.

The relationship of theory of mind and executive functions to symptom type and severity in children with autism.

PubMed

Joseph, Robert M; Tager-Flusberg, Helen

2004-01-01

Although neurocognitive impairments in theory of mind and in executive functions have both been hypothesized to play a causal role in autism, there has been little research investigating the explanatory power of these impairments with regard to autistic symptomatology. The present study examined the degree to which individual differences in theory of mind and executive functions could explain variations in the severity of autism symptoms. Participants included 31 verbal, school-aged children with autism who were administered a battery of tests assessing the understanding of mental states (knowledge and false belief) and executive control skills (working memory, combined working memory and inhibitory control, and planning) and who were behaviorally evaluated for autism severity in the three core symptom domains. Whereas theory of mind and executive control abilities explained the significant variance beyond that accounted for by language level in communication symptoms, neither explained the significant variance in reciprocal social interaction or repetitive behaviors symptoms. These findings are discussed in terms of a proposed distinction between higher level, cognitive-linguistic aspects of theory of mind and related executive control skills, and more fundamental social-perceptual processes involved in the apprehension of mental state information conveyed through eyes, faces, and voices, which may be more closely linked to autistic deficits in social reciprocity.

Neural and psychological mechanisms underlying compulsive drug seeking habits and drug memories--indications for novel treatments of addiction.

PubMed

Everitt, Barry J

2014-07-01

This review discusses the evidence for the hypothesis that the development of drug addiction can be understood in terms of interactions between Pavlovian and instrumental learning and memory mechanisms in the brain that underlie the seeking and taking of drugs. It is argued that these behaviours initially are goal-directed, but increasingly become elicited as stimulus-response habits by drug-associated conditioned stimuli that are established by Pavlovian conditioning. It is further argued that compulsive drug use emerges as the result of a loss of prefrontal cortical inhibitory control over drug seeking habits. Data are reviewed that indicate these transitions from use to abuse to addiction depend upon shifts from ventral to dorsal striatal control over behaviour, mediated in part by serial connectivity between the striatum and midbrain dopamine systems. Only some individuals lose control over their drug use, and the importance of behavioural impulsivity as a vulnerability trait predicting stimulant abuse and addiction in animals and humans, together with consideration of an emerging neuroendophenotype for addiction are discussed. Finally, the potential for developing treatments for addiction is considered in light of the neuropsychological advances that are reviewed, including the possibility of targeting drug memory reconsolidation and extinction to reduce Pavlovian influences on drug seeking as a means of promoting abstinence and preventing relapse. © 2014 The Author. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

High PD-L1/CD86 MFI ratio and IL-10 secretion characterize human regulatory dendritic cells generated for clinical testing in organ transplantation.

PubMed

Zahorchak, Alan F; Macedo, Camila; Hamm, David E; Butterfield, Lisa H; Metes, Diana M; Thomson, Angus W

2018-01-01

Human regulatory dendritic cells (DCreg) were generated from CD14 immunobead-purified or elutriated monocytes in the presence of vitamin D3 and IL-10. They exhibited similar, low levels of costimulatory CD80 and CD86, but comparatively high levels of co-inhibitory programed death ligand-1 (PD-L1) and IL-10 production compared to control immature DC (iDC). Following Toll-like receptor 4 ligation, unlike control iDC, DCreg resisted phenotypic and functional maturation and further upregulated PD-L1:CD86 expression. Whereas LPS-stimulated control iDC (mature DC; matDC) secreted pro-inflammatory tumor necrosis factor but no IL-10, the converse was observed for LPS-stimulated DCreg. DCreg weakly stimulated naïve and memory allogeneic CD4 + and CD8 + T cell proliferation and IFNγ, IL-17A and perforin/granzyme B production in MLR. Their stimulatory function was enhanced however, by blocking PD-1 ligation. High-throughput T cell receptor (TCR) sequencing revealed that, among circulating T cell subsets, memory CD8 + T cells contained the most alloreactive TCR clonotypes and that, while matDC expanded these alloreactive memory CD8 TCR clonotypes, DCreg induced more attenuated responses. These findings demonstrate the feasibility of generating highly-purified GMP-grade DCreg for systemic infusion, their influence on the alloreactive T cell response, and a key mechanistic role of the PD1 pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

Better Movers and Thinkers (BMT): An Exploratory Study of an Innovative Approach to Physical Education

PubMed Central

Dalziell, Andrew; Boyle, James; Mutrie, Nanette

2015-01-01

Recent research has confirmed a positive relationship between levels of physical activity and academic achievement. Some of these studies have been informed by neurological models of Executive Functioning (EF). There is a general consensus within the literature that the three core EF skills are; working memory, inhibitory control and cognitive flexibility. The development of these core EF skills has been linked with learning and academic achievement and is an essential component in the delivery of PE using a new and innovative approach called ‘Better Movers and Thinkers (BMT).’ A mixed methods design was used to investigate the effectiveness and feasibility of a 16-week intervention programme using BMT where 46 children were tested on two separate occasions for coordination and balance control, academic skills, working memory and non-verbal reasoning skills. One school acted as the control condition (21 students, aged 9 – 10 years) and another school acted as the intervention condition (25 students, aged 9 – 10 years). Quantitative data revealed an effect between pre and post-test conditions in the areas of phonological skills (p = .042), segmentation skills (p = .014) and working memory (p = .040) in favour of the intervention condition. Further analysis identified a gender-interaction with male students in the intervention condition making significant gains in phonological skills (p = .005) segmentation skills (p = .014) and spelling (p = .007) compared to boys in the control condition. Analysis of qualitative data from a sample of students from the intervention condition and their class teacher indicated good acceptability of BMT as an alternative approach to PE. PMID:27247688

Relationship between microstructure, cytotoxicity and corrosion properties of a Cu-Al-Ni shape memory alloy.

PubMed

Colić, Miodrag; Rudolf, Rebeka; Stamenković, Dragoslav; Anzel, Ivan; Vucević, Dragana; Jenko, Monika; Lazić, Vojkan; Lojen, Gorazd

2010-01-01

Cu-Al-Ni shape memory alloys (SMAs) have been investigated as materials for medical devices, but their biomedical application is still limited. The aim of this work was to compare the microstructure, corrosion and cytotoxicity in vitro of a Cu-Al-Ni SMA. Rapidly solidified (RS) thin ribbons, manufactured via melt spinning, were used for the tests. The control alloy was a permanent mould casting of the same composition, but without shape memory effect. The results show that RS ribbons are significantly more resistant to corrosion compared with the control alloy, as judged by the lesser release of Cu and Ni into the conditioning medium. These results correlate with the finding that RS ribbons were not cytotoxic to L929 mouse fibroblasts and rat thymocytes. In addition, the RS ribbon conditioning medium inhibited cellular proliferation and IL-2 production by activated rat splenocytes to a much lesser extent. The inhibitory effects were almost completely abolished by conditioning the RS ribbons in culture medium for 4 weeks. Microstructural analysis showed that RS ribbons are martensitic, with boron particles as a minor phase. In contrast, the control Cu-Al-Ni alloy had a complex multiphase microstructure. Examination of the alloy surfaces after conditioning by energy dispersive X-ray and Auger electron spectroscopy showed the formation of Cu and Al oxide layers and confirmed that the metals in RS ribbons are less susceptible to oxidation and corrosion compared with the control alloy. In conclusion, these results suggest that rapid solidification significantly improves the corrosion stability and biocompatibility in vitro of Cu-Al-Ni SMA ribbons.

Cognitive outcomes of TMS treatment in bipolar depression: Safety data from a randomized controlled trial.

PubMed

Myczkowski, Martin L; Fernandes, Adriano; Moreno, Marina; Valiengo, Leandro; Lafer, Beny; Moreno, Ricardo A; Padberg, Frank; Gattaz, Wagner; Brunoni, Andre R

2018-08-01

Bipolar depression (BD) is a highly prevalent condition associated with marked cognitive deficits that persist even in the euthymic phase of the illness. Pharmacological treatments for BD might further aggravate cognitive impairment, highlighting the need of developing interventions that present cognitive safety. In this study, we evaluated the cognitive effects of H1-coil (deep) transcranial magnetic stimulation (TMS) in patients with treatment-resistant bipolar depression. Fourty-three patients were randomized to receive 20 sessions of active (55 trains, 18 Hz, 120% resting motor threshold intensity) or sham rTMS within a double-blind, sham-controlled trial. A battery of 20 neuropsychological assessments, grouped in 6 domains (attention and processing speed, working memory and executive function, inhibitory control, language, immediate verbal memory, and long-term verbal memory) was performed at baseline and after 4 and 8 weeks of trial onset. Depressive symptoms were assessed with the 17-item Hamilton Rating Scale for Depression. Cognitive improvement was shown for all cognitive domains. It occurred regardless of intervention group and depression improvement. For the language domain, greater improvement was observed in the sham group over time. No correlations between depression (at baseline or during treatment) and cognitive improvement were found. Absence of healthy control group. The results of this exploratory study provide evidence on the cognitive safety of H1-coil TMS for BD patients. Putative pro-cognitive effects of rTMS in BD were not observed and thus should be further investigated. Copyright © 2018 Elsevier B.V. All rights reserved.

Stop feeling: inhibition of emotional interference following stop-signal trials.

PubMed

Kalanthroff, Eyal; Cohen, Noga; Henik, Avishai

2013-01-01

Although a great deal of literature has been dedicated to the mutual links between emotion and the selective attention component of executive control, there is very little data regarding the links between emotion and the inhibitory component of executive control. In the current study we employed an emotional stop-signal task in order to examine whether emotion modulates and is modulated by inhibitory control. Results replicated previous findings showing reduced inhibitory control [longer stop-signal reaction time (SSRT)] following negative, compared to neutral pictures. Most importantly, results show decreased emotional interference following stop-signal trials. These results show that the inhibitory control component of executive control can serve to decrease emotional effects. We suggest that inhibitory control and emotion have a two-way connection in which emotion disrupts inhibitory control and activation of inhibitory control disrupts emotion.

Role of Dopamine Receptors Subtypes, D1-Like and D2-Like, within the Nucleus Accumbens Subregions, Core and Shell, on Memory Consolidation in the One-Trial Inhibitory Avoidance Task

ERIC Educational Resources Information Center

Manago, Francesca; Castellano, Claudio; Oliverio, Alberto; Mele, Andrea; De Leonibus, Elvira

2009-01-01

Recent evidence demonstrated that dopamine within the nucleus accumbens mediates consolidation of both associative and nonassociative memories. However, the specific contribution of the nucleus accumbens subregions, core and shell, and of D1 and D2 receptors subtypes has not been yet clarified. The aim of this study was, therefore, to directly…

Effects of retrieval practice on consumer memory for brand attributes.

PubMed

Parker, Andrew; Dagnall, Neil

2007-08-01

The effect of retrieval practice on memory for brand attributes was examined. Participants were presented with advertisements for fictional products so each contained a number of brand attributes relating to the nature of the product and its qualities. Following this, participants practiced recalling a subset of those attributes either 3 or 6 times. The act of retrieving some brand information inhibited the recall of other brand information that was not practiced, but only when repeated retrieval practice took place 6 times. This is the first demonstration of inhibitory effects in consumers' memory using the retrieval practice paradigm.

A controlled investigation of right hemispheric processing enhancement after restricted environmental stimulation (REST) with floatation.

PubMed

Raab, J; Gruzelier, J

1994-05-01

Two groups of 16 subjects, 8 of each gender, were examined on two occasions, one group before and after restricted environmental stimulation with floatation, and the other group without floatation was the control group. They were examined with a tactile object discrimination task carried out with each hand separately while blindfolded, and with a recognition memory test for words and unfamiliar faces, a test validated on neurological patients with left and right hemispheric lesions respectively. Consistent with both tasks the floatation group showed a significantly greater enhancement of right hemispheric processing after floatation than was found when retesting the controls. The results were distinguished from previous research on hypnosis where the same relative state of hemispheric imbalance was achieved with the same tasks, but largely through inhibitory influences on the left hemisphere.

Theories of Memory and Aging: A Look at the Past and a Glimpse of the Future

PubMed Central

Festini, Sara B.

2017-01-01

The present article reviews theories of memory and aging over the past 50 years. Particularly notable is a progression from early single-mechanism perspectives to complex multifactorial models proposed to account for commonly observed age deficits in memory function. The seminal mechanistic theories of processing speed, limited resources, and inhibitory deficits are discussed and viewed as especially important theories for understanding age-related memory decline. Additionally, advances in multivariate techniques including structural equation modeling provided new tools that led to the development of more complex multifactorial theories than existed earlier. The important role of neuroimaging is considered, along with the current prevalence of intervention studies. We close with predictions about new directions that future research on memory and aging will take. PMID:27257229

Sequential inhibitory control processes assessed through simultaneous EEG-fMRI.

PubMed

Baumeister, Sarah; Hohmann, Sarah; Wolf, Isabella; Plichta, Michael M; Rechtsteiner, Stefanie; Zangl, Maria; Ruf, Matthias; Holz, Nathalie; Boecker, Regina; Meyer-Lindenberg, Andreas; Holtmann, Martin; Laucht, Manfred; Banaschewski, Tobias; Brandeis, Daniel

2014-07-01

Inhibitory response control has been extensively investigated in both electrophysiological (ERP) and hemodynamic (fMRI) studies. However, very few multimodal results address the coupling of these inhibition markers. In fMRI, response inhibition has been most consistently linked to activation of the anterior insula and inferior frontal cortex (IFC), often also the anterior cingulate cortex (ACC). ERP work has established increased N2 and P3 amplitudes during NoGo compared to Go conditions in most studies. Previous simultaneous EEG-fMRI imaging reported association of the N2/P3 complex with activation of areas like the anterior midcingulate cortex (aMCC) and anterior insula. In this study we investigated inhibitory control in 23 healthy young adults (mean age=24.7, n=17 for EEG during fMRI) using a combined Flanker/NoGo task during simultaneous EEG and fMRI recording. Separate fMRI and ERP analysis yielded higher activation in the anterior insula, IFG and ACC as well as increased N2 and P3 amplitudes during NoGo trials in accordance with the literature. Combined analysis modelling sequential N2 and P3 effects through joint parametric modulation revealed correlation of higher N2 amplitude with deactivation in parts of the default mode network (DMN) and the cingulate motor area (CMA) as well as correlation of higher central P3 amplitude with activation of the left anterior insula, IFG and posterior cingulate. The EEG-fMRI results resolve the localizations of these sequential activations. They suggest a general role for allocation of attentional resources and motor inhibition for N2 and link memory recollection and internal reflection to P3 amplitude, in addition to previously described response inhibition as reflected by the anterior insula. Copyright © 2014 Elsevier Inc. All rights reserved.

The Role of Inhibitory Control in Behavioral and Physiological Expressions of Toddler Executive Function

PubMed Central

Morasch, Katherine C.; Bell, Martha Ann

2010-01-01

Eighty-one toddlers (ranging from 24 to 27 months) participated in a biobehavioral investigation of inhibitory control. Maternal-report measures of inhibitory control were related to laboratory tasks assessing inhibitory abilities under conditions of conflict, delay, and compliance challenge as well as toddler verbal ability. Additionally, unique variance in inhibitory control was explained by task-related changes in brain electrical activity at lateral frontal scalp sites as well as concurrent inhibitory task performance. Implications regarding neural correlates of executive function in early development and a central, organizing role of inhibitory processing in toddlerhood are discussed. PMID:20719337

Neuropsychological Profiles Correlated with Clinical and Behavioral Impairments in a Sample of Brazilian Children with Attention-Deficit Hyperactivity Disorder

PubMed Central

Rizzutti, Sueli; Schuch, Viviane; Augusto, Bruno Muszkat; Coimbra, Caio Colturato; Pereira, João Pedro Cabrera; Bueno, Orlando Francisco Amodeo

2015-01-01

Attention-deficit hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder that implies several-step process, and there is no single test to diagnose both ADHD and associated comorbidities, such as oppositional-defiant disorder (ODD), anxiety disorder, depression, and certain types of learning disabilities. The purpose of the present study was to examine correlations between behavioral and clinical symptoms by administering an extensive neuropsychological battery to a sample of children and adolescents from a developing country. The sample was divided into three groups: non-ADHD, ADHD-non-comorbid, and ADHD + comorbidity. A full neuropsychological battery and clinical assessment found that 105 children met DSM-5 criteria, of whom 46.6% had the predominantly inattentive presentation, 37.3% had combined presentation, and 16% were predominantly hyperactive/impulsive presentation. The internal correlation between neuropsychological tests did not reach statistical significance in the comparison between ADHD and non-ADHD cases (p < 0.17). Clinical ADHD cases, including both + comorbidity and non-comorbid groups, performed substantially worse on continuous performance test (CPT), working memory. Comparing ADHD-non-comorbid and ADHD + comorbidity groups, the latter did significantly worse on inhibitory control, time processing, and the level of perseveration response on CPT indexes, as well as on working memory performance and child behavior checklist (CBCL) tests particularly the CBCL-deficient emotional self-regulation test in the ADHD + comorbidity group. Children diagnosed as ODD or with conduct disorder showed close correlations between clinical CBCL profiles and externalized symptoms. Our findings suggest that ADHD + comorbidity and ADHD non-comorbid cases may be differentiated by a number of neuropsychological measures, such as processing speed, inhibitory control, and working memory, that may reflect different levels of involvement of the hot and cool executive domains, which are more impaired in cases of severe symptomatic-externalized behavior and emotional regulation problems. Therefore, profiles based on clinical and behavioral findings can help clinicians select better strategies for detecting neuropsychological impairment in Brazilian children with ADHD. PMID:26635638

A pilot investigation of acute inhibitory control training in cocaine users.

PubMed

Alcorn, Joseph L; Pike, Erika; Stoops, William S; Lile, Joshua A; Rush, Craig R

2017-05-01

Disrupted response inhibition and presence of drug-cue attentional bias in cocaine-using individuals have predicted poor treatment outcomes. Inhibitory control training could help improve treatment outcomes by strengthening cognitive control. This pilot study assessed the effects of acute inhibitory control training to drug- and non-drug-related cues on response inhibition performance and cocaine-cue attentional bias in cocaine-using individuals. Participants who met criteria for a cocaine-use disorder underwent five sessions of inhibitory control training to either non-drug-related cues (i.e., rectangles) or cocaine cues (n=10/condition) in a single day. Response inhibition and attentional bias were assessed prior to and following training using the stop-signal task and visual-probe task with eye tracking, respectively. Training condition groups did not differ on demographics, inhibitory control training performance, response inhibition, or cocaine-cue attentional bias. Response inhibition performance improved as a function of inhibitory control training in both conditions. Cocaine-cue attentional bias was observed, but did not change as a function of inhibitory control training in either condition. Response inhibition in cocaine-using individuals was augmented by acute inhibitory control training, which may improve treatment outcomes through better behavioral inhibition. Future studies should investigate longer-term implementation of inhibitory control training, as well as combining inhibitory control training with other treatment modalities. Copyright © 2017 Elsevier B.V. All rights reserved.

Cognitive dysfunction in schizophrenia: convergence of gamma-aminobutyric acid and glutamate alterations.

PubMed

Lewis, David A; Moghaddam, Bita

2006-10-01

Impairments in certain cognitive functions mediated by the dorsolateral prefrontal cortex, such as working memory, are core features of schizophrenia. Convergent findings suggest that these disturbances are associated with alterations in markers of inhibitory gamma-aminobutyric acid and excitatory glutamate neurotransmission in the dorsolateral prefrontal cortex. Specifically, reduced gamma-aminobutyric acid synthesis is present in the subpopulation of gamma-aminobutyric acid neurons that express the calcium-binding protein parvalbumin. Despite presynaptic and postsynaptic compensatory responses, the resulting impaired inhibitory regulation of pyramidal neurons contributes to a reduction in the synchronized neuronal activity that is required for working memory function. Several lines of evidence suggest that these changes may be either secondary to or exacerbated by impaired signaling via the N-methyl-d-aspartate class of glutamate receptors. These findings suggest specific targets for therapeutic interventions to improve cognitive function in individuals with schizophrenia.

Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males.

PubMed

Mokrysz, C; Freeman, T P; Korkki, S; Griffiths, K; Curran, H V

2016-11-29

Preclinical research demonstrates that cannabinoids have differing effects in adolescent and adult animals. Whether these findings translate to humans has not yet been investigated. Here we believe we conducted the first study to compare the acute effects of cannabis in human adolescent (n=20; 16-17 years old) and adult (n=20; 24-28 years old) male cannabis users, in a placebo-controlled, double-blind cross-over design. After inhaling vaporized active or placebo cannabis, participants completed tasks assessing spatial working memory, episodic memory and response inhibition, alongside measures of blood pressure and heart rate, psychotomimetic symptoms and subjective drug effects (for example, 'stoned', 'want to have cannabis'). Results showed that on active cannabis, adolescents felt less stoned and reported fewer psychotomimetic symptoms than adults. Further, adults but not adolescents were more anxious and less alert during the active cannabis session (both pre- and post-drug administration). Following cannabis, cognitive impairment (reaction time on spatial working memory and prose recall following a delay) was greater in adults than adolescents. By contrast, cannabis impaired response inhibition accuracy in adolescents but not in adults. Moreover, following drug administration, the adolescents did not show satiety; instead they wanted more cannabis regardless of whether they had taken active or placebo cannabis, while the opposite was seen for adults. These contrasting profiles of adolescent resilience (blunted subjective, memory, physiological and psychotomimetic effects) and vulnerability (lack of satiety, impaired inhibitory processes) show some degree of translation from preclinical findings, and may contribute to escalated cannabis use by human adolescents.

Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males

PubMed Central

Mokrysz, C; Freeman, T P; Korkki, S; Griffiths, K; Curran, H V

2016-01-01

Preclinical research demonstrates that cannabinoids have differing effects in adolescent and adult animals. Whether these findings translate to humans has not yet been investigated. Here we believe we conducted the first study to compare the acute effects of cannabis in human adolescent (n=20; 16–17 years old) and adult (n=20; 24–28 years old) male cannabis users, in a placebo-controlled, double-blind cross-over design. After inhaling vaporized active or placebo cannabis, participants completed tasks assessing spatial working memory, episodic memory and response inhibition, alongside measures of blood pressure and heart rate, psychotomimetic symptoms and subjective drug effects (for example, ‘stoned', ‘want to have cannabis'). Results showed that on active cannabis, adolescents felt less stoned and reported fewer psychotomimetic symptoms than adults. Further, adults but not adolescents were more anxious and less alert during the active cannabis session (both pre- and post-drug administration). Following cannabis, cognitive impairment (reaction time on spatial working memory and prose recall following a delay) was greater in adults than adolescents. By contrast, cannabis impaired response inhibition accuracy in adolescents but not in adults. Moreover, following drug administration, the adolescents did not show satiety; instead they wanted more cannabis regardless of whether they had taken active or placebo cannabis, while the opposite was seen for adults. These contrasting profiles of adolescent resilience (blunted subjective, memory, physiological and psychotomimetic effects) and vulnerability (lack of satiety, impaired inhibitory processes) show some degree of translation from preclinical findings, and may contribute to escalated cannabis use by human adolescents. PMID:27898071

Top-Down Modulation of Auditory-Motor Integration during Speech Production: The Role of Working Memory.

PubMed

Guo, Zhiqiang; Wu, Xiuqin; Li, Weifeng; Jones, Jeffery A; Yan, Nan; Sheft, Stanley; Liu, Peng; Liu, Hanjun

2017-10-25

Although working memory (WM) is considered as an emergent property of the speech perception and production systems, the role of WM in sensorimotor integration during speech processing is largely unknown. We conducted two event-related potential experiments with female and male young adults to investigate the contribution of WM to the neurobehavioural processing of altered auditory feedback during vocal production. A delayed match-to-sample task that required participants to indicate whether the pitch feedback perturbations they heard during vocalizations in test and sample sequences matched, elicited significantly larger vocal compensations, larger N1 responses in the left middle and superior temporal gyrus, and smaller P2 responses in the left middle and superior temporal gyrus, inferior parietal lobule, somatosensory cortex, right inferior frontal gyrus, and insula compared with a control task that did not require memory retention of the sequence of pitch perturbations. On the other hand, participants who underwent extensive auditory WM training produced suppressed vocal compensations that were correlated with improved auditory WM capacity, and enhanced P2 responses in the left middle frontal gyrus, inferior parietal lobule, right inferior frontal gyrus, and insula that were predicted by pretraining auditory WM capacity. These findings indicate that WM can enhance the perception of voice auditory feedback errors while inhibiting compensatory vocal behavior to prevent voice control from being excessively influenced by auditory feedback. This study provides the first evidence that auditory-motor integration for voice control can be modulated by top-down influences arising from WM, rather than modulated exclusively by bottom-up and automatic processes. SIGNIFICANCE STATEMENT One outstanding question that remains unsolved in speech motor control is how the mismatch between predicted and actual voice auditory feedback is detected and corrected. The present study provides two lines of converging evidence, for the first time, that working memory cannot only enhance the perception of vocal feedback errors but also exert inhibitory control over vocal motor behavior. These findings represent a major advance in our understanding of the top-down modulatory mechanisms that support the detection and correction of prediction-feedback mismatches during sensorimotor control of speech production driven by working memory. Rather than being an exclusively bottom-up and automatic process, auditory-motor integration for voice control can be modulated by top-down influences arising from working memory. Copyright © 2017 the authors 0270-6474/17/3710324-11$15.00/0.

Neural coding in graphs of bidirectional associative memories.

PubMed

Bouchain, A David; Palm, Günther

2012-01-24

In the last years we have developed large neural network models for the realization of complex cognitive tasks in a neural network architecture that resembles the network of the cerebral cortex. We have used networks of several cortical modules that contain two populations of neurons (one excitatory, one inhibitory). The excitatory populations in these so-called "cortical networks" are organized as a graph of Bidirectional Associative Memories (BAMs), where edges of the graph correspond to BAMs connecting two neural modules and nodes of the graph correspond to excitatory populations with associative feedback connections (and inhibitory interneurons). The neural code in each of these modules consists essentially of the firing pattern of the excitatory population, where mainly it is the subset of active neurons that codes the contents to be represented. The overall activity can be used to distinguish different properties of the patterns that are represented which we need to distinguish and control when performing complex tasks like language understanding with these cortical networks. The most important pattern properties or situations are: exactly fitting or matching input, incomplete information or partially matching pattern, superposition of several patterns, conflicting information, and new information that is to be learned. We show simple simulations of these situations in one area or module and discuss how to distinguish these situations based on the overall internal activation of the module. This article is part of a Special Issue entitled "Neural Coding". Copyright © 2011 Elsevier B.V. All rights reserved.

Working memory capacity predicts listwise directed forgetting in adults and children.

PubMed

Aslan, Alp; Zellner, Martina; Bäuml, Karl-Heinz T

2010-05-01

In listwise directed forgetting, participants are cued to forget previously studied material and to learn new material instead. Such cueing typically leads to forgetting of the first set of material and to memory enhancement of the second. The present study examined the role of working memory capacity in adults' and children's listwise directed forgetting. Working memory capacity was assessed with complex span tasks. In Experiment 1 working memory capacity predicted young adults' directed-forgetting performance, demonstrating a positive relationship between working memory capacity and each of the two directed-forgetting effects. In Experiment 2 we replicated the finding with a sample of first and a sample of fourth-grade children, and additionally showed that working memory capacity can account for age-related increases in directed-forgetting efficiency between the two age groups. Following the view that directed forgetting is mediated by inhibition of the first encoded list, the results support the proposal of a close link between working memory capacity and inhibitory function.

Inhibitory Control and Emotion Regulation in Preschool Children

ERIC Educational Resources Information Center

Carlson, Stephanie M.; Wang, Tiffany S.

2007-01-01

This research investigated the relation between individual differences in inhibitory control and emotion regulation. Preschool children (N=53) ages 4-6 (M=5; 0) were assessed on brief batteries of inhibitory control of prepotent responses and emotion regulation. Individual differences in inhibitory control were significantly correlated with…

Abnormal response to methylphenidate across multiple fMRI procedures in cocaine use disorder: feasibility study.

PubMed

Moeller, Scott J; Konova, Anna B; Tomasi, Dardo; Parvaz, Muhammad A; Goldstein, Rita Z

2016-07-01

The indirect dopamine agonist methylphenidate remediates cognitive deficits in psychopathology, but the individual characteristics that determine its effects on the brain are not known. We aimed to determine whether targeted dopaminergically modulated traits and individual differences could predict neural response to methylphenidate across multiple functional magnetic resonance imaging (fMRI) procedures. We combined neural measures from three separate procedures (two inhibitory control tasks differing in their degree of emotional salience and resting-state functional connectivity) during methylphenidate (20 mg oral, versus randomized and counterbalanced placebo) and correlated these aggregated responses with cocaine use disorder diagnosis (22 cocaine abusers, 21 controls), symptoms of attention deficit hyperactivity disorder, and working memory capacity. Cocaine abusers, relative to controls, had a lower response in the dorsolateral prefrontal cortex to methylphenidate across all three procedures, driven by responses to the two inhibitory control tasks; reduced methylphenidate fMRI response in this region further correlated with more frequent cocaine use. Cocaine abuse (and its frequency), associated with lower tonic dopamine levels, correlated with a reduction in activation to methylphenidate (versus placebo). These initial results provide feasibility to the idea that multimodal fMRI tasks can be meaningfully aggregated, and that these aggregated procedures show a common disruption in addiction in a highly anticipated region relevant to cognitive control. Results also suggest that drug use frequency may represent an important modulatory variable in interpreting the efficacy of pharmacologically enhanced cognitive interventions in addiction.

[Inhibition and resource capacity during normal aging: a confrontation of the dorsal-ventral and frontal models in a modified version of negative priming].

PubMed

Martin, S; Brouillet, D; Guerdoux, E; Tarrago, R

2006-01-01

Over the past decades, cognitive psychology contribution to our understanding of aging relies on two major perspectives, focusing on the selective impact of age on either cognitive multiple-systems or global factors of cognition: slowing, working memory and inhibition. In the latter, reduction in inhibitory control during aging (in its access, deletion or restraint functions) is associated with poorer performance on a variety of tasks referring to memory, comprehension or language [Hasher, Zacks and May (16)]. The attractiveness of inhibition as an explanatory factor results in part in the absence of negative priming during aging. Negative priming refers to the slow down of latencies when individuals have to respond to recently ignored informations, compared to unrelated informations. The dissociation, between a preserved location negative priming and an absence of identity negative priming during aging, supports the dorsal-ventral model of inhibition which suggests that spatial and identity inhibition are supported by different and independent visual pathways. An alternative model, directly at odds, is that inhibitory mechanisms are supported by the frontal lobe. In this perspective, inhibition is not a central process responsible for the control of working memory contents, but an automatic and local mechanism whose triggering depends on controlled attention. Therefore, working memory drives efficient inhibition by sustaining task instructions and appropriate responses throughout task execution. This hypothesis is consistent with Houghton and Tipper's (17) architecture of selective attention. According to the authors, the presence or absence of automatic inhibition is very closely linked to a Match/Mismatch field whose function is to compare the present stimulus to an internal self-generated internal template. When an information fails to match the subject's current goals, the match/mismatch field causes an automatic inhibitory imbalance which reduces the to-be-ignored properties' responsiveness. In contrast, information matching subjects' goal is enhanced through an automatic excitatory imbalance. The accurate functioning of the Match/Mismatch field requires efficient executive functioning responsible for the uphold of goals and correct responses. In the case of negative priming, manipulating the efficiency of working memory is of interest as it should affect the triggering of slowing, ie, an indirect inhibitory deficit, when the task is resource demanding [Conwayet al. (6)]. Moreover, if inhibition, as reflected by negative priming, is mediated by individual resource capacity, then NP should disappear during aging only when individuals are engaged in a resource-demanding task. To address this issue, we examine whether cognitive control load in a gender decision task contributed to the presence or absence of NP during aging. According to the dorsal-ventral model, task complexity should not have any impact on performance, since gender decision task relies on a conceptual analysis of information. In turn, the frontal model predicts that age differences in performance profile will only differ when individual resource capacity is overloaded. Sixty-four participants (32 young and 32 older adults) performed a gender categorisation task through two experiments. Trials involved two stimuli presented successively at the same location. A word served as a prime and a word as a target. Both prime and target could be male or female. When prime and target matched on gender, we talked about VALID pairs (or compatible). When prime and target mismatched on the manipulated features, we talked about INVALID pairs (or incompatible). Participants' task was to identify the gender of the target. They were explicitly instructed not to respond to primes but to read them silently. Our interest was in response latencies for valid versus invalid pairs. We manipulated task complexity by the absence (experiment 1) or presence (experiment 2) of a distractor during probe trials. For younger adults, primes presented before targets gave rise to behavioural costs when pairs were mapped to the same response compared to pairs that were mapped to opposite ones. This slowing, called Negative Compatibility Effect (NCE), was independent of the presence or absence of a distractor. NCE was reliable for the elderly patients only under condition of no interfering information during the probe trial: pattern of performance of older participants was identical to that of young adults (experiment 1). This effect disappeared as task complexity increased (experiment 2). This result suggests that NCE triggering is dependant on the amount of cognitive control engaged by the task, and therefore that the ability to inhibit irrelevant information is secondary to a general capacity of the working memory. The implications of our data are consistent with the level of processing account, as well as the recent neuroimaging contributions which suggest, for example, the involvement of the dorso-lateral prefrontal cortex (sensitive to aging) when task demands are high, and a ventro-lateral prefrontal implication when demands are low [see Eenshuistra et al. for a review (10)].

The consolidation of inhibitory avoidance memory in mice depends on the intensity of the aversive stimulus: The involvement of the amygdala, dorsal hippocampus and medial prefrontal cortex.

PubMed

Canto-de-Souza, L; Mattioli, R

2016-04-01

Several studies using inhibitory avoidance models have demonstrated the importance of limbic structures, such as the amygdala, dorsal hippocampus and medial prefrontal cortex, in the consolidation of emotional memory. However, we aimed to investigate the role of the amygdala (AMG), dorsal hippocampus (DH) and medial prefrontal cortex (mPFC) of mice in the consolidation of step-down inhibitory avoidance and whether this avoidance would be conditioned relative to the intensity of the aversive stimulus. To test this, we bilaterally infused anisomycin (ANI-40μg/μl, a protein synthesis inhibitor) into one of these three brain areas in mice. These mice were then exposed to one of two different intensities (moderate: 0.5mA or intense: 1.5mA) in a step-down inhibitory avoidance task. We found that consolidation of both of the aversive experiences was mPFC dependent, while the AMG and DH were only required for the consolidation of the intense experience. We suggest that in moderately aversive situations, which do not represent a severe physical risk to the individual, the consolidation of aversive experiences does not depend on protein synthesis in the AMG or the DH, but only the mPFC. However, for intense aversive stimuli all three of these limbic structures are essential for the consolidation of the experience. Copyright © 2016 Elsevier Inc. All rights reserved.

Interaction of inhibitory and facilitatory effects of conditioning trials on long-term memory formation

PubMed Central

Hosono, Shouhei; Matsumoto, Yukihisa

2016-01-01

Animals learn through experience and consolidate the memories into long-time storage. Conditioning parameters to induce protein synthesis-dependent long-term memory (LTM) have been the subject of extensive studies in many animals. Here we found a case in which a conditioning trial inhibits or facilitates LTM formation depending on the intervals from preceding trials. We studied the effects of conditioning parameters on LTM formation in olfactory conditioning of maxillary-palpi extension response with sucrose reward in the cockroach Periplaneta americana. We found, at first, that translation- and transcription-dependent LTM forms 1 h after training, the fastest so far reported in insects. Second, we observed that multiple-trial training with an intertrial interval (ITI) of 20 or 30 sec, often called massed training, is more effective than spaced training for LTM formation, an observation that differs from the results of most studies in other animals. Third, we found that a conditioning trial inhibits LTM formation when the intervals from preceding trials were in the range of 10–16 min. This inhibitory effect is pairing-specific and is not due to decreased motivation for learning (overtraining effect). To our knowledge, no similar inhibition of LTM formation by a conditioning trial has been reported in any animals. We propose a model to account for the effects of trial number and ITIs on LTM formation. Olfactory conditioning in cockroaches should provide pertinent materials in which to study neuronal and molecular mechanisms underlying the inhibitory and facilitatory processes for LTM formation. PMID:27918270

Hippocampal awake replay in fear memory retrieval

PubMed Central

Wu, Chun-Ting; Haggerty, Daniel; Kemere, Caleb; Ji, Daoyun

2017-01-01

Hippocampal place cells are key to episodic memories. How these cells participate in memory retrieval remains unclear. Here, after rats acquired a fear memory by receiving mild foot-shocks at a shock zone of a track, we analyzed place cells when the animals were placed back to the track and displayed an apparent memory retrieval behavior: avoidance of the shock zone. We found that place cells representing the shock zone were reactivated, despite the fact that the animals did not enter the shock zone. This reactivation occurred in ripple-associated awake replay of place cell sequences encoding the paths from the animal’s current positions to the shock zone, but not in place cell sequences within individual cycles of theta oscillation. The result reveals a specific place cell pattern underlying the inhibitory avoidance behavior and provides strong evidence for the involvement of awake replay in fear memory retrieval. PMID:28218916

Analysis of memory consolidation and evocation in rats by proton induced X-ray emission

NASA Astrophysics Data System (ADS)

Jobim, P. F. C.; dos Santos, C. E. I.; Maurmann, N.; Reolon, G. K.; Debastiani, R.; Pedroso, T. R.; Carvalho, L. M.; Dias, J. F.

2014-08-01

It is well known that trace elements such as Mg, Ca, Fe, Cu and Zn have a key role in synapse plasticity and learning. Learning process is conventionally divided in three distinct and complementary stages: memory acquisition, consolidation and evocation. Consolidation is the stabilization of the synaptic trace formed by acquisition, while evocation is the recall of this trace. Ion-based techniques capable of providing information concerning the elemental composition of organic tissues may be helpful to improve our understanding on memory consolidation and evocation processes. In particular, the Particle-Induced X-ray Emission (PIXE) technique can be used to analyze different biological tissues with good accuracy. In this work we explore the versatility of PIXE to measure the elemental concentrations in rat brain tissues in order to establish any possible correlation between them and the memory consolidation and evocation processes. To this end, six groups of middle-age male Wistar rats were trained and tested in a step-down Inhibitory Avoidance conditioning. After the behavior tests, the animals were decapitated in accordance with the legal procedures and their brains were removed and dissected for the PIXE analyses. The results demonstrated that there are differences in the elemental concentration among the groups and such variations may be associated with their availability to the learning processes (by memory consolidation and evocation). Moreover, the control groups circumvent the possibility that a non-specific event involved in learning tasks cause such variations. Our results suggest that PIXE may be a useful tool to investigate memory consolidation and evocation in animal models.

Lithium prevents REM sleep deprivation-induced impairments on memory consolidation.

PubMed

Ota, Simone M; Moreira, Karin Di Monteiro; Suchecki, Deborah; Oliveira, Maria Gabriela M; Tiba, Paula A

2013-11-01

Pre-training rapid eye movement sleep (REMS) deprivation affects memory acquisition and/or consolidation. It also produces major REMS rebound at the cost of waking and slow wave sleep (SWS). Given that both SWS and REMS appear to be important for memory processes, REMS rebound after training may disrupt the organization of sleep cycles, i.e., excessive amount of REMS and/or little SWS after training could be harmful for memory formation. To examine whether lithium, a drug known to increase SWS and reduce REMS, could prevent the memory impairment induced by pre-training sleep deprivation. Animals were divided in 2 groups: cage control (CC) and REMS-deprived (REMSDep), and then subdivided into 4 subgroups, treated either with vehicle or 1 of 3 doses of lithium (50, 100, and 150 mg/kg) 2 h before training on the multiple trial inhibitory avoidance task. Animals were tested 48 h later to make sure that the drug had been already metabolized and eliminated. Another set of animals was implanted with electrodes and submitted to the same experimental protocol for assessment of drug-induced sleep-wake changes. Wistar male rats weighing 300-400 g. Sleep deprived rats required more trials to learn the task and still showed a performance deficit during test, except from those treated with 150 mg/kg of lithium, which also reduced the time spent in REM sleep during sleep recovery. Lithium reduced rapid eye movement sleep and prevented memory impairment induced by sleep deprivation. These results indicate that these phenomena may be related, but cause-effect relationship cannot be ascertained.

NF-kappaB transcription factor is required for inhibitory avoidance long-term memory in mice.

PubMed

Freudenthal, Ramiro; Boccia, Mariano M; Acosta, Gabriela B; Blake, Mariano G; Merlo, Emiliano; Baratti, Carlos M; Romano, Arturo

2005-05-01

Although it is generally accepted that memory consolidation requires regulation of gene expression, only a few transcription factors (TFs) have been clearly demonstrated to be specifically involved in this process. Increasing research data point to the participation of the Rel/nuclear factor-kappaB (NF-kappaB) family of TFs in memory and neural plasticity. Here we found that two independent inhibitors of NF-kappaB induced memory impairment in the one-trial step-through inhibitory avoidance paradigm in mice: post-training administration of the drug sulfasalazine and 2 h pretraining administration of a double-stranded DNA oligonucleotide containing the NF-kappaB consensus sequence (kappaB decoy). Conversely, one base mutation of the kappaB decoy (mut-kappaB decoy) injection did not affect long-term memory. Accordingly, the kappaB decoy inhibited NF-kappaB in hippocampus 2 h after injection but no inhibition was found with mut-kappaB decoy administration. A temporal course of hippocampal NF-kappaB activity after training was determined. Unexpectedly, an inhibition of NF-kappaB was found 15 min after training in shocked and unshocked groups when compared with the naïve group. Hippocampal NF-kappaB was activated 45 min after training in both shocked and unshocked groups, decreasing 1 h after training and returning to basal levels 2 and 4 h after training. On the basis of the latter results, we propose that activation of NF-kappaB in hippocampus is part of the molecular mechanism involved in the storage of contextual features that constitute the conditioned stimulus representation. The results presented here provide the first evidence to support NF-kappaB activity being regulated in hippocampus during consolidation, stressing the role of this TF as a conserved molecular mechanism for memory storage.

Does PKM(zeta) maintain memory?

PubMed

Kwapis, Janine L; Helmstetter, Fred J

2014-06-01

Work on the long-term stability of memory has identified a potentially critical role for protein kinase Mzeta (PKMζ) in maintaining established memory. PKMζ, an autonomously active isoform of PKC, is hypothesized to sustain those changes that occurred during memory formation in order to preserve the memory engram over time. Initial studies investigating the role of PKMζ were largely successful in demonstrating a role for the kinase in memory maintenance; disrupting PKMζ activity with ζ-inhibitory peptide (ZIP) was successful in disrupting a variety of established associations in a number of key brain regions. More recent work, however, has questioned both the role of PKMζ in memory maintenance and the effectiveness of ZIP as a specific inhibitor of PKMζ activity. Here, we outline the research both for and against the idea that PKMζ is a memory maintenance mechanism and discuss how these two lines of research can be reconciled. We conclude by proposing a number of studies that would help to clarify the role of PKMζ in memory and define other mechanisms the brain may use to maintain memory. Copyright © 2013 Elsevier Inc. All rights reserved.

Stuck in default mode: inefficient cross-frequency synchronization may lead to age-related short-term memory decline.

PubMed

Pinal, Diego; Zurrón, Montserrat; Díaz, Fernando; Sauseng, Paul

2015-04-01

Aging-related decline in short-term memory capacity seems to be caused by deficient balancing of task-related and resting state brain networks activity; however, the exact neural mechanism underlying this deficit remains elusive. Here, we studied brain oscillatory activity in healthy young and old adults during visual information maintenance in a delayed match-to-sample task. Particular emphasis was on long range phase:amplitude coupling of frontal alpha (8-12 Hz) and posterior fast oscillatory activity (>30 Hz). It is argued that through posterior fast oscillatory activity nesting into the excitatory or the inhibitory phase of frontal alpha wave, long-range networks can be efficiently coupled or decoupled, respectively. On the basis of this mechanism, we show that healthy, elderly participants exhibit a lack of synchronization in task-relevant networks while maintaining synchronized regions of the resting state network. Lacking disconnection of this resting state network is predictive of aging-related short-term memory decline. These results support the idea of inefficient orchestration of competing brain networks in the aging human brain and identify the neural mechanism responsible for this control breakdown. Copyright © 2015 Elsevier Inc. All rights reserved.

Neurofibromatosis type 1 and attention deficit hyperactivity disorder: a case study and literature review

PubMed Central

Miguel, Carmen Sílvia; Chaim-Avancini, Tiffany M; Silva, Maria Aparecida; Louzã, Mario Rodrigues

2015-01-01

Background The cognitive profile of children with neurofibromatosis type 1 (NF1) and attention deficit hyperactivity disorder (ADHD) has been well characterized, but few studies have evaluated the cognitive abilities of adults with NF1 and ADHD. Objectives We investigated 1) the cognitive profile of an adult patient with NF1 and inattention problems, 2) changes in his cognition after 14 months of follow-up, and 3) whether the patient exhibited comorbid NF1 and ADHD or secondary ADHD-like symptoms. Methods We administered neuropsychological tests of executive function, attention, verbal and visual memory, visuospatial function, and language during two evaluations separated by 14 months. Results We found no changes in sustained attention, language, or verbal memory. Visual memory, verbal learning, selective attention inhibitory control, and problem solving declined over time, whereas visual search, psychomotor speed, visuospatial function, and mental flexibility improved. Conclusion Our patient exhibited a cognitive profile characteristic of both NF1 and ADHD, leading to the hypothesis that the patient had comorbid ADHD instead of secondary ADHD-like symptoms. More studies are necessary to characterize the cognition of patients with NF1 and ADHD. PMID:25848279

Hormones and the hippocampus.

PubMed

Lathe, R

2001-05-01

Hippocampal lesions produce memory deficits, but the exact function of the hippocampus remains obscure. Evidence is presented that its role in memory may be ancillary to physiological regulation. Molecular studies demonstrate that the hippocampus is a primary target for ligands that reflect body physiology, including ion balance and blood pressure, immunity, pain, reproductive status, satiety and stress. Hippocampal receptors are functional, probably accessible to their ligands, and mediate physiological and cognitive changes. This argues that an early role of the hippocampus may have been in sensing soluble molecules (termed here 'enteroception') in blood and cerebrospinal fluid, perhaps reflecting a common evolutionary origin with the olfactory system ('exteroception'). Functionally, hippocampal enteroception may reflect feedback control; evidence is reviewed that the hippocampus modulates body physiology, including the activity of the hypothalamus-pituitary-adrenal axis, blood pressure, immunity, and reproductive function. It is suggested that the hippocampus operates, in parallel with the amygdala, to modulate body physiology in response to cognitive stimuli. Hippocampal outputs are predominantly inhibitory on downstream neuroendocrine activity; increased synaptic efficacy in the hippocampus (e.g. long-term potentiation) could facilitate throughput inhibition. This may have implications for the role of the hippocampus and long-term potentiation in memory.

Executive function in children with high and low attentional skills: correspondences between behavioural and cognitive profiles.

PubMed

Scope, Alison; Empson, Janet; McHale, Sue

2010-06-01

Cognitive performance was compared between two groups of typically developing children, who had been observed and rated as differing significantly in their attentional skills at school. The participants were 24 8- and 9-year-old children scoring poorly relative to peers, on a classroom observation scale and teacher rating scale for attention, hyperactivity, and impulsivity [low-attentional skills (LAS) group] and 24 sex- and age-matched children scoring at a high level compared to peers [high-attentional skills (HAS) group]. The two groups were compared on a series of cognitive tasks to assess executive function (EF). The LAS group performed within the typical range yetat a significantly lower level than the HAS group on the majority of the EF tasks administered, namely working memory and inhibition measures, even though there were no significant differences between the groups on a measure of intellectual ability. Working memory measures followed by measures of inhibition emerged as the best predictors of group membership. These findings provide empirical evidence that there are individual differences in attentional skills. Specifically, that there is a relationship between behavioural inattention, hyperactivity, and impulsivity and cognitive performance on working memory and inhibitory control tasks.

Lithium Prevents REM Sleep Deprivation-Induced Impairments on Memory Consolidation

PubMed Central

Ota, Simone M.; Moreira, Karin Di Monteiro; Suchecki, Deborah; Oliveira, Maria Gabriela M.; Tiba, Paula A.

2013-01-01

Background: Pre-training rapid eye movement sleep (REMS) deprivation affects memory acquisition and/or consolidation. It also produces major REMS rebound at the cost of waking and slow wave sleep (SWS). Given that both SWS and REMS appear to be important for memory processes, REMS rebound after training may disrupt the organization of sleep cycles, i.e., excessive amount of REMS and/or little SWS after training could be harmful for memory formation. Objective: To examine whether lithium, a drug known to increase SWS and reduce REMS, could prevent the memory impairment induced by pre-training sleep deprivation. Design: Animals were divided in 2 groups: cage control (CC) and REMS-deprived (REMSDep), and then subdivided into 4 subgroups, treated either with vehicle or 1 of 3 doses of lithium (50, 100, and 150 mg/kg) 2 h before training on the multiple trial inhibitory avoidance task. Animals were tested 48 h later to make sure that the drug had been already metabolized and eliminated. Another set of animals was implanted with electrodes and submitted to the same experimental protocol for assessment of drug-induced sleep-wake changes. Subjects: Wistar male rats weighing 300-400 g. Results: Sleep deprived rats required more trials to learn the task and still showed a performance deficit during test, except from those treated with 150 mg/kg of lithium, which also reduced the time spent in REM sleep during sleep recovery. Conclusion: Lithium reduced rapid eye movement sleep and prevented memory impairment induced by sleep deprivation. These results indicate that these phenomena may be related, but cause-effect relationship cannot be ascertained. Citation: Ota SM; Moreira KDM; Suchecki D; Oliveira MGM; Tiba PA. Lithium prevents REM sleep deprivation-induced impairments on memory consolidation. SLEEP 2013;36(11):1677-1684. PMID:24179301

Environmental manganese exposure and associations with memory, executive functions, and hyperactivity in Brazilian children.

PubMed

Carvalho, Chrissie Ferreira de; Oulhote, Youssef; Martorelli, Marina; Carvalho, Carla Oliveira de; Menezes-Filho, José Antônio; Argollo, Nayara; Abreu, Neander

2018-02-09

Manganese (Mn) is an essential element, however high levels of Mn have been associated with lower neuropsychological performance and behavioral problems in children. We investigated the associations between hair Mn concentrations and neuropsychological and behavioral performances among children with long-term exposure to airborne Mn aged between 7 and 12 years. Neuropsychological performance included tests of: verbal memory, inhibitory control, cognitive flexibility, verbal fluency, and motor function. We used the Conners Abbreviated Rating Scale for teachers to assess students' behaviors of hyperactivity. Hair manganese (MnH) concentrations in children and exposure to airborne manganese from a ferro-manganese alloy plant were analyzed and correlated with tests scores. Multivariable linear models adjusting for potential confounders showed that elevated levels of MnH were associated with lower performance in verbal memory, as measured by the free recall after interference (β = - 1.8; 95% CI: - 3.4, - 0.2), which indicates susceptibility to interference, and Delayed Effect (β = -2.0; 95% CI: -3.7, - 0.2), representing a loss of information over time. Additionally, we found patterns of effect modification by sex in three subtests measuring verbal memory: the free recall after interference score, Interference Effect, and Delayed Effect (all at p < 0.10). Overall, the results suggest that long-term airborne Mn exposure may be associated with lower performance in verbal memory, and hyperactivity behaviors. Copyright © 2018 Elsevier B.V. All rights reserved.

‘Forget me (not)?’ – Remembering Forget-Items Versus Un-Cued Items in Directed Forgetting

PubMed Central

Zwissler, Bastian; Schindler, Sebastian; Fischer, Helena; Plewnia, Christian; Kissler, Johanna M.

2015-01-01

Humans need to be able to selectively control their memories. This capability is often investigated in directed forgetting (DF) paradigms. In item-method DF, individual items are presented and each is followed by either a forget- or remember-instruction. On a surprise test of all items, memory is then worse for to-be-forgotten items (TBF) compared to to-be-remembered items (TBR). This is thought to result mainly from selective rehearsal of TBR, although inhibitory mechanisms also appear to be recruited by this paradigm. Here, we investigate whether the mnemonic consequences of a forget instruction differ from the ones of incidental encoding, where items are presented without a specific memory instruction. Four experiments were conducted where un-cued items (UI) were interspersed and recognition performance was compared between TBR, TBF, and UI stimuli. Accuracy was encouraged via a performance-dependent monetary bonus. Experiments varied the number of items and their presentation speed and used either letter-cues or symbolic cues. Across all experiments, including perceptually fully counterbalanced variants, memory accuracy for TBF was reduced compared to TBR, but better than for UI. Moreover, participants made consistently fewer false alarms and used a very conservative response criterion when responding to TBF stimuli. Thus, the F-cue results in active processing and reduces false alarm rate, but this does not impair recognition memory beyond an un-cued baseline condition, where only incidental encoding occurs. Theoretical implications of these findings are discussed. PMID:26635657

Multiple trial inhibitory avoidance acquisition and retrieval are resistant to chronic stress.

PubMed

Raya, J; Girardi, C E N; Esumi, L A; Ferreira, L B T; Hipólide, D C

2018-02-01

Chronic mild stress (CMS) is a widely accepted animal model relevant to depression that among other consequences, is chiefly known to induce anhedonia, often assessed as decreased preference for sucrose solution. CMS is also known to affect cognition, particularly memory tasks. In this study we have employed the multiple-trial inhibitory avoidance memory task (MTIA) to assess CMS effects on memory acquisition and retrieval. MTIA consists of repeated exposures to the unconditioned stimulus until a learning criterion is reached. Wistar rats underwent CMS for 5 weeks, and sucrose consumption was assessed once a week. At the end of CMS, animals were evaluated in the MTIA task. Overall decreased sucrose solution preference was highly variable. Further analyses showed that a subset of animals expressed resilience while another subset was sensitive to stress. CMS did not affect the number of acquisition sessions before reaching criterion or retrieval latency of MTIA task in neither sensitive nor resilient groups. Although tasks that assess learning ability in animal models relevant to depression indicate cognitive deficits, the ability to learn the association between compartment crossing and the aversive electric foot shock, which is strongly dependent on emotional aspects, was intact. Copyright © 2017 Elsevier B.V. All rights reserved.

Transcription Factor IRF4 Promotes CD8+ T Cell Exhaustion and Limits the Development of Memory-like T Cells during Chronic Infection.

PubMed

Man, Kevin; Gabriel, Sarah S; Liao, Yang; Gloury, Renee; Preston, Simon; Henstridge, Darren C; Pellegrini, Marc; Zehn, Dietmar; Berberich-Siebelt, Friederike; Febbraio, Mark A; Shi, Wei; Kallies, Axel

2017-12-19

During chronic stimulation, CD8 + T cells acquire an exhausted phenotype characterized by expression of inhibitory receptors, down-modulation of effector function, and metabolic impairments. T cell exhaustion protects from excessive immunopathology but limits clearance of virus-infected or tumor cells. We transcriptionally profiled antigen-specific T cells from mice infected with lymphocytic choriomeningitis virus strains that cause acute or chronic disease. T cell exhaustion during chronic infection was driven by high amounts of T cell receptor (TCR)-induced transcription factors IRF4, BATF, and NFATc1. These regulators promoted expression of inhibitory receptors, including PD-1, and mediated impaired cellular metabolism. Furthermore, they repressed the expression of TCF1, a transcription factor required for memory T cell differentiation. Reducing IRF4 expression restored the functional and metabolic properties of antigen-specific T cells and promoted memory-like T cell development. These findings indicate that IRF4 functions as a central node in a TCR-responsive transcriptional circuit that establishes and sustains T cell exhaustion during chronic infection. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Inhibitory control and the onset of combustible cigarette, e-cigarette, and hookah use in early adolescence: The moderating role of socioeconomic status.

PubMed

Riggs, Nathaniel R; Pentz, Mary Ann

2016-01-01

The purpose of the study was to test the moderating influence of socioeconomic status (SES) on the associations between inhibitory control and the onset of combustible cigarette, electronic (e-) cigarette, and hookah use in early adolescence. A total of 407 adolescents self-reported nicotine use, inhibitory control, and SES. The hypothesis that inhibitory control would be significantly associated with nicotine use onset (i.e., combustible cigarettes, e-cigarettes, and hookah) only under the condition of low SES was tested. Direct associations were found for inhibitory control on "ever use" of all three nicotine use variables. A moderating effect was also found whereby low inhibitory control was significantly associated with nicotine use onset when participants were from low, but not high, SES families. Findings illustrate one contextual condition under which inhibitory control is associated with early onset of nicotine use.

Extinction Generates Outcome-Specific Conditioned Inhibition.

PubMed

Laurent, Vincent; Chieng, Billy; Balleine, Bernard W

2016-12-05

Extinction involves altering a previously established predictive relationship between a cue and its outcome by repeatedly presenting that cue alone. Although it is widely accepted that extinction generates some form of inhibitory learning [1-4], direct evidence for this claim has been lacking, and the nature of the associative changes induced by extinction have, therefore, remained a matter of debate [5-8]. In the current experiments, we used a novel behavioral approach that we recently developed and that provides a direct measure of conditioned inhibition [9] to compare the influence of extinguished and non-extinguished cues on choice between goal-directed actions. Using this approach, we provide direct evidence that extinction generates outcome-specific conditioned inhibition. Furthermore, we demonstrate that this inhibitory learning is controlled by the infralimbic cortex (IL); inactivation of the IL using M4 DREADDs abolished outcome-specific inhibition and rendered the cue excitatory. Importantly, we found that context modulated this inhibition. Outside its extinction context, the cue was excitatory and functioned as a specific predictor of its previously associated outcome, biasing choice toward actions earning the same outcome. In its extinction context, however, the cue acted as a specific inhibitor and biased choice toward actions earning different outcomes. Context modulation of these excitatory and inhibitory memories was mediated by the dorsal hippocampus (HPC), suggesting that the HPC and IL act in concert to control the influence of conditioned inhibitors on choice. These findings demonstrate for the first time that extinction turns a cue into a net inhibitor that can influence choice via counterfactual action-outcome associations. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Effects of Donepezil, an Acetylcholinesterase Inhibitor, on Impaired Learning and Memory in Rodents.

PubMed

Shin, Chang Yell; Kim, Hae-Sun; Cha, Kwang-Ho; Won, Dong Han; Lee, Ji-Yun; Jang, Sun Woo; Sohn, Uy Dong

2018-05-01

A previous study in humans demonstrated the sustained inhibitory effects of donepezil on acetylcholinesterase (AChE) activity; however, the effective concentration of donepezil in humans and animals is unclear. This study aimed to characterize the effective concentration of donepezil on AChE inhibition and impaired learning and memory in rodents. A pharmacokinetic study of donepezil showed a mean peak plasma concentration of donepezil after oral treatment (3 and 10 mg/kg) of approximately 1.2 ± 0.4 h and 1.4 ± 0.5 h, respectively; absolute bioavailability was calculated as 3.6%. Further, AChE activity was inhibited by increasing plasma concentrations of donepezil, and a maximum inhibition of 31.5 ± 5.7% was observed after donepezil treatment in hairless rats. Plasma AChE activity was negatively correlated with plasma donepezil concentration. The pharmacological effects of donepezil are dependent upon its concentration and AChE activity; therefore, we assessed the effects of donepezil on learning and memory using a Y-maze in mice. Donepezil treatment (3 mg/kg) significantly prevented the progression of scopolamine-induced memory impairment in mice. As the concentration of donepezil in the brain increased, the recovery of spontaneous alternations also improved; maximal improvement was observed at 46.5 ± 3.5 ng/g in the brain. In conclusion, our findings suggest that the AChE inhibitory activity and pharmacological effects of donepezil can be predicted by the concentration of donepezil. Further, 46.5 ± 3.5 ng/g donepezil is an efficacious target concentration in the brain for treating learning and memory impairment in rodents.

Lesions of the thalamic reuniens cause impulsive but not compulsive responses.

PubMed

Prasad, Judy A; Macgregor, Emily M; Chudasama, Yogita

2013-01-01

On account of its strong efferent projections to the hippocampus, recent animal studies have emphasized an important role for the nucleus reuniens (NRe) of the midline thalamus in spatial memory. However, by virtue of its reciprocal connections with the orbital and ventromedial prefrontal cortex, the NRe may also be involved in aspects of executive inhibition. To date, there has been no systematic attempt to examine the role of the NRe in inhibitory mechanisms of response control. Accordingly, we compared rats with neurotoxic lesions of the NRe with sham surgery controls on performance of the 5-choice reaction time task, a test of visuospatial attention and inhibitory control. When tested post-operatively, rats with NRe lesions were unable to actively inhibit premature responses when the intertrial interval was varied. However, the same rats with NRe lesions showed normal inhibition of perseverative responses, and under some conditions were less perseverative than shams. The NRe lesion was also associated with a reduction in omissions and fast reward collection latencies, which persisted 2 months following surgery. The NRe lesion did not affect response accuracy or latency to respond correctly throughout the course of experimental testing. Together, these results signify the important role of the NRe in impulse inhibition, especially when slight changes are made to the temporal demands of the environment, and reveal the potential contribution of the NRe in motivational processes.

Cardiorespiratory Fitness and Motor Skills in Relation to Cognition and Academic Performance in Children – A Review

PubMed Central

Haapala, Eero A.

2013-01-01

Different elements of physical fitness in children have shown a declining trend during the past few decades. Cardiorespiratory fitness and motor skills have been associated with cognition, but the magnitude of this association remains unknown. The purpose of this review is to provide an overview of the relationship of cardiorespiratory fitness and motor skills with cognitive functions and academic performance in children up to 13 years of age. Cross-sectional studies suggest that children with higher cardiorespiratory fitness have more efficient cognitive processing at the neuroelectric level, as well as larger hippocampal and basal ganglia volumes, compared to children with lower cardiorespiratory fitness. Higher cardiorespiratory fitness has been associated with better inhibitory control in tasks requiring rigorous attention allocation. Better motor skills have been related to more efficient cognitive functions including inhibitory control and working memory. Higher cardiorespiratory fitness and better motor skills have also been associated with better academic performance. Furthermore, none of the studies on cardiorespiratory fitness have revealed independent associations with cognitive functions by controlling for motor skills. Studies concerning the relationship between motor skills and cognitive functions also did not consider cardiorespiratory fitness in the analyses. The results of this review suggest that high levels of cardiorespiratory fitness and motor skills may be beneficial for cognitive development and academic performance but the evidence relies mainly on cross-sectional studies. PMID:23717355

The influence of emotions on cognitive control: feelings and beliefs—where do they meet?

PubMed Central

Harlé, Katia M.; Shenoy, Pradeep; Paulus, Martin P.

2013-01-01

The influence of emotion on higher-order cognitive functions, such as attention allocation, planning, and decision-making, is a growing area of research with important clinical applications. In this review, we provide a computational framework to conceptualize emotional influences on inhibitory control, an important building block of executive functioning. We first summarize current neuro-cognitive models of inhibitory control and show how Bayesian ideal observer models can help reframe inhibitory control as a dynamic decision-making process. Finally, we propose a Bayesian framework to study emotional influences on inhibitory control, providing several hypotheses that may be useful to conceptualize inhibitory control biases in mental illness such as depression and anxiety. To do so, we consider the neurocognitive literature pertaining to how affective states can bias inhibitory control, with particular attention to how valence and arousal may independently impact inhibitory control by biasing probabilistic representations of information (i.e., beliefs) and valuation processes (e.g., speed-error tradeoffs). PMID:24065901

The effects of sequential attention shifts within visual working memory.

PubMed

Li, Qi; Saiki, Jun

2014-01-01

Previous studies have shown conflicting data as to whether it is possible to sequentially shift spatial attention among visual working memory (VWM) representations. The present study investigated this issue by asynchronously presenting attentional cues during the retention interval of a change detection task. In particular, we focused on two types of sequential attention shifts: (1) orienting attention to one location, and then withdrawing attention from it, and (2) switching the focus of attention from one location to another. In Experiment 1, a withdrawal cue was presented after a spatial retro-cue to measure the effect of withdrawing attention. The withdrawal cue significantly reduced the cost of invalid spatial cues, but surprisingly, did not attenuate the benefit of valid spatial cues. This indicates that the withdrawal cue only triggered the activation of facilitative components but not inhibitory components of attention. In Experiment 2, two spatial retro-cues were presented successively to examine the effect of switching the focus of attention. We observed equivalent benefits of the first and second spatial cues, suggesting that participants were able to reorient attention from one location to another within VWM, and the reallocation of attention did not attenuate memory at the first-cued location. In Experiment 3, we found that reducing the validity of the preceding spatial cue did lead to a significant reduction in its benefit. However, performance was still better at first-cued locations than at uncued and neutral locations, indicating that the first cue benefit might have been preserved both partially under automatic control and partially under voluntary control. Our findings revealed new properties of dynamic attentional control in VWM maintenance.

Preschool Inhibitory Control Predicts ADHD Group Status and Inhibitory Weakness in School.

PubMed

Jacobson, Lisa A; Schneider, Heather; Mahone, E Mark

2017-12-26

Discriminative utility of performance measures of inhibitory control was examined in preschool children with and without ADHD to determine whether performance measures added to diagnostic prediction and to prediction of informant-rated day-to-day executive function. Children ages 4-5 years (N = 105, 61% boys; 54 ADHD, medication-naïve) were assessed using performance measures (Auditory Continuous Performance Test for Preschoolers-Commission errors, Conflicting Motor Response Test, NEPSY Statue) and caregiver (parent, teacher) ratings of inhibition (Behavior Rating Inventory of Executive Function-Preschool version). Performance measures and parent and teacher reports of inhibitory control significantly and uniquely predicted ADHD group status; however, performance measures did not add to prediction of group status beyond parent reports. Performance measures did significantly predict classroom inhibitory control (teacher ratings), over and above parent reports of inhibitory control. Performance measures of inhibitory control may be adequate predictors of ADHD status and good predictors of young children's classroom inhibitory control, demonstrating utility as components of clinical assessments. © The Author(s) 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Beneficial effect of commercial Rhodiola extract in rats with scopolamine-induced memory impairment on active avoidance.

PubMed

Vasileva, Liliya V; Getova, Damianka P; Doncheva, Nina D; Marchev, Andrey S; Georgiev, Milen I

2016-12-04

Rhodiola rosea L., family Crassulaceae also known as Golden Root or Arctic root is one of the most widely used medicinal plants with effect on cognitive dysfunction, psychological stress and depression. The aim of the study was to examine the effect of a standardized commercial Rhodiola extract on learning and memory processes in naive rats as well as its effects in rats with scopolamine-induced memory impairment. Sixty male Wistar rats were used in the study. The experiment was conducted in two series - on naive rats and on rats with scopolamine-induced model of impaired memory. The active avoidance test was performed in an automatic conventional shuttle box set-up. The criteria used were the number of conditional stimuli (avoidances), the number of unconditioned stimuli (escapes) as well as the number of intertrial crossings. The chemical fingerprinting of the standardized commercial Rhodiola extract was performed by means of nuclear magnetic resonance (NMR). Naive rats treated with standardized Rhodiola extract increased the number of avoidances during the learning session and memory retention test compared to the controls. Rats with scopolamine-induced memory impairment treated with Rhodiola extract showed an increase in the number of avoidances during the learning session and on the memory tests compared to the scopolamine group. The other two parameters were not changed in rats treated with the extract of Rhodiola in the two series. It was found that the studied Rhodiola extract exerts a beneficial effect on learning and memory processes in naive rats and rats with scopolamine-induced memory impairment. The observed effect is probably due to multiple underlying mechanisms including its modulating effect on acetylcholine levels in the brain and MAO-inhibitory activity leading to stimulation of the monoamines' neurotransmission. In addition the pronounced stress-protective properties of Rhodiola rosea L. could also play a role in the improvement of cognitive functions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cognitive profile in Wilson's disease: a case series of 31 patients.

PubMed

Wenisch, E; De Tassigny, A; Trocello, J-M; Beretti, J; Girardot-Tinant, N; Woimant, F

2013-12-01

Wilson's disease (WD) is a rare autosomal recessive disorder of copper metabolism. If untreated, WD, which is initially a liver disease, can turn into a multi-systemic disease with neurological involvement. Very few studies have described cognitive impairment in WD. The aim of this study is to report the cognitive profile of 31 treated WD patients. Patients were classed into two groups using the Unified Wilson Disease Rating Scale (UWDRS): WD patients without neurological signs (WD-N(-)) (n=13), and WD patients with neurological signs (WD-N(+)) (n=18). The patients participated in a neuropsychological assessment evaluating memory, executive function and visuo-spatial abilities. Both groups performed well for verbal intelligence and episodic memory skills. However, the majority of these patients exhibited altered performance for at least one cognitive test, particularly in the executive domain. The WD-N(+) group performed less well than the WD-N(-) group on cognitive tests involving rapid motor function, abstract thinking, working memory and top-down inhibitory control. Cognitive impairment in treated WD patients essentially affects executive function involving fronto-striatal circuits. Verbal intelligence and episodic memory abilities seem to be remarkably preserved. Neuropsychological assessment is a valuable tool to evaluate the presence and the consequences of these cognitive impairments in WD patients with or without neurological signs in the course of this chronic disease. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Age-related changes in decision making: comparing informed and noninformed situations.

PubMed

Van Duijvenvoorde, Anna C K; Jansen, Brenda R J; Bredman, Joren C; Huizenga, Hilde M

2012-01-01

Advantageous decision making progressively develops into early adulthood, most specifically in complex and motivationally salient decision situations in which direct feedback on gains and losses is provided (Figner & Weber, 2011). However, the factors that underlie this developmental improvement in decision making are still not well understood. The current study therefore investigates 2 potential factors, long-term memory and working memory, by assigning a large developmental sample (7-29 years of age) to a condition with either high or low demands on long-term and working memory. The first condition featured an age-adapted version of the Iowa Gambling Task (IGT; Bechara, Damasio, Damasio, & Anderson, 1994; i.e., a noninformed situation), whereas the second condition provided an external store where explicit information on gains, losses, and probabilities per choice option was presented (i.e., an informed situation). Consistent with previous developmental IGT studies, children up to age 12 did not learn to prefer advantageous options in the noninformed condition. In contrast, all age groups learned to prefer the advantageous options in the informed conditions, although a slight developmental increase in advantageous decision making remained. These results indicate that lowering dependence on long-term and working memory improves children's advantageous decision making. The results additionally suggest that other factors, like inhibitory control processes, may play an additional role in the development of advantageous decision making.

The role of decision-making ability in HIV/AIDS: impact on prospective memory.

PubMed

Coulehan, Kelly; Byrd, Desiree; Arentoft, Alyssa; Monzones, Jennifer; Fuentes, Armando; Fraser, Felicia; Rosario, Ana; Morgello, Susan; Mindt, Monica Rivera

2014-01-01

Prospective memory (ProM), a form of episodic memory related to execution of future intentions, is important for everyday functioning. Among persons living with HIV (PLWH), executive dysfunction is implicated in ProM impairments. However, specific subcomponents of executive functioning involved in ProM deficits remain poorly understood. Unlike more "traditional" neurocognitive (NC) measures of executive functioning associated with dorsolateral prefrontal cortex (i.e., conceptual reasoning, abstraction), those associated with medial orbitofrontal/ventromedial prefrontal (mOF/vmP) cortex (i.e., decision making, inhibitory control, goal-oriented behavior) have yet to be examined in ProM. This study characterized ProM ability in a sample of 89 HIV-seropositive adults and examined the unique role of decision-making ability in ProM. Participants completed a standard NC battery, the Iowa Gambling Task (IGT; a decision-making measure), and the Memory for Intentions Screening Test (MIST; a ProM measure). Correlational analyses revealed that both traditional executive functioning measures and the IGT were associated with ProM. Regression analyses revealed that the IGT significantly predicted ProM, even after accounting for NC measures. Among all NC measures, only executive functioning significantly contributed to ProM. Further examination of mOF/vmP-sensitive executive dysfunction within this population is needed as PLWH may require more tailored treatment recommendations due to specific decision-making difficulties that can impact medication management.

No evidence for true training and transfer effects after inhibitory control training in young healthy adults.

PubMed

Enge, Sören; Behnke, Alexander; Fleischhauer, Monika; Küttler, Lena; Kliegel, Matthias; Strobel, Alexander

2014-07-01

Recent studies reported that training of working memory may improve performance in the trained function and beyond. Other executive functions, however, have been rarely or not yet systematically examined. The aim of this study was to test the effectiveness of inhibitory control (IC) training to produce true training-related function improvements in a sample of 122 healthy adults using a randomized, double-blind pretest/posttest/follow-up design. Two groups performed either adaptive (training group) or nonadaptive (active control) versions of go/no-go and stop-signal tasks for 3 weeks. Training gains as well as near-transfer to an untrained Stroop task and far-transfer to psychometric fluid intelligence were explored. Although the adaptive group could substantially improve overall IC task performance after training, no differences to the active control group occurred, neither at posttest nor at follow-up testing. A large decrease in response latency from pre- to posttest (and from pretest to 4 months' follow-up testing) was found when the training group was compared to the passive control group, which, however, does not sufficiently control for possible confounds. Thus, no conclusive evidence was found that this performance increase mirrors a true increase in IC function. The fact that training improvement was mainly related to response latency may indicate that individuals were more focused on performance gains in the prepotent go trials but less on the stop trials to meet the requirements of the tasks as well as possible. The challenges for response inhibition training studies are extensively discussed. PsycINFO Database Record (c) 2014 APA, all rights reserved.

The contribution of executive functions to emergent mathematic skills in preschool children.

PubMed

Espy, Kimberly Andrews; McDiarmid, Melanie M; Cwik, Mary F; Stalets, Melissa Meade; Hamby, Arlena; Senn, Theresa E

2004-01-01

Mathematical ability is related to both activation of the prefrontal cortex in neuroimaging studies of adults and to executive functions in school-age children. The purpose of this study was to determine whether executive functions were related to emergent mathematical proficiency in preschool children. Preschool children (N = 96) were administered an executive function battery that was reduced empirically to working memory (WM), inhibitory control (IC), and shifting abilities by calculating composite scores derived from principal component analysis. Both WM and IC predicted early arithmetic competency, with the observed relations robust after controlling statistically for child age, maternal education, and child vocabulary. Only IC accounted for unique variance in mathematical skills, after the contribution of other executive functions were controlled statistically as well. Specific executive functions are related to emergent mathematical proficiency in this age range. Longitudinal studies using structural equation modeling are necessary to better characterize these ontogenetic relations.

Executive function predicts artificial language learning

PubMed Central

Kapa, Leah L.; Colombo, John

2017-01-01

Previous research suggests executive function (EF) advantages among bilinguals compared to monolingual peers, and these advantages are generally attributed to experience controlling two linguistic systems. However, the possibility that the relationship between bilingualism and EF might be bidirectional has not been widely considered; while experience with two languages might improve EF, better EF skills might also facilitate language learning. In the current studies, we tested whether adults’ and preschool children’s EF abilities predicted success in learning a novel artificial language. After controlling for working memory and English receptive vocabulary, adults’ artificial language performance was predicted by their inhibitory control ability (Study 1) and children’s performance was predicted by their attentional monitoring and shifting ability (Study 2). These findings provide preliminary evidence suggesting that EF processes may be employed during initial stages of language learning, particularly vocabulary acquisition, and support the possibility of a bidirectional relationship between EF and language acquisition. PMID:29129958

The effect of retrieval on recall of information in individuals with posttraumatic stress disorder.

PubMed

Amir, Nader; Badour, Christal L; Freese, Bettina

2009-05-01

Cognitive theories of posttraumatic stress disorder (PTSD) suggest that associative memory processes may play a crucial role in the development and maintenance of the disorder. In the current study we examined the effect of associative pair rehearsal on recall ability for threatening and non-threatening information using the retrieval-practice paradigm in individuals with PTSD, traumatized controls (TC), and non-traumatized controls (NAC). Across word type, NACs demonstrated a typical retrieval-induced forgetting effect. However, individuals with PTSD benefited less from rehearsal, and failed to inhibit recall of unpracticed words in practiced categories. Participants in the TC group displayed a retrieval-induced forgetting effect similar to those individuals in the PTSD group. These findings are consistent with research indicating that individuals with PTSD may derive less benefit from rehearsal and display general inhibitory difficulties when compared to non-traumatized controls.

Treadmill training as an augmentation treatment for Alzheimer's disease: a pilot randomized controlled study.

PubMed

Arcoverde, Cynthia; Deslandes, Andrea; Moraes, Helena; Almeida, Cloyra; Araujo, Narahyana Bom de; Vasques, Paulo Eduardo; Silveira, Heitor; Laks, Jerson

2014-03-01

To assess the effect of aerobic exercise on the cognition and functional capacity in Alzheimer's disease (AD) patients. Elderly (n=20) with mild dementia (NINCDS-ADRDA/CDR1) were randomly assigned to an exercise group (EG) on a treadmill (30 minutes, twice a week and moderate intensity of 60% VO₂max) and control group (GC) 10 patients. The primary outcome measure was the cognitive function using Cambridge Cognitive Examination (CAMCOG). Specifics instruments were also applied to evaluate executive function, memory, attention and concentration, cognitive flexibility, inhibitory control and functional capacity. After 16 weeks, the EG showed improvement in cognition CAMCOG whereas the CG declined. Compared to the CG, the EG presented significant improvement on the functional capacity. The analysis of the effect size has shown a favorable response to the physical exercise in all dependent variables. Walking on treadmill may be recommended as an augmentation treatment for patients with AD.

Task-Based and Questionnaire Measures of Inhibitory Control Are Differentially Affected by Acute Food Restriction and by Motivationally Salient Food Stimuli in Healthy Adults

PubMed Central

Bartholdy, Savani; Cheng, Jiumu; Schmidt, Ulrike; Campbell, Iain C.; O'Daly, Owen G.

2016-01-01

Adaptive eating behaviors are dependent on an interaction between motivational states (e.g., hunger) and the ability to control one's own behavior (inhibitory control). Indeed, behavioral paradigms are emerging that seek to train inhibitory control to improve eating behavior. However, inhibitory control is a multifaceted concept, and it is not yet clear how different types (e.g., reactive motor inhibition, proactive motor inhibition, reward-related inhibition) are affected by hunger. Such knowledge will provide insight into the contexts in which behavioral training paradigms would be most effective. The present study explored the impact of promoting a “need” state (hunger) together with motivationally salient distracting stimuli (food/non-food images) on inhibitory control in 46 healthy adults. Participants attended two study sessions, once after eating breakfast as usual and once after acute food restriction on the morning of the session. In each session, participants completed questionnaires on hunger, mood and inhibitory control, and undertook task-based measures of inhibitory control, and had physiological measurements (height, weight, and blood glucose) obtained by a researcher. Acute food restriction influenced task-based assessments but not questionnaire measures of inhibitory control, suggesting that hunger affects observable behavioral control but not self-reported inhibitory control. After acute food restriction, participants showed greater temporal discounting (devaluation of future rewards), and subjective hunger and these were inversely correlated with stop accuracy on the stop signal task. Finally, participants generally responded faster when food-related distractor images were presented, compared to non-food images, independent of state. This suggests that although food stimuli motivate approach behavior, stimulus relevance does not impact inhibitory control in healthy individuals, nor interact with motivational state. These findings may provide some explanation for poorer inhibitory control often reported in studies of individuals who practice restraint over eating. PMID:27621720

14- to 16-Month-Olds Attend to Distinct Labels in an Inductive Reasoning Task.

PubMed

Switzer, Jessica L; Graham, Susan A

2017-01-01

We examined how naming objects with unique labels influenced infants' reasoning about the non-obvious properties of novel objects. Seventy 14- to 16-month-olds participated in an imitation-based inductive inference task during which they were presented with target objects possessing a non-obvious sound property, followed by test objects that varied in shape similarity in comparison to the target. Infants were assigned to one of two groups: a No Label group in which objects were introduced with a general attentional phrase (i.e., "Look at this one") and a Distinct Label group in which target and test objects were labeled with two distinct count nouns (i.e., fep vs. wug ). Infants in the Distinct Label group performed significantly fewer target actions on the high-similarity objects than infants in the No Label group but did not differ in performance of actions on the low-similarity object. Within the Distinct Label group, performance on the inductive inference task was related to age, but not to working memory, inhibitory control, or vocabulary. Within the No Label condition, performance on the inductive inference task was related to a measure of inhibitory control. Our findings suggest that between 14- and 16-months, infants begin to use labels to carve out distinct categories, even when objects are highly perceptually similar.

Voluntary inhibitory motor control over involuntary tic movements.

PubMed

Ganos, Christos; Rothwell, John; Haggard, Patrick

2018-03-06

Inhibitory control is crucial for normal adaptive motor behavior. In hyperkinesias, such as tics, disinhibition within the cortico-striato-thalamo-cortical loops is thought to underlie the presence of involuntary movements. Paradoxically, tics are also subject to voluntary inhibitory control. This puzzling clinical observation questions the traditional definition of tics as purely involuntary motor behaviors. Importantly, it suggests novel insights into tic pathophysiology. In this review, we first define voluntary inhibitory tic control and compare it with other notions of tic control from the literature. We then examine the association between voluntary inhibitory tic control with premonitory urges and review evidence linking voluntary tic inhibition to other forms of executive control of action. We discuss the somatotopic selectivity and the neural correlates of voluntary inhibitory tic control. Finally, we provide a scientific framework with regard to the clinical relevance of the study of voluntary inhibitory tic control within the context of the neurodevelopmental disorder of Tourette syndrome. We identify current knowledge gaps that deserve attention in future research. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

Predictors of Longitudinal Growth in Inhibitory Control in Early Childhood

PubMed Central

Moilanen, Kristin L.; Shaw, Daniel S.; Dishion, Thomas J.; Gardner, Frances; Wilson, Melvin

2009-01-01

In the current study, we examined latent growth in 731 young children’s inhibitory control from ages 2 to 4, and whether demographic characteristics or parenting behaviors were related to initial levels and growth in inhibitory control. As part of an ongoing longitudinal evaluation of the Family Check-Up (FCU), children’s inhibitory control was assessed yearly at ages 2, 3, and 4. Inhibitory control was initially low and increased linearly to age 4. High levels of harsh parenting and male gender were associated with low initial status in inhibitory control. High levels of supportive parenting were associated with faster growth. Extreme family poverty and African American ethnicity were also associated with slower growth. The results highlight parenting as a target for early interventions in contexts of high socioeconomic risk. PMID:20376201

Inhibitory control and harsh discipline as predictors of externalizing problems in young children: a comparative study of U.S., Chinese, and Japanese preschoolers.

PubMed

Olson, Sheryl L; Tardif, Twila Z; Miller, Alison; Felt, Barbara; Grabell, Adam S; Kessler, Daniel; Wang, Li; Karasawa, Mayumi; Hirabayashi, Hidemi

2011-11-01

We examined associations between child inhibitory control, harsh parental discipline and externalizing problems in 120 4 year-old boys and girls in the US, China, and Japan. Individual differences in children's inhibitory control abilities, assessed using behavioral tasks and maternal ratings, were related to child externalizing problems reported by mothers. As predicted, both child inhibitory control and maternal harsh discipline made significant contributions to child externalizing problems in all three countries. Across countries, child inhibitory control and maternal harsh discipline made significant independent contributions to early externalizing problems, suggesting an additive model of association. Our findings supported the cross-cultural generalizability of child inhibitory control and parental harsh punishment as key contributors to disruptive behavior in young children.

INHIBITORY EFFECTS OF PERCHLOROETHYLENE ON HUMAN NEURONAL NICOTINIC ACETYLCHOLINE RECEPTORS.

EPA Science Inventory

Perchloroethylene (PERC) is a volatile organic solvent with a variety of industrial uses. PERC exposure has been shown to cause adverse neurological effects including deficits in vision and memory in exposed individuals. Despite knowledge of these effects, the mechanisms by whi...

Alcohol-induced impairment of inhibitory control is linked to attenuated brain responses in right fronto-temporal cortex

PubMed Central

Gan, Gabriela; Guevara, Alvaro; Marxen, Michael; Neumann, Maike; Jünger, Elisabeth; Kobiella, Andrea; Mennigen, Eva; Pilhatsch, Maximilian; Schwarz, Daniel; Zimmermann, Ulrich S.; Smolka, Michael N.

2014-01-01

Background A self-enhancing loop between impaired inhibitory control under alcohol and alcohol consumption has been proposed as a possible mechanism underlying dysfunctional drinking in susceptible people. However, the neural underpinnings of alcohol-induced impairment of inhibitory control are widely unknown. Methods We measured inhibitory control in fifty young adults with a stop-signal task (SST) during functional magnetic resonance imaging (fMRI). In a single-blind placebo-controlled cross-over design, all participants performed the SST once under alcohol with a breath alcohol concentration (BrAC) of 0.6 g/kg, and once under placebo. In addition, alcohol consumption was assessed using a free-access alcohol self-administration (ASA) paradigm in the same participants. Results Inhibitory control was robustly decreased under alcohol compared to placebo indicated by longer stop-signal reaction times (SSRTs). On the neural level, impaired inhibitory control under alcohol was associated with attenuated brain responses in the right fronto-temporal portion of the inhibition network that supports the attentional capture of infrequent stop-signals, and subsequent updating of action plans from response execution to inhibition. Furthermore, the extent of alcohol-induced impairment of inhibitory control predicted free-access alcohol consumption. Conclusion We suggest that during inhibitory control alcohol affects cognitive processes preceding actual motor inhibition. Under alcohol, decreased brain responses in right fronto-temporal areas might slow down the attentional capture of infrequent stop-signals and subsequent updating of action plans which leads to impaired inhibitory control. In turn, pronounced alcohol-induced impairment of inhibitory control may enhance alcohol consumption in young adults which might promote future alcohol problems. PMID:24560581

Alcohol-induced impairment of inhibitory control is linked to attenuated brain responses in right fronto-temporal cortex.

PubMed

Gan, Gabriela; Guevara, Alvaro; Marxen, Michael; Neumann, Maike; Jünger, Elisabeth; Kobiella, Andrea; Mennigen, Eva; Pilhatsch, Maximilian; Schwarz, Daniel; Zimmermann, Ulrich S; Smolka, Michael N

2014-11-01

A self-enhancing loop between impaired inhibitory control under alcohol and alcohol consumption has been proposed as a possible mechanism underlying dysfunctional drinking in susceptible people. However, the neural underpinnings of alcohol-induced impairment of inhibitory control are widely unknown. We measured inhibitory control in 50 young adults with a stop-signal task during functional magnetic resonance imaging. In a single-blind placebo-controlled cross-over design, all participants performed the stop-signal task once under alcohol with a breath alcohol concentration of .6 g/kg and once under placebo. In addition, alcohol consumption was assessed with a free-access alcohol self-administration paradigm in the same participants. Inhibitory control was robustly decreased under alcohol compared with placebo, indicated by longer stop-signal reaction times. On the neural level, impaired inhibitory control under alcohol was associated with attenuated brain responses in the right fronto-temporal portion of the inhibition network that supports the attentional capture of infrequent stop-signals and subsequent updating of action plans from response execution to inhibition. Furthermore, the extent of alcohol-induced impairment of inhibitory control predicted free-access alcohol consumption. We suggest that during inhibitory control alcohol affects cognitive processes preceding actual motor inhibition. Under alcohol, decreased brain responses in right fronto-temporal areas might slow down the attentional capture of infrequent stop-signals and subsequent updating of action plans, which leads to impaired inhibitory control. In turn, pronounced alcohol-induced impairment of inhibitory control might enhance alcohol consumption in young adults, which might promote future alcohol problems. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

The Role of Inhibitory Control in Behavioral and Physiological Expressions of Toddler Executive Function

ERIC Educational Resources Information Center

Morasch, Katherine C.; Bell, Martha Ann

2011-01-01

A total of 81 toddlers (24-27 months of age) participated in a biobehavioral investigation of inhibitory control. Maternal report measures of inhibitory control were related to laboratory tasks assessing inhibitory abilities under conditions of conflict, delay, and compliance challenge as well as toddler verbal ability. In addition, unique…

A role for hippocampal gastrin-releasing peptide receptors in extinction of aversive memory.

PubMed

Luft, Tatiana; Flores, Debora G; Vianna, Monica R M; Schwartsmann, Gilberto; Roesler, Rafael; Izquierdo, Ivan

2006-06-26

Although the gastrin-releasing peptide receptor has been implicated in memory consolidation, previous studies have not examined whether it is involved in extinction. Here we show that gastrin-releasing peptide receptor blockade in the hippocampus disrupts extinction of aversive memory. Male rats were trained in inhibitory avoidance conditioning and then returned repeatedly to the training context without shock on a daily basis for 3 days. Infusion of a gastrin-releasing peptide receptor antagonist or the protein synthesis inhibitor anisomycin into the dorsal hippocampus immediately after the first extinction session blocked extinction. These drugs did not affect performance in subsequent sessions when the first extinction session (1 day after training) was omitted. The results indicate that hippocampal gastrin-releasing peptide receptors are involved in memory extinction.

Parallel prefrontal pathways reach distinct excitatory and inhibitory systems in memory-related rhinal cortices.

PubMed

Bunce, Jamie G; Zikopoulos, Basilis; Feinberg, Marcia; Barbas, Helen

2013-12-15

To investigate how prefrontal cortices impinge on medial temporal cortices we labeled pathways from the anterior cingulate cortex (ACC) and posterior orbitofrontal cortex (pOFC) in rhesus monkeys to compare their relationship with excitatory and inhibitory systems in rhinal cortices. The ACC pathway terminated mostly in areas 28 and 35 with a high proportion of large terminals, whereas the pOFC pathway terminated mostly through small terminals in area 36 and sparsely in areas 28 and 35. Both pathways terminated in all layers. Simultaneous labeling of pathways and distinct neurochemical classes of inhibitory neurons, followed by analyses of appositions of presynaptic and postsynaptic fluorescent signal, or synapses, showed overall predominant association with spines of putative excitatory neurons, but also significant interactions with presumed inhibitory neurons labeled for calretinin, calbindin, or parvalbumin. In the upper layers of areas 28 and 35 the ACC pathway was associated with dendrites of neurons labeled with calretinin, which are thought to disinhibit neighboring excitatory neurons, suggesting facilitated hippocampal access. In contrast, in area 36 pOFC axons were associated with dendrites of calbindin neurons, which are poised to reduce noise and enhance signal. In the deep layers, both pathways innervated mostly dendrites of parvalbumin neurons, which strongly inhibit neighboring excitatory neurons, suggesting gating of hippocampal output to other cortices. These findings suggest that the ACC, associated with attention and context, and the pOFC, associated with emotional valuation, have distinct contributions to memory in rhinal cortices, in processes that are disrupted in psychiatric diseases. Copyright © 2013 Wiley Periodicals, Inc.

Memory Erasure Experiments Indicate a Critical Role of CaMKII in Memory Storage.

PubMed

Rossetti, Tom; Banerjee, Somdeb; Kim, Chris; Leubner, Megan; Lamar, Casey; Gupta, Pooja; Lee, Bomsol; Neve, Rachael; Lisman, John

2017-09-27

The abundant synaptic protein CaMKII is necessary for long-term potentiation (LTP) and memory. However, whether CaMKII is required only during initial processes or whether it also mediates memory storage remains unclear. The most direct test of a storage role is the erasure test. In this test, a putative memory molecule is inhibited after learning. The key prediction is that this should produce persistent memory erasure even after the inhibitory agent is removed. We conducted this test using transient viral (HSV) expression of dominant-negative CaMKII-alpha (K42M) in the hippocampus. This produced persistent erasure of conditioned place avoidance. As an additional test, we found that expression of activated CaMKII (T286D/T305A/T306A) impaired place avoidance, a result not expected if a process other than CaMKII stores memory. Our behavioral results, taken together with prior experiments on LTP, strongly support a critical role of CaMKII in LTP maintenance and memory storage. Copyright © 2017 Elsevier Inc. All rights reserved.

Modulating inhibitory control with direct current stimulation of the superior medial frontal cortex.

PubMed

Hsu, Tzu-Yu; Tseng, Lin-Yuan; Yu, Jia-Xin; Kuo, Wen-Jui; Hung, Daisy L; Tzeng, Ovid J L; Walsh, Vincent; Muggleton, Neil G; Juan, Chi-Hung

2011-06-15

The executive control of voluntary action involves not only choosing from a range of possible actions but also the inhibition of responses as circumstances demand. Recent studies have demonstrated that many clinical populations, such as people with attention-deficit hyperactivity disorder, exhibit difficulties in inhibitory control. One prefrontal area that has been particularly associated with inhibitory control is the pre-supplementary motor area (Pre-SMA). Here we applied non-invasive transcranial direct current stimulation (tDCS) over Pre-SMA to test its role in this behavior. tDCS allows for current to be applied in two directions to selectively excite or suppress the neural activity of Pre-SMA. Our results showed that anodal tDCS improved efficiency of inhibitory control. Conversely, cathodal tDCS showed a tendency towards impaired inhibitory control. To our knowledge, this is the first demonstration of non-invasive intervention tDCS altering subjects' inhibitory control. These results further our understanding of the neural bases of inhibitory control and suggest a possible therapeutic intervention method for clinical populations. Copyright © 2011 Elsevier Inc. All rights reserved.

GABA from reactive astrocytes impairs memory in mouse models of Alzheimer's disease.

PubMed

Jo, Seonmi; Yarishkin, Oleg; Hwang, Yu Jin; Chun, Ye Eun; Park, Mijeong; Woo, Dong Ho; Bae, Jin Young; Kim, Taekeun; Lee, Jaekwang; Chun, Heejung; Park, Hyun Jung; Lee, Da Yong; Hong, Jinpyo; Kim, Hye Yun; Oh, Soo-Jin; Park, Seung Ju; Lee, Hyo; Yoon, Bo-Eun; Kim, YoungSoo; Jeong, Yong; Shim, Insop; Bae, Yong Chul; Cho, Jeiwon; Kowall, Neil W; Ryu, Hoon; Hwang, Eunmi; Kim, Daesoo; Lee, C Justin

2014-08-01

In Alzheimer's disease (AD), memory impairment is the most prominent feature that afflicts patients and their families. Although reactive astrocytes have been observed around amyloid plaques since the disease was first described, their role in memory impairment has been poorly understood. Here, we show that reactive astrocytes aberrantly and abundantly produce the inhibitory gliotransmitter GABA by monoamine oxidase-B (Maob) and abnormally release GABA through the bestrophin 1 channel. In the dentate gyrus of mouse models of AD, the released GABA reduces spike probability of granule cells by acting on presynaptic GABA receptors. Suppressing GABA production or release from reactive astrocytes fully restores the impaired spike probability, synaptic plasticity, and learning and memory in the mice. In the postmortem brain of individuals with AD, astrocytic GABA and MAOB are significantly upregulated. We propose that selective inhibition of astrocytic GABA synthesis or release may serve as an effective therapeutic strategy for treating memory impairment in AD.

High sucrose consumption induces memory impairment in rats associated with electrophysiological modifications but not with metabolic changes in the hippocampus.

PubMed

Lemos, C; Rial, D; Gonçalves, F Q; Pires, J; Silva, H B; Matheus, F C; da Silva, A C; Marques, J M; Rodrigues, R J; Jarak, I; Prediger, R D; Reis, F; Carvalho, R A; Pereira, F C; Cunha, R A

2016-02-19

High sugar consumption is a risk factor for metabolic disturbances leading to memory impairment. Thus, rats subject to high sucrose intake (HSu) develop a metabolic syndrome and display memory deficits. We now investigated if these HSu-induced memory deficits were associated with metabolic and electrophysiological alterations in the hippocampus. Male Wistar rats were submitted for 9 weeks to a sucrose-rich diet (35% sucrose solution) and subsequently to a battery of behavioral tests; after sacrifice, their hippocampi were collected for ex vivo high-resolution magic angle spinning (HRMAS) metabolic characterization and electrophysiological extracellular recordings in slices. HSu rats displayed a decreased memory performance (object displacement and novel object recognition tasks) and helpless behavior (forced swimming test), without altered locomotion (open field). HRMAS analysis indicated a similar hippocampal metabolic profile of HSu and control rats. HSu rats also displayed no change of synaptic transmission and plasticity (long-term potentiation) in hippocampal Schaffer fibers-CA1 pyramid synapses, but had decreased amplitude of long-term depression in the temporoammonic (TA) pathway. Furthermore, HSu rats had an increased density of inhibitory adenosine A1 receptors (A1R), that translated into a greater potency of A1R in Schaffer fiber synapses, but not in the TA pathway, whereas the endogenous activation of A1R in HSu rats was preserved in the TA pathway but abolished in Schaffer fiber synapses. These results suggest that HSu triggers a hippocampal-dependent memory impairment that is not associated with altered hippocampal metabolism but is probably related to modified synaptic plasticity in hippocampal TA synapses. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Standardized extract of Lactuca sativa Linn. and its fractions abrogates scopolamine-induced amnesia in mice: A possible cholinergic and antioxidant mechanism.

PubMed

Malik, Jai; Kaur, Jagpreet; Choudhary, Sunayna

2018-06-01

The present study was designed to evaluate the efficacy of Lactuca sativa (LS) Linn. (Asteraceae) against scopolamine-induced amnesia and to validate its traditional claim as memory enhancer. Ethanol extract of fresh LS leaves (LSEE), standardized on the basis of quercetin content, was successively partitioned using various solvents viz., hexane, ethyl acetate, and n-butanol in increasing order of polarity. LSEE (50, 100, and 200 mg/kg) and its various fractions (at a dose equivalent to dose of LSEE exhibiting maximum activity), administered orally for 14 days, were evaluated for their memory enhancing effect against scopolamine-induced (1 mg/kg, i.p.) amnesia in 3-4 months old male Laca mice (n = 6 in each group). The memory enhancing effect was evaluated using behavioural (elevated plus maze, novel object recognition and Morris water maze tests) and biochemical parameters (acetylcholinesterase activity, malonaldehyde, superoxide dismutase, nitrite, catalase, and reduced gultathione content). The results of the test substances were compared with both scopolamine and donepezil that was used as a standard memory enhancer and acetylcholinesterase inhibitor. Scopolamine elicit marked deterioration of memory and alteration in biochemical parameters in comparison to the control group. LSEE and its n-butanol and aqueous fractions significantly (P < 0.05) attenuated the scopolamine-induced amnesia that was evident in all the behavioural and biochemical test parameters. LSEE (200 mg/kg) and n-butanol fraction (15 mg/kg) exhibited maximum anti-amnesic effect among various tested dose levels. The results exhibited that LS prophylaxis attenuated scopolamine-induced memory impairment through its acetylcholinesterase inhibitory and antioxidant activity validating its traditional claim.

Measures of Dogs' Inhibitory Control Abilities Do Not Correlate across Tasks

PubMed Central

Brucks, Désirée; Marshall-Pescini, Sarah; Wallis, Lisa Jessica; Huber, Ludwig; Range, Friederike

2017-01-01

Inhibitory control, the ability to overcome prepotent but ineffective behaviors, has been studied extensively across species, revealing the involvement of this ability in many different aspects of life. While various different paradigms have been created in order to measure inhibitory control, only a limited number of studies have investigated whether such measurements indeed evaluate the same underlying mechanism, especially in non-human animals. In humans, inhibitory control is a complex construct composed of distinct behavioral processes rather than of a single unified measure. In the current study, we aimed to investigate the validity of inhibitory control paradigms in dogs. Sixty-seven dogs were tested in a battery consisting of frequently used inhibitory control tests. Additionally, dog owners were asked to complete an impulsivity questionnaire about their dog. No correlation of dogs' performance across tasks was found. In order to understand whether there are some underlying behavioral aspects explaining dogs' performance across tests, we performed principle component analyses. Results revealed that three components (persistency, compulsivity and decision speed) explained the variation across tasks. The questionnaire and dogs' individual characteristics (i.e., age and sex) provided only limited information for the derived components. Overall, results suggest that no unique measurement for inhibitory control exists in dogs, but tests rather measure different aspects of this ability. Considering the context-specificity of inhibitory control in dogs and most probably also in other non-human animals, extreme caution is needed when making conclusions about inhibitory control abilities based on a single test. PMID:28596749

Rosemary, the beneficial chemistry of a garden herb.

PubMed

Hanson, James R

2016-01-01

The major natural products that are present in the garden herb, rosemary (Rosmarinus officinalis) including the mono di- and triterpenoid, flavonoid and phenolic constituents together with their biological activity as anti-microbial, anti-oxidant, anti-inflammatory, memory-enhancing and tumour-inhibitory agents, are reviewed.

Sociodemographic risk, parenting, and inhibitory control in early childhood: the role of respiratory sinus arrhythmia.

PubMed

Holochwost, Steven J; Volpe, Vanessa V; Gueron-Sela, Noa; Propper, Cathi B; Mills-Koonce, W Roger

2018-03-13

Deficits of inhibitory control in early childhood are linked to externalizing behaviors and attention problems. While environmental factors and physiological processes are associated with its etiology, few studies have examined how these factors jointly predict inhibitory control. This study examined whether respiratory sinus arrhythmia (RSA) functioned as a mediator or moderator of both cumulative sociodemographic risk and parenting behaviors on inhibitory control during early childhood. The sample included 206 children and their biological mothers. At 24, 30, and 36 months of child age dyads participated in a series of laboratory visits in which sociodemographic, parenting, and baseline RSA (RSAB) data were collected. Inhibitory control was assessed at 36 months using a gift-wrap delay task. A series of structural equation models yielded no evidence that RSAB mediated the relations of risk or parenting and inhibitory control. RSAB moderated the effects of risk, such that high-risk children with low RSAB performed more poorly on tasks of inhibitory control, while high-risk children with high RSAB did not. These results suggest that higher levels of RSAB may mitigate the influence of environmental risk on the development of inhibitory control early childhood. © 2018 Association for Child and Adolescent Mental Health.

The Plasticity of Extinction: Contribution of the Prefrontal Cortex in Treating Addiction through Inhibitory Learning

PubMed Central

Gass, J. T.; Chandler, L. J.

2013-01-01

Theories of drug addiction that incorporate various concepts from the fields of learning and memory have led to the idea that classical and operant conditioning principles underlie the compulsiveness of addictive behaviors. Relapse often results from exposure to drug-associated cues, and the ability to extinguish these conditioned behaviors through inhibitory learning could serve as a potential therapeutic approach for those who suffer from addiction. This review will examine the evidence that extinction learning alters neuronal plasticity in specific brain regions and pathways. In particular, subregions of the prefrontal cortex (PFC) and their projections to other brain regions have been shown to differentially modulate drug-seeking and extinction behavior. Additionally, there is a growing body of research demonstrating that manipulation of neuronal plasticity can alter extinction learning. Therefore, the ability to alter plasticity within areas of the PFC through pharmacological manipulation could facilitate the acquisition of extinction and provide a novel intervention to aid in the extinction of drug-related memories. PMID:23750137

A novel UCS memory retrieval-extinction procedure to inhibit relapse to drug seeking.

PubMed

Luo, Yi-xiao; Xue, Yan-xue; Liu, Jian-feng; Shi, Hai-shui; Jian, Min; Han, Ying; Zhu, Wei-li; Bao, Yan-ping; Wu, Ping; Ding, Zeng-bo; Shen, Hao-wei; Shi, Jie; Shaham, Yavin; Lu, Lin

2015-07-14

We recently reported that a conditioned stimulus (CS) memory retrieval-extinction procedure decreases reinstatement of cocaine and heroin seeking in rats and heroin craving in humans. Here we show that non-contingent cocaine or methylphenidate injections (UCS retrieval) 1 h before the extinction sessions decreases cocaine-priming-induced reinstatement, spontaneous recovery, and renewal of cocaine seeking in rats. Unlike the CS-based memory retrieval-extinction procedure, the UCS memory retrieval manipulation decreases renewal and reinstatement of cocaine seeking in the presence of cocaine cues that were not present during extinction training and also decreases cocaine seeking when the procedure commences after 28 days of abstinence. The inhibitory effect of the UCS retrieval manipulation on cocaine-priming-induced reinstatement is mediated by regulation of AMPA-receptor endocytosis in the basolateral amygdala. The UCS memory retrieval-extinction procedure has superior relapse prevention characteristics than the CS memory retrieval-extinction procedure and could be a promising method for decreasing relapse in human addicts.

A novel UCS memory retrieval-extinction procedure to inhibit relapse to drug seeking

PubMed Central

Luo, Yi-xiao; Xue, Yan-xue; Liu, Jian-feng; Shi, Hai-shui; Jian, Min; Han, Ying; Zhu, Wei-li; Bao, Yan-ping; Wu, Ping; Ding, Zeng-bo; Shen, Hao-wei; Shi, Jie; Shaham, Yavin; Lu, Lin

2015-01-01

We recently reported that a conditioned stimulus (CS) memory retrieval-extinction procedure decreases reinstatement of cocaine and heroin seeking in rats and heroin craving in humans. Here we show that non-contingent cocaine or methylphenidate injections (UCS retrieval) 1 h before the extinction sessions decreases cocaine-priming-induced reinstatement, spontaneous recovery, and renewal of cocaine seeking in rats. Unlike the CS-based memory retrieval-extinction procedure, the UCS memory retrieval manipulation decreases renewal and reinstatement of cocaine seeking in the presence of cocaine cues that were not present during extinction training and also decreases cocaine seeking when the procedure commences after 28 days of abstinence. The inhibitory effect of the UCS retrieval manipulation on cocaine-priming-induced reinstatement is mediated by regulation of AMPA-receptor endocytosis in the basolateral amygdala. The UCS memory retrieval-extinction procedure has superior relapse prevention characteristics than the CS memory retrieval-extinction procedure and could be a promising method for decreasing relapse in human addicts. PMID:26169171

Suppressing unwanted memories reduces their unconscious influence via targeted cortical inhibition

PubMed Central

Gagnepain, Pierre; Henson, Richard N.; Anderson, Michael C.

2014-01-01

Suppressing retrieval of unwanted memories reduces their later conscious recall. It is widely believed, however, that suppressed memories can continue to exert strong unconscious effects that may compromise mental health. Here we show that excluding memories from awareness not only modulates medial temporal lobe regions involved in explicit retention, but also neocortical areas underlying unconscious expressions of memory. Using repetition priming in visual perception as a model task, we found that excluding memories of visual objects from consciousness reduced their later indirect influence on perception, literally making the content of suppressed memories harder for participants to see. Critically, effective connectivity and pattern similarity analysis revealed that suppression mechanisms mediated by the right middle frontal gyrus reduced activity in neocortical areas involved in perceiving objects and targeted the neural populations most activated by reminders. The degree of inhibitory modulation of the visual cortex while people were suppressing visual memories predicted, in a later perception test, the disruption in the neural markers of sensory memory. These findings suggest a neurobiological model of how motivated forgetting affects the unconscious expression of memory that may be generalized to other types of memory content. More generally, they suggest that the century-old assumption that suppression leaves unconscious memories intact should be reconsidered. PMID:24639546

Got Rhythm? Better Inhibitory Control Is Linked with More Consistent Drumming and Enhanced Neural Tracking of the Musical Beat in Adult Percussionists and Nonpercussionists.

PubMed

Slater, Jessica; Ashley, Richard; Tierney, Adam; Kraus, Nina

2018-01-01

Musical rhythm engages motor and reward circuitry that is important for cognitive control, and there is evidence for enhanced inhibitory control in musicians. We recently revealed an inhibitory control advantage in percussionists compared with vocalists, highlighting the potential importance of rhythmic expertise in mediating this advantage. Previous research has shown that better inhibitory control is associated with less variable performance in simple sensorimotor synchronization tasks; however, this relationship has not been examined through the lens of rhythmic expertise. We hypothesize that the development of rhythm skills strengthens inhibitory control in two ways: by fine-tuning motor networks through the precise coordination of movements "in time" and by activating reward-based mechanisms, such as predictive processing and conflict monitoring, which are involved in tracking temporal structure in music. Here, we assess adult percussionists and nonpercussionists on inhibitory control, selective attention, basic drumming skills (self-paced, paced, and continuation drumming), and cortical evoked responses to an auditory stimulus presented on versus off the beat of music. Consistent with our hypotheses, we find that better inhibitory control is correlated with more consistent drumming and enhanced neural tracking of the musical beat. Drumming variability and the neural index of beat alignment each contribute unique predictive power to a regression model, explaining 57% of variance in inhibitory control. These outcomes present the first evidence that enhanced inhibitory control in musicians may be mediated by rhythmic expertise and provide a foundation for future research investigating the potential for rhythm-based training to strengthen cognitive function.

Successful Vaccination Induces Multifunctional Memory T-Cell Precursors Associated with Early Control of Hepatitis C Virus

PubMed Central

Park, Su-Hyung; Shin, Eui-Cheol; Capone, Stefania; Caggiari, Laura; De Re, Valli; Nicosia, Alfredo; Folgori, Antonella; Rehermann, Barbara

2012-01-01

Background & Aims T cells are an important component for development of a vaccine against hepatitis C virus (HCV), but little is known about the features of successful vaccine-induced T cells. Methods We compared the phenotype, function, and kinetics of vaccine-induced and infection-induced T cells in chimpanzees with HCV infection using multicolor flow cytometry and real-time PCR. Results In chimpanzees successfully vaccinated with recombinant adenovirus and DNA against HCV NS3-NS5, HCV-specific T cells appeared earlier, maintained better functionality, and persisted at higher frequencies, for a longer time after HCV-challenge, than those of mock-vaccinated chimpanzees. Vaccine-induced T cells displayed higher levels of CD127, a marker of memory precursors, and lower levels of programmed death (PD)-1 than infection-induced T cells. Vaccine-induced, but not infection-induced T cells, were multifunctional; their ability to secrete interferon-γ and tumor necrosis factor-α correlated with early expression of CD127 but not PD-1. Based on a comparison of vaccine-induced and infection-induced T cells from the same chimpanzee, the CD127+ memory precursor phenotype was induced by the vaccine itself, rather than by low viremia. In contrast, PD-1 induction correlated with viremia, and levels of intrahepatic PD-1, PD-L1, and 2,5-OAS-1 mRNAs correlated with peak titers of HCV. Conclusions Compared with infection, vaccination induced HCV-specific CD127+ T cells with high functionality that persisted at higher levels for a longer time. Control of viremia prevented upregulation of PD-1 on T cells, and induction of PD-1, PD-L1, and 2,5-OAS-1 in the liver. Early development of a memory T-cell phenotype and, via control of viremia, attenuation of the inhibitory PD1–PD-L1 pathway might be necessary components of successful vaccine-induced protection against HCV. PMID:22705008

Antioxidant and acetylcholinesterase inhibitory activities in vitro of different fraction of Huperzia squarrosa (Forst.) Trevis extract and attenuation of scopolamine-induced cognitive impairment in mice.

PubMed

Tung, Bui Thanh; Hai, Nguyen Thanh; Thu, Dang Kim

2017-02-23

Huperzia squarrosa (Forst.) Trevis is used in traditional medicine for improving memory deficits. Alkaloids, triterpenoids, flavonoids are main bioactive compounds of Huperzia squarrosa (Forst.) Trevis. This study aimed to investigate the antioxidant, AChE inhibitory activities in vitro of differents fraction of Huperzia squarrosa (Forst.) Trevis extract and neuroprotective effects of EtOAc fraction on scopolamine-induced cognitive impairment in mice. Antioxidant activity was measured by DPPH assay. AChE inhibitory effect in vitro and detail kinetic inhibition mechanism was evaluated by Ellman's assay. For in vivo assay, mice were administrated orally EtOAc fraction (150 and 300mg/kg) for fourteen days, and injected scopolamine at a dose of 1mg/kg intraperitoneally for four days to induce memory injured. The memory behaviors were evaluated using the Morris water maze. ACh levels were measured in brain tissue. Superoxide dismutase (SOD), glutathione peroxidase (GPx) activities, malondialdehyde and protein thiol groups were also evaluated in the brains. Our data also demonstrated that EtOAc fraction had the strongest antioxidant with an IC 50 value of 9.35±1.68µg/mL and AChE inhibitory activity with an IC 50 value of 23.44±3.14μg/mL in a concentration-dependent manner. Kinetic inhibition analysis indicated that EtOAc fraction was mixed inhibition type with Ki (representing the affinity of the enzyme and inhibitor) was 34.75±1.42µg/mL. Scopolamine significantly increased the escape latency time, reduced the crossings number, and swimming time in the target quadrant, while EtOAc fraction reversed these scopolamine-induced effects. EtOAc fraction significantly increased levels of acetylcholine in the brain. EtOAc fraction also significantly decreased oxidative stress in mice. Our data suggest that EtOAc fraction of Huperzia squarrosa extract exhibited a strong neuroprotective effect on cognitive impairment, and may be a potential candidate for the treatment of Alzheimer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Isolation of prolyl endopeptidase inhibitory peptides from a sodium caseinate hydrolysate.

PubMed

Hsieh, Cheng-Hong; Wang, Tzu-Yuan; Hung, Chuan-Chuan; Hsieh, You-Liang; Hsu, Kuo-Chiang

2016-01-01

Prolyl endopeptidase (PEP) has been associated with neurodegenerative disorders, and the PEP inhibitors can restore the memory loss caused by amnesic compounds. In this study, we investigated the PEP inhibitory activity of the enzymatic hydrolysates from various food protein sources, and isolated and identified the PEP inhibitory peptides. The hydrolysate obtained from sodium caseinate using bromelain (SC/BML) displayed the highest inhibitory activity of 86.8% at 5 mg mL(-1) in the present study, and its IC50 value against PEP was 0.77 mg mL(-1). The F-5 fraction by RP-HPLC (reversed-phase high performance liquid chromatography) from SC/BML showed the highest PEP inhibition rate of 88.4%, and 9 peptide sequences were identified. The synthetic peptides (1245.63-1787.94 Da) showed dose-dependent inhibition effects on PEP as competitive inhibitors with IC50 values between 29.8 and 650.5 μM. The results suggest that the peptides derived from sodium caseinate have the potential to be PEP inhibitors.

Alkaloids from roots of Stephania rotunda and their cholinesterase inhibitory activity.

PubMed

Hung, Tran Manh; Dang, Nguyen Hai; Kim, Jin Cheol; Jang, Han-Su; Ryoo, Sung-Woo; Lee, Jeong Hyung; Choi, Jae Sue; Bae, Kihwan; Min, Byung Sun

2010-10-01

In the course of screening plants used in folk medicine as memory enhancers, a 70% ethanolic extract of Stephania rotunda roots showed significant AChE inhibitory activity. Repeated column chromatography led to the isolation of a new protoberberine alkaloid, which we named stepharotudine (1), and seven known compounds (2-8). The chemical structures of the isolated compounds were elucidated based on extensive 1D and 2D NMR spectroscopic data. Compounds 1-8 were investigated in vitro for their anticholinesterase activity using a rat cortex AChE enzyme. © Georg Thieme Verlag KG Stuttgart · New York.

Inhibitory control and moral emotions: relations to reparation in early and middle childhood.

PubMed

Colasante, Tyler; Zuffianò, Antonio; Bae, Na Young; Malti, Tina

2014-01-01

This study examined links between inhibitory control, moral emotions (sympathy and guilt), and reparative behavior in an ethnically diverse sample of 4- and 8-year-olds (N = 162). Caregivers reported their children's reparative behavior, inhibitory control, and moral emotions through a questionnaire, and children reported their guilt feelings in response to a series of vignettes depicting moral transgressions. A hypothesized meditation model was tested with inhibitory control relating to reparative behavior through sympathy and guilt. In support of this model, results revealed that high levels of inhibitory control were associated with high levels of reparative behavior through high levels of sympathy and guilt. However, the mediation of inhibitory control to reparation through guilt was significant for 4-year-olds only. Results are discussed in relation to the temperamental, regulatory, and affective-moral precursors of reparative behavior in early and middle childhood.

Competition as rational action: Why young children cannot appreciate competitive games

PubMed Central

Priewasser, Beate; Roessler, Johannes; Perner, Josef

2013-01-01

Understanding rational actions requires perspective taking both with respect to means and with respect to objectives. This study addresses the question of whether the two kinds of perspective taking develop simultaneously or in sequence. It is argued that evidence from competitive behavior is best suited for settling this issue. A total of 71 kindergarten children between 3 and 5 years of age participated in a competitive game of dice and were tested on two traditional false belief stories as well as on several control tasks (verbal intelligence, inhibitory control, and working memory). The frequency of competitive poaching moves in the game correlated with correct predictions of mistaken actions in the false belief task. Hierarchical linear regression after controlling for age and control variables showed that false belief understanding significantly predicted the amount of poaching moves. The results speak for an interrelated development of the capacity for “instrumental” and “telic” perspective taking. They are discussed in the light of teleology as opposed to theory use and simulation. PMID:23182381

Attention problems, inhibitory control, and intelligence index overlapping genetic factors: a study in 9-, 12-, and 18-year-old twins.

PubMed

Polderman, Tinca J C; de Geus, Eco J C; Hoekstra, Rosa A; Bartels, Meike; van Leeuwen, Marieke; Verhulst, Frank C; Posthuma, Danielle; Boomsma, Dorret I

2009-05-01

It is assumed that attention problems (AP) are related to impaired executive functioning. We investigated the association between AP and inhibitory control and tested to what extent the association was due to genetic factors shared with IQ. Data were available from 3 independent samples of 9-, 12-, and 18-year-old twins and their siblings (1,209 participants). AP were assessed with checklists completed by multiple informants. Inhibitory control was measured with the Stroop Color Word Task (Stroop, 1935), and IQ with the Wechsler Intelligence Scale for Children (Wechsler et al., 2002) or Wechsler Adult Intelligence Scale (Wechsler, 1997). AP and inhibitory control were only correlated in the 12-year-old cohort (r = .18), but appeared non-significant after controlling for IQ. Significant correlations existed between AP and IQ in 9- and 12-year olds (r = -.26/-.34). Inhibitory control and IQ were correlated in all cohorts (r = -.16, -.24 and -.35, respectively). Genetic factors that influenced IQ also influenced inhibitory control. We conclude that the association between AP and inhibitory control as reported in the literature may largely derive from genetic factors that are shared with IQ.

Inhibitory control in bulimic-type eating disorders: a systematic review and meta-analysis.

PubMed

Wu, Mudan; Hartmann, Mechthild; Skunde, Mandy; Herzog, Wolfgang; Friederich, Hans-Christoph

2013-01-01

The aim of this meta-analysis was to summarise data from neuropsychological studies on inhibitory control to general and disease-salient (i.e., food/eating, body/shape) stimuli in bulimic-type eating disorders (EDs). A systematic literature search was conducted to identify eligible experimental studies. The outcome measures studied included the performance on established inhibitory control tasks in bulimic-type EDs. Effect sizes (Hedges' g) were pooled using random-effects models. For inhibitory control to general stimuli, 24 studies were included with a total of 563 bulimic-type ED patients: 439 had bulimia nervosa (BN), 42 had anorexia nervosa of the binge/purge subtype (AN-b), and 82 had binge eating disorder (BED). With respect to inhibitory control to disease-salient stimuli, 12 studies were included, representing a total of 218 BN patients. A meta-analysis of these studies showed decreased inhibitory control to general stimuli in bulimic-type EDs (g = -0.32). Subgroup analysis revealed impairments with a large effect in the AN-b group (g = -0.91), impairments with a small effect in the BN group (g = -0.26), and a non-significant effect in the BED group (g = -0.16). Greater impairments in inhibitory control were observed in BN patients when confronted with disease-salient stimuli (food/eating: g = -0.67; body/shape: g = -0.61). In conclusion, bulimic-type EDs showed impairments in inhibitory control to general stimuli with a small effect size. There was a significantly larger impairment in inhibitory control to disease salient stimuli observed in BN patients, constituting a medium effect size.

Negative Priming in Free Recall Reconsidered

ERIC Educational Resources Information Center

Hanczakowski, Maciej; Beaman, C. Philip; Jones, Dylan M.

2016-01-01

Negative priming in free recall is the finding of impaired memory performance when previously ignored auditory distracters become targets of encoding and retrieval. This negative priming has been attributed to an aftereffect of deploying inhibitory mechanisms that serve to suppress auditory distraction and minimize interference with learning and…

Dose-Response Effects of Exercise Duration and Recovery on Cognitive Functioning.

PubMed

Crush, Elizabeth A; Loprinzi, Paul D

2017-12-01

We examined the effects of different acute exercise durations and recovery periods on cognitive function in a counterbalanced, cross-over randomized controlled experiment. We placed 352 participants, aged 18 to 35 years into one of 16 experimental groups. Each participant visited the laboratory twice, separated by a 1-week washout period. Either Visit 1 or 2 consisted of an acute bout of moderate-intensity treadmill exercise (10, 20, 30, 45, or 60 minutes) followed by a period of rest (5, 15, or 30 minutes) before taking a set of five cognitive tests; the other visit consisted only of completing the cognitive tests (no exercise). Cognitive tests sampled multiple cognitive parameters, including reasoning, concentration, memory, attention, and planning. We found that a short recovery period (i.e., 5 minutes) may have a less favorable effect on planning ability but may be beneficial for memory. In addition, for various exercise durations and recovery periods, a Group × Time × Resting (nonexercise) A cognitive interaction effect was observed such that for both memory and inhibitory cognitive ability, acute exercise (vs. no exercise) had an enhancement effect for those with lower resting cognitive functioning. The length of the acute exercise recovery period and resting cognitive ability most influenced the association between exercise and cognitive function.

Neurocognitive effects of multivitamin supplementation on the steady state visually evoked potential (SSVEP) measure of brain activity in elderly women.

PubMed

Macpherson, Helen; Silberstein, Richard; Pipingas, Andrew

2012-10-10

Growing evidence suggests that dietary supplementation with selected micronutrients and nutraceuticals may have the potential to improve cognition in older adults. Fewer studies have investigated the effects of these substances on brain activity. This study was a randomised, double-blind, placebo-controlled trial, conducted to explore the effects of 16 weeks supplementation with a combined multivitamin, mineral and herbal formula on the steady state visually evoked potential (SSVEP) measure of brain electrical activity. Participants were elderly women aged between 64 and 79 years, with subjective memory complaints. Baseline and post-treatment SSVEP data was obtained for 22 participants in the multivitamin group and 19 in the placebo group. A spatial working memory delayed response task (DRT) was performed during the recording of the SSVEP. The results revealed that when compared to placebo, multivitamin supplementation delayed SSVEP latency during retrieval, interpreted as an increase in inhibitory neural processes. Behavioural performance on the DRT was not improved by the multivitamin, however improved performance accuracy was associated with increased midline central SSVEP latency. There were no multivitamin-related effects on SSVEP amplitude. These findings indicate that in the elderly, multivitamin supplementation may enhance neural efficiency during memory retrieval. Copyright © 2012 Elsevier Inc. All rights reserved.

Macrophage migration inhibitory factor as an incriminating agent in vitiligo.

PubMed

Farag, Azza Gaber Antar; Hammam, Mostafa Ahmed; Habib, Mona SalahEldeen; Elnaidany, Nada Farag; Kamh, Mona Eaid

2018-03-01

Vitiligo is an autoimmune skin disorder in which the loss of melanocytes is mainly attributed to defective autoimmune mechanisms and, lately, there has been more emphasis on autoinflammatory mediators. Among these is the macrophage migration inhibitory factor, which is involved in many autoimmune skin diseases. However, little is known about the contribution of this factor to vitiligo vulgaris. To determine the hypothesized role of migration inhibitory factor in vitiligo via estimation of serum migration inhibitory factor levels and migration inhibitory factor mRNA concentrations in patients with vitiligo compared with healthy controls. We also aimed to assess whether there is a relationship between the values of serum migration inhibitory factor and/or migration inhibitory factor mRNA with disease duration, clinical type and severity in vitiligo patients. Evaluation of migration inhibitory factor serum level and migration inhibitory factor mRNA expression by ELISA and real-time PCR, respectively, were performed for 50 patients with different degrees of vitiligo severity and compared to 15 age- and gender-matched healthy volunteers as controls. There was a highly significant increase in serum migration inhibitory factor and migration inhibitory factor mRNA levels in vitiligo cases when compared to controls (p<0.001). There was a significant positive correlation between both serum migration inhibitory factor and migration inhibitory factor mRNA concentrations in vitiligo patients, and each of them with duration and severity of vitiligo. In addition, patients with generalized vitiligo have significantly elevated serum migration inhibitory factor and mRNA levels than control subjects. Small number of investigated subjects. Migration inhibitory factor may have an active role in the development of vitiligo, and it may also be a useful index of disease severity. Consequently, migration inhibitory factor may be a new treatment target for vitiligo patients.

Temporal integration and 1/f power scaling in a circuit model of cerebellar interneurons.

PubMed

Maex, Reinoud; Gutkin, Boris

2017-07-01

Inhibitory interneurons interconnected via electrical and chemical (GABA A receptor) synapses form extensive circuits in several brain regions. They are thought to be involved in timing and synchronization through fast feedforward control of principal neurons. Theoretical studies have shown, however, that whereas self-inhibition does indeed reduce response duration, lateral inhibition, in contrast, may generate slow response components through a process of gradual disinhibition. Here we simulated a circuit of interneurons (stellate and basket cells) of the molecular layer of the cerebellar cortex and observed circuit time constants that could rise, depending on parameter values, to >1 s. The integration time scaled both with the strength of inhibition, vanishing completely when inhibition was blocked, and with the average connection distance, which determined the balance between lateral and self-inhibition. Electrical synapses could further enhance the integration time by limiting heterogeneity among the interneurons and by introducing a slow capacitive current. The model can explain several observations, such as the slow time course of OFF-beam inhibition, the phase lag of interneurons during vestibular rotation, or the phase lead of Purkinje cells. Interestingly, the interneuron spike trains displayed power that scaled approximately as 1/ f at low frequencies. In conclusion, stellate and basket cells in cerebellar cortex, and interneuron circuits in general, may not only provide fast inhibition to principal cells but also act as temporal integrators that build a very short-term memory. NEW & NOTEWORTHY The most common function attributed to inhibitory interneurons is feedforward control of principal neurons. In many brain regions, however, the interneurons are densely interconnected via both chemical and electrical synapses but the function of this coupling is largely unknown. Based on large-scale simulations of an interneuron circuit of cerebellar cortex, we propose that this coupling enhances the integration time constant, and hence the memory trace, of the circuit. Copyright © 2017 the American Physiological Society.

Cognitive Consequences of Trilingualism

PubMed Central

Schroeder, Scott R.; Marian, Viorica

2017-01-01

Aims and Objectives The objectives of the present research were to examine the cognitive consequences of trilingualism and explain them relative to the cognitive consequences of bilingualism. Approach A comparison of cognitive abilities in trilinguals and bilinguals was conducted. In addition, we proposed a cognitive plasticity framework to account for cognitive differences and similarities between trilinguals and bilinguals. Data and Analysis Three aspects of cognition were analyzed: (1) cognitive reserve in older adults, as measured by age of onset of Alzheimer’s disease and mild cognitive impairment; (2) inhibitory control in children and younger adults, as measured by response times on behavioral Simon and flanker tasks; and (3) memory generalization in infants and toddlers, as measured by accuracy on behavioral deferred imitation tasks. Results were considered within a framework of cognitive plasticity, which took into account several factors that may affect plasticity, including the age of learning a third language and the extent to which additional cognitive resources are needed to learn the third language. Findings A mixed pattern of results was observed. In some cases, such as cognitive reserve in older adults, trilinguals showed larger advantages than bilinguals. On other measures, for example inhibitory control in children and younger adults, trilinguals were found to exhibit the same advantages as bilinguals. In still other cases, like memory generalization in infants and toddlers, trilinguals did not demonstrate the advantages seen in bilinguals. Originality This study is the first comprehensive analysis of how learning a third language affects the cognitive abilities that are modified by bilingual experience, and the first to propose a cognitive plasticity framework that can explain and predict trilingual-bilingual differences. Significance This research shows that the cognitive consequences of trilingualism are not simply an extension of bilingualism’s effects; rather, trilingualism has distinct consequences, with theoretical implications for our understanding of linguistic and cognitive processes and their plasticity, as well as applied-science implications for using second and third language learning in educational and rehabilitative contexts to foster successful cognitive development and aging. PMID:29151803

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 contributes to clinically relevant cognitive deficits, and we consider pharmacological strategies for ameliorating cognitive deficits by rebalancing disinhibition-induced aberrant neural activity. Linked Articles This article is part of a themed section on Pharmacology of Cognition: a Panacea for Neuropsychiatric Disease? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.19/issuetoc. © 2017 The British Pharmacological Society.

Inhibitory Phenotype of HBV-Specific CD4+ T-Cells Is Characterized by High PD-1 Expression but Absent Coregulation of Multiple Inhibitory Molecules

PubMed Central

Kurktschiev, Peter; Schraut, Winfried; Zachoval, Reinhart; Wendtner, Clemens; Wächtler, Martin; Spannagl, Michael; Denk, Gerald; Ulsenheimer, Axel; Bengsch, Bertram; Pircher, Hanspeter; Diepolder, Helmut M.; Grüner, Norbert H.; Jung, Maria-Christina

2014-01-01

Background T-cell exhaustion seems to play a critical role in CD8+ T-cell dysfunction during chronic viral infections. However, up to now little is known about the mechanisms underlying CD4+ T-cell dysfunction during chronic hepatitis B virus (CHB) infection and the role of inhibitory molecules such as programmed death 1 (PD-1) for CD4+ T-cell failure. Methods The expression of multiple inhibitory molecules such as PD-1, CTLA-4, TIM-3, CD244, KLRG1 and markers defining the grade of T-cell differentiation as CCR7, CD45RA, CD57 and CD127 were analyzed on virus-specific CD4+ T-cells from peripheral blood using a newly established DRB1*01-restricted MHC class II Tetramer. Effects of in vitro PD-L1/2 blockade were defined by investigating changes in CD4+ T-cell proliferation and cytokine production. Results CD4+ T-cell responses during chronic HBV infection was characterized by reduced Tetramer+CD4+ T-cell frequencies, effector memory phenotype, sustained PD-1 but low levels of CTLA-4, TIM-3, KLRG1 and CD244 expression. PD-1 blockade revealed individualized patterns of in vitro responsiveness with partly increased IFN-γ, IL-2 and TNF-α secretion as well as enhanced CD4+ T-cell expansion almost in treated patients with viral control. Conclusion HBV-specific CD4+ T-cells are reliably detectable during different courses of HBV infection by MHC class II Tetramer technology. CD4+ T-cell dysfunction during chronic HBV is basically linked to strong PD-1 upregulation but absent coregulation of multiple inhibitory receptors. PD-L1/2 neutralization partly leads to enhanced CD4+ T-cell functionality with heterogeneous patterns of CD4+ T-cell rejunivation. PMID:25144233

Parental Education and Aggressive Behavior in Children: A Moderated-Mediation Model for Inhibitory Control and Gender

PubMed Central

Cabello, Rosario; Gutiérrez-Cobo, María J.; Fernández-Berrocal, Pablo

2017-01-01

Aggressive behaviors are highly prevalent in children. Given their negative consequences, it is necessary to look for protective factors that prevent or reduce their progress in early development before they become highly unshakable. With a sample of 147 children, the present study aimed to assess the relation between parental education and inhibitory control in the aggressive behavior of children aged from 7 to 10 years. The participants completed a go/no-go task to assess inhibitory control, whilst their parents reported their education level, and their teachers rated the aggressive behavior of the children through the Teacher Rating Scale (TRS) of the Behavior Assessment System for Children 2 (BASC-2). The results showed that both parental education and inhibitory control determined aggressive behavior in children. In addition, inhibitory control partially mediated the associations between parental education and aggressive behavior after accounting for age. However, a moderated mediation model revealed that lower parental education was associated with higher levels of aggressive behavior, which, in girls occurred independently of inhibitory control. In contrast, inhibitory control mediated this relation in boys. These results suggest the importance of parental education and inhibitory control in the aggressive behavior of children, supporting the idea that both constructs are relevant for understanding these conduct problems in schools, particularly in boys. The clinical implications of these findings are discussed, along with possible future lines of investigation. PMID:28740476

Parental Education and Aggressive Behavior in Children: A Moderated-Mediation Model for Inhibitory Control and Gender.

PubMed

Cabello, Rosario; Gutiérrez-Cobo, María J; Fernández-Berrocal, Pablo

2017-01-01

Aggressive behaviors are highly prevalent in children. Given their negative consequences, it is necessary to look for protective factors that prevent or reduce their progress in early development before they become highly unshakable. With a sample of 147 children, the present study aimed to assess the relation between parental education and inhibitory control in the aggressive behavior of children aged from 7 to 10 years. The participants completed a go/no-go task to assess inhibitory control, whilst their parents reported their education level, and their teachers rated the aggressive behavior of the children through the Teacher Rating Scale (TRS) of the Behavior Assessment System for Children 2 (BASC-2). The results showed that both parental education and inhibitory control determined aggressive behavior in children. In addition, inhibitory control partially mediated the associations between parental education and aggressive behavior after accounting for age. However, a moderated mediation model revealed that lower parental education was associated with higher levels of aggressive behavior, which, in girls occurred independently of inhibitory control. In contrast, inhibitory control mediated this relation in boys. These results suggest the importance of parental education and inhibitory control in the aggressive behavior of children, supporting the idea that both constructs are relevant for understanding these conduct problems in schools, particularly in boys. The clinical implications of these findings are discussed, along with possible future lines of investigation.

Inhibitory Control Mediates the Association between Perceived Stress and Secure Relationship Quality.

PubMed

Herd, Toria; Li, Mengjiao; Maciejewski, Dominique; Lee, Jacob; Deater-Deckard, Kirby; King-Casas, Brooks; Kim-Spoon, Jungmeen

2018-01-01

Past research has demonstrated negative associations between exposure to stressors and quality of interpersonal relationships among children and adolescents. Nevertheless, underlying mechanisms of this association remain unclear. Chronic stress has been shown to disrupt prefrontal functioning in the brain, including inhibitory control abilities, and evidence is accumulating that inhibitory control may play an important role in secure interpersonal relationship quality, including peer problems and social competence. In this prospective longitudinal study, we examine whether changes in inhibitory control, measured at both behavioral and neural levels, mediate the association between stress and changes in secure relationship quality with parents and peers. The sample included 167 adolescents (53% males) who were first recruited at age 13 or 14 years and assessed annually three times. Adolescents' inhibitory control was measured by their behavioral performance and brain activities, and adolescents self-reported perceived stress levels and relationship quality with mothers, fathers, and peers. Results suggest that behavioral inhibitory control mediates the association between perceived stress and adolescent's secure relationship quality with their mothers and fathers, but not their peers. In contrast, given that stress was not significantly correlated with neural inhibitory control, we did not further test the mediation path. Our results highlight the role of inhibitory control as a process through which stressful life experiences are related to impaired secure relationship quality between adolescents and their mothers and fathers.

Inhibitory Control Mediates the Association between Perceived Stress and Secure Relationship Quality

PubMed Central

Herd, Toria; Li, Mengjiao; Maciejewski, Dominique; Lee, Jacob; Deater-Deckard, Kirby; King-Casas, Brooks; Kim-Spoon, Jungmeen

2018-01-01

Past research has demonstrated negative associations between exposure to stressors and quality of interpersonal relationships among children and adolescents. Nevertheless, underlying mechanisms of this association remain unclear. Chronic stress has been shown to disrupt prefrontal functioning in the brain, including inhibitory control abilities, and evidence is accumulating that inhibitory control may play an important role in secure interpersonal relationship quality, including peer problems and social competence. In this prospective longitudinal study, we examine whether changes in inhibitory control, measured at both behavioral and neural levels, mediate the association between stress and changes in secure relationship quality with parents and peers. The sample included 167 adolescents (53% males) who were first recruited at age 13 or 14 years and assessed annually three times. Adolescents’ inhibitory control was measured by their behavioral performance and brain activities, and adolescents self-reported perceived stress levels and relationship quality with mothers, fathers, and peers. Results suggest that behavioral inhibitory control mediates the association between perceived stress and adolescent’s secure relationship quality with their mothers and fathers, but not their peers. In contrast, given that stress was not significantly correlated with neural inhibitory control, we did not further test the mediation path. Our results highlight the role of inhibitory control as a process through which stressful life experiences are related to impaired secure relationship quality between adolescents and their mothers and fathers. PMID:29535664

A cross-cultural investigation of inhibitory control, generative fluency, and anxiety symptoms in Romanian and Russian preschoolers.

PubMed

Cheie, Lavinia; Veraksa, Aleksander; Zinchenko, Yuri; Gorovaya, Alexandra; Visu-Petra, Laura

2015-01-01

The current study focused on the early development of inhibitory control in 5- to 7-year-old children attending kindergarten in two Eastern-European countries, Romania and Russia. These two countries share many aspects of child-rearing and educational practices, previously documented to influence the development of inhibitory control. Using the Lurian-based developmental approach offered by the Developmental Neuropsychological Assessment battery, the study aimed to contribute to cross-cultural developmental neuropsychology by exploring (a) early interrelationships between subcomponents of inhibitory control (response suppression and attention control) and generative fluency (verbal and figural) in these two cultures, as well as (b) the predictive value of external factors (culture and maternal education) and individual differences (age, gender, nonverbal intelligence, trait anxiety) on inhibitory control and fluency outcomes in children from both countries. First, findings in both culture samples suggest that even at this young age, the construct of inhibitory control cannot be considered a unitary entity. Second, differences in maternal education were not predictive of either inhibitory control or fluency scores. However, children's attention control performance varied as a function of culture, and the direction of these cultural effects differed by whether the target outcome involved performance accuracy versus efficiency as an output. Findings also confirmed the previously documented intensive developmental improvement in preschoolers' inhibitory control during this period, influencing measures of response suppression and particularly attention control. Finally, the results further stress the importance of individual differences effects in trait anxiety on attention control efficiency across cultures.

Focalised stimulation using high definition transcranial direct current stimulation (HD-tDCS) to investigate declarative verbal learning and memory functioning.

PubMed

Nikolin, Stevan; Loo, Colleen K; Bai, Siwei; Dokos, Socrates; Martin, Donel M

2015-08-15

Declarative verbal learning and memory are known to be lateralised to the dominant hemisphere and to be subserved by a network of structures, including those located in frontal and temporal regions. These structures support critical components of verbal memory, including working memory, encoding, and retrieval. Their relative functional importance in facilitating declarative verbal learning and memory, however, remains unclear. To investigate the different functional roles of these structures in subserving declarative verbal learning and memory performance by applying a more focal form of transcranial direct current stimulation, "High Definition tDCS" (HD-tDCS). Additionally, we sought to examine HD-tDCS effects and electrical field intensity distributions using computer modelling. HD-tDCS was administered to the left dorsolateral prefrontal cortex (LDLPFC), planum temporale (PT), and left medial temporal lobe (LMTL) to stimulate the hippocampus, during learning on a declarative verbal memory task. Sixteen healthy participants completed a single blind, intra-individual cross-over, sham-controlled study which used a Latin Square experimental design. Cognitive effects on working memory and sustained attention were additionally examined. HD-tDCS to the LDLPFC significantly improved the rate of verbal learning (p=0.03, η(2)=0.29) and speed of responding during working memory performance (p=0.02, η(2)=0.35), but not accuracy (p=0.12, η(2)=0.16). No effect of tDCS on verbal learning, retention, or retrieval was found for stimulation targeted to the LMTL or the PT. Secondary analyses revealed that LMTL stimulation resulted in increased recency (p=0.02, η(2)=0.31) and reduced mid-list learning effects (p=0.01, η(2)=0.39), suggesting an inhibitory effect on learning. HD-tDCS to the LDLPFC facilitates the rate of verbal learning and improved efficiency of working memory may underlie performance effects. This focal method of administrating tDCS has potential for probing and enhancing cognitive functioning. Copyright © 2015 Elsevier Inc. All rights reserved.

The effects of sequential attention shifts within visual working memory

PubMed Central

Li, Qi; Saiki, Jun

2014-01-01

Previous studies have shown conflicting data as to whether it is possible to sequentially shift spatial attention among visual working memory (VWM) representations. The present study investigated this issue by asynchronously presenting attentional cues during the retention interval of a change detection task. In particular, we focused on two types of sequential attention shifts: (1) orienting attention to one location, and then withdrawing attention from it, and (2) switching the focus of attention from one location to another. In Experiment 1, a withdrawal cue was presented after a spatial retro-cue to measure the effect of withdrawing attention. The withdrawal cue significantly reduced the cost of invalid spatial cues, but surprisingly, did not attenuate the benefit of valid spatial cues. This indicates that the withdrawal cue only triggered the activation of facilitative components but not inhibitory components of attention. In Experiment 2, two spatial retro-cues were presented successively to examine the effect of switching the focus of attention. We observed equivalent benefits of the first and second spatial cues, suggesting that participants were able to reorient attention from one location to another within VWM, and the reallocation of attention did not attenuate memory at the first-cued location. In Experiment 3, we found that reducing the validity of the preceding spatial cue did lead to a significant reduction in its benefit. However, performance was still better at first-cued locations than at uncued and neutral locations, indicating that the first cue benefit might have been preserved both partially under automatic control and partially under voluntary control. Our findings revealed new properties of dynamic attentional control in VWM maintenance. PMID:25237306

Orthopedic Surgery and Post-Operative Cognitive Decline in Idiopathic Parkinson’s Disease: Considerations from a Pilot Study

PubMed Central

Price, Catherine C.; Levy, Shellie-Anne; Tanner, Jared; Garvan, Cyndi; Ward, Jade; Akbar, Farheen; Bowers, Dawn; Rice, Mark; Okun, Michael

2016-01-01

BACKGROUND Post-operative cognitive dysfunction (POCD) demarks cognitive decline after major surgery but has been studied to date in “healthy” adults. Although individuals with neurodegenerative disorders such as Parkinson’s disease (PD) commonly undergo elective surgery, these individuals have yet to be prospectively followed despite hypotheses of increased POCD risk. OBJECTIVE To conduct a pilot study examining cognitive change pre-post elective orthopedic surgery for PD relative to surgery and non-surgery peers. METHODS A prospective one-year longitudinal design. No-dementia idiopathic PD individuals were actively recruited along with non-PD “healthy” controls (HC) undergoing knee replacement surgery. Non-surgical PD and HC controls were also recruited. Attention/processing speed, inhibitory function, memory recall, animal (semantic) fluency, and motor speed were assessed at baseline (pre-surgery), three-weeks, three-months, and one-year post- orthopedic surgery. Reliable change methods examined individual changes for PD individuals relative to control surgery and control non-surgery peers. RESULTS Over two years we screened 152 older adult surgery or non-surgery candidates with 19 of these individuals having a diagnosis of PD. Final participants included 8 PD (5 surgery, 3 non-surgery), 47 Control Surgery, and 21 Control Non-Surgery. Eighty percent (4 of the 5) PD surgery declined greater than 1.645 standard deviations from their baseline performance on measures assessing processing speed and inhibitory function. This was not observed for the non-surgery PD individuals. CONCLUSION This prospective pilot study demonstrated rationale and feasibility for examining cognitive decline in at-risk neurodegenerative populations. We discuss recruitment and design challenges for examining post-operative cognitive decline in neurodegenerative samples. PMID:26683785

The neural networks of inhibitory control in posttraumatic stress disorder

PubMed Central

Falconer, Erin; Bryant, Richard; Felmingham, Kim L.; Kemp, Andrew H.; Gordon, Evian; Peduto, Anthony; Olivieri, Gloria; Williams, Leanne M.

2008-01-01

Objective Posttraumatic stress disorder (PTSD) involves deficits in information processing that may reflect hypervigilence and deficient inhibitory control. To date, however, no PTSD neuroimaging study has directly examined PTSD-related changes in executive inhibition. Our objective was to investigate the hypothesis that executive inhibitory control networks are compromised in PTSD. Methods Functional magnetic resonance imaging (fMRI) was used during a Go/No-Go inhibition task completed by a sample of patients with PTSD (n = 23), a matched sample of healthy (i.e. without trauma exposure) control participants (n = 23) and a sample of control participants with trauma exposure who did not meet criteria for PTSD (n = 17). Results Participants with PTSD showed more inhibition-related errors than did individuals without trauma exposure. During inhibition, control participants activated a right-lateralized cortical inhibitory network, whereas patients with PTSD activated only the left lateral frontal cortex. PTSD was associated with a reduction in right cortical activation and increased activation of striatal and somatosensory regions. Conclusion The increased inhibitory error and reduced right frontal cortical activation are consistent with compromised inhibitory control in PTSD, while the increased activation of brain regions associated with sensory processing and a greater demand on inhibitory control may reflect enhanced stimulus processing in PTSD, which may undermine cortical control mechanisms. PMID:18787658

Immunotherapy by targeting of VGKC complex for seizure control and prevention of cognitive impairment in a mouse model of epilepsy.

PubMed

Fan, Zhiliang; Feng, Xiaojuan; Fan, Zhigang; Zhu, Xingyuan; Yin, Shaohua

2018-05-09

Epilepsy is a type of refractory neurologic disorder mental disease, which is associated with cognitive impairments and memory dysfunction. However, the potential mechanisms of epilepsy are not well understood. Previous evidence has identified the voltage gated potassium channel complex (VGKC) as a target in various cohorts of patients with epilepsy. In the present study, the efficacy of an antibody against VGKC (anti‑VGKC) for the treatment of epilepsy in mice was investigated. A mouse model of lithium‑pilocarpine temporal lobe epilepsy was established and anti‑VGKC treatment was administered for 30 days. Memory impairment, anxiety, visual attention, inhibitory control and neuronal loss were measured in the mouse model of lithium‑pilocarpine temporal lobe epilepsy. The results revealed that epileptic mice treated with anti‑VGKC were able to learn the task and presented attention impairment, even a tendency toward impulsivity and compulsivity. It was also exhibited that anti‑VGKC treatment decreased neuronal loss in structures classically associated with attentional performance in hippocampus. Mice who received Anti‑VGKC treatment had inhibited motor seizures and hippocampal damage as compared with control mice. In conclusion, these results indicated that anti‑VGKC treatment may present benefits for improvements of the condition of motor attention impairment and cognitive competence, which suggests that VGKC may be a potential target for the treatment of epilepsy.

Inhibitory control and adaptive behaviour in children with mild intellectual disability.

PubMed

Gligorović, M; Buha Ðurović, N

2014-03-01

Inhibitory control, as one of the basic mechanisms of executive functions, is extremely important for adaptive behaviour. The relation between inhibitory control and adaptive behaviour is the most obvious in cases of behavioural disorders and psychopathology. Considering the lack of studies on this relation in children with disabilities, the aim of our research is to determine the relation between inhibitory control and adaptive behaviour in children with mild intellectual disability. The sample consists of 53 children with mild intellectual disability. Selection criteria were: IQ between 50 and 70, age between 10 and 14, absence of bilingualism, and with no medical history of neurological impairment, genetic and/or emotional problems. Modified Day-Night version of the Stroop task, and Go-no-Go Tapping task were used for the assessment of inhibitory control. Data on adaptive behaviour were obtained by applying the first part of AAMR (American Association on Mental Retardation) Adaptive Behaviour Scale-School, Second Edition (ABS-S:2). Significant relationships were determined between some aspects of inhibitory control and the most of assessed domains of adaptive behaviour. Inhibitory control measures, as a unitary inhibition model, significantly predict results on Independent Functioning, Economic Activity, Speech and Language Development, and Number and Times domains of the ABS-S:2. Inhibitory control, assessed by second part of the Stroop task, proved to be a significant factor in practical (Independent Functioning) and conceptual (Economic Activity, Speech and Language Development, and Numbers and Time) adaptive skills. The first part of the Stroop task, as a measure of selective attention, proved to be a significant factor in language and numerical demands, along with second one. Inhibitory control through motor responses proved to be a significant factor in independent functioning, economic activities, language and self-direction skills. We can conclude that inhibitory control represents a significant developmental factor of different adaptive behaviour domains in children with mild intellectual disability. © 2012 The Authors. Journal of Intellectual Disability Research © 2012 John Wiley & Sons Ltd, MENCAP & IASSIDD.

Cognitive performance in multiple sclerosis: the contribution of intellectual enrichment and brain MRI measures.

PubMed

Santangelo, Gabriella; Bisecco, Alvino; Trojano, Luigi; Sacco, Rosaria; Siciliano, Mattia; d'Ambrosio, Alessandro; Della Corte, Marida; Lavorgna, Luigi; Bonavita, Simona; Tedeschi, Gioacchino; Gallo, Antonio

2018-05-26

Cognitive reserve (CR) is a construct that originates from the observation of poor correspondence between brain damage and clinical symptoms. The aim of the study was to investigate the association between cognitive reserve (CR), brain reserve (BR) and cognitive functions and to evaluate whether CR might attenuate/moderate the negative impact of brain atrophy and lesion load on cognitive functions in multiple sclerosis (MS). To achieve these aims, ninety-eight relapsing-remitting MS patients underwent the brief repeatable battery of neuropsychological tests and Stroop test (ST). CR was assessed by vocabulary-based estimate of lifetime intellectual enrichment. All patients underwent a 3T MRI to assess T2-lesion load and atrophy measures, including normalized gray matter and white matter (nWMV) volumes. The BR was evaluated by maximal lifetime brain volume expressed by intracranial volume (ICV). Hierarchical regressions were used to investigate whether higher BR and/or CR is related to better cognitive performances after controlling for potentially confounding factors. The ICV was not associated with any cognitive tests. Intellectual enrichment was positively associated with performance on tests assessing memory, attention and information processing speed, verbal fluency and inhibitory control. Significant relationship between nWMV and ST was moderated by intellectual enrichment. In conclusion, the findings suggested that CR seems to mitigate cognitive dysfunction in MS patients and can reduce the negative impact of brain atrophy on inhibitory control, relevant for integrity of instrumental activities of daily living.

The role of decision-making ability in HIV/AIDS: Impact on prospective memory

PubMed Central

Coulehan, Kelly; Byrd, Desiree; Arentoft, Alyssa; Monzones, Jennifer; Fuentes, Armando; Fraser, Felicia; Rosario, Ana; Morgello, Susan; Rivera Mindt, Monica

2017-01-01

Background Prospective memory (ProM), a form of episodic memory related to execution of future intentions, is important for everyday functioning. Among persons living with HIV (PLWH), executive dysfunction is implicated in ProM impairments. However, specific subcomponents of executive functioning involved in ProM deficits remain poorly understood. Unlike more “traditional” neurocognitive (NC) measures of executive functioning associated with dorsolateral prefrontal cortex (i.e., conceptual reasoning, abstraction), those associated with medial orbitofrontal/ventromedial prefrontal (mOF/vmP) cortex (i.e., decision making, inhibitory control, goal-oriented behavior) have yet to be examined in ProM. Method This study characterized ProM ability in a sample of 89 HIV-seropositive adults and examined the unique role of decision-making ability in ProM. Participants completed a standard NC battery, the Iowa Gambling Task (IGT; a decision-making measure), and the Memory for Intentions Screening Test (MIST; a ProM measure). Results Correlational analyses revealed that both traditional executive functioning measures and the IGT were associated with ProM. Regression analyses revealed that the IGT significantly predicted ProM, even after accounting for NC measures. Among all NC measures, only executive functioning significantly contributed to ProM. Discussion Further examination of mOF/vmP-sensitive executive dysfunction within this population is needed as PLWH may require more tailored treatment recommendations due to specific decision-making difficulties that can impact medication management. PMID:25089330

Ameliorating effects of ethyl acetate fraction from onion (Allium cepa L.) flesh and peel in mice following trimethyltin-induced learning and memory impairment.

PubMed

Park, Seon Kyeong; Jin, Dong Eun; Park, Chang Hyeon; Seung, Tae Wan; Guo, Tian Jiao; Song, Jong Wook; Kim, Jong Hwan; Kim, Dae Ok; Heo, Ho Jin

2015-09-01

The anti-amnesic effects of onion (Allium cepa L.) flesh (OF) 1 and peel (OP) 2 on trimethyltin (TMT) 3 -induced learning and memory dysfunction were investigated to confirm learning and memory function. The inhibitory effect against cellular acetylcholinesterase (AChE) 4 showed that the EtOAc fraction of OP (EOP 5 , IC 50 value=37.11μg/mL) was higher than the EtOAc fraction of OF (EOF 6 , IC 50 value=433.34μg/mL). The cognitive effects in ICR mice were also evaluated using Y-maze, passive avoidance, and Morris water maze tests. After the behavioral tests, AChE activity (control=100%, TMT=128%, EOF 20=108%, EOP 10=104%, and EOP 20=98%), superoxide dismutase (SOD) 7 activity, oxidized glutathione (GSSG) 8 /total glutathione (GSH) 9 and malondialdehyde (MDA) 10 production were examined. These results indicate that both EOF and EOP improved learning and memory function. The main compounds of the EOF and EOP were analyzed by Q-TOF UPLC/MS, and the results were as follows: The EOF (quercetin and quercetin-4'-glucoside) and the EOP (quercetin-4'-glucoside and isorhamnetin-4'-glucoside). Consequently, our results suggest that both EOF and EOP could be efficacious in improving cognitive function through AChE inhibition and antioxidant activity in mice brains. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Valepotriate Fraction of Valeriana glechomifolia Shows Sedative and Anxiolytic Properties and Impairs Recognition But Not Aversive Memory in Mice

PubMed Central

Maurmann, Natasha; Reolon, Gustavo Kellermann; Rech, Sandra Beatriz; Fett-Neto, Arthur Germano; Roesler, Rafael

2011-01-01

Plants of the genus Valeriana (Valerianaceae) are used in traditional medicine as a mild sedative, antispasmodic and tranquilizer in many countries. This study was undertaken to explore the neurobehavioral effects of systemic administration of a valepotriate extract fraction of known quantitative composition of Valeriana glechomifolia (endemic of southern Brazil) in mice. Adult animals were treated with a single intraperitoneal injection of valepotriate fraction (VF) in the concentrations of 1, 3 or 10 mg kg−1, or with vehicle in the pre-training period before each behavioral test. During the exploration of an open field, mice treated with 10 mg kg−1 of VF showed reduced locomotion and exploratory behavior. Although overall habituation sessions for locomotion and exploratory behavior among vehicle control and doses of VF were not affected, comparison between open-field and habituation sessions within each treatment showed that VF administration at 1 and 10 mg kg−1 impaired habituation. In the elevated plus-maze test, mice treated with VF (10 mg kg−1) showed a significant increase in the percentage of time spent in the open arms without significant effects in the number of total arm entries. VF at 3 mg kg−1 produced an impairment of novel-object recognition memory. In contrast, VF did not affect fear-related memory assessed in an inhibitory avoidance task. The results indicate that VF can have sedative effects and affect behavioral parameters related to recognition memory. PMID:20047889

Abnormal brain activation during directed forgetting of negative memory in depressed patients.

PubMed

Yang, Wenjing; Chen, Qunlin; Liu, Peiduo; Cheng, Hongsheng; Cui, Qian; Wei, Dongtao; Zhang, Qinglin; Qiu, Jiang

2016-01-15

The frequent occurrence of uncontrollable negative thoughts and memories is a troubling aspect of depression. Thus, knowledge on the mechanism underlying intentional forgetting of these thoughts and memories is crucial to develop an effective emotion regulation strategy for depressed individuals. Behavioral studies have demonstrated that depressed participants cannot intentionally forget negative memories. However, the neural mechanism underlying this process remains unclear. In this study, participants completed the directed forgetting task in which they were instructed to remember or forget neutral or negative words. Standard univariate analysis based on the General Linear Model showed that the depressed participants have higher activation in the inferior frontal gyrus (IFG), superior frontal gyrus (SFG), superior parietal gyrus (SPG), and inferior temporal gyrus (ITG) than the healthy individuals. The results indicated that depressed participants recruited more frontal and parietal inhibitory control resources to inhibit the TBF items, but the attempt still failed because of negative bias. We also used the Support Vector Machine to perform multivariate pattern classification based on the brain activation during directed forgetting. The pattern of brain activity in directed forgetting of negative words allowed correct group classification with an overall accuracy of 75% (P=0.012). The brain regions which are critical for this discrimination showed abnormal activation when depressed participants were attempting to forget negative words. These results indicated that the abnormal neural circuitry when depressed individuals tried to forget the negative words might provide neurobiological markers for depression. Copyright © 2015 Elsevier B.V. All rights reserved.

REM Theta Activity Enhances Inhibitory Control in Typically Developing Children but not Children with ADHD Symptoms

PubMed Central

Cremone, Amanda; Lugo-Candelas, Claudia I.; Harvey, Elizabeth A.; McDermott, Jennifer M.; Spencer, Rebecca M. C.

2017-01-01

Sleep disturbances impair cognitive functioning in typically developing populations. Children with attention-deficit/hyperactivity disorder (ADHD), a disorder characterized by impaired inhibitory control and attention, commonly experience sleep disturbances. Whether inhibitory impairments are related to sleep deficits in children with ADHD is unknown. Children with ADHD (n = 18; Mage = 6.70 years) and typically developing controls (n = 15; Mage = 6.73 years) completed a Go/No-Go task to measure inhibitory control and sustained attention before and after polysomnography-monitored overnight sleep. Inhibitory control and sustained attention were improved following overnight sleep in typically developing children. Moreover, morning inhibitory control was positively correlated with rapid eye movement (REM) theta activity in this group. Although REM theta activity was greater in children with ADHD compared to typically developing children, it was functionally insignificant. Neither inhibitory control nor sustained attention were improved following overnight sleep in children with ADHD symptoms, and neither of these behaviors was associated with REM theta activity in this group. Taken together, these results indicate that elevated REM theta activity may be functionally related to ADHD symptomology, possibly reflecting delayed cortical maturation. PMID:28246970

Do detour tasks provide accurate assays of inhibitory control?

PubMed Central

Whiteside, Mark A.; Laker, Philippa R.; Beardsworth, Christine E.

2018-01-01

Transparent Cylinder and Barrier tasks are used to purportedly assess inhibitory control in a variety of animals. However, we suspect that performances on these detour tasks are influenced by non-cognitive traits, which may result in inaccurate assays of inhibitory control. We therefore reared pheasants under standardized conditions and presented each bird with two sets of similar tasks commonly used to measure inhibitory control. We recorded the number of times subjects incorrectly attempted to access a reward through transparent barriers, and their latencies to solve each task. Such measures are commonly used to infer the differential expression of inhibitory control. We found little evidence that their performances were consistent across the two different Putative Inhibitory Control Tasks (PICTs). Improvements in performance across trials showed that pheasants learned the affordances of each specific task. Critically, prior experience of transparent tasks, either Barrier or Cylinder, also improved subsequent inhibitory control performance on a novel task, suggesting that they also learned the general properties of transparent obstacles. Individual measures of persistence, assayed in a third task, were positively related to their frequency of incorrect attempts to solve the transparent inhibitory control tasks. Neophobia, Sex and Body Condition had no influence on individual performance. Contrary to previous studies of primates, pheasants with poor performance on PICTs had a wider dietary breadth assayed using a free-choice task. Our results demonstrate that in systems or taxa where prior experience and differences in development cannot be accounted for, individual differences in performance on commonly used detour-dependent PICTS may reveal more about an individual's prior experience of transparent objects, or their motivation to acquire food, than providing a reliable measure of their inhibitory control. PMID:29593115

Theory of mind, inhibitory control, and preschool-age children's suggestibility in different interviewing contexts.

PubMed

Scullin, Matthew H; Bonner, Karri

2006-02-01

The current study examined the relations among 3- to 5-year-olds' theory of mind, inhibitory control, and three measures of suggestibility: yielding to suggestive questions (yield), shifting answers in response to negative feedback (shift), and accuracy in response to misleading questions during a pressured interview about a live event. Theory of mind aided in the prediction of suggestibility about the live event, and inhibitory control was a moderator variable affecting the consistency of children's sensitivity to social pressure across situations. The findings indicate that theory of mind and inhibitory control predict children's suggestibility about a live event above and beyond yield, shift, and age and that the construct validity of shift may improve as children's inhibitory control develops.

The effect of articulatory suppression on implicit and explicit false memory in the DRM paradigm.

PubMed

Van Damme, Ilse; Menten, Jan; d'Ydewalle, Gery

2010-11-01

Several studies have shown that reliable implicit false memory can be obtained in the DRM paradigm. There has been considerable debate, however, about whether or not conscious activation of critical lures during study is a necessary condition for this. Recent findings have revealed that articulatory suppression prevents subsequent false priming in an anagram task (Lovden & Johansson, 2003). The present experiment sought to replicate and extend these findings to an implicit word stem completion task, and to additionally investigate the effect of articulatory suppression on explicit false memory. Results showed an inhibitory effect of articulatory suppression on veridical memory, as well as on implicit false memory, whereas the level of explicit false memory was heightened. This suggests that articulatory suppression did not merely eliminate conscious lure activation, but had a more general capacity-delimiting effect. The drop in veridical memory can be attributed to diminished encoding of item-specific information. Superficial encoding also limited the spreading of semantic activation during study, which inhibited later false priming. In addition, the lack of item-specific and phenomenological details caused impaired source monitoring at test, resulting in heightened explicit false memory.

Bombesin administration impairs memory and does not reverse memory deficit caused by sleep deprivation.

PubMed

Ferreira, L B T; Oliveira, S L B; Raya, J; Esumi, L A; Hipolide, D C

2017-07-28

Sleep deprivation impairs performance in emotional memory tasks, however this effect on memory is not completely understood. Possible mechanisms may involve an alteration in neurotransmission systems, as shown by the fact that many drugs that modulate neural pathways can prevent memory impairment by sleep loss. Gastrin releasing peptide (GRP) is a neuropeptide that emerged as a regulatory molecule of emotional memory through the modulation of other neurotransmission systems. Thus, the present study addressed the effect of intraperitoneal (IP) administration of bombesin (BB) (2.5, 5.0 and 10.0μg/kg), a GRP agonist, on the performance of Wistar rats in a multiple trail inhibitory avoidance (MTIA) task, after sleep deprivation, using the modified multiple platforms method (MMPM). Sleep deprived animals exhibited acquisition and retention impairment that was not prevented by BB injection. In addition, non-sleep deprived animals treated with BB before and after the training session, but not before the test, have shown a retention deficit. In summary, BB did not improve the memory impairment by sleep loss and, under normal conditions, produced a memory consolidation deficit. Copyright © 2017 Elsevier B.V. All rights reserved.

Tracking the Time-Dependent Role of the Hippocampus in Memory Recall Using DREADDs.

PubMed

Varela, Carmen; Weiss, Sarah; Meyer, Retsina; Halassa, Michael; Biedenkapp, Joseph; Wilson, Matthew A; Goosens, Ki Ann; Bendor, Daniel

2016-01-01

The hippocampus is critical for the storage of new autobiographical experiences as memories. Following an initial encoding stage in the hippocampus, memories undergo a process of systems-level consolidation, which leads to greater stability through time and an increased reliance on neocortical areas for retrieval. The extent to which the retrieval of these consolidated memories still requires the hippocampus is unclear, as both spared and severely degraded remote memory recall have been reported following post-training hippocampal lesions. One difficulty in definitively addressing the role of the hippocampus in remote memory retrieval is the precision with which the entire volume of the hippocampal region can be inactivated. To address this issue, we used Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), a chemical-genetic tool capable of highly specific neuronal manipulation over large volumes of brain tissue. We find that remote (>7 weeks after acquisition), but not recent (1-2 days after acquisition) contextual fear memories can be recalled after injection of the DREADD agonist (CNO) in animals expressing the inhibitory DREADD in the entire hippocampus. Our data demonstrate a time-dependent role of the hippocampus in memory retrieval, supporting the standard model of systems consolidation.

Tracking the Time-Dependent Role of the Hippocampus in Memory Recall Using DREADDs

PubMed Central

Varela, Carmen; Weiss, Sarah; Meyer, Retsina; Halassa, Michael; Biedenkapp, Joseph; Wilson, Matthew A.; Goosens, Ki Ann

2016-01-01

The hippocampus is critical for the storage of new autobiographical experiences as memories. Following an initial encoding stage in the hippocampus, memories undergo a process of systems-level consolidation, which leads to greater stability through time and an increased reliance on neocortical areas for retrieval. The extent to which the retrieval of these consolidated memories still requires the hippocampus is unclear, as both spared and severely degraded remote memory recall have been reported following post-training hippocampal lesions. One difficulty in definitively addressing the role of the hippocampus in remote memory retrieval is the precision with which the entire volume of the hippocampal region can be inactivated. To address this issue, we used Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), a chemical-genetic tool capable of highly specific neuronal manipulation over large volumes of brain tissue. We find that remote (>7 weeks after acquisition), but not recent (1–2 days after acquisition) contextual fear memories can be recalled after injection of the DREADD agonist (CNO) in animals expressing the inhibitory DREADD in the entire hippocampus. Our data demonstrate a time-dependent role of the hippocampus in memory retrieval, supporting the standard model of systems consolidation. PMID:27145133

Cognitive aging and hearing acuity: modeling spoken language comprehension.

PubMed

Wingfield, Arthur; Amichetti, Nicole M; Lash, Amanda

2015-01-01

The comprehension of spoken language has been characterized by a number of "local" theories that have focused on specific aspects of the task: models of word recognition, models of selective attention, accounts of thematic role assignment at the sentence level, and so forth. The ease of language understanding (ELU) model (Rönnberg et al., 2013) stands as one of the few attempts to offer a fully encompassing framework for language understanding. In this paper we discuss interactions between perceptual, linguistic, and cognitive factors in spoken language understanding. Central to our presentation is an examination of aspects of the ELU model that apply especially to spoken language comprehension in adult aging, where speed of processing, working memory capacity, and hearing acuity are often compromised. We discuss, in relation to the ELU model, conceptions of working memory and its capacity limitations, the use of linguistic context to aid in speech recognition and the importance of inhibitory control, and language comprehension at the sentence level. Throughout this paper we offer a constructive look at the ELU model; where it is strong and where there are gaps to be filled.

The effect of CA1 dopaminergic system on amnesia induced by harmane in mice.

PubMed

Nasehi, Mohammad; Hasanvand, Simin; Khakpai, Fatemeh; Zarrindast, Mohammad-Reza

2018-05-16

In the present study, the effects of bilateral injections of dopaminergic drugs into the hippocampal CA1 regions (intra-CA1) on harmane-induced amnesia were examined in mice. We used a single-trial step-down inhibitory avoidance task for the assessment of memory acquisition in adult male mice. Our data indicated that pre-training intra-peritoneal (i.p.) administration of harmane (12 mg/kg) impaired memory acquisition. Moreover, intra-CA1 administration of dopamine D1 receptor agonist, SKF38393 (0.25 µg/mouse), dopamine D1 receptor antagonist, SCH23390 (0.25 µg/mouse), dopamine D2 receptor agonist, quinpirole (0.125 and 0.25 µg/mouse) and dopamine D2 receptor antagonist, sulpiride (0.2 and 0.4 µg/mouse) decreased the learning of a single-trial inhibitory avoidance task. Furthermore, pre-training intra-CA1 injection of sub-threshold doses of SKF38393 (0.0625 µg/mouse) or sulpiride (0.1 µg/mouse) increased pre-training harmane (4 and 8 mg/kg, i.p.)-induced amnesia. On the other hand, pre-training intra-CA1 injection of a sub-threshold dose of SCH23390 (0.0625 µg/mouse) reversed amnesia induced by an effective dose of harmane (12 mg/kg; i.p.). In addition, Pre-training intra-CA1 injection of quinpirole (0.0625 µg/mouse) had no effect on memory impairment induced by harmane. These findings indicate the involvement of CA1 dopaminergic system on harmane-induced impairment of memory acquisition.

Learning a Foreign Language: A New Path to Enhancement of Cognitive Functions.

PubMed

Shoghi Javan, Sara; Ghonsooly, Behzad

2018-02-01

The complicated cognitive processes involved in natural (primary) bilingualism lead to significant cognitive development. Executive functions as a fundamental component of human cognition are deemed to be affected by language learning. To date, a large number of studies have investigated how natural (primary) bilingualism influences executive functions; however, the way acquired (secondary) bilingualism manipulates executive functions is poorly understood. To fill this gap, controlling for age, gender, IQ, and socio-economic status, the researchers compared 60 advanced learners of English as a foreign language (EFL) to 60 beginners on measures of executive functions involving Stroop, Wisconsin Card Sorting Task (WCST) and Wechsler's digit span tasks. The results suggested that mastering English as a foreign language causes considerable enhancement in two components of executive functions, namely cognitive flexibility and working memory. However, no significant difference was observed in inhibitory control between the advanced EFL learners and beginners.

Residential Mobility, Inhibitory Control, and Academic Achievement in Preschool

ERIC Educational Resources Information Center

Schmitt, Sara A.; Finders, Jennifer K.; McClelland, Megan M.

2015-01-01

The present study investigated the direct effects of residential mobility on children's inhibitory control and academic achievement during the preschool year. It also explored fall inhibitory control and academic skills as mediators linking residential mobility and spring achievement. Participants included 359 preschool children (49% female)…

Residential Mobility, Inhibitory Control, and Academic Achievement in Preschool

ERIC Educational Resources Information Center

Schmitt, Sara A.; Finders, Jennifer K.; McClelland, Megan M.

2015-01-01

Research Findings: The present study investigated the direct effects of residential mobility on children's inhibitory control and academic achievement during the preschool year. It also explored fall inhibitory control and academic skills as mediators linking residential mobility and spring achievement. Participants included 359 preschool children…

14- to 16-Month-Olds Attend to Distinct Labels in an Inductive Reasoning Task

PubMed Central

Switzer, Jessica L.; Graham, Susan A.

2017-01-01

We examined how naming objects with unique labels influenced infants’ reasoning about the non-obvious properties of novel objects. Seventy 14- to 16-month-olds participated in an imitation-based inductive inference task during which they were presented with target objects possessing a non-obvious sound property, followed by test objects that varied in shape similarity in comparison to the target. Infants were assigned to one of two groups: a No Label group in which objects were introduced with a general attentional phrase (i.e., “Look at this one”) and a Distinct Label group in which target and test objects were labeled with two distinct count nouns (i.e., fep vs. wug). Infants in the Distinct Label group performed significantly fewer target actions on the high-similarity objects than infants in the No Label group but did not differ in performance of actions on the low-similarity object. Within the Distinct Label group, performance on the inductive inference task was related to age, but not to working memory, inhibitory control, or vocabulary. Within the No Label condition, performance on the inductive inference task was related to a measure of inhibitory control. Our findings suggest that between 14- and 16-months, infants begin to use labels to carve out distinct categories, even when objects are highly perceptually similar. PMID:28484410

The utility of event-related potentials (ERPs) in understanding food-related cognition: A systematic review and recommendations.

PubMed

Carbine, Kaylie A; Rodeback, Rebekah; Modersitzki, Erin; Miner, Marshall; LeCheminant, James D; Larson, Michael J

2018-05-19

Daily dietary decisions have the potential to impact our physical, mental, and emotional health. Event-related potentials (ERPs) can provide insight into cognitive processes, such as attention, working memory, and inhibitory control, that may influence the food-related decisions we make on a daily basis. We conducted a systematic review of the food-related cognition and ERP research in order to summarize the extant literature, identify future research questions, synthesize how food-related ERP components relate to eating habits and appetite, and demonstrate the utility of ERPs in examining food-related cognition. Forty-three articles were systematically extracted. In general, results indicated food cues compared to less palatable foods or neutral cues elicited greater ERP amplitudes reflecting early or late attention allocation (e.g., increased P2, P3, late positive potential amplitudes). Food cues were associated with increased frontocentral P3 and N2 ERP amplitudes compared to neutral or less palatable food cues, suggesting increased recruitment of inhibitory control and conflict monitoring resources. However, there was significant heterogeneity in the literature, as experimental tasks, stimuli, and examined ERP components varied widely across studies, and therefore replication studies are needed. In-depth research is also needed to establish how food-related ERPs differ by BMI groups and relate to real-world eating habits and appetite, in order to establish the ecological validity. Copyright © 2018. Published by Elsevier Ltd.

Behavioral and Neural Inhibitory Control Moderates the Effects of Reward Sensitivity on Adolescent Substance Use

PubMed Central

Kim-Spoon, Jungmeen; Deater-Deckard, Kirby; Holmes, Christopher; Lee, Jacob; Chiu, Pearl; King-Casas, Brooks

2016-01-01

The developmental period of adolescence is characterized by increasing incidence of health risk behaviors, including experimenting with drugs and alcohol. We examined how inhibitory control interacts with reward and punishment sensitivity to predict substance use severity and age of onset among early adolescents. The sample was comprised of 157 early adolescents (13-14 years of age, 52% male). Composite scores for behavioral activation system (BAS), behavioral inhibition system (BIS), and substance use severity and onset were computed using adolescents’ questionnaire data, and inhibitory control was assessed based on adolescents’ behavioral performance and brain imaging during the Multiple Source Interference Task (MSIT). Structural equation modeling analyses indicated that for both behavioral performance and neural activity indicators of inhibitory control, high levels of BAS predicted earlier onset of substance use among adolescents with low inhibitory control—but not among adolescents with high inhibitory control. BIS was not related to substance use severity and onset among adolescents. The results support the theoretically hypothesized moderating role of inhibitory control and its associated frontal cortex functioning, and offer new insights into the identification of adolescents with neurobehavioral vulnerabilities to developing maladaptive substance use behaviors. PMID:27580969

Heterogeneity in Maltreated and Non-maltreated Preschool Children’s Inhibitory Control: The Interplay Between Parenting Quality and Child Temperament

PubMed Central

Cipriano-Essel, Elizabeth; Skowron, Elizabeth A.; Stifter, Cynthia A.; Teti, Douglas M.

2014-01-01

This study examined the contribution of child temperament, parenting, and their interaction on inhibitory control development in a sample of maltreated and non-maltreated preschool children. One hundred and eighteen mother–child dyads were drawn from predominantly low-income, rural communities. Dyads participated in a laboratory session in which maternal warm autonomy support, warm guidance, and strict/hostile control were observationally coded during a joint teaching task. Independent assessments of children’s inhibitory control were obtained, and observers rated children’s temperament. After relevant covariates, including income, maternal education, and child age and IQ were controlled for, there were no differences between the maltreatment and non-maltreatment groups in either children’s inhibitory control or mothers’ behaviours in the laboratory session. Even after much of the variance in children’s inhibitory control was accounted for from the covariates, children’s temperamental negativity moderated the effects of warm autonomy support on inhibitory control in both maltreatment and non-maltreatment groups. Temperamentally negative children whose mothers displayed more warm autonomy support showed greater inhibitory control, at levels on par with low-negative children. Findings suggest that heterogeneity in children’s self-regulation may be due in part to individual differences in sensitivity to caregiver support for children’s independence, even among those exposed to maltreatment. PMID:24729743

Inhibitory control and counterintuitive science and maths reasoning in adolescence.

PubMed

Brookman-Byrne, Annie; Mareschal, Denis; Tolmie, Andrew K; Dumontheil, Iroise

2018-01-01

Existing concepts can be a major barrier to learning new counterintuitive concepts that contradict pre-existing experience-based beliefs or misleading perceptual cues. When reasoning about counterintuitive concepts, inhibitory control is thought to enable the suppression of incorrect concepts. This study investigated the association between inhibitory control and counterintuitive science and maths reasoning in adolescents (N = 90, 11-15 years). Both response and semantic inhibition were associated with counterintuitive science and maths reasoning, when controlling for age, general cognitive ability, and performance in control science and maths trials. Better response inhibition was associated with longer reaction times in counterintuitive trials, while better semantic inhibition was associated with higher accuracy in counterintuitive trials. This novel finding suggests that different aspects of inhibitory control may offer unique contributions to counterintuitive reasoning during adolescence and provides further support for the hypothesis that inhibitory control plays a role in science and maths reasoning.

Inhibiting food reward: delay discounting, food reward sensitivity, and palatable food intake in overweight and obese women

PubMed Central

Appelhans, Bradley M.; Woolf, Kathleen; Pagoto, Sherry L.; Schneider, Kristin L.; Whited, Matthew C.; Liebman, Rebecca

2012-01-01

Overeating is believed to result when the appetitive motivation to consume palatable food exceeds an individual’s capacity for inhibitory control of eating. This hypothesis was supported in recent studies involving predominantly normal weight women, but has not been tested in obese populations. The current study tested the interaction between food reward sensitivity and inhibitory control in predicting palatable food intake among energy-replete overweight and obese women (N=62). Sensitivity to palatable food reward was measured with the Power of Food Scale. Inhibitory control was assessed with a computerized choice task that captures the tendency to discount large delayed rewards relative to smaller immediate rewards. Participants completed an eating in the absence of hunger protocol in which homeostatic energy needs were eliminated with a bland preload of plain oatmeal, followed by a bogus laboratory taste test of palatable and bland snacks. The interaction between food reward sensitivity and inhibitory control was a significant predictor of palatable food intake in regression analyses controlling for body mass index and the amount of preload consumed. Probing this interaction indicated that higher food reward sensitivity predicted greater palatable food intake at low levels of inhibitory control, but was not associated with intake at high levels of inhibitory control. As expected, no associations were found in a similar regression analysis predicting intake of bland foods. Findings support a neurobehavioral model of eating behavior in which sensitivity to palatable food reward drives overeating only when accompanied by insufficient inhibitory control. Strengthening inhibitory control could enhance weight management programs. PMID:21475139

Proactive Inhibitory Control of Response as the Default State of Executive Control

PubMed Central

Criaud, Marion; Wardak, Claire; Ben Hamed, Suliann; Ballanger, Bénédicte; Boulinguez, Philippe

2012-01-01

Refraining from reacting does not only involve reactive inhibitory mechanisms. It was recently found that inhibitory control also relies strongly on proactive mechanisms. However, since most available studies have focused on reactive stopping, little is known about how proactive inhibition of response is implemented. Two behavioral experiments were conducted to identify the temporal dynamics of this executive function. They manipulated respectively the time during which inhibitory control must be sustained until a stimulus occurs, and the time limit allowed to set up inhibition before a stimulus occurs. The results show that inhibitory control is not set up after but before instruction, and is not transient and sporadic but sustained across time. Consistent with our previous neuroimaging findings, these results suggest that proactive inhibition of response is the default mode of executive control. This implies that top-down control of sensorimotor reactivity would consist of a temporary release (up to several seconds), when appropriate (when the environment becomes predictable), of the default locking state. This conclusion is discussed with regard to current anatomo-functional models of inhibitory control, and to methodological features of studies of attention and sensorimotor control. PMID:22403563

Proactive inhibitory control of response as the default state of executive control.

PubMed

Criaud, Marion; Wardak, Claire; Ben Hamed, Suliann; Ballanger, Bénédicte; Boulinguez, Philippe

2012-01-01

Refraining from reacting does not only involve reactive inhibitory mechanisms. It was recently found that inhibitory control also relies strongly on proactive mechanisms. However, since most available studies have focused on reactive stopping, little is known about how proactive inhibition of response is implemented. Two behavioral experiments were conducted to identify the temporal dynamics of this executive function. They manipulated respectively the time during which inhibitory control must be sustained until a stimulus occurs, and the time limit allowed to set up inhibition before a stimulus occurs. The results show that inhibitory control is not set up after but before instruction, and is not transient and sporadic but sustained across time. Consistent with our previous neuroimaging findings, these results suggest that proactive inhibition of response is the default mode of executive control. This implies that top-down control of sensorimotor reactivity would consist of a temporary release (up to several seconds), when appropriate (when the environment becomes predictable), of the default locking state. This conclusion is discussed with regard to current anatomo-functional models of inhibitory control, and to methodological features of studies of attention and sensorimotor control.

Tracking KLRC2 (NKG2C)+ memory-like NK cells in SIV+ and rhCMV+ rhesus macaques.

PubMed

Ram, Daniel R; Manickam, Cordelia; Hueber, Brady; Itell, Hannah L; Permar, Sallie R; Varner, Valerie; Reeves, R Keith

2018-05-01

Natural killer (NK) cells classically typify the nonspecific effector arm of the innate immune system, but have recently been shown to possess memory-like properties against multiple viral infections, most notably CMV. Expression of the activating receptor NKG2C is elevated on human NK cells in response to infection with CMV as well as HIV, and may delineate cells with memory and memory-like functions. A better understanding of how NKG2C+ NK cells specifically respond to these pathogens could be significantly advanced using nonhuman primate (NHP) models but, to date, it has not been possible to distinguish NKG2C from its inhibitory counterpart, NKG2A, in NHP because of unfaithful antibody cross-reactivity. Using novel RNA-based flow cytometry, we identify for the first time true memory NKG2C+ NK cells in NHP by gene expression (KLRC2), and show that these cells have elevated frequencies and diversify their functional repertoire specifically in response to rhCMV and SIV infections.

Source monitoring and false memories in children: relation to certainty and executive functioning.

PubMed

Ruffman, T; Rustin, C; Garnham, W; Parkin, A J

2001-10-01

We presented children aged 6, 8, and 10 years with a video and then an audio tape about a dog named Mick. Some information was repeated in the two sources and some was unique to one source. We examined: (a) children's hit rate for remembering whether events occurred and their tendency to make false alarms, (b) their memory for the context in which events occurred (source monitoring), (c) their certainty about hits, false alarms, and source, and (d) whether working memory and inhibition were related to hits, false alarms, and source monitoring. The certainty ratings revealed deficits in children's understanding of when they had erred on source questions and of when they had made false alarms. In addition, inhibitory ability accounted for unique variance in the ability to avoid false alarms and in some kinds of source monitoring but not hits. In contrast, working memory tended to correlate with all forms of memory including hits. Copyright 2001 Academic Press.

Tactile Ranschburg effects: facilitation and inhibitory repetition effects analogous to verbal memory.

PubMed

Roe, Daisy; Miles, Christopher; Johnson, Andrew J

2017-07-01

The present paper examines the effect of within-sequence item repetitions in tactile order memory. Employing an immediate serial recall procedure, participants reconstructed a six-item sequence tapped upon their fingers by moving those fingers in the order of original stimulation. In Experiment 1a, within-sequence repetition of an item separated by two-intervening items resulted in a significant reduction in recall accuracy for that repeated item (i.e., the Ranschburg effect). In Experiment 1b, within-sequence repetition of an adjacent item resulted in significant recall facilitation for that repeated item. These effects mirror those reported for verbal stimuli (e.g., Henson, 1998a . Item repetition in short-term memory: Ranschburg repeated. Journal of Experimental Psychology: Learning, Memory, and Cognition, 24(5), 1162-1181. doi:doi.org/10.1037/0278-7393.24.5.1162). These data are the first to demonstrate the Ranschburg effect with non-verbal stimuli and suggest further cross-modal similarities in order memory.

Multilingual Stroop Performance: Effects of Trilingualism and Proficiency on Inhibitory Control

ERIC Educational Resources Information Center

Marian, Viorica; Blumenfeld, Henrike K.; Mizrahi, Elena; Kania, Ursula; Cordes, Anne-Kristin

2013-01-01

Previous research suggests that multilinguals' languages are constantly co-activated and that experience managing this co-activation changes inhibitory control function. The present study examined language interaction and inhibitory control using a colour-word Stroop task. Multilingual participants were tested in their three most proficient…

Sex differences in how erotic and painful stimuli impair inhibitory control.

PubMed

Yu, Jiaxin; Hung, Daisy L; Tseng, Philip; Tzeng, Ovid J L; Muggleton, Neil G; Juan, Chi-Hung

2012-08-01

Witnessing emotional events such as arousal or pain may impair ongoing cognitive processes such as inhibitory control. We found that this may be true only half of the time. Erotic images and painful video clips were shown to men and women shortly before a stop signal task, which measures cognitive inhibitory control. These stimuli impaired inhibitory control only in men and not in women, suggesting that emotional stimuli may be processed with different weights depending on gender. Copyright © 2012 Elsevier B.V. All rights reserved.

Measuring the development of inhibitory control: The challenge of heterotypic continuity

PubMed Central

Petersen, Isaac T.; Hoyniak, Caroline P.; McQuillan, Maureen E.; Bates, John E.; Staples, Angela D.

2016-01-01

Inhibitory control is thought to demonstrate heterotypic continuity, in other words, continuity in its purpose or function but changes in its behavioral manifestation over time. This creates major methodological challenges for studying the development of inhibitory control in childhood including construct validity, developmental appropriateness and sensitivity of measures, and longitudinal factorial invariance. We meta-analyzed 198 studies using measures of inhibitory control, a key aspect of self-regulation, to estimate age ranges of usefulness for each measure. The inhibitory control measures showed limited age ranges of usefulness owing to ceiling/floor effects. Tasks were useful, on average, for a developmental span of less than 3 years. This suggests that measuring inhibitory control over longer spans of development may require use of different measures at different time points, seeking to measure heterotypic continuity. We suggest ways to study the development of inhibitory control, with overlapping measurement in a structural equation modeling framework and tests of longitudinal factorial or measurement invariance. However, as valuable as this would be for the area, we also point out that establishing longitudinal factorial invariance is neither sufficient nor necessary for examining developmental change. Any study of developmental change should be guided by theory and construct validity, aiming toward a better empirical and theoretical approach to the selection and combination of measures. PMID:27346906

Reduced attention and increased impulsivity in mice lacking NPY Y2 receptors: relation to anxiolytic-like phenotype.

PubMed

Greco, Barbara; Carli, Mirjana

2006-05-15

Neuropeptide (NPY) Y2 receptors play an important role in some anxiety-related and stress-related behaviours in mice. Changes in the level of anxiety can affect some cognitive functions such as memory, attention and inhibitory response control. We investigated the effects of NPY Y2 receptor deletion (Y2(-/-)) in mice on visual attention and response control using the five-choice serial reaction time (5-CSRT) task in which accuracy of detection of a brief visual stimulus across five spatial locations may serve as a valid behavioural index of attentional functioning. Anticipatory and perseverative responses provide a measure of inhibitory response control. During training, the Y2(-/-) mice had lower accuracy (% correct), and made more anticipatory responses. At stimulus durations of 2 and 4s the Y2(-/-) were as accurate as the Y2(+/+) mice but still more impulsive than Y(+/+). At stimulus durations of 0.25 and 0.5s both groups performed worse but the Y2(-/-) mice made significantly fewer correct responses than the Y2(+/+) controls. The anxiolytic drug diazepam at 2mg/kg IP greatly increased the anticipatory responding of Y2(-/-) mice compared to Y2(+/+). The anxiogenic inverse benzodiazepine agonist, FG 7142, at 10mg/kg IP reduced the anticipatory responding of Y2(-/-) but not Y2(+/+) mice. These data suggest that NPY Y2 receptors make an important contribution to mechanisms controlling attentional functioning and "impulsivity". They also show that "impulsivity" of NPY Y2(-/-) mice may depend on their level of anxiety. These findings may help in understanding the pathophysiology of stress disorders and depression.

Rapid Long-Range Disynaptic Inhibition Explains the Formation of Cortical Orientation Maps

PubMed Central

Antolík, Ján

2017-01-01

Competitive interactions are believed to underlie many types of cortical processing, ranging from memory formation, attention and development of cortical functional organization (e.g., development of orientation maps in primary visual cortex). In the latter case, the competitive interactions happen along the cortical surface, with local populations of neurons reinforcing each other, while competing with those displaced more distally. This specific configuration of lateral interactions is however in stark contrast with the known properties of the anatomical substrate, i.e., excitatory connections (mediating reinforcement) having longer reach than inhibitory ones (mediating competition). No satisfactory biologically plausible resolution of this conflict between anatomical measures, and assumed cortical function has been proposed. Recently a specific pattern of delays between different types of neurons in cat cortex has been discovered, where direct mono-synaptic excitation has approximately the same delay, as the combined delays of the disynaptic inhibitory interactions between excitatory neurons (i.e., the sum of delays from excitatory to inhibitory and from inhibitory to excitatory neurons). Here we show that this specific pattern of delays represents a biologically plausible explanation for how short-range inhibition can support competitive interactions that underlie the development of orientation maps in primary visual cortex. We demonstrate this statement analytically under simplifying conditions, and subsequently show using network simulations that development of orientation maps is preserved when long-range excitation, direct inhibitory to inhibitory interactions, and moderate inequality in the delays between excitatory and inhibitory pathways is added. PMID:28408869

A Longitudinal Study of Memory Advantages in Bilinguals

PubMed Central

Ljungberg, Jessica K.; Hansson, Patrik; Andrés, Pilar; Josefsson, Maria; Nilsson, Lars-Göran

2013-01-01

Typically, studies of cognitive advantages in bilinguals have been conducted previously by using executive and inhibitory tasks (e.g. Simon task) and applying cross-sectional designs. This study longitudinally investigated bilingual advantages on episodic memory recall, verbal letter and categorical fluency during the trajectory of life. Monolingual and bilingual participants (n = 178) between 35–70 years at baseline were drawn from the Betula Prospective Cohort Study of aging, memory, and health. Results showed that bilinguals outperformed monolinguals at the first testing session and across time both in episodic memory recall and in letter fluency. No interaction with age was found indicating that the rate of change across ages was similar for bilinguals and monolinguals. As predicted and in line with studies applying cross-sectional designs, no advantages associated with bilingualism were found in the categorical fluency task. The results are discussed in the light of successful aging. PMID:24023803

Modulating effect of COMT Val(158)Met polymorphism on interference resolution during a working memory task.

PubMed

Jaspar, Mathieu; Dideberg, Vinciane; Bours, Vincent; Maquet, Pierre; Collette, Fabienne

2015-04-01

Genetic variability related to the catechol-O-methyltransferase (COMT) gene has received increasing attention in the last 15years, in particular as a potential modulator of the neural substrates underlying inhibitory processes and updating in working memory (WM). In an event-related functional magnetic resonance imaging (fMRI) study, we administered a modified version of the Sternberg probe recency task (Sternberg, 1966) to 43 young healthy volunteers, varying the level of interference across successive items. The task was divided into two parts (high vs. low interference) to induce either proactive or reactive control processes. The participants were separated into three groups according to their COMT Val(158)Met genotype [Val/Val (VV); Val/Met (VM); Met/Met (MM)]. The general aim of the study was to determine whether COMT polymorphism has a modulating effect on the neural substrates of interference resolution during WM processing. Results indicate that interfering trials were associated with greater involvement of frontal cortices (bilateral medial frontal gyrus, left precentral and superior frontal gyri, right inferior frontal gyrus) in VV homozygous subjects (by comparison to Met allele carriers) only in the proactive condition of the task. In addition, analysis of peristimulus haemodynamic responses (PSTH) revealed that the genotype-related difference observed in the left SFG was specifically driven by a larger increase in activity from the storage to the recognition phase of the interfering trials in VV homozygous subjects. These results confirm the impact of COMT genotype on inhibitory processes during a WM task, with an advantage for Met allele carriers. Interestingly, this impact on frontal areas is present only when the level of interference is high, and especially during the transition from storage to recognition in the left superior frontal gyrus. Copyright © 2015 Elsevier Inc. All rights reserved.

Eye movement analysis and cognitive processing: detecting indicators of conversion to Alzheimer’s disease

PubMed Central

Pereira, Marta LG Freitas; Camargo, Marina von Zuben A; Aprahamian, Ivan; Forlenza, Orestes V

2014-01-01

A great amount of research has been developed around the early cognitive impairments that best predict the onset of Alzheimer’s disease (AD). Given that mild cognitive impairment (MCI) is no longer considered to be an intermediate state between normal aging and AD, new paths have been traced to acquire further knowledge about this condition and its subtypes, and to determine which of them have a higher risk of conversion to AD. It is now known that other deficits besides episodic and semantic memory impairments may be present in the early stages of AD, such as visuospatial and executive function deficits. Furthermore, recent investigations have proven that the hippocampus and the medial temporal lobe structures are not only involved in memory functioning, but also in visual processes. These early changes in memory, visual, and executive processes may also be detected with the study of eye movement patterns in pathological conditions like MCI and AD. In the present review, we attempt to explore the existing literature concerning these patterns of oculomotor changes and how these changes are related to the early signs of AD. In particular, we argue that deficits in visual short-term memory, specifically in iconic memory, attention processes, and inhibitory control, may be found through the analysis of eye movement patterns, and we discuss how they might help to predict the progression from MCI to AD. We add that the study of eye movement patterns in these conditions, in combination with neuroimaging techniques and appropriate neuropsychological tasks based on rigorous concepts derived from cognitive psychology, may highlight the early presence of cognitive impairments in the course of the disease. PMID:25031536

Zinc supplementation in rats impairs hippocampal-dependent memory consolidation and dampens post-traumatic recollection of stressful event.

PubMed

Contestabile, Antonio; Peña-Altamira, Emiliano; Virgili, Marco; Monti, Barbara

2016-06-01

Zinc is a trace element important for synaptic plasticity, learning and memory. Zinc deficiency, both during pregnancy and after birth, impairs cognitive performance and, in addition to memory deficits, also results in alterations of attention, activity, neuropsychological behavior and motor development. The effects of zinc supplementation on cognition, particularly in the adult, are less clear. We demonstrate here in adult rats, that 4 week-long zinc supplementation given by drinking water, and approximately doubling normal daily intake, strongly impairs consolidation of hippocampal-dependent memory, tested through contextual fear conditioning and inhibitory avoidance. Furthermore, the same treatment started after memory consolidation of training for the same behavioral tests, substantially dampens the recall of the stressful event occurred 4 weeks before. A molecular correlate of the amnesic effect of zinc supplementation is represented by a dysregulated function of GSK-3ß in the hippocampus, a kinase that participates in memory processes. The possible relevance of these data for humans, in particular regarding post-traumatic stress disorders, is discussed in view of future investigation. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Methylprednisolone as a memory enhancer in rats: Effects on aversive memory, long-term potentiation and calcium influx.

PubMed

de Vargas, Liane da Silva; Gonçalves, Rithiele; Lara, Marcus Vinícius S; Costa-Ferro, Zaquer S M; Salamoni, Simone Denise; Domingues, Michelle Flores; Piovesan, Angela Regina; de Assis, Dênis Reis; Vinade, Lucia; Corrado, Alexandre P; Alves-Do-Prado, Wilson; Correia-de-Sá, Paulo; da Costa, Jaderson Costa; Izquierdo, Ivan; Dal Belo, Cháriston A; Mello-Carpes, Pâmela B

2017-09-01

It is well recognized that stress or glucocorticoids hormones treatment can modulate memory performance in both directions, either impairing or enhancing it. Despite the high number of studies aiming at explaining the effects of glucocorticoids on memory, this has not yet been completely elucidated. Here, we demonstrate that a low daily dose of methylprednisolone (MP, 5mg/kg, i.p.) administered for 10-days favors aversive memory persistence in adult rats, without any effect on the exploring behavior, locomotor activity, anxiety levels and pain perception. Enhanced performance on the inhibitory avoidance task was correlated with long-term potentiation (LTP), a phenomenon that was strengthen in hippocampal slices of rats injected with MP (5mg/kg) during 10days. Additionally, in vitro incubation with MP (30-300µM) concentration-dependently increased intracellular [Ca 2+ ] i in cultured hippocampal neurons depolarized by KCl (35mM). In conclusion, a low daily dose of MP for 10days may promote aversive memory persistence in rats. Copyright © 2017 Elsevier B.V. All rights reserved.

"Forget to whom you have told this proverb": directed forgetting of destination memory in Alzheimer's disease.

PubMed

El Haj, Mohamad; Gandolphe, Marie-Charlotte; Allain, Philippe; Fasotti, Luciano; Antoine, Pascal

2015-01-01

Destination memory is the ability to remember the receiver of transmitted information. By means of a destination memory directed forgetting task, we investigated whether participants with Alzheimer's Disease (AD) were able to suppress irrelevant information in destination memory. Twenty-six AD participants and 30 healthy elderly subjects were asked to tell 10 different proverbs to 10 different celebrities (List 1). Afterwards, half of the participants were instructed to forget the destinations (i.e., the celebrities) whereas the other half were asked to keep them in mind. After telling 10 other proverbs to 10 other celebrities (List 2), participants were asked to read numbers aloud. Subsequently, all the participants were asked to remember the destinations of List 1 and List 2, regardless of the forget or remember instructions. The results show similar destination memory in AD participants who were asked to forget the destinations of List 1 and those who were asked to retain them. These findings are attributed to inhibitory deficits, by which AD participants have difficulties to suppress irrelevant information in destination memory.

“Forget to Whom You Have Told This Proverb”: Directed Forgetting of Destination Memory in Alzheimer's Disease

PubMed Central

El Haj, Mohamad; Gandolphe, Marie-Charlotte; Allain, Philippe; Fasotti, Luciano; Antoine, Pascal

2015-01-01

Destination memory is the ability to remember the receiver of transmitted information. By means of a destination memory directed forgetting task, we investigated whether participants with Alzheimer's Disease (AD) were able to suppress irrelevant information in destination memory. Twenty-six AD participants and 30 healthy elderly subjects were asked to tell 10 different proverbs to 10 different celebrities (List 1). Afterwards, half of the participants were instructed to forget the destinations (i.e., the celebrities) whereas the other half were asked to keep them in mind. After telling 10 other proverbs to 10 other celebrities (List 2), participants were asked to read numbers aloud. Subsequently, all the participants were asked to remember the destinations of List 1 and List 2, regardless of the forget or remember instructions. The results show similar destination memory in AD participants who were asked to forget the destinations of List 1 and those who were asked to retain them. These findings are attributed to inhibitory deficits, by which AD participants have difficulties to suppress irrelevant information in destination memory. PMID:25918456

An integrative neuroscience model of "significance" processing.

PubMed

Williams, Leanne M

2006-03-01

The Gordon [37-40] framework of Integrative Neuroscience is used to develop a continuum model for understanding the central role of motivationally-determined "significance" in organizing human information processing. Significance is defined as the property which gives a stimulus relevance to our core motivation to minimize danger and maximize pleasure. Within this framework, the areas of cognition and emotion, theories of motivational arousal and orienting, and the current understanding of neural systems are brought together. The basis of integration is a temporal continuum in which significance processing extends from the most rapid millisecond time scale of automatic, nonconscious mechanisms to the time scale of seconds, in which memory is shaped, to the controlled and conscious mechanisms unfolding over minutes. Over this continuum, significant stimuli are associated with a spectrum of defensive (or consumptive) behaviors through to volitional regulatory behaviors for danger (versus pleasure) and associated brainstem, limbic, medial forebrain bundle and prefrontal circuits, all of which reflect a balance of excitatory (predominant at rapid time scales) to inhibitory mechanisms. Across the lifespan, the negative and positive outcomes of significance processing, coupled with constitutional and genetic factors, will contribute to plasticity, shaping individual adaptations and maladaptions in the balance of excitatory-inhibitory mechanisms.

Aerobic exercise effects upon cognition in Mild Cognitive Impairment: A systematic review of randomized controlled trials.

PubMed

Cammisuli, D M; Innocenti, A; Franzoni, F; Pruneti, C

2017-07-01

Several studies have shown that physical activity has positive effects on cognition in healthy older adults without cognitive complains but lesser is known about the effectiveness of aerobic exercise in patients suffering from Mild Cognitive Impairment (MCI). The aim of the present study was to systematically review the evidence from randomized controlled trials (RCTs) about the effects of aerobic exercise upon cognition in MCI patients. To this end, PubMed, Cochrane and Web of Science databases were analytically searched for RCTs including aerobic exercise interventions for MCI patients. There is evidence that aerobic exercise improves cognition in MCI patients. Overall research reported moderate effects for global cognition, logical memory, inhibitory control and divided attention. Due to methodological limitations of the investigated studies, findings should be interpreted with caution. Standardized training protocols, larger scale interventions and follow-ups may also provide better insight into the preventive effects of aerobic exercise on cognitive deterioration in MCI and its conversion into dementia.

Short-term plasticity as a neural mechanism supporting memory and attentional functions.

PubMed

Jääskeläinen, Iiro P; Ahveninen, Jyrki; Andermann, Mark L; Belliveau, John W; Raij, Tommi; Sams, Mikko

2011-11-08

Based on behavioral studies, several relatively distinct perceptual and cognitive functions have been defined in cognitive psychology such as sensory memory, short-term memory, and selective attention. Here, we review evidence suggesting that some of these functions may be supported by shared underlying neuronal mechanisms. Specifically, we present, based on an integrative review of the literature, a hypothetical model wherein short-term plasticity, in the form of transient center-excitatory and surround-inhibitory modulations, constitutes a generic processing principle that supports sensory memory, short-term memory, involuntary attention, selective attention, and perceptual learning. In our model, the size and complexity of receptive fields/level of abstraction of neural representations, as well as the length of temporal receptive windows, increases as one steps up the cortical hierarchy. Consequently, the type of input (bottom-up vs. top down) and the level of cortical hierarchy that the inputs target, determine whether short-term plasticity supports purely sensory vs. semantic short-term memory or attentional functions. Furthermore, we suggest that rather than discrete memory systems, there are continuums of memory representations from short-lived sensory ones to more abstract longer-duration representations, such as those tapped by behavioral studies of short-term memory. Copyright © 2011 Elsevier B.V. All rights reserved.

Cognitive deficits in adult rats by lead intoxication are related with regional specific inhibition of cNOS.

PubMed

García-Arenas, Guadalupe; Ramírez-Amaya, Victor; Balderas, Israela; Sandoval, Jimena; Escobar, Martha L; Ríos, Camilo; Bermúdez-Rattoni, Federico

2004-02-04

It is well known that lead can affect several cognitive abilities in developing animals. In this work, we investigate the effects of different sub-chronic lead doses (0, 65, 125, 250 and 500 ppm of lead acetate in their drinking water for 14 days) in the performance of male adult rats in a water maze, cue maze and inhibitory avoidance tasks. We found that the acquisition of these tasks was not affected by lead, however, the highest dosage of lead (500 ppm) impaired memory consolidation in spatial and inhibitory avoidance tasks, but not in cue maze task while the 250 ppm dose only affected retrieval of spatial memory. Additionally, hippocampal long-term potentiation (LTP) induction in the perforant path after exposing adult rats to different doses of lead was studied. LTP induction was affected in a dose-dependent manner, and treatments of 250 and 500 ppm completely blocked LTP. We investigated the effects of lead intoxication on the activity of constitutive nitric oxide synthase (cNOS) in different brain regions of adult animals. The activity of cNOS was significantly inhibited in the hippocampus and cerebellum but not in the frontal cortex and brain stem, although lead had accumulated in all brain regions. These results suggest that lead intoxication can impair memory in adult animals and this impairment might be related with region-specific effects on cNOS activity.

Inhibition in movement plan competition: reach trajectories curve away from remembered and task-irrelevant present but not from task-irrelevant past visual stimuli.

PubMed

Moehler, Tobias; Fiehler, Katja

2017-11-01

The current study investigated the role of automatic encoding and maintenance of remembered, past, and present visual distractors for reach movement planning. The previous research on eye movements showed that saccades curve away from locations actively kept in working memory and also from task-irrelevant perceptually present visual distractors, but not from task-irrelevant past distractors. Curvature away has been associated with an inhibitory mechanism resolving the competition between multiple active movement plans. Here, we examined whether reach movements underlie a similar inhibitory mechanism and thus show systematic modulation of reach trajectories when the location of a previously presented distractor has to be (a) maintained in working memory or (b) ignored, or (c) when the distractor is perceptually present. Participants performed vertical reach movements on a computer monitor from a home to a target location. Distractors appeared laterally and near or far from the target (equidistant from central fixation). We found that reaches curved away from the distractors located close to the target when the distractor location had to be memorized and when it was perceptually present, but not when the past distractor had to be ignored. Our findings suggest that automatically encoding present distractors and actively maintaining the location of past distractors in working memory evoke a similar response competition resolved by inhibition, as has been previously shown for saccadic eye movements.

Sex-specific effect of the anabolic steroid, 17α-methyltestosterone, on inhibitory avoidance learning in periadolescent rats

PubMed Central

Ramos-Pratts, Keyla; Rosa-González, Dariana; Pérez-Acevedo, Nivia L.; Cintrón-López, Dahima; Barreto-Estrada, Jennifer L.

2013-01-01

The illicit use of anabolic androgenic steroids (AAS) has gained popularity among adolescents in the last decade. However, although it is known that exposure to AAS impairs cognition in adult animal models, the cognitive effects during adolescence remain undetermined. An inhibitory avoidance task (IAT) was used to assess the effect of AAS (17α-methyltestosterone; 17α-meT-7.5 mg/kg) in male and female periadolescent rats. A single injection of 17α-meT immediately before the footshock produced significant impairment of inhibitory avoidance learning in males but not females. Generalized anxiety, locomotion, and risk assessment behaviors (RAB) were not affected. Our results show that exposure to a single pharmacological dose of 17α-meT during periadolescence exerts sex-specific cognitive effects without affecting anxiety. Thus, disruption of the hormonal milieu during this early developmental period might have negative impact on learning and memory. PMID:23792034

Semantic Integration as a Boundary Condition on Inhibitory Processes in Episodic Retrieval

ERIC Educational Resources Information Center

Goodmon, Leilani B.; Anderson, Michael C.

2011-01-01

Recalling an experience often impairs the later retention of related traces, a phenomenon known as retrieval-induced forgetting (RIF). Research has shown that episodic associations protect competing memories from RIF (Anderson & McCulloch, 1999). We report 4 experiments that examined whether semantic associations also protect against RIF. In…

The Development of Two Types of Inhibitory Control in Monolingual and Bilingual Children

ERIC Educational Resources Information Center

Martin-Rhee, Michelle M.; Bialystok, Ellen

2008-01-01

Previous research has shown that bilingual children excel in tasks requiring inhibitory control to ignore a misleading perceptual cue. The present series of studies extends this finding by identifying the degree and type of inhibitory control for which bilingual children demonstrate this advantage. Study 1 replicated the earlier research by…

Inhibitory Control and Empathy-Related Personality Traits: Sex-Linked Associations

ERIC Educational Resources Information Center

Hansen, Stefan

2011-01-01

We here report two studies exploring associations between inhibitory control (measured with the Sustained Attention to Response Task, SART) on the one hand, and self-reports of trait cooperativeness and empathy on the other. A coherent picture was obtained in women whose inhibitory control proficiency predicted higher scores on the Temperament and…

Statistical mechanics of neocortical interactions. Derivation of short-term-memory capacity

NASA Astrophysics Data System (ADS)

Ingber, Lester

1984-06-01

A theory developed by the author to describe macroscopic neocortical interactions demonstrates that empirical values of chemical and electrical parameters of synaptic interactions establish several minima of the path-integral Lagrangian as a function of excitatory and inhibitory columnar firings. The number of possible minima, their time scales of hysteresis and probable reverberations, and their nearest-neighbor columnar interactions are all consistent with well-established empirical rules of human short-term memory. Thus, aspects of conscious experience are derived from neuronal firing patterns, using modern methods of nonlinear nonequilibrium statistical mechanics to develop realistic explicit synaptic interactions.

Out with the old and in with the new: Synaptic mechanisms of extinction in the amygdala

PubMed Central

Maren, Stephen

2014-01-01

Considerable research indicates that long-term synaptic plasticity in the amygdala underlies the acquisition of emotional memories, including those learned during Pavlovian fear conditioning. Much less is known about the synaptic mechanisms involved in other forms of associative learning, including extinction, that update fear memories. Extinction learning might reverse conditioning-related changes (e.g., depotentiation) or induce plasticity at inhibitory synapses (e.g., long-term potentiation) to suppress conditioned fear responses. Either mechanism must account for fear recovery phenomena after extinction, as well as savings of extinction after fear recovery. PMID:25312830

Determinants of aggressive behavior: Interactive effects of emotional regulation and inhibitory control.

PubMed

Hsieh, I-Ju; Chen, Yung Y

2017-01-01

Aggressive behavior can be defined as any behavior intended to hurt another person, and it is associated with many individual and social factors. This study examined the relationship between emotional regulation and inhibitory control in predicting aggressive behavior. Seventy-eight participants (40 males) completed self-report measures (Negative Mood Regulation Scale and Buss-Perry Aggression Questionnaire), a stop signal task, and engaged in a modified version of Taylor Aggression Paradigm (TAP) exercise, in which the outcome was used as a measure of direct physical aggression. We used a hierarchical, mixed-model multiple regression analysis test to examine the effects of emotion regulation and inhibitory control on physical reactive aggression. Results indicated an interaction between emotion regulation and inhibitory control on aggression. For participants with low inhibitory control only, there was a significant difference between high and low emotion regulation on aggression, such that low emotion regulation participants registered higher aggression than high emotion regulation participants. This difference was not found among participants with high inhibitory control. These results have implications for refining and targeting training and rehabilitation programs aimed at reducing aggressive behavior.

High-disinhibition restrained eaters are disinhibited by self-regulatory depletion in the food-related inhibitory control.

PubMed

Zhou, Yizhou; Gao, Xiao; Chen, Hong; Kong, Fanchang

2017-08-01

Restrained eating for weight control and loss is becoming highly prevalent in many affluent societies, while most of the restrained eaters are rather unsuccessful in the long term. According to the strength model of self-control, the disinhibition effect of restrained eaters may occur after the depletion of self-control resources. However, no work has examined the direct impact of self-control resources on inhibitory control ability of restrained eaters. This study investigated the influences of self-control resources on the food-related inhibitory control among high-restraint/low-disinhibition restrained eaters, high-restraint/high-disinhibition restrained eaters and unrestrained eaters using stop signal task. Results reveal that there's no difference of food-related inhibitory control between three groups when the self-control resources are non-depleted, while high-restraint/high-disinhibition restrained eaters showing a decrease of food-related inhibitory control after ego-depletion. This disinhibition effect only seems to occur in samples of restrained eaters with a high tendency toward overeating. Copyright © 2017 Elsevier Ltd. All rights reserved.

Replay of Episodic Memories in the Rat.

PubMed

Panoz-Brown, Danielle; Iyer, Vishakh; Carey, Lawrence M; Sluka, Christina M; Rajic, Gabriela; Kestenman, Jesse; Gentry, Meredith; Brotheridge, Sydney; Somekh, Isaac; Corbin, Hannah E; Tucker, Kjersten G; Almeida, Bianca; Hex, Severine B; Garcia, Krysten D; Hohmann, Andrea G; Crystal, Jonathon D

2018-05-21

Vivid episodic memories in people have been characterized as the replay of multiple unique events in sequential order [1-3]. The hippocampus plays a critical role in episodic memories in both people and rodents [2, 4-6]. Although rats remember multiple unique episodes [7, 8], it is currently unknown if animals "replay" episodic memories. Therefore, we developed an animal model of episodic memory replay. Here, we show that rats can remember a trial-unique stream of multiple episodes and the order in which these events occurred by engaging hippocampal-dependent episodic memory replay. We document that rats rely on episodic memory replay to remember the order of events rather than relying on non-episodic memories. Replay of episodic memories survives a long retention-interval challenge and interference from the memory of other events, which documents that replay is part of long-term episodic memory. The chemogenetic activating drug clozapine N-oxide (CNO), but not vehicle, reversibly impairs episodic memory replay in rats previously injected bilaterally in the hippocampus with a recombinant viral vector containing an inhibitory designer receptor exclusively activated by a designer drug (DREADD; AAV8-hSyn-hM4Di-mCherry). By contrast, two non-episodic memory assessments are unaffected by CNO, showing selectivity of this hippocampal-dependent impairment. Our approach provides an animal model of episodic memory replay, a process by which the rat searches its representations in episodic memory in sequential order to find information. Our findings using rats suggest that the ability to replay a stream of episodic memories is quite old in the evolutionary timescale. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects of sales promotions, weight status, and impulsivity on purchases in a supermarket.

PubMed

Nederkoorn, Chantal

2014-05-01

Several environmental factors contribute to increased food consumption and play a role in the prevalence of obesity, like portion size, accessibility and relative price of high caloric foods, food commercials, and sales promotions. However, not everyone seems equally sensitive to these environmental cues and both obesity and impulsivity appears to play a role. In this study, food purchases in an internet supermarket are tested in 118 participants, with or without sales promotions for snack foods. Both weight status and response inhibition, an index of impulsivity, are measured. Participants with less inhibitory control purchased in total more calories from the internet supermarket then participants with more inhibitory control. In addition, sales promotion, weight status, and inhibitory control appeared to interact in their effect on snack food purchases: participants with less inhibitory control and overweight bought more calories of snacks in the sales promotions condition, but not in the control condition. For the other participants, with normal weight and/or high inhibitory control, sales promotions had no effect on their purchases of calories of snacks. It seems that especially the combination of low inhibitory control and overweight makes participants vulnerable for environmental cues. Copyright © 2013 The Obesity Society.

Recurrent Coupling Improves Discrimination of Temporal Spike Patterns

PubMed Central

Yuan, Chun-Wei; Leibold, Christian

2012-01-01

Despite the ubiquitous presence of recurrent synaptic connections in sensory neuronal systems, their general functional purpose is not well understood. A recent conceptual advance has been achieved by theories of reservoir computing in which recurrent networks have been proposed to generate short-term memory as well as to improve neuronal representation of the sensory input for subsequent computations. Here, we present a numerical study on the distinct effects of inhibitory and excitatory recurrence in a canonical linear classification task. It is found that both types of coupling improve the ability to discriminate temporal spike patterns as compared to a purely feed-forward system, although in different ways. For a large class of inhibitory networks, the network’s performance is optimal as long as a fraction of roughly 50% of neurons per stimulus is active in the resulting population code. Thereby the contribution of inactive neurons to the neural code is found to be even more informative than that of the active neurons, generating an inherent robustness of classification performance against temporal jitter of the input spikes. Excitatory couplings are found to not only produce a short-term memory buffer but also to improve linear separability of the population patterns by evoking more irregular firing as compared to the purely inhibitory case. As the excitatory connectivity becomes more sparse, firing becomes more variable, and pattern separability improves. We argue that the proposed paradigm is particularly well-suited as a conceptual framework for processing of sensory information in the auditory pathway. PMID:22586392

CD4 memory T cells develop and acquire functional competence by sequential cognate interactions and stepwise gene regulation

PubMed Central

Kaji, Tomohiro; Hijikata, Atsushi; Ishige, Akiko; Kitami, Toshimori; Watanabe, Takashi; Ohara, Osamu; Yanaka, Noriyuki; Okada, Mariko; Shimoda, Michiko; Taniguchi, Masaru

2016-01-01

Memory CD4+ T cells promote protective humoral immunity; however, how memory T cells acquire this activity remains unclear. This study demonstrates that CD4+ T cells develop into antigen-specific memory T cells that can promote the terminal differentiation of memory B cells far more effectively than their naive T-cell counterparts. Memory T cell development requires the transcription factor B-cell lymphoma 6 (Bcl6), which is known to direct T-follicular helper (Tfh) cell differentiation. However, unlike Tfh cells, memory T cell development did not require germinal center B cells. Curiously, memory T cells that develop in the absence of cognate B cells cannot promote memory B-cell recall responses and this defect was accompanied by down-regulation of genes associated with homeostasis and activation and up-regulation of genes inhibitory for T-cell responses. Although memory T cells display phenotypic and genetic signatures distinct from Tfh cells, both had in common the expression of a group of genes associated with metabolic pathways. This gene expression profile was not shared to any great extent with naive T cells and was not influenced by the absence of cognate B cells during memory T cell development. These results suggest that memory T cell development is programmed by stepwise expression of gatekeeper genes through serial interactions with different types of antigen-presenting cells, first licensing the memory lineage pathway and subsequently facilitating the functional development of memory T cells. Finally, we identified Gdpd3 as a candidate genetic marker for memory T cells. PMID:26714588

Structural network heterogeneities and network dynamics: a possible dynamical mechanism for hippocampal memory reactivation.

NASA Astrophysics Data System (ADS)

Jablonski, Piotr; Poe, Gina; Zochowski, Michal

2007-03-01

The hippocampus has the capacity for reactivating recently acquired memories and it is hypothesized that one of the functions of sleep reactivation is the facilitation of consolidation of novel memory traces. The dynamic and network processes underlying such a reactivation remain, however, unknown. We show that such a reactivation characterized by local, self-sustained activity of a network region may be an inherent property of the recurrent excitatory-inhibitory network with a heterogeneous structure. The entry into the reactivation phase is mediated through a physiologically feasible regulation of global excitability and external input sources, while the reactivated component of the network is formed through induced network heterogeneities during learning. We show that structural changes needed for robust reactivation of a given network region are well within known physiological parameters.

Structural network heterogeneities and network dynamics: A possible dynamical mechanism for hippocampal memory reactivation

NASA Astrophysics Data System (ADS)

Jablonski, Piotr; Poe, Gina R.; Zochowski, Michal

2007-01-01

The hippocampus has the capacity for reactivating recently acquired memories and it is hypothesized that one of the functions of sleep reactivation is the facilitation of consolidation of novel memory traces. The dynamic and network processes underlying such a reactivation remain, however, unknown. We show that such a reactivation characterized by local, self-sustained activity of a network region may be an inherent property of the recurrent excitatory-inhibitory network with a heterogeneous structure. The entry into the reactivation phase is mediated through a physiologically feasible regulation of global excitability and external input sources, while the reactivated component of the network is formed through induced network heterogeneities during learning. We show that structural changes needed for robust reactivation of a given network region are well within known physiological parameters.

Sex Differences in How Erotic and Painful Stimuli Impair Inhibitory Control

ERIC Educational Resources Information Center

Yu, Jiaxin; Hung, Daisy L.; Tseng, Philip; Tzeng, Ovid J. L.; Muggleton, Neil G.; Juan, Chi-Hung

2012-01-01

Witnessing emotional events such as arousal or pain may impair ongoing cognitive processes such as inhibitory control. We found that this may be true only half of the time. Erotic images and painful video clips were shown to men and women shortly before a stop signal task, which measures cognitive inhibitory control. These stimuli impaired…

Working Memory Training for Healthy Older Adults: The Role of Individual Characteristics in Explaining Short- and Long-Term Gains

PubMed Central

Borella, Erika; Carbone, Elena; Pastore, Massimiliano; De Beni, Rossana; Carretti, Barbara

2017-01-01

Objective: The aim of the present study was to explore whether individual characteristics such as age, education, vocabulary, and baseline performance in a working memory (WM) task—similar to the one used in the training (criterion task)—predict the short- and long-term specific gains and transfer effects of a verbal WM training for older adults. Method: Four studies that adopted the Borella et al. (2010) verbal WM training procedure were found eligible for our analysis as they included: healthy older adults who attended either the training sessions (WM training group), or alternative activities (active control group); the same measures for assessing specific gains (on the criterion WM task), and transfer effects (nearest on a visuo-spatial WM task, near on short-term memory tasks and far on a measure of fluid intelligence, a measure of processing speed and two inhibitory measures); and a follow-up session. Results: Linear mixed models confirmed the overall efficacy of the training, in the short-term at least, and some maintenance effects. In the trained group, the individual characteristics considered were found to contribute (albeit only modestly in some cases) to explaining the effects of the training. Conclusions: Overall, our findings suggest the importance of taking individual characteristics and individual differences into account when examining WM training gains in older adults. PMID:28381995

Executive function and childhood stuttering: Parent ratings and evidence from a behavioral task.

PubMed

Ntourou, Katerina; Anderson, Julie D; Wagovich, Stacy A

2018-06-01

The purpose of this study was to examine the executive function (EF) abilities of preschool children who do (CWS) and do not stutter (CWNS) using a parent-report questionnaire and a behavioral task. Participants were 75 CWS and 75 CWNS between the ages of 3;0 and 5;11 (years; months). Parents rated their children's EF abilities using the Behavioral Rating Inventory of Executive Function-Preschool Version (BRIEF-P; Gioia, Espy, & Isquith, 2003). Children's ability to integrate cognitive flexibility, inhibitory control, and working memory was measured using a behavioral task, the Head-Toes-Knees-Shoulders (HTKS; Cameron Ponitz, McClelland, Matthews, & Morrison, 2009). The CWS were judged by their parents as being less proficient in working memory, shift/flexibility, and overall EF than the parents of the CWNS. Children in the CWS group were also 2½ to 7 times more likely than children in the CWNS group to exhibit clinically significant difficulties with EF. Behavioral task findings revealed that 3-year old CWS performed more poorly than their peers on the HTKS. Parental ratings of executive function and working memory were significantly and moderately correlated with receptive and expressive vocabulary skills only for the CWNS group. CWS have more difficulty with EF in everyday life and may experience early delays in their ability to integrate aspects of attention and EF compared to CWNS. Copyright © 2018 Elsevier Inc. All rights reserved.

GABAergic Synapses at the Axon Initial Segment of Basolateral Amygdala Projection Neurons Modulate Fear Extinction.

PubMed

Saha, Rinki; Knapp, Stephanie; Chakraborty, Darpan; Horovitz, Omer; Albrecht, Anne; Kriebel, Martin; Kaphzan, Hanoch; Ehrlich, Ingrid; Volkmer, Hansjürgen; Richter-Levin, Gal

2017-01-01

Inhibitory synaptic transmission in the amygdala has a pivotal role in fear learning and its extinction. However, the local circuits formed by GABAergic inhibitory interneurons within the amygdala and their detailed function in shaping these behaviors are not well understood. Here we used lentiviral-mediated knockdown of the cell adhesion molecule neurofascin in the basolateral amygdala (BLA) to specifically remove inhibitory synapses at the axon initial segment (AIS) of BLA projection neurons. Quantitative analysis of GABAergic synapse markers and measurement of miniature inhibitory postsynaptic currents in BLA projection neurons after neurofascin knockdown ex vivo confirmed the loss of GABAergic input. We then studied the impact of this manipulation on anxiety-like behavior and auditory cued fear conditioning and its extinction as BLA related behavioral paradigms, as well as on long-term potentiation (LTP) in the ventral subiculum-BLA pathway in vivo. BLA knockdown of neurofascin impaired ventral subiculum-BLA-LTP. While this manipulation did not affect anxiety-like behavior and fear memory acquisition and consolidation, it specifically impaired extinction. Our findings indicate that modification of inhibitory synapses at the AIS of BLA projection neurons is sufficient to selectively impair extinction behavior. A better understanding of the role of distinct GABAergic synapses may provide novel and more specific targets for therapeutic interventions in extinction-based therapies.

Lithium activates brain phospholipase A2 and improves memory in rats: implications for Alzheimer's disease.

PubMed

Mury, Fábio B; da Silva, Weber C; Barbosa, Nádia R; Mendes, Camila T; Bonini, Juliana S; Sarkis, Jorge Eduardo Souza; Cammarota, Martin; Izquierdo, Ivan; Gattaz, Wagner F; Dias-Neto, Emmanuel

2016-10-01

Phospholipase A2 (Pla2) is required for memory retrieval, and its inhibition in the hippocampus has been reported to impair memory acquisition in rats. Moreover, cognitive decline and memory deficits showed to be reduced in animal models after lithium treatment, prompting us to evaluate possible links between Pla2, lithium and memory. Here, we evaluated the possible modulation of Pla2 activity by a long-term treatment of rats with low doses of lithium and its impact in memory. Wistar rats were trained for the inhibitory avoidance task, treated with lithium for 100 days and tested for perdurability of long-term memory. Hippocampal samples were used for quantifying the expression of 19 brain-expressed Pla2 genes and for evaluating the enzymatic activity of Pla2 using group-specific radio-enzymatic assays. Our data pointed to a significant perdurability of long-term memory, which correlated with increased transcriptional and enzymatic activities of certain members of the Pla2 family (iPla2 and sPla2) after the chronic lithium treatment. Our data suggest new possible targets of lithium, add more information on its pharmacological activity and reinforce the possible use of low doses of lithium for the treatment of neurodegenerative conditions such as the Alzheimer's disease.

Differential patterns of functional and structural plasticity within and between inferior frontal gyri support training-induced improvements in inhibitory control proficiency.

PubMed

Chavan, Camille F; Mouthon, Michael; Draganski, Bogdan; van der Zwaag, Wietske; Spierer, Lucas

2015-07-01

Ample evidence indicates that inhibitory control (IC), a key executive component referring to the ability to suppress cognitive or motor processes, relies on a right-lateralized fronto-basal brain network. However, whether and how IC can be improved with training and the underlying neuroplastic mechanisms remains largely unresolved. We used functional and structural magnetic resonance imaging to measure the effects of 2 weeks of training with a Go/NoGo task specifically designed to improve frontal top-down IC mechanisms. The training-induced behavioral improvements were accompanied by a decrease in neural activity to inhibition trials within the right pars opercularis and triangularis, and in the left pars orbitalis of the inferior frontal gyri. Analyses of changes in brain anatomy induced by the IC training revealed increases in grey matter volume in the right pars orbitalis and modulations of white matter microstructure in the right pars triangularis. The task-specificity of the effects of training was confirmed by an absence of change in neural activity to a control working memory task. Our combined anatomical and functional findings indicate that differential patterns of functional and structural plasticity between and within inferior frontal gyri enhanced the speed of top-down inhibition processes and in turn IC proficiency. The results suggest that training-based interventions might help overcoming the anatomic and functional deficits of inferior frontal gyri manifesting in inhibition-related clinical conditions. More generally, we demonstrate how multimodal neuroimaging investigations of training-induced neuroplasticity enable revealing novel anatomo-functional dissociations within frontal executive brain networks. © 2015 Wiley Periodicals, Inc.

Native language change during early stages of second language learning.

PubMed

Bice, Kinsey; Kroll, Judith F

2015-11-11

Research on proficient bilinguals has demonstrated that both languages are always active, even when only one is required. The coactivation of the two languages creates both competition and convergence, facilitating the processing of cognate words, but slowing lexical access when there is a requirement to engage control mechanisms to select the target language. Critically, these consequences are evident in the native language (L1) as well as in the second language (L2). The present study questioned whether L1 changes can be detected at early stages of L2 learning and how they are modulated by L2 proficiency. Native English speakers learning Spanish performed an English (L1) lexical decision task that included cognates while event-related potentials were recorded. They also performed verbal fluency, working memory, and inhibitory control tasks. A group of matched monolinguals performed the same tasks in English only. The results revealed that intermediate learners demonstrate a reduced N400 for cognates compared with noncognates in English (L1), and an emerging effect is visually present in beginning learners as well; however, no behavioral cognate effect was present for either group. In addition, slower reaction times in English (L1) are related to a larger cognate N400 magnitude in English (L1) and Spanish (L2), and to better inhibitory control for learners but not for monolinguals. The results suggest that contrary to the claim that L2 affects L1 only when L2 speakers are highly proficient, L2 learning begins to impact L1 early in the development of the L2 skill.

Boswellic Acid Improves Cognitive Function in a Rat Model Through Its Antioxidant Activity

PubMed Central

Ebrahimpour, Saeedeh; Fazeli, Mehdi; Mehri, Soghra; Taherianfard, Mahnaz; Hosseinzadeh, Hossein

2017-01-01

Objectives: Boswellic acid (BA), a compound isolated from the gum-resin of Boswellia carterii, is a pentacyclic terpenoid that is active against many inflammatory diseases, including cancer, arthritis, chronic colitis, ulcerative colitis, Crohn's disease, and memory impairment, but the mechanism is poorly understood. This study investigated the effects of boswellic acid on spatial learning and memory impairment induced by trimethyltin (TMT) in Wistar rats. Methods: Forty male Wistar rats were randomly divided into 5 groups: Normal group, TMT-administrated rats (8.0 mg/kg, Intraperitoneally, i.p.) and TMT + BA (40, 80 and 160 mg/kg, i.p.)-administrated rats. BA was used daily for 21 days. To evaluate the cognitive improving of BA, we performed the Morris water maze test. Moreover, to investigate the neuroprotective effect of BA, we determined the acetylcholinesterase (AchE) activity, the malondialdehyde (MDA) level as a marker of lipid peroxidation, and the glutathione (GSH) content in the cerebral cortex. Results: Treatment with TMT impaired learning and memory, and treatment with BA at a dose of 160 mg/kg produced a significant improvement in learning and memory abilities in the water maze tasks. Consistent with behavioral data, the activity of AChE was significantly increased in the TMT-injected rats compared to the control group (P < 0.01) whereas all groups treated with BA presented a more significant inhibitory effect against AChE than the TMT-injected animals. In addition, TMT reduced the GSH content and increased the MDA level in the cerebral cortex as compared to the control group) P < 0.01). On the other hand, treatment with BA at 160 mg/kg slightly increased the GSH content and reduced the MDA level in comparison to the TMT-administered group (P < 0.01). Conclusion: The above results suggest that the effect of BA in improving the cognitive function may be mediated through its antioxidant activity. PMID:28392957

The role of NPY in learning and memory.

PubMed

Gøtzsche, C R; Woldbye, D P D

2016-02-01

High levels of NPY expression in brain regions important for learning and memory together with its neuromodulatory and neurotrophic effects suggest a regulatory role for NPY in memory processes. Therefore it is not surprising that an increasing number of studies have provided evidence for NPY acting as a modulator of neuroplasticity, neurotransmission, and memory. Here these results are presented in relation to the types of memory affected by NPY and its receptors. NPY can exert both inhibitory and stimulatory effects on memory, depending on memory type and phase, dose applied, brain region, and NPY receptor subtypes. Thus NPY act as a resilience factor by impairing associative implicit memory after stressful and aversive events, as evident in models of fear conditioning, presumably via Y1 receptors in the amygdala and prefrontal cortex. In addition, NPY impairs acquisition but enhances consolidation and retention in models depending on spatial and discriminative types of associative explicit memory, presumably involving Y2 receptor-mediated regulations of hippocampal excitatory transmission. Moreover, spatial memory training leads to increased hippocampal NPY gene expression that together with Y1 receptor-mediated neurogenesis could constitute necessary steps in consolidation and long-term retention of spatial memory. Altogether, NPY-induced effects on learning and memory seem to be biphasic, anatomically and temporally differential, and in support of a modulatory role of NPY at keeping the system in balance. Obtaining further insight into memory-related effects of NPY could inspire the engineering of new therapeutics targeting diseases where impaired learning and memory are central elements. Copyright © 2015 Elsevier Ltd. All rights reserved.