Development and characterization of a novel human Waldenström macroglobulinemia cell line: RPCI-WM1, Roswell Park Cancer Institute - Waldenström Macroglobulinemia 1.

PubMed

Chitta, Kasyapa S; Paulus, Aneel; Ailawadhi, Sikander; Foster, Barbara A; Moser, Michael T; Starostik, Petr; Masood, Aisha; Sher, Taimur; Miller, Kena C; Iancu, Dan M; Conroy, Jeffrey; Nowak, Norma J; Sait, Sheila N; Personett, David A; Coleman, Morton; Furman, Richard R; Martin, Peter; Ansell, Stephen M; Lee, Kelvin; Chanan-Khan, Asher A

2013-02-01

Understanding the biology of Waldenström macroglobulinemia is hindered by a lack of preclinical models. We report a novel cell line, RPCI-WM1, from a patient treated for WM. The cell line secretes human immunoglobulin M (h-IgM) with κ-light chain restriction identical to the primary tumor. The cell line has a modal chromosomal number of 46 and harbors chromosomal changes such as deletion of 6q21, monoallelic deletion of 9p21 (CDKN2A), 13q14 (RB1) and 18q21 (BCL-2), with a consistent amplification of 14q32 (immunoglobulin heavy chain; IgH) identical to its founding tumor sample. The clonal relationship is confirmed by identical CDR3 length and single nucleotide polymorphisms as well as a matching IgH sequence of the cell line and founding tumor. Both also harbor a heterozygous, non-synonymous mutation at amino acid 265 in the MYD88 gene (L265P). The cell line expresses most of the cell surface markers present on the parent cells. Overall, RPCI-WM1 represents a valuable model to study Waldenström macroglobulinemia.

Mast cells in Waldenstrom's macroglobulinemia support lymphoplasmacytic cell growth through CD154/CD40 signaling.

PubMed

Tournilhac, O; Santos, D D; Xu, L; Kutok, J; Tai, Y-T; Le Gouill, S; Catley, L; Hunter, Z; Branagan, A R; Boyce, J A; Munshi, N; Anderson, K C; Treon, S P

2006-08-01

Bone marrow (BM) mast cells (MC) are commonly found in association with lymphoplasmacytic cells (LPC) in patients with Waldenström's macroglobulinemia (WM). We therefore sought to clarify the role of MC in WM. Co-culture of sublethally irradiated HMC-1 MC, KU812 basophilic cells, or autologous BM MC along with BM LPC from WM patients resulted in MC dose-dependent tumor colony formation and/or proliferation as assessed by 3H-thymidine uptake studies. Furthermore, by immunohistochemistry, multicolor flow cytometry and/or RT-PCR analysis, CD40 ligand (CD154), a potent inducer of B-cell expansion, was expressed on BM MC from 32 of 34 (94%), 11 of 13 (85%), and 7 of 9 (78%) patients, respectively. In contrast, MC from five healthy donors did not express CD154. By multicolor flow cytometry, CD154 was expressed on BM LPC from 35 of 38 (92%) patients and functionality was confirmed by CD154 and CD40 agonistic antibody stimulation, which induced proliferation, support survival and/or pERK phosphorylation of LPC. Moreover, MC induced expansion of LPC from 3 of 5 patients was blocked in a dose dependent manner by use of a CD154 blocking protein. These studies demonstrate that in WM, MC may support tumor cell expansion through constitutive CD154-CD40 signaling and therefore provide the framework for therapeutic targeting of MC and MC-WM cell interactions in WM.

Treatment of Waldenstrom's macroglobulinemia with very low doses of alpha interferon.

PubMed

Legouffe, E; Rossi, J F; Laporte, J P; Isnard, F; Oziol, E; Fabbro, M; Janbon, C; Jourdan, J; Najman, A

1995-10-01

Waldenström's macroglobulinemia (WM) is a differentiated B-cell malignancy which is usually less responsive to standard chemotherapy because of low-proliferating cells. Interferon alpha has been shown to possess a therapeutic action in numerous B-cell malignancies including the early stage of chronic lymphocytic leukemia, multiple myeloma, follicular lymphoma and hairy cell leukemia. Fourteen patients with progressive WM were included in a pilot study using very low dose of interferon alpha-2a (1 Million Units 3 times a week). The mean duration of treatment was 10.3 months (range 2-44). Six of 14 (42%) patients presented an increase in the hemoglobin level (> or = 0.9 g/dL) and 4/14 (28%) had a substantial decrease of the monoclonal component (> or = 20% of reduction). Only two patients presented both types of response, while the others with an increase in the hemoglobin level had a slight decrease in the monoclonal component (MC) (1 patient), a stable MC (1 patient) or a slight increase of MC (1 patient). One additional patient had a 15% decrease of the MC with a stable hemoglobin level. Response was observed within 3 months with a median duration of 6 months. Treatment was stopped for 3 patients because of flu-like symptoms (2 patients), or thrombocytopenia (1 patient). Follow up was possible in 12 patients lasting up to a maximum of 30 months after discontinuing treatment. Seven patients died, including 4 with progressive disease, two of infection and one of cardiac failure. In the view of these results, very low dose of interferon alpha may constitute a new approach for treatment of some cases of WM.

Development and characterization of a novel human Waldenström Macroglobulinemia cell line (RPCI-WM1; Roswell Park Cancer Institute-Waldenström Macroglobulinemia 1)

PubMed Central

Chitta, Kasyapa S.; Paulus, Aneel; Ailawadhi, Sikander; Foster, Barbara A.; Moser, Michael T.; Starostik, Petr; Masood, Aisha; Sher, Taimur; Miller, Kena C.; Iancu, Dan M.; Conroy, Jeffrey; Nowak, Norma J.; Sait, Sheila N.; Personett, David A.; Coleman, Morton; Furman, Richard R.; Martin, Peter; Ansell, Stephen M.; Lee, Kelvin; Chanan-Khan, Asher A.

2015-01-01

Understanding the biology of Waldenström Macroglobulinemia is hindered by a lack of preclinical models. We report a novel cell line, RPCI-WM1, from a patient treated for WM. The cell line secreted human IgM (hIgM) with k-light chain restriction identical to the primary tumor. The cell line has a modal chromosomal number of 46 and harbors chromosomal changes such as deletion of 6q21, monoallelic deletion of 9p21 (CDKN2A), 13q14 (RB1) and 18q21 (BCL-2) with a consistent amplification of 14q32 (IgH) identical to its founding tumor sample. Clonal relationship was confirmed by identical CDR3 length and single nucleotide polymorphisms as well as a matching IgH sequence of the cell line and founding tumor. Both also harbor a heterozygous, non-synonymous mutation at amino acid 265 in MYD88 gene (L265P). The cell line expresses most of the cell surface markers present on the parent cells. Over all, RPCI-WM1 represents a valuable model to study WM. PMID:22812491

Treatment recommendations for patients with Waldenström macroglobulinemia (WM) and related disorders: IWWM-7 consensus

PubMed Central

Kastritis, Efstathios; Owen, Roger G.; Kyle, Robert A.; Landgren, Ola; Morra, Enrica; Leleu, Xavier; García-Sanz, Ramón; Munshi, Nikhil; Anderson, Kenneth C.; Terpos, Evangelos; Ghobrial, Irene M.; Morel, Pierre; Maloney, David; Rummel, Mathias; Leblond, Véronique; Advani, Ranjana H.; Gertz, Morie A.; Kyriakou, Charalampia; Thomas, Sheeba K.; Barlogie, Bart; Gregory, Stephanie A.; Kimby, Eva; Merlini, Giampaolo; Treon, Steven P.

2014-01-01

Waldenström macroglobulinemia (WM) is a distinct B-cell lymphoproliferative disorder for which clearly defined criteria for the diagnosis, initiation of therapy, and treatment strategy have been proposed as part of the consensus panels of International Workshops on WM (IWWM). As part of the IWWM-7 and based on recently published and ongoing clinical trials, the panels updated treatment recommendations. Therapeutic strategy in WM should be based on individual patient and disease characteristics (age, comorbidities, need for rapid disease control, candidacy for autologous transplantation, cytopenias, IgM-related complications, hyperviscosity, and neuropathy). Mature data show that rituximab combinations with cyclophosphamide/dexamethasone, bendamustine, or bortezomib/dexamethasone provided durable responses and are indicated for most patients. New monoclonal antibodies (ofatumumab), second-generation proteasome inhibitors (carfilzomib), mammalian target of rapamycin inhibitors, and Bruton's tyrosine kinase inhibitors are promising and may expand future treatment options. A different regimen is typically recommended for relapsed or refractory disease. In selected patients with relapsed disease after long-lasting remission, reuse of a prior effective regimen may be appropriate. Autologous stem cell transplantation may be considered in young patients with chemosensitive disease and in newly diagnosed patients with very-high-risk features. Active enrollment of patients with WM in clinical trials is encouraged. PMID:25027391

Alkylating agents for Waldenstrom's macroglobulinaemia.

PubMed

Yang, Kun; Tan, Jianlong; Wu, Taixiang

2009-01-21

Waldenstrom's macroglobulinaemia (WM) is an uncommon B-cell lymphoproliferative disorder characterized by bone marrow infiltration and production of monoclonal immunoglobulin. Uncertainty remains if alkylating agents, such as chlorambucil, melphalan or cyclophosphamide, are an effective form of management. To assess the effects and safety of the alkylating agents on Waldenstrom's macroglobulinaemia (WM). We searched the Cochrane Central Register of Controlled Trials (Issue 1, 2008), MEDLINE (1966 to 2008), EMBASE (1980 to 2008), the Chinese Biomedical Base (1982 to 2008) and reference lists of articles.We also handsearched relevant conference proceedings from 1990 to 2008. Randomised controlled trials (RCTs) comparing alkylating agents given concomitantly with radiotherapy, splenectomy, plasmapheresis, stem-cell transplantation in patients with a confirmed diagnosis of WM. Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected adverse effects information from the trials. One trial involving 92 participants with pretreated/relapsed WM compared the effect of fludarabine versus the combination of cyclophosphamide (the alkylating agent), doxorubicin and prednisone (CAP). Compared to CAP, the Hazard ratio (HR) for deaths of treatment with fludarabine was estimated to be 1.04, with a standard error of 0.30 (95% CI 0.58 to 1.48) and it indicated that the mean difference of median survival time was -4.00 months, and 16.00 months for response duration. The relative risks (RR) of response rate was 2.80 (95% CI 1.10 to 7.12). There were no statistically difference in overall survival rate and median survival months, while on the basis of response rate and response duration, fludarabine seemed to be superior to CAP for pretreated/relapsed patients with macroglobulinaemia. Although alkylating agents have been used for decades they have never actually been tested in a proper randomised trial. This

Bendamustine and rituximab (BR) versus dexamethasone, rituximab, and cyclophosphamide (DRC) in patients with Waldenström macroglobulinemia.

PubMed

Paludo, Jonas; Abeykoon, Jithma P; Shreders, Amanda; Ansell, Stephen M; Kumar, Shaji; Ailawadhi, Sikander; King, Rebecca L; Koehler, Amber B; Reeder, Craig B; Buadi, Francis K; Dispenzieri, Angela; Lacy, Martha Q; Dingli, David; Witzig, Thomas E; Go, Ronald S; Gonsalves, Wilson I; Kourelis, Taxiarchis; Warsame, Rahma; Leung, Nelson; Habermann, Thomas M; Hayman, Suzanne; Lin, Yi; Kyle, Robert A; Rajkumar, S Vincent; Gertz, Morie A; Kapoor, Prashant

2018-04-03

The treatment approaches for Waldenstrom macroglobulinemia (WM) are largely based upon information from single-arm phase II trials, without comparative data. We compared the efficacy of two commonly used regimens in routine practice (bendamustine-rituximab (BR) and dexamethasone, rituximab plus cyclophosphamide (DRC)) and evaluated their activity with respect to the patients' MYD88 L265P mutation status. Of 160 consecutive patients, 60 received BR (43 with relapsed/refractory WM) and 100 received DRC (50 had relapsed/refractory WM). In the treatment-naïve setting, overall response rate (ORR) was 93% with BR versus 96% with DRC (p = 0.55). Two-year progression-free survival (PFS) with BR and DRC was 88 and 61%, respectively (p = 0.07). In salvage setting, ORR was 95% with BR versus 87% with DRC, p = 0.45; median PFS with BR was 58 versus 32 months with DRC (2-year PFS was 66 versus 53%; p = 0.08). Median disease-specific survival was not reached with BR versus 166 months with DRC (p = 0.51). The time-to-event endpoints and depth of response were independent of the MYD88 mutation status. Grade ≥ 3 adverse events of both regimens were comparable. A trend for longer PFS was observed with BR although the regimens have comparable toxicities. The activity of BR and DRC appears to be unaffected by patients' MYD88 mutation status.

New developments in the management of Waldenström macroglobulinemia.

PubMed

Abeykoon, Jithma P; Yanamandra, Uday; Kapoor, Prashant

2017-01-01

Waldenström macroglobulinemia (WM) is a rare, immunoglobulin M -associated lymphoplasmacytic lymphoma. With the recent discoveries of CXCR warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) and MYD88 mutations, our understanding of the biology of WM has expanded substantially. While WM still remains incurable, the field is rapidly evolving, and a number of promising agents with significant activity in this malignancy are being evaluated currently. In this review, we discuss the new developments that have occurred in WM over the past 15 years, with a focus on the role of ibrutinib, an oral Bruton's tyrosine kinase inhibitor that has recently been approved for WM in the United States, Europe, and Canada.

Immunoglobulin M myeloma: evaluation of molecular features and cytokine expression.

PubMed

Konduri, Kartik; Sahota, Surinder S; Babbage, Gavin; Tong, Alex W; Kumar, Padmasini; Newman, Joseph T; Stone, Marvin J

2005-03-01

Immunoglobulin (Ig) M myeloma is a distinct entity with features of multiple myeloma (MM) and Waldenstrom's macroglobulinemia (WM). The malignant cells in IgM myeloma have a distinctive chromosomal translocation that differentiates them from WM. These cells are postgerminal-center in origin with isotype-switch transcripts. They appear to be arrested at a point of maturation between that of WM and MM. Preliminary data indicate that a pattern of osteoclast-activating factor and osteoprotegerin expression similar to that observed in classic MM is present in IgM myeloma. Additional studies on patients with this rare tumor may provide further insight into the pathogenesis of bone disease in plasma cell dyscrasias.

Ibrutinib in Waldenström macroglobulinemia: latest evidence and clinical experience

PubMed Central

Castillo, Jorge J.; Palomba, M. Lia; Advani, Ranjana; Treon, Steven P.

2016-01-01

Ibrutinib is an oral Bruton’s tyrosine kinase (BTK) inhibitor, which has recently gained approval by the United States (US) Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of patients with symptomatic Waldenström macroglobulinemia (WM). Herein, we review the role of BTK in the pathophysiology of WM, and present the results of the preclinical and clinical studies that led to the initial investigation and later approval of ibrutinib in WM. We also discuss aspects associated with ibrutinib therapy in WM patients, especially focusing on genomic profiling and the impact on response to ibrutinib, and the management of adverse events. PMID:27493708

Diagnosis and Management of Waldenström Macroglobulinemia

PubMed Central

Kapoor, Prashant; Ansell, Stephen M.; Fonseca, Rafael; Chanan-Khan, Asher; Kyle, Robert A.; Kumar, Shaji K.; Mikhael, Joseph R.; Witzig, Thomas E.; Mauermann, Michelle; Dispenzieri, Angela; Ailawadhi, Sikander; Stewart, A. Keith; Lacy, Martha Q.; Thompson, Carrie A.; Buadi, Francis K.; Dingli, David; Morice, William G.; Go, Ronald S.; Jevremovic, Dragan; Sher, Taimur; King, Rebecca L.; Braggio, Esteban; Novak, Ann; Roy, Vivek; Ketterling, Rhett P.; Greipp, Patricia T.; Grogan, Martha; Micallef, Ivana N.; Bergsagel, P. Leif; Colgan, Joseph P.; Leung, Nelson; Gonsalves, Wilson I.; Lin, Yi; Inwards, David J.; Hayman, Suzanne R.; Nowakowski, Grzegorz S.; Johnston, Patrick B.; Russell, Steven J.; Markovic, Svetomir N.; Zeldenrust, Steven R.; Hwa, Yi L.; Lust, John A.; Porrata, Luis F.; Habermann, Thomas M.; Rajkumar, S. Vincent; Gertz, Morie A.; Reeder, Craig B.

2017-01-01

IMPORTANCE Waldenström macroglobulinemia (WM), an IgM-associated lymphoplasmacytic lymphoma, has witnessed several practice-altering advances in recent years. With availability of a wider array of therapies, the management strategies have become increasingly complex. Our multidisciplinary team appraised studies published or presented up to December 2015 to provide consensus recommendations for a risk-adapted approach to WM, using a grading system. OBSERVATIONS Waldenström macroglobulinemia remains a rare, incurable cancer, with a heterogeneous disease course. The major classes of effective agents in WM include monoclonal antibodies, alkylating agents, purine analogs, proteasome inhibitors, immunomodulatory drugs, and mammalian target of rapamycin inhibitors. However, the highest-quality evidence from rigorously conducted randomized clinical trials remains scant. CONCLUSIONS AND RELEVANCE Recognizing the paucity of data, we advocate participation in clinical trials, if available, at every stage of WM. Specific indications exist for initiation of therapy. Outside clinical trials, based on the synthesis of available evidence, we recommend bendamustine-rituximab as primary therapy for bulky disease, profound hematologic compromise, or constitutional symptoms attributable to WM. Dexamethasone-rituximab-cyclophosphamide is an alternative, particularly for nonbulky WM. Routine rituximab maintenance should be avoided. Plasma exchange should be promptly initiated before cytoreduction for hyperviscosity-related symptoms. Stem cell harvest for future use may be considered in first remission for patients 70 years or younger who are potential candidates for autologous stem cell transplantation. At relapse, retreatment with the original therapy is reasonable in patients with prior durable responses (time to next therapy≥3 years) and good tolerability to previous regimen. Ibrutinib is efficacious in patients with relapsed or refractory disease harboring MYD88 L265P mutation

Waldenström Macroglobulinemia

PubMed Central

Ghobrial, Irene M.; Witzig, Thomas E.

2011-01-01

Opinion statement Waldenström macroglobulinemia (WM) is a low-grade lymphoproliferative disorder characterized by the presence of an immunoglobulin M monoclonal protein in the blood and monoclonal small lymphocytes and lymphoplasmacytoid cells in the marrow. The disease is uncommon and there is a lack of clear diagnostic criteria. WM is treatable but not curable and long-term survival is possible. Therefore, the treating physician needs to carefully balance the risks and benefits of treatment. Treatments are aimed at relieving symptoms resulting from marrow infiltration and the hyperviscosity syndrome. Therapies available for initiation of treatment include alkylating agents, purine nucleoside analogs, and rituximab. Chlorambucil has been the mainstay of treatment for many years and remains useful, especially in older patients. Rituximab has become an important new therapy for this disease because of its positive treatment responses, acceptable toxicity, and lack of therapy-associated myelosuppression and myelodysplasia. Currently, rituximab is being combined with chemotherapy. Other options of treatment include interferon and corticosteroids. Emerging therapies include stem cell transplantation (autologous and allogeneic) for younger patients. Currently, there are few comparative data on which to state an absolute opinion concerning the best available treatment for patients with WM. PMID:15115652

Distinctive clinical and histological features of Waldenström's macroglobulinemia and splenic marginal zone lymphoma.

PubMed

Arcaini, Luca; Varettoni, Marzia; Boveri, Emanuela; Orlandi, Ester; Rattotti, Sara; Zibellini, Silvia; Merli, Michele; Lucioni, Marco; Rizzi, Silvia; Gotti, Manuel; Morello, Lucia; Pascutto, Cristiana; Paulli, Marco

2011-02-01

We studied 122 patients with Waldenström's macroglobulinemia (WM) and 98 with splenic marginal zone lymphoma (SMZL); 29 SMZL patients (30%) had a serum MC (IgM in 17 patients). SMZL differed from WM for female prevalence, abdominal and superficial adenopathy, spleen and liver involvement, positive HCV. The median MC level was 2.0 g/dL in WM and 0.95 g/dL in SMZL (P<.001). On BM histology, SMZL was characterized by sinusoidal infiltration (70% of cases) and by a more frequent nodular pattern (P<.01) while WM had a higher incidence of interstitial BM localization. After a median follow-up of 5.3 years, median OS was not reached for SMZL and was 12 years for WM (P=.23; 14 years for asymptomatic WM, 8 years for symptomatic WM). In conclusion, despite similar outcomes of these 2 entities, SMZL appears as a disease with distinct clinical features and BM histology and a peculiar association with HCV infection.

Macroglobulinemia of Waldenstrom

MedlinePlus

... or T immune cells start dividing rapidly. The exact cause of too much production of the IgM ... must be authorized in writing by ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get ...

How I treat Waldenström macroglobulinemia.

PubMed

Treon, Steven P

2015-08-06

Waldenström macroglobulinemia (WM) is a B-cell neoplasm manifested by the accumulation of clonal immunoglobulin (Ig)M-secreting lymphoplasmacytic cells. MYD88 and CXCR4 warts, hypogammaglobulinemia, infections, myelokathexis syndrome-like somatic mutations are present in >90% and 30% to 35% of WM patients, respectively, and impact disease presentation, treatment outcome, and overall survival. Familial predisposition is common in WM. Asymptomatic patients should be observed. Patients with disease-related hemoglobin <10 g/L, platelets <100 × 10(9)/L, bulky adenopathy and/or organomegaly, symptomatic hyperviscosity, peripheral neuropathy, amyloidosis, cryoglobulinemia, cold-agglutinin disease, or transformed disease should be considered for therapy. Plasmapheresis should be used for patients with symptomatic hyperviscosity and before rituximab for those with high serum IgM levels to preempt a symptomatic IgM flare. Treatment choice should take into account specific goals of therapy, necessity for rapid disease control, risk of treatment-related neuropathy, immunosuppression and secondary malignancies, and planning for future autologous stem cell transplantation. Frontline treatments include rituximab alone or rituximab combined with alkylators (bendamustine and cyclophosphamide), proteasome inhibitors (bortezomib and carfilzomib), nucleoside analogs (fludarabine and cladribine), and ibrutinib. In the salvage setting, an alternative frontline regimen, ibrutinib, everolimus, or stem cell transplantation can be considered. Investigational therapies under development for WM include agents that target MYD88, CXCR4, BCL2, and CD27/CD70 signaling, novel proteasome inhibitors, and chimeric antigen receptor-modified T-cell therapy. © 2015 by The American Society of Hematology.

How we treat Waldenström's macroglobulinemia.

PubMed

Dimopoulos, Meletios A; Merlini, Giampaolo; Leblond, Veronique; Anagnostopoulos, Athanasios; Alexanian, Raymond

2005-01-01

Waldenström's macroglobulinemia (WM) is a lymphoplasmacytic lymphoma which produces monoclonal immunoglobulin M (IgM). Over the last decade, new treatment modalites have been developed for the management of this disorder. Our objective is to provide treatment recommendations for WM. A review of published reports was facilitated by a MEDLINE computer search and by a manual search of Index Medicus. Other sources included abstracts and conference proceedings. Most patients with WM who are diagnosed by chance without symptoms should not be treated. Initiation of treatment should not be based on level of serum monoclonal protein per se. The presence of cytopenia, significant adenopathy or organomegaly, symptomatic hyperviscosity, severe neuropathy or cryoglobulinemia indicates the need for treatment. The main choices for primary treatment of symptomatic patients with WM include alkylating agents, the nucleoside analogs fludarabine or cladribine and the monoclonal antibody rituximab or combinations of these programs. There are no data from prospective randomized studies to recommend the use of one program over another. Nevertheless, the need for rapid disease control may favor the use of nucleoside analogs, whereas the presence of significant cytopenia may favor rituximab. High dose therapy with autologous stem cell transplantation may induce responses even in patients with resistance to all three class of agents. It may be prudent to avoid nucleoside analogs in patients who are candidates for high dose therapy. Despite the lack of randomized trials, a rational approach to the treatment of patients with WM is possible. Several factors, including the presence of cytopenias, need for rapid disease control, candidacy for autologous stem cell transplantation, age and co-morbid conditions, should be taken into consideration when choosing the most appropriate primary treatment.

Bevacizumab Therapy and Multimodal Ultra-widefield Imaging in Immunogammopathy Maculopathy Secondary to Waldenstrom’s Macroglobulinemia

PubMed Central

Xu, Lucy T.; Courtney, Robert J.; Ehlers, Justis P

2015-01-01

Waldenstrom’s macroglobulinemia (WM) is associated with retinal findings of hyperviscosity such as venous dilation, and findings of immunogammopathy maculopathy such as serous macular detachment. The report describes a case of bilateral serous macular detachment with intraretinal schisis-like fluid in a patient with WM. Enhanced depth imaging OCT revealed a thickened choroid with hyper-reflective accumulations in the RPE layer. The ultra-widefield fundus autofluorescence demonstrated a central area of hyperautofluorescence corresponding to the area of serous macular detachment. Ultra-widefield fluorescein angiography was characteristically silent. Intravitreal bevacizumab therapy resulted in significant reduction in intraretinal fluid, but minimal change in subretinal fluid. Long-term follow-up demonstrated alterations in retinal architecture and improved serous detachments. PMID:25707055

B-Cell Hematologic Malignancy Vaccination Registry

ClinicalTrials.gov

2017-12-29

Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Waldenstrom Macroglobulinemia; Lymphocytosis; Lymphoma, Non-Hodgkin; B-Cell Chronic Lymphocytic Leukemia; Hematological Malignancies

Pembrolizumab in Untreated B-Cell Non-Hodgkin Lymphoproliferative Diseases

ClinicalTrials.gov

2018-04-06

B-Cell Non-Hodgkin Lymphoma; Waldenstrom Macroglobulinemia; Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; Lymphoplasmacytic Lymphoma; Follicular Lymphoma; Indolent Non-Hodgkin Lymphoma; Marginal Zone Lymphoma

Waldenström Macroglobulinemia: Clinical and Immunological Aspects, Natural History, Cell of Origin, and Emerging Mouse Models

PubMed Central

2013-01-01

Waldenström macroglobulinemia (WM) is a rare and currently incurable neoplasm of IgM-expressing B-lymphocytes that is characterized by the occurrence of a monoclonal IgM (mIgM) paraprotein in blood serum and the infiltration of the hematopoietic bone marrow with malignant lymphoplasmacytic cells. The symptoms of patients with WM can be attributed to the extent and tissue sites of tumor cell infiltration and the magnitude and immunological specificity of the paraprotein. WM presents fascinating clues on neoplastic B-cell development, including the recent discovery of a specific gain-of-function mutation in the MYD88 adapter protein. This not only provides an intriguing link to new findings that natural effector IgM+IgD+ memory B-cells are dependent on MYD88 signaling, but also supports the hypothesis that WM derives from primitive, innate-like B-cells, such as marginal zone and B1 B-cells. Following a brief review of the clinical aspects and natural history of WM, this review discusses the thorny issue of WM's cell of origin in greater depth. Also included are emerging, genetically engineered mouse models of human WM that may enhance our understanding of the biologic and genetic underpinnings of the disease and facilitate the design and testing of new approaches to treat and prevent WM more effectively. PMID:24106612

21 CFR 866.5520 - Immunoglobulin G (Fab fragment specific) immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... multiple myeloma (tumor of bone marrow cells), Waldenstrom's macroglobulinemia (increased immunoglobulin production by the spleen and bone marrow cells), and lymphoma (tumor of the lymphoid tissues). (b...

21 CFR 866.5520 - Immunoglobulin G (Fab fragment specific) immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... multiple myeloma (tumor of bone marrow cells), Waldenstrom's macroglobulinemia (increased immunoglobulin production by the spleen and bone marrow cells), and lymphoma (tumor of the lymphoid tissues). (b...

21 CFR 866.5520 - Immunoglobulin G (Fab fragment specific) immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... multiple myeloma (tumor of bone marrow cells), Waldenstrom's macroglobulinemia (increased immunoglobulin production by the spleen and bone marrow cells), and lymphoma (tumor of the lymphoid tissues). (b...

21 CFR 866.5520 - Immunoglobulin G (Fab fragment specific) immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... multiple myeloma (tumor of bone marrow cells), Waldenstrom's macroglobulinemia (increased immunoglobulin production by the spleen and bone marrow cells), and lymphoma (tumor of the lymphoid tissues). (b...

Clonal B cells in Waldenström's macroglobulinemia exhibit functional features of chronic active B-cell receptor signaling

PubMed Central

Argyropoulos, K V; Vogel, R; Ziegler, C; Altan-Bonnet, G; Velardi, E; Calafiore, M; Dogan, A; Arcila, M; Patel, M; Knapp, K; Mallek, C; Hunter, Z R; Treon, S P; van den Brink, M R M; Palomba, M L

2016-01-01

Waldenström's macroglobulinemia (WM) is a B-cell non-Hodgkin's lymphoma (B-NHL) characterized by immunoglobulin M (IgM) monoclonal gammopathy and the medullary expansion of clonal lymphoplasmacytic cells. Neoplastic transformation has been partially attributed to hyperactive MYD88 signaling, secondary to the MYD88 L265P mutation, occurring in the majority of WM patients. Nevertheless, the presence of chronic active B-cell receptor (BCR) signaling, a feature of multiple IgM+ B-NHL, remains a subject of speculation in WM. Here, we interrogated the BCR signaling capacity of primary WM cells by utilizing multiparametric phosphoflow cytometry and found heightened basal phosphorylation of BCR-related signaling proteins, and augmented phosphoresponses on surface IgM (sIgM) crosslinking, compared with normal B cells. In support of those findings we observed high sIgM expression and loss of phosphatase activity in WM cells, which could both lead to signaling potentiation in clonal cells. Finally, led by the high-signaling heterogeneity among WM samples, we generated patient-specific phosphosignatures, which subclassified patients into a ‘high' and a ‘healthy-like' signaling group, with the second corresponding to patients with a more indolent clinical phenotype. These findings support the presence of chronic active BCR signaling in WM while providing a link between differential BCR signaling utilization and distinct clinical WM subgroups. PMID:26867669

Highly sensitive MYD88L265P mutation detection by droplet digital PCR in Waldenström Macroglobulinemia.

PubMed

Drandi, Daniela; Genuardi, Elisa; Dogliotti, Irene; Ferrante, Martina; Jiménez, Cristina; Guerrini, Francesca; Lo Schirico, Mariella; Mantoan, Barbara; Muccio, Vittorio; Lia, Giuseppe; Zaccaria, Gian Maria; Omedè, Paola; Passera, Roberto; Orsucci, Lorella; Benevolo, Giulia; Cavallo, Federica; Galimberti, Sara; García-Sanz, Ramón; Boccadoro, Mario; Ladetto, Marco; Ferrero, Simone

2018-03-22

We here describe a novel method for MYD88 L265P mutation detection and minimal residual disease monitoring in Waldenström Macroglobulinemia, by droplet digital PCR, in bone marrow and peripheral blood cells, as well as in circulating cell free DNA. Our method shows a sensitivity of 5.00E-05, by far superior to the widely used allele-specific polymerase chain reaction (1.00E-03). Overall, 291 unsorted samples from 148 patients (133 Waldenstrom 11 IgG-lymphoplasmacytic lymphoma and 4 IgM-monoclonal gammopathy of undetermined significance), 194 baseline and 97 follow-up, were analyzed. 122/128 (95.3%) bone marrow and 47/66 (71.2%) baseline peripheral blood samples scored positive for MYD88 L265P Moreover, to investigate whether MYD88 L265P by droplet digital PCR could be used for minimal residual disease monitoring, mutation levels were compared with IGH-based minimal residual disease analysis in 10 patients, showing to be as informative as to the classical, standardized but not yet validated in Waldenström Macroglobulinemia, IGH-based minimal residual disease assay (r 2 =0.64). Finally, MYD88 L265P detection performed by droplet digital PCR on plasmatic circulating tumor DNA from 60 patients showed a good correlation with bone marrow (bone marrow median mutational value 1.92E-02, plasmatic circulating tumor DNA value: 1.4E-02, peripheral blood value: 1.03E-03). This study indicates that droplet digital PCR MYD88 L265P assay is a feasible and sensitive tool for mutational screening and minimal residual disease monitoring in Waldenström Macroglobulinemia. Both unsorted bone marrow and peripheral blood samples can be reliably tested, as well as circulating tumor DNA, that represents an attractive, less invasive alternative to bone marrow for MYD88 L265P detection. Copyright © 2018, Ferrata Storti Foundation.

Nimbolide targets BCL2 and induces apoptosis in preclinical models of Waldenströms macroglobulinemia

PubMed Central

Chitta, K; Paulus, A; Caulfield, T R; Akhtar, S; Blake, M-KK; Ailawadhi, S; Knight, J; Heckman, M G; Pinkerton, A; Chanan-Khan, A

2014-01-01

Neem leaf extract (NLE) has medicinal properties, which have been attributed to its limonoid content. We identified the NLE tetranorterpenoid, nimbolide, as being the key limonoid responsible for the cytotoxicity of NLE in various preclinical models of human B-lymphocyte cancer. Of the models tested, Waldenströms macroglobulinemia (WM) cells were most sensitive to nimbolide, undergoing significant mitochondrial mediated apoptosis. Notably, nimbolide toxicity was also observed in drug-resistant (bortezomib or ibrutinib) WM cells. To identify putative targets of nimbolide, relevant in WM, we used chemoinformatics-based approaches comprised of virtual in silico screening, molecular modeling and target–ligand reverse docking. In silico analysis revealed the antiapoptotic protein BCL2 was the preferential binding partner of nimbolide. The significance of this finding was further tested in vitro in RS4;11 (BCL2-dependent) tumor cells, in which nimbolide induced significantly more apoptosis compared with BCL2 mutated (Jurkat BCL2Ser70-Ala) cells. Lastly, intraperitoneal administration of nimbolide in WM tumor xenografted mice, significantly reduced tumor growth and IgM secretion in vivo, while modulating the expression of several proteins as seen on immunohistochemistry. Overall, our data demonstrate that nimbolide is highly active in WM cells, as well as other B-cell cancers, and engages BCL2 to exert its cytotoxic activity. PMID:25382610

Dexamethasone, rituximab and cyclophosphamide for relapsed and/or refractory and treatment-naïve patients with Waldenstrom macroglobulinemia.

PubMed

Paludo, Jonas; Abeykoon, Jithma P; Kumar, Shaji; Shreders, Amanda; Ailawadhi, Sikander; Gertz, Morie A; Kourelis, Taxiarchis; King, Rebecca L; Reeder, Craig B; Leung, Nelson; Kyle, Robert A; Buadi, Francis K; Habermann, Thomas M; Dingli, David; Witzig, Thomas E; Dispenzieri, Angela; Lacy, Martha Q; Go, Ronald S; Lin, Yi; Gonsalves, Wilson I; Warsame, Rahma; Lust, John A; Rajkumar, S Vincent; Ansell, Stephen M; Kapoor, Prashant

2017-10-01

The management of Waldenström macroglobulinaemia (WM) relies predominantly on small trials, one of which has demonstrated activity of dexamethasone, rituximab and cyclophosphamide (DRC) in the frontline setting. We report on the efficacy of DRC, focusing on relapsed/refractory (R/R) patients. Ibrutinib, a recently approved agent in WM demonstrated limited activity in patients with MYD88 WT genotype. Herein, we additionally report on the activity of DRC based on the MYD88 L265P mutation status. Of 100 WM patients evaluated between January 2007 and December 2014 who received DRC, 50 had R/R WM. The overall response rate (ORR) was 87%. The median progression-free survival (PFS) and time-to-next-therapy (TTNT) were 32 (95% confidence interval [CI]: 15-51) and 50 (95% CI: 35-60) months, respectively. In the previously untreated cohort (n = 50), the ORR was 96%, and the median PFS and TTNT were 34 months (95% CI: 23-not reached [NR]) and NR (95% CI: 37-NR), respectively. Twenty-five (86%) of 29 genotyped patients harbored MYD88 L265P . The response rates and outcomes were independent of MYD88 mutation status. Grade ≥3 adverse effects included neutropenia (20%), thrombocytopenia (7%) and infections (3%). Similar to the frontline setting, DRC is an effective and well-tolerated salvage regimen for WM. In contrast to ibrutinib, DRC offers a less expensive, fixed-duration option, with preliminary data suggesting efficacy independent of the patients' MYD88 status. © 2017 John Wiley & Sons Ltd.

Safety and Tolerability Study of PCI-32765 in B Cell Lymphoma and Chronic Lymphocytic Leukemia

ClinicalTrials.gov

2018-04-03

B-cell Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Diffuse Well-differentiated Lymphocytic Lymphoma; B Cell Lymphoma; Follicular Lymphoma; Mantle Cell Lymphoma; Non-Hodgkin's Lymphoma; Waldenstrom Macroglobulinemia; Burkitt Lymphoma; B-Cell Diffuse Lymphoma

A Phase II Study of Doxycycline in Relapsed NHL

ClinicalTrials.gov

2016-10-27

Adult Diffuse Large B-Cell Lymphoma; Mantle Cell Lymphoma Recurrent; Lymphoma, Follicular; Marginal Zone B-Cell Lymphoma; Malignant Lymphoma - Lymphoplasmacytic; Waldenstrom Macroglobulinemia; Small Lymphocytic Lymphoma; Chronic Lymphocytic Leukemia (CLL); T-Cell Lymphoma

Low expression of pro-apoptotic Bcl-2 family proteins sets the apoptotic threshold in Waldenström Macroglobulinemia

PubMed Central

Gaudette, Brian T.; Dwivedi, Bhakti; Chitta, Kasyapa S.; Poulain, Stéphanie; Powell, Doris; Vertino, Paula; Leleu, Xavier; Lonial, Sagar; Chanan-Khan, Asher A.; Kowalski, Jeanne; Boise, Lawrence H.

2015-01-01

Waldenström Macroglobulinemia (WM) is a proliferative disorder of IgM secreting, lymphoplasmacytoid cells that inhabit the lymph nodes and bone marrow. The disease carries a high prevalence of activating mutations in MyD88 (91%) and CXCR4 (28%). Because signaling through these pathways leads to Bcl-xL induction, we examined Bcl-2 family expression in WM patients and cell lines. Unlike other B-lymphocyte-derived malignancies, which become dependent on expression of anti-apoptotic proteins to counter expression of pro-apoptotic proteins, WM samples expressed both pro- and anti-apoptotic Bcl-2 proteins at low levels similar to their normal B-cell and plasma cell counterparts. Three WM cell lines expressed pro-apoptotic Bcl-2 family members Bim or Bax and Bak at low levels which determined their sensitivity to inducers of intrinsic apoptosis. In two cell lines, miR-155 upregulation, which is common in WM, was responsible for inhibition of FOXO3a and Bim expression. Both antagonizing miR-155 to induce Bim and proteasome inhibition increased the sensitivity to ABT-737 in these lines indicating a lowering of the apoptotic threshold. In this manner, treatments that increase pro-apoptotic protein expression increase the efficacy of agents treated in combination in addition to direct killing. PMID:25893290

Pentostatin and Lymphocyte Infusion in Preventing Graft Rejection in Patients Who Have Undergone Donor Stem Cell Transplant

ClinicalTrials.gov

2018-05-24

Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Graft Versus Host Disease; Hodgkin Lymphoma; Myelodysplastic/Myeloproliferative Neoplasm; Non-Hodgkin Lymphoma; Plasma Cell Myeloma; Waldenstrom Macroglobulinemia

Ibrutinib

MedlinePlus

Ibrutinib is used to treat people with mantle cell lymphoma (MCL; a fast-growing cancer that begins ... cancer that begins mostly in the lymph nodes). Ibrutinib is used to treat people with Waldenstrom's macroglobulinemia ( ...

Study of MGUS, Smoldering Myeloma, Early MDS and CLL to Assess Molecular Events of Progression and Clinical Outcome

ClinicalTrials.gov

2017-08-25

Monoclonal Gammopathy of Undetermined Significance (MGUS); Chronic Lymphocytic Leukemia (CLL); Myelodysplastic-Myeloproliferative Diseases; Hematological Malignancies; B-cell Malignancy, Low-grade; Myelodysplastic Syndrome With Low-grade Lesions; IgG Monoclonal Gammopathy of Uncertain Significance; Smoldering Multiple Myeloma; Waldenstrom Macroglobulinemia

Allogeneic Transplantation for Relapsed Waldenström Macroglobulinemia and Lymphoplasmacytic Lymphoma

PubMed Central

Cornell, Robert F.; Bachanova, Veronika; D'Souza, Anita; Woo-Ahn, Kwang; Martens, Michael; Huang, Jiaxing; Al-Homsi, A. Samer; Chhabra, Saurabh; Copelan, Edward; Diaz, Miguel-Angel; Freytes, Cesar O.; Gale, Robert Peter; Ganguly, Siddhartha; Hamadani, Mehdi; Hildebrandt, Gerhard; Kamble, Rammurti T.; Kharfan-Dabaja, Mohamed; Kindwall-Keller, Tamila; Lazarus, Hillard M.; Marks, David I.; Nishihori, Taiga; Olsson, Richard F.; Saad, Ayman; Usmani, Saad; Vesole, David H.; Yared, Jean; Mark, Tomer; Nieto, Yago; Hari, Parameswaran

2016-01-01

Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) is characterized by lymphoplasmacytic proliferation, lymph node and spleen enlargement, bone marrow involvement, and immunoglobulin M production. Treatment varies based on the extent and biology of disease. In some patients, the use of allogeneic hematopoietic cell transplantation (alloHCT) may have curative potential. We evaluated long-term outcomes of 144 patients that received adult alloHCT for WM/LPL. Data was obtained from the Center for International Blood and Marrow Transplant Research database (2001-2013). Patients received myeloablative (n=67) or reduced intensity conditioning (RIC; n=67). Median age at alloHCT was 53 years, and median time from diagnosis to transplantation was 41 months. Thirteen percent (n=18) failed prior autologous hematopoietic cell transplantation. About half (n=82, 57%) had chemo-sensitive disease at the time of transplantation, while 22% had progressive disease. Progression free survival, overall survival, rate of relapse, and non-relapse mortality at 5-years were 46%, 52%, 24%, and 30% respectively. Patients with chemo-sensitive disease and better pre-transplant disease status experienced significantly superior overall survival. There were no significant differences in progression-free survival based on conditioning (myeloablative 50% vs. RIC 41%) or graft source. Conditioning intensity did not impact treatment-related mortality or relapse. The most common causes of death were primary disease and graft-versus-host disease (GVHD). AlloHCT yielded durable survival in select patients with WM/LPL. Strategies to reduce mortality from GVHD and post-transplant relapse are necessary to improve this approach. PMID:27789362

Nonmyeloablative Allogeneic Transplant

ClinicalTrials.gov

2013-12-05

Aplastic Anemia; Paroxysmal Nocturnal Hemoglobinuria; Acute Myelogenous Leukemia; Acute Lymphocytic Leukemia; Myelodysplastic Syndrome; Chronic Myelogenous Leukemia; Chronic Lymphocytic Leukemia; Hodgkin's Lymphoma; Non-Hodgkin's Lymphoma; Mantle Cell Lymphoma; Multiple Myeloma; Waldenstrom Macroglobulinemia; Breast Cancer; Renal Cell Carcinoma; Melanoma; Sarcoma; Ovarian Cancer; Thymoma

Immunoglobulin M monoclonal gammopathies of undetermined significance and indolent Waldenstrom's macroglobulinemia recognize the same determinants of evolution into symptomatic lymphoid disorders: proposal for a common prognostic scoring system.

PubMed

Baldini, Luca; Goldaniga, Maria; Guffanti, Andrea; Broglia, Chiara; Cortelazzo, Sergio; Rossi, Andrea; Morra, Enrica; Colombi, Mariangela; Callea, Vincenzo; Pogliani, Enrico; Ilariucci, Fiorella; Luminari, Stefano; Morel, Pierre; Merlini, Giampaolo; Gobbi, Paolo

2005-07-20

To evaluate the clinicohematologic variables at diagnosis that are prognostically related to neoplastic progression in patients with immunoglobulin M (IgM) monoclonal gammopathies of undetermined significance (MGUS), and indolent Waldenström's macroglobulinemia (IWM), and propose a scoring system to identify subsets of patients at different risk. We evaluated 217 patients with IgM MGUS and 201 with IWM (male-female ratio, 131:86 and 117:84; mean age, 63.7 and 63.6 years, respectively) diagnosed on the basis of serum monoclonal component (MC) levels and bone marrow lymphoplasmacytic infiltration degree. The variables selected by univariate analyses were multivariately investigated; on the basis of their individual relative hazards, a scoring system was devised to identify subsets of patients at different risk of evolution. After a median follow-up of 56.1 and 60.2 months, 15 of 217 MGUS and 45 of 201 IWM patients, respectively, required chemotherapy for symptomatic WM (13 and 36), non-Hodgkin's lymphoma (2 and 6) and amyloidosis (0 and 3). The median time to evolution (TTE) was not reached for MGUS and was 141.5 months for IWM. The variables adversely related to evolution were qualitatively the same in both groups: MC levels, Hb concentrations and sex. A scoring system based on these parameters identified three risk groups with highly significant differences in TTE in both groups (P < .0001). MGUS and IWM identify disease entities with different propensities for symptomatic neoplastic evolution. As both have the same prognostic determinants of progression, we propose a practical scoring system that, identifying different risks of malignant evolution, may allow an individualized clinical approach.

Adult Non-Hodgkin Lymphoma Treatment (PDQ®)—Health Professional Version

Cancer.gov

Non-Hodgkin lymphomas (NHL) include indolent types (follicular lymphoma, Waldenstrom macroglobulinemia, and MALT) and aggressive types (diffuse large cell, Burkitt, and mantle cell). Treatment and prognosis depend on the specific type. Get comprehensive information on NHL classification and treatment in this clinician summary.

Acquired mutations associated with ibrutinib resistance in Waldenström macroglobulinemia.

PubMed

Xu, Lian; Tsakmaklis, Nicholas; Yang, Guang; Chen, Jiaji G; Liu, Xia; Demos, Maria; Kofides, Amanda; Patterson, Christopher J; Meid, Kirsten; Gustine, Joshua; Dubeau, Toni; Palomba, M Lia; Advani, Ranjana; Castillo, Jorge J; Furman, Richard R; Hunter, Zachary R; Treon, Steven P

2017-05-04

Ibrutinib produces high response rates and durable remissions in Waldenström macroglobulinemia (WM) that are impacted by MYD88 and CXCR4 WHIM mutations. Disease progression can develop on ibrutinib, although the molecular basis remains to be clarified. We sequenced sorted CD19 + lymphoplasmacytic cells from 6 WM patients who progressed after achieving major responses on ibrutinib using Sanger, TA cloning and sequencing, and highly sensitive and allele-specific polymerase chain reaction (AS-PCR) assays that we developed for Bruton tyrosine kinase ( BTK ) mutations. AS-PCR assays were used to screen patients with and without progressive disease on ibrutinib, and ibrutinib-naïve disease. Targeted next-generation sequencing was used to validate AS-PCR findings, assess for other BTK mutations, and other targets in B-cell receptor and MYD88 signaling. Among the 6 progressing patients, 3 had BTK Cys481 variants that included BTK Cys481Ser(c.1635G>C and c.1634T>A) and BTK Cys481Arg(c.1634T>C) Two of these patients had multiple BTK mutations. Screening of 38 additional patients on ibrutinib without clinical progression identified BTK Cys481 mutations in 2 (5.1%) individuals, both of whom subsequently progressed. BTK Cys481 mutations were not detected in baseline samples or in 100 ibrutinib-naive WM patients. Using mutated MYD88 as a tumor marker, BTK Cys481 mutations were subclonal, with a highly variable clonal distribution. Targeted deep-sequencing confirmed AS-PCR findings, and identified an additional BTK Cys481Tyr(c.1634G>A) mutation in the 2 patients with multiple other BTK Cys481 mutations, as well as CARD11 Leu878Phe(c.2632C>T) and PLCγ2 Tyr495His(c.1483T>C) mutations. Four of the 5 patients with BTK C481 variants were CXCR4 mutated. BTK Cys481 mutations are common in WM patients with clinical progression on ibrutinib, and are associated with mutated CXCR4 . © 2017 by The American Society of Hematology.

Monoclonal Gammopathy Associated Peripheral Neuropathy: Diagnosis and Management

PubMed Central

Chaudhry, Hafsa M.; Mauermann, Michelle L.; Rajkumar, S. Vincent

2017-01-01

Monoclonal gammopathies consist of a spectrum of clonal plasma cell disorders that includes monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM) and Waldenstrom Macroglobulinemia (WM). In this review, we outline the epidemiology, etiology, classification, diagnosis, and treatment of monoclonal gammopathy associated peripheral neuropathy. Monoclonal gammopathy of undetermined significance (MGUS) is relatively common in the general population, with a prevalence of 3–4% among those over the age of 50. Therefore, the presence of M protein in a patient with neuropathy does not automatically indicate a causal relationship. Monoclonal gammopathy associated peripheral neuropathy is often a difficult diagnosis with limited treatment options. Studies addressing the optimal approach to diagnosis and management of this entity are limited. In addition to a review of the literature, we present a diagnostic approach to patients with monoclonal gammopathy associated peripheral neuropathy and discuss available data and options for treatment. PMID:28473042

A mutation in MYD88 (L265P) supports the survival of lymphoplasmacytic cells by activation of Bruton tyrosine kinase in Waldenström macroglobulinemia.

PubMed

Yang, Guang; Zhou, Yangsheng; Liu, Xia; Xu, Lian; Cao, Yang; Manning, Robert J; Patterson, Christopher J; Buhrlage, Sara J; Gray, Nathanael; Tai, Yu-Tzu; Anderson, Kenneth C; Hunter, Zachary R; Treon, Steven P

2013-08-15

Myeloid differentiation factor 88 (MYD88) L265P somatic mutation is highly prevalent in Waldenström macroglobulinemia (WM) and supports malignant growth through nuclear factor κB (NF-κB). The signaling cascade(s) by which MYD88 L265P promotes NF-κB activation in WM remain unclear. By lentiviral knockdown or use of a MYD88 inhibitor, decreased phosphorylation of the NF-κB gatekeeper IκBα and survival occurred in MYD88 L265P-expressing WM cells. Conversely, WM cells engineered to overexpress MYD88 L265P showed enhanced survival. Coimmunoprecipitation studies identified Bruton tyrosine kinase (BTK) complexed to MYD88 in L265P-expressing WM cells, with preferential binding of MYD88 to phosphorylated BTK (pBTK). Increased pBTK was also observed in WM cells transduced to overexpress L265P vs wild-type MYD88. Importantly, MYD88 binding to BTK was abrogated following treatment of MYD88 L265P-expressing cells with a BTK kinase inhibitor. Inhibition of BTK or interleukin-1 receptor-associated kinase 1 and 4 (IRAK-1 and -4) kinase activity induced apoptosis of WM cells, and their combination resulted in more robust inhibition of NF-κB signaling and synergistic WM cell killing. The results establish BTK as a downstream target of MYD88 L265P signaling, and provide a framework for the study of BTK inhibitors alone, and in combination with IRAK inhibitors for the treatment of WM.

Chemotherapy, Total Body Irradiation, and Post-Transplant Cyclophosphamide in Reducing Rates of Graft Versus Host Disease in Patients With Hematologic Malignancies Undergoing Donor Stem Cell Transplant

ClinicalTrials.gov

2018-03-05

Acute Myeloid Leukemia in Remission; Adult Acute Lymphoblastic Leukemia in Complete Remission; Chronic Myelogenous Leukemia, BCR-ABL1 Positive in Remission; Chronic Myelomonocytic Leukemia in Remission; Graft Versus Host Disease; Hodgkin Lymphoma; Minimal Residual Disease; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Non-Hodgkin Lymphoma; Plasma Cell Myeloma; Severe Aplastic Anemia; Waldenstrom Macroglobulinemia

Rituxan/Bendamustine/PCI-32765 in Relapsed DLBCL, MCL, or Indolent Non-Hodgkin's Lymphoma

ClinicalTrials.gov

2017-11-07

Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

Total-Body Irradiation With or Without Fludarabine Phosphate Followed By Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer

ClinicalTrials.gov

2017-04-07

Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia in Remission; Aggressive Non-Hodgkin Lymphoma; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Diffuse Large B-Cell Lymphoma; Hematopoietic and Lymphoid Cell Neoplasm; Indolent Non-Hodgkin Lymphoma; Mantle Cell Lymphoma; Myelodysplastic/Myeloproliferative Neoplasm; Plasma Cell Myeloma; Refractory Chronic Lymphocytic Leukemia; Refractory Hodgkin Lymphoma; Waldenstrom Macroglobulinemia

Cost-effectiveness analysis of ibrutinib in patients with Waldenström macroglobulinemia in Italy.

PubMed

Aiello, Andrea; D'Ausilio, Anna; Lo Muto, Roberta; Randon, Francesca; Laurenti, Luca

2017-01-01

Background and Objective: Ibrutinib has recently been approved in Europe for Waldenström Macroglobulinemia (WM) in symptomatic patients who have received at least one prior therapy, or in first-line treatment for patients unsuitable for chemo-immunotherapy. The aim of the study is to estimate the incremental cost-effectiveness ratio (ICER) of ibrutinib in relapse/refractory WM, compared with the Italian current therapeutic pathways (CTP). Methods: A Markov model was adapted for Italy considering the National Health System perspective. Input data from literature as well as global trials were used. The percentage use of therapies, and healthcare resources consumption were estimated according to expert panel advice. Drugs ex-factory prices and national tariffs were used for estimating costs. The model had a 15-year time horizon, with a 3.0% discount rate for both clinical and economic data. Deterministic and probabilistic sensitivity analyses were performed to test the results strength. Results: Ibrutinib resulted in increased Life Years Gained (LYGs) and increased costs compared to CTP, with an ICER of €52,698/LYG. Sensitivity analyses confirmed the results of the BaseCase. Specifically, in the probabilistic analysis, at a willingness to pay threshold of €60,000/LYG ibrutinib was cost-effective in 84% of simulations. Conclusions: Ibrutinib has demonstrated a positive cost-effectiveness profile in Italy.

Circulating Soluble Receptor Activator of Nuclear Factor Kappa B Ligand and C-C Motif Ligand 3 Correlate With Survival in Patients With Waldenström Macroglobulinemia.

PubMed

Eleutherakis-Papaiakovou, Evangelos; Kastritis, Efstathios; Gavriatopoulou, Maria; Christoulas, Dimitrios; Roussou, Maria; Ntanasis-Stathopoulos, Ioannis; Kanellias, Nikolaos; Papatheodorou, Athanasios; Dimopoulos, Meletios A; Terpos, Evangelos

2018-06-01

Serum receptor activator of nuclear factor κB ligand (sRANKL) and chemokine (C-C) motif ligand 3 (CCL-3) have been reported to be elevated in Waldenström macroglobulinemia (WM) patients. However, there are no published data regarding the prognostic value of these molecules in WM regarding progression-free and overall survival. To evaluate the effect of these markers of bone remodeling on survival parameters, we prospectively evaluated serum cytokines and biological markers in 55 patients with symptomatic WM before they received any kind of treatment. Serum levels of CCL-3 and bone remodeling markers were also evaluated in asymptomatic WM and IgM monoclonal gammopathy of undetermined significance. Furthermore, we assessed bone marrow biopsy samples from newly diagnosed WM patients for CCL-3 and RANKL expression. High circulating sRANKL values predicted shorter median overall survival (46 months vs. not reached, P = .025). High serum levels of CCL-3 predicted shorter median progression-free survival (27 months vs. not reached, P = .048). At bone marrow biopsy evaluation, the whole number of the neoplastic cells revealed strong cytoplasmic positivity for CCL-3, while the neoplastic clone did not express RANKL. We conclude that WM cells produce CCL-3 and possibly enhance the production of RANKL in the bone microenvironment. The correlation of sRANKL and CCL-3 with survival reveals the importance of these cytokines in disease biology and highlights the significance of the interactions between WM and stromal cells for the development of WM. Finally, these findings provide the rationale for the use of anti-RANKL and anti-CCL-3 drugs in animal models of WM before their clinical evaluation. Copyright © 2018 Elsevier Inc. All rights reserved.

Immune-Related and Inflammatory Conditions and Risk of Lymphoplasmacytic Lymphoma or Waldenström Macroglobulinemia

PubMed Central

Koshiol, Jill; Björkholm, Magnus; Goldin, Lynn R.; McMaster, Mary L.; Turesson, Ingemar; Landgren, Ola

2010-01-01

Background Chronic immune stimulation appears to be associated with lymphoplasmacytic lymphoma (LPL)-Waldenström macroglobulinemia (WM); however, available information is sparse. We conducted, to our knowledge, the most comprehensive study to date to evaluate associations between a personal or family history of many immune-related and/or inflammatory disorders and the subsequent risk of LPL-WM. Methods We used Swedish population-based registries to identify 2470 case patients with LPL-WM, 9698 matched control subjects, and almost 30 000 first-degree relatives of either case patients or control subjects. We evaluated a wide range of autoimmune, infectious, allergic, and inflammatory conditions. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for each condition by use of logistic regression. Results An increased risk of LPL-WM was associated with a personal history of the following autoimmune diseases: systemic sclerosis (OR = 4.7, 95% CI = 1.4 to 15.3), Sjögren syndrome (OR = 12.1, 95% CI = 3.3 to 45.0), autoimmune hemolytic anemia (OR = 24.2, 95% CI = 5.4 to 108.2), polymyalgia rheumatica (OR = 2.9, 95% CI = 1.6 to 5.2), and giant cell arteritis (OR = 8.3, 95% CI = 2.1 to 33.1). An increased risk of LPL-WM was associated with a personal history of the following infectious diseases: pneumonia (OR = 1.4, 95% CI = 1.1 to 1.7), septicemia (OR = 2.4, 95% CI = 1.2 to 4.3), pyelonephritis (OR = 1.7, 95% CI = 1.1 to 2.5), sinusitis (OR = 2.7, 95% CI = 1.4 to 4.9), herpes zoster (OR = 3.4, 95% CI = 2.0 to 5.6), and influenza (OR = 2.9, 95% CI = 1.7 to 5.0). An increased risk of LPL-WM was associated with a family history of the following autoimmune or infectious diseases: Sjögren syndrome (OR = 5.0, 95% CI = 2.1 to 12.0), autoimmune hemolytic anemia (OR = 3.8, 95% CI = 1.1 to 13.2), Guillain–Barré syndrome (OR = 4.1, 95% CI = 1.8 to 9.4), cytomegalovirus (OR = 2.7, 95% CI = 1.4 to 5.3), gingivitis and periodontitis (OR = 1.9, 95% CI = 1.3 to 2

Genetics Home Reference: Waldenström macroglobulinemia

MedlinePlus

... shortage of normal blood cells (pancytopenia). Excessive tiredness (fatigue) due to a reduction in red blood cells ( ... of Waldenström's macroglobulinemia. Curr Oncol Rep. 2013 Oct;15(5):450-6. doi: 10.1007/s11912-013-0331- ...

Comparison of Triple GVHD Prophylaxis Regimens for Nonmyeloablative or Reduced Intensity Conditioning Unrelated Mobilized Blood Cell Transplantation

ClinicalTrials.gov

2018-05-09

Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Aggressive Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Diffuse Large B-Cell Lymphoma; Hematopoietic Cell Transplantation Recipient; Loss of Chromosome 17p; Mantle Cell Lymphoma; Myelodysplastic Syndrome; Myelodysplastic/Myeloproliferative Neoplasm; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Hodgkin Lymphoma; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Recurrent Waldenstrom Macroglobulinemia

Nivolumab and Lenalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin or Hodgkin Lymphoma

ClinicalTrials.gov

2018-01-25

Grade 3a Follicular Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Waldenstrom Macroglobulinemia; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Mantle Cell Lymphoma

Fusion Protein Cytokine Therapy After Rituximab in Treating Patients With B-Cell Non-Hodgkin Lymphoma

ClinicalTrials.gov

2015-06-03

Anaplastic Large Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation, and Donor Bone Marrow Transplant Followed by Donor Natural Killer Cell Therapy, Mycophenolate Mofetil, and Tacrolimus in Treating Patients With Hematologic Cancer

ClinicalTrials.gov

2017-11-08

Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Aggressive Non-Hodgkin Lymphoma; Diffuse Large B-Cell Lymphoma; Previously Treated Myelodysplastic Syndrome; Recurrent Chronic Lymphocytic Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Indolent Adult Non-Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hodgkin Lymphoma; Refractory Plasma Cell Myeloma; Refractory Small Lymphocytic Lymphoma; Waldenstrom Macroglobulinemia

Detection of L265P MYD-88 mutation in a series of clonal B-cell lymphocytosis of marginal zone origin (CBL-MZ).

PubMed

Kalpadakis, Christina; Pangalis, Gerassimos A; Vassilakopoulos, Theodoros P; Roumelioti, Maria; Sachanas, Sotirios; Korkolopoulou, Penelope; Koulieris, Efstathios; Moschogiannis, Maria; Yiakoumis, Xanthi; Tsirkinidis, Pantelis; Pontikoglou, Charalampos; Rondoyianni, Dimitra; Papadaki, Helen A; Panayiotidis, Panayiotidis; Angelopoulou, Maria K

2017-12-01

Clonal B-cell lymphocytosis of marginal zone origin (CBL-MZ) is a recently described entity characterized by the presence of clonal B cells in the blood and/or bone marrow (BM) with morphologic and immunophenotypic features consistent with marginal zone derivation in otherwise healthy individuals. CBL-MZ is commonly associated with paraproteinemia, usually immunoglobulin M (IgM), raising diagnostic difficulties from Waldenstrom macroglobulinemia (WM). The aim of the present study was to determine the presence of MYD-88 L265P mutation in a well-characterized series of CBL-MZ to identify cases that may in fact represent WM. Fifty-three CBL-MZ cases were retrospectively evaluated. MYD-88 L265P mutation was determined by allele-specific polymerase chain reaction in blood and/or BM mononuclear cells. Almost half of the CBL-MZ cases (49%) were associated with paraproteinemia mainly of the IgM type (65%). MYD-88 L265P mutation was identified in 10 cases (19%). These cases may truly represent WM, whereas 43 cases (81%) are still classified as CBL-MZ. Mutated cases were all associated with paraproteinemia compared with 37% of the nonmutated ones (P < .0001). In addition, mutated cases displayed more frequently CD38 and CD25 positivity (P = .002 and P = .005, respectively). Moreover, cases without paraproteinemia presented more frequently with lymphocytosis, irrespective of the presence of the MYD-88 mutation (P = .02). The present study demonstrates that MYD-88 L265P mutation may represent the only sensitive marker for the differentiation of CBL-MZ from probable WM. However, further studies are warranted to better define the biological significance of MYD-88 L265P mutation and to clarify whether the presence of the mutation establishes WM diagnosis or that it can also be present in borderline cases associated with paraproteinemia. Copyright © 2016 John Wiley & Sons, Ltd.

Graft-Versus-Host Disease Prophylaxis in Treating Patients With Hematologic Malignancies Undergoing Unrelated Donor Peripheral Blood Stem Cell Transplant

ClinicalTrials.gov

2018-02-13

Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Aggressive Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Diffuse Large B-Cell Lymphoma; Hematopoietic and Lymphoid Cell Neoplasm; Indolent Non-Hodgkin Lymphoma; Mantle Cell Lymphoma; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Plasma Cell Myeloma; Refractory Chronic Lymphocytic Leukemia; Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Refractory Hodgkin Lymphoma; Small Lymphocytic Lymphoma; T-Cell Chronic Lymphocytic Leukemia; Waldenstrom Macroglobulinemia

Selinexor Plus Combination Chemotherapy in Treating Patients With Advanced B Cell Non-Hodgkin Lymphoma

ClinicalTrials.gov

2018-02-12

Diffuse Large B-Cell Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Extranodal Marginal Zone Lymphoma; Recurrent Follicular Lymphoma; Recurrent Indolent Adult Non-Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Waldenstrom Macroglobulinemia; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Extranodal Marginal Zone Lymphoma; Refractory Follicular Lymphoma; Refractory Mantle Cell Lymphoma; Stage III Non-Hodgkin Lymphoma; Stage IV Non-Hodgkin Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

Primary Macroglobulinemia

PubMed Central

Edwards, A. M.; Costopoulous, L. B.; Bell, H. E.

1964-01-01

Clinical features presented by a patient with primary macroglobulinemia over a four-year period included cachexia, weight loss, bleeding tendency, anemia, lymphadenopathy, hepatosplenomegaly and recurrent pulmonary bacterial infections. Immunoelectrophoresis demonstrated the presence of a β2 macroglobulin which, on ultracentrifugation, was found to have a sedimentation constant of 14.9 S20, w; this macroglobulin constituted over 40% of the total serum protein. Postmortem findings included the typical “naked” lymphocyte infiltration of the reticuloendothelial system, with septic embolization from a terminal Gram-negative bacteremia, associated with a mesenteric vascular occlusion. A feature of particular interest was the antemortem appearance of gas in the portal venous system, shown on two abdominal scout radiographs taken one and two hours before death. The diagnostic significance of this rare radiologic sign is discussed. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11Fig. 12Fig. 13Fig. 14Fig. 15 PMID:14226112

Autologous Peripheral Blood Stem Cell Transplant Followed by Donor Bone Marrow Transplant in Treating Patients With High-Risk Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Multiple Myeloma, or Chronic Lymphocytic Leukemia

ClinicalTrials.gov

2017-12-26

B-Cell Prolymphocytic Leukemia; Hypodiploidy; Loss of Chromosome 17p; Plasma Cell Leukemia; Progression of Multiple Myeloma or Plasma Cell Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Childhood Hodgkin Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Non-Hodgkin Lymphoma; Refractory Plasma Cell Myeloma; Refractory Small Lymphocytic Lymphoma; t(14;16); t(4;14); T-Cell Prolymphocytic Leukemia; Waldenstrom Macroglobulinemia

TAK-228 (formerly MLN0128), an investigational oral dual TORC1/2 inhibitor: A phase I dose escalation study in patients with relapsed or refractory multiple myeloma, non-Hodgkin lymphoma, or Waldenström's macroglobulinemia.

PubMed

Ghobrial, Irene M; Siegel, David S; Vij, Ravi; Berdeja, Jesus G; Richardson, Paul G; Neuwirth, Rachel; Patel, Chirag G; Zohren, Fabian; Wolf, Jeffrey L

2016-06-01

The PI3K/AKT/mTOR signaling pathways are frequently dysregulated in multiple human cancers, including multiple myeloma (MM), non-Hodgkin lymphoma (NHL), and Waldenström's macroglobulinemia (WM). This was the first clinical study to evaluate the safety, tolerability, maximal-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics, and preliminary clinical activity of TAK-228, an oral TORC1/2 inhibitor, in patients with MM, NHL, or WM. Thirty-nine patients received TAK-228 once daily (QD) at 2, 4, 6, or 7 mg, or QD for 3 days on and 4 days off each week (QDx3d QW) at 9 or 12 mg, in 28-day cycles. The overall median age was 61.0 years (range 46-85); 31 patients had MM, four NHL, and four WM. Cycle 1 DLTs occurred in five QD patients (stomatitis, urticaria, blood creatinine elevation, fatigue, and nausea and vomiting) and four QDx3d QW patients (erythematous rash, fatigue, asthenia, mucosal inflammation, and thrombocytopenia). The MTDs were determined to be 4 mg QD and 9 mg QDx3d QW. Thirty-six patients (92%) reported at least one drug-related toxicity; the most common grade ≥3 drug-related toxicities were thrombocytopenia (15%), fatigue (10%), and neutropenia (5%). TAK-228 exhibited a dose-dependent increase in plasma exposure and no appreciable accumulation with repeat dosing; mean plasma elimination half-life was 6-8 hr. Of the 33 response-evaluable patients, one MM patient had a minimal response, one WM patient achieved partial response, one WM patient had a minor response, and 18 patients (14 MM, two NHL, and two WM) had stable disease. These findings encourage further studies including combination strategies. © 2016 Wiley Periodicals, Inc.

Primary Therapy of Waldenström Macroglobulinemia With Bortezomib, Dexamethasone, and Rituximab: WMCTG Clinical Trial 05-180

PubMed Central

Treon, Steven P.; Ioakimidis, Leukothea; Soumerai, Jacob D.; Patterson, Christopher J.; Sheehy, Patricia; Nelson, Marybeth; Willen, Michael; Matous, Jeffrey; Mattern, John; Diener, Jakow G.; Keogh, George P.; Myers, Thomas J.; Boral, Andy; Birner, Ann; Esseltine, Dixie L.; Ghobrial, Irene M.

2009-01-01

Purpose We examined the activity of bortezomib, dexamethasone, and rituximab (BDR) in patients with symptomatic, untreated Waldenström macroglobulinemia (WM). Patients and Methods A cycle of therapy consisted of bortezomib 1.3 mg/m2 intravenously; dexamethasone 40 mg on days 1, 4, 8, and 11; and rituximab 375 mg/m2 on day 11. Patients received four consecutive cycles for induction therapy and then four more cycles, each given 3 months apart, for maintenance therapy. Twenty-three patients received a median of seven cycles of treatment. Results Median bone marrow disease involvement declined from 55% to 10% (P = .0004), serum immunoglobulin M levels declined from 4,830 to 1,115 mg/dL (P < .0001), and hematocrit increased from 29.8% to 38.2% (P = .0002) at best response. The overall response rates and major response rates were 96% and 83% with three complete responses, two near complete responses, three very good partial responses, 11 partial responses, and three minor responses. Responses occurred at a median of 1.4 months. With a median follow-up of 22.8 months, 18 of 23 patients remained free of disease progression. Peripheral neuropathy was the most common toxicity, and it resolved to grade ≤ 1 in 13 of 16 patients at a median of 6.0 months. Four of the first seven treated patients developed herpes zoster, resulting in the institution of prophylactic antiviral therapy. Conclusion The results demonstrate that BDR produces rapid and durable responses, along with high rates of response and complete remissions in WM. Herpes zoster prophylaxis is necessary with BDR, and reversible peripheral neuropathy was the most common toxicity leading to premature discontinuation of bortezomib in 61% of patients. Exploration of alternative schedules for bortezomib administration that includes weekly dosing should be pursued. PMID:19506160

Bruton's tyrosine kinase (BTK) inhibitors in clinical trials.

PubMed

Burger, Jan A

2014-03-01

BTK is a cytoplasmic, non-receptor tyrosine kinase that transmits signals from a variety of cell-surface molecules, including the B-cell receptor (BCR) and tissue homing receptors. Genetic BTK deletion causes B-cell immunodeficiency in humans and mice, making this kinase an attractive therapeutic target for B-cell disorders. The BTK inhibitor ibrutinib (PCI-32765, brand name: Imbruvica) demonstrated high clinical activity in B-cell malignancies, especially in patients with chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and Waldenstrom's macroglobulinemia (WM). Therefore, ibrutinib was granted a 'breakthrough therapy' designation for these indications and was recently approved for the treatment of relapsed MCL by the U.S. Food and Drug Administration. Other BTK inhibitors in earlier clinical development include CC-292 (AVL-292), and ONO-4059. In CLL and MCL, ibrutinib characteristically induces redistribution of malignant B cells from tissue sites into the peripheral blood, along with rapid resolution of enlarged lymph nodes and a surge in lymphocytosis. With continuous ibrutinib therapy, growth- and survival-inhibitory activities of ibrutinib result in the normalization of lymphocyte counts and remissions in a majority of patients. This review discusses the clinical advances with BTK inhibitor therapy, as well as its pathophysiological basis, and outlines perspectives for future use of BTK inhibitors.

Everolimus and Lenalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin or Hodgkin Lymphoma

ClinicalTrials.gov

2018-02-07

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor.

PubMed

Wu, Jingjing; Zhang, Mingzhi; Liu, Delong

2016-03-09

More and more targeted agents become available for B cell malignancies with increasing precision and potency. The first-in-class Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib, has been in clinical use for the treatment of chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. More selective BTK inhibitors (ACP-196, ONO/GS-4059, BGB-3111, CC-292) are being explored. Acalabrutinib (ACP-196) is a novel irreversible second-generation BTK inhibitor that was shown to be more potent and selective than ibrutinib. This review summarized the preclinical research and clinical data of acalabrutinib.

Donor Atorvastatin Treatment in Preventing Severe Acute GVHD After Nonmyeloablative Peripheral Blood Stem Cell Transplant in Patients With Hematological Malignancies

ClinicalTrials.gov

2018-02-08

Aggressive Non-Hodgkin Lymphoma; Blasts Under 5 Percent of Bone Marrow Nucleated Cells; Chronic Lymphocytic Leukemia; Loss of Chromosome 17p; Myelodysplastic/Myeloproliferative Neoplasm; Non-Hodgkin Lymphoma; Prolymphocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Aggressive Adult Non-Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Waldenstrom Macroglobulinemia

Pembrolizumab Alone or With Idelalisib or Ibrutinib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Non-Hodgkin Lymphomas

ClinicalTrials.gov

2017-06-30

Recurrent Chronic Lymphocytic Leukemia; Recurrent Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Nodal Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Recurrent Splenic Marginal Zone Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Nodal Marginal Zone Lymphoma; Refractory Small Lymphocytic Lymphoma; Refractory Splenic Marginal Zone Lymphoma; Richter Syndrome; Waldenstrom Macroglobulinemia

Sirolimus, Cyclosporine, and Mycophenolate Mofetil in Preventing Graft-versus-Host Disease in Treating Patients With Blood Cancer Undergoing Donor Peripheral Blood Stem Cell Transplant

ClinicalTrials.gov

2017-10-30

Adult Acute Lymphoblastic Leukemia; Adult Acute Myeloid Leukemia; Adult Diffuse Large B-Cell Lymphoma; Adult Myelodysplastic Syndrome; Adult Non-Hodgkin Lymphoma; Aggressive Non-Hodgkin Lymphoma; Childhood Acute Lymphoblastic Leukemia; Childhood Acute Myeloid Leukemia; Childhood Diffuse Large B-Cell Lymphoma; Childhood Myelodysplastic Syndrome; Childhood Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Chronic Lymphocytic Leukemia in Remission; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Hematopoietic and Lymphoid Cell Neoplasm; Mantle Cell Lymphoma; Plasma Cell Myeloma; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Refractory Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia; Waldenstrom Macroglobulinemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Hodgkin Lymphoma

Linear Tidal Vestige Found in the WM Sheet

NASA Astrophysics Data System (ADS)

Lee, Jounghun; Kim, Suk; Rey, Soo-Chang

2018-06-01

We present a vestige of the linear tidal influence on the spin orientations of the constituent galaxies of the WM sheet discovered in the vicinity of the Virgo Cluster and the Local Void. The WM sheet is chosen as an optimal target since it has a rectangular parallelepiped-like shape whose three sides are in parallel with the supergalactic Cartesian axes. Determining three probability density functions of the absolute values of the supergalactic Cartesian components of the spin vectors of the WM sheet galaxies, we investigate their alignments with the principal directions of the surrounding large-scale tidal field. When the WM sheet galaxies located in the central region within the distance of 2 h ‑1 Mpc are excluded, the spin vectors of the remaining WM sheet galaxies are found to be weakly aligned, strongly aligned, and strongly anti-aligned with the minor, intermediate, and major principal directions of the surrounding large-scale tidal field, respectively. To examine whether or not the origin of the observed alignment tendency from the WM sheet is the linear tidal effect, we infer the eigenvalues of the linear tidal tensor from the axial ratios of the WM sheet with the help of the Zeldovich approximation and conduct a full analytic evaluation of the prediction of the linear tidal torque model for the three probability density functions. A detailed comparison between the analytical and the observational results reveals a good quantitative agreement not only in the behaviors but also in the amplitudes of the three probability density functions.

Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenström's macroglobulinemia.

PubMed

Nguyen-Khac, Florence; Lambert, Jerome; Chapiro, Elise; Grelier, Aurore; Mould, Sarah; Barin, Carole; Daudignon, Agnes; Gachard, Nathalie; Struski, Stéphanie; Henry, Catherine; Penther, Dominique; Mossafa, Hossein; Andrieux, Joris; Eclache, Virginie; Bilhou-Nabera, Chrystèle; Luquet, Isabelle; Terre, Christine; Baranger, Laurence; Mugneret, Francine; Chiesa, Jean; Mozziconacci, Marie-Joelle; Callet-Bauchu, Evelyne; Veronese, Lauren; Blons, Hélène; Owen, Roger; Lejeune, Julie; Chevret, Sylvie; Merle-Beral, Hélène; Leblondon, Véronique

2013-04-01

Waldenström's macroglobulinemia is a disease of mature B cells, the genetic basis of which is poorly understood. Few recurrent chromosomal abnormalities have been reported, and their prognostic value is not known. We conducted a prospective cytogenetic study of Waldenström's macroglobulinemia and examined the prognostic value of chromosomal aberrations in an international randomized trial. The main aberrations were 6q deletions (30%), trisomy 18 (15%), 13q deletions (13%), 17p (TP53) deletions (8%), trisomy 4 (8%), and 11q (ATM) deletions (7%). There was a significant association between trisomy of chromosome 4 and trisomy of chromosome 18. Translocations involving the IGH genes were rare (<5%). Deletion of 6q and 11q, and trisomy 4, were significantly associated with adverse clinical and biological parameters. Patients with TP53 deletion had short progression-free survival and short disease-free survival. Although rare (<5%), trisomy 12 was associated with short progression-free survival. In conclusion, the cytogenetic profile of Waldenström's macroglobulinemia appears to differ from that of other B-cell lymphomas. Chromosomal abnormalities may help with diagnosis and prognostication, in conjunction with other clinical and biological characteristics.

Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenström's macroglobulinemia

PubMed Central

Nguyen-Khac, Florence; Lambert, Jerome; Chapiro, Elise; Grelier, Aurore; Mould, Sarah; Barin, Carole; Daudignon, Agnes; Gachard, Nathalie; Struski, Stéphanie; Henry, Catherine; Penther, Dominique; Mossafa, Hossein; Andrieux, Joris; Eclache, Virginie; Bilhou-Nabera, Chrystèle; Luquet, Isabelle; Terre, Christine; Baranger, Laurence; Mugneret, Francine; Chiesa, Jean; Mozziconacci, Marie-Joelle; Callet-Bauchu, Evelyne; Veronese, Lauren; Blons, Hélène; Owen, Roger; Lejeune, Julie; Chevret, Sylvie; Merle-Beral, Hélène; Leblondon, Véronique

2013-01-01

Waldenström's macroglobulinemia is a disease of mature B cells, the genetic basis of which is poorly understood. Few recurrent chromosomal abnormalities have been reported, and their prognostic value is not known. We conducted a prospective cytogenetic study of Waldenström's macroglobulinemia and examined the prognostic value of chromosomal aberrations in an international randomized trial. The main aberrations were 6q deletions (30%), trisomy 18 (15%), 13q deletions (13%), 17p (TP53) deletions (8%), trisomy 4 (8%), and 11q (ATM) deletions (7%). There was a significant association between trisomy of chromosome 4 and trisomy of chromosome 18. Translocations involving the IGH genes were rare (<5%). Deletion of 6q and 11q, and trisomy 4, were significantly associated with adverse clinical and biological parameters. Patients with TP53 deletion had short progression-free survival and short disease-free survival. Although rare (<5%), trisomy 12 was associated with short progression-free survival. In conclusion, the cytogenetic profile of Waldenström's macroglobulinemia appears to differ from that of other B-cell lymphomas. Chromosomal abnormalities may help with diagnosis and prognostication, in conjunction with other clinical and biological characteristics. This trial is registered with Clinicaltrials.gov, numbers NCT00566332 and NCT00608374. PMID:23065509

[Diagnostic approach of an IgM monoclonal gammopathy and clinical importance of gene MYD88 L265P mutation].

PubMed

Cilla, N; Vercruyssen, M; Ameye, L; Paesmans, M; de Wind, A; Heimann, P; Meuleman, N; Bron, D

2018-05-30

An IgM monoclonal gammopathy points to a diagnosis of Waldenstrom's Macroglobulinemia. Other B lymphoproliferatives disorders should be ruled out but the limits are sometimes difficult to define. The discovery of the L265P mutation of the MYD88 gene simplified potentially the situation. 383 patients of the Jules Bordet Institute with an IgM level above 2 g/L were reviewed. For the 49 who had a monoclonal peak, we analysed the underlying pathology in termes of general, clinical and biological characteristics. We checked if the MYD88 mutation had been detected. The overall survival rate was studied. 5 histological groups were identified: Waldenstrom's Macroglobulinemia (MW, N = 27), lymphoplasmacytic lymphoma (LLP, N = 10), marginal zone lymphoma (LMZ, N = 7), monoclonal gammopathy of unknown significance and multiple myeloma (MGUS/MM, N = 5). The MW group was compared to the other groups. Regarding biological characteristics, the IgM level upon diagnosis was statistically higher in the MW group with a median level at 19.5 g/L (2.3-101 g/L) (p-value = 0,0001). Concerning the clinical characteristics, a splenomegaly was more frequent in the LMZ group (p-value = 0,04). The L265P mutation of the MYD88 gene was found in 77 % of patients in the MW group, 60 % of patients in the LLP group and 67 % in the LMZ group (p-value = 0,38). For the 49 patients, the 10-yearoverall survival was 85 % (CI 95 %, 67 % to 94 %) and the 15-year-overall survival was 65 % (CI 95 %, 41 % to 81 %). A monoclonal IgM peak suggests a MW but other B lymphoproliferatives disorders should be excluded. Even if the L265P mutation is frequent in the LLP/MW, it is not specific. A precise diagnosis requires collating clinical, histological, immunophenotypical and genetical data.

Bilinguals’ Working Memory (WM) Advantage and Their Dual Language Practices

PubMed Central

Yang, Eunju

2017-01-01

The present study investigates a possible working memory (WM) difference between monolingual and bilingual groups and explores the relationship between their WM advantage and language practices. A mixed methods design was employed for the study. To measure participants’ WM, auditory and visual digit span tasks were conducted on the different language groups: 20 Korean near-monolinguals, and 40 Korean–English bilinguals with two different levels of second language (L2) proficiency. Bilinguals’ daily language practices were explored through semi-structured interviews with eight bilinguals. The convergence of the findings from both tests and interview data suggests that knowing two languages does not guarantee bilingual WM advantages over monolinguals, but the advantage might be linked to bilinguals’ unique L2 use environment where they need to hold incoming L2 information while decoding it. PMID:28718840

Kidney Involvement of Patients with Waldenström Macroglobulinemia and Other IgM-Producing B Cell Lymphoproliferative Disorders.

PubMed

Higgins, Larissa; Nasr, Samih H; Said, Samar M; Kapoor, Prashant; Dingli, David; King, Rebecca L; Rajkumar, S Vincent; Kyle, Robert A; Kourelis, Taxiarchis; Gertz, Morie A; Dispenzieri, Angela; Lacy, Martha Q; Buadi, Francis K; Ansell, Stephen M; Gonsalves, Wilson I; Thompson, Carrie A; Fervenza, Fernando C; Zand, Ladan; Hwa, Yi L; Jevremovic, Dragan; Shi, Min; Leung, Nelson

2018-05-30

Kidney involvement in Waldenström macroglobulinemia is less well described compared with kidney manifestations in multiple myeloma. Of the 1363 patients seen with Waldenström macroglobulinemia and other IgM-secreting B cell lymphoproliferative disorders seen at the Mayo Clinic between 1996 and 2015, 57 kidney biopsies were retrospectively studied. The biopsy findings were correlated with clinical, kidney, and hematologic characteristics. Criteria for inclusion were evidence of a monoclonal IgM protein and availability of a kidney and a bone marrow biopsy for review. Glomerular and tubulointerstitial pathologies were categorized according to whether they were related to the monoclonal IgM. Of the 57 patients identified, monoclonal gammopathy-related kidney lesions were identified in 82% (47 of 57 biopsies), whereas nonmonoclonal gammopathy-related kidney lesions were seen in 18% (ten of 57). Monoclonal gammopathy-related kidney lesions included monoclonal Ig-related amyloidosis ( n =19; 33%), nonamyloid glomerulopathy ( n =20, 35%), and tubulointerstitial nephropathies ( n =8; 14%). The most common monoclonal gammopathy-related kidney lesion was monoclonal Ig-related amyloidosis ( n =19; 33%) followed by cryoglobulinemic GN ( n =13; 28%). Lymphoma infiltration was the most common tubulointerstitial lesion ( n =4; 9%). The hematologic diagnosis was Waldenström macroglobulinemia in 74% ( n =42), monoclonal gammopathy of renal significance in 16% ( n =9), and marginal zone lymphoma ( n =2), chronic lymphocytic leukemia ( n =2), and low-grade B cell lymphoma ( n =2) in 4% each. Our study confirms a diverse variety of kidney lesions in patients with monoclonal IgM gammopathy. Copyright © 2018 by the American Society of Nephrology.

How Common are WM Deficits in Children with Difficulties in Reading and Mathematics?

PubMed

Gathercole, Susan E; Woolgar, Francesca; Kievit, Rogier A; Astle, Duncan; Manly, Tom; Holmes, Joni

2016-12-01

The extent to which deficits in working memory (WM) are characteristic of children with reading and mathematics difficulties was investigated in a large sample aged 5-15 years reported to have problems in attention, learning and memory. WM performance was highly correlated with reading and mathematics scores. Although deficits in individual tests of short-term memory (STM) and WM occurred in less than half of the children with detected learning difficulties, three-quarters of the children with low reading and mathematics scores obtained one or more WM scores in the deficit range. These findings are consistent with proposals that WM or the broader cognitive dimensions it taps impede school-based learning, and point to the importance of managing WM loads in the classroom.

BDR in newly diagnosed patients with WM: final analysis of a phase 2 study after a minimum follow-up of 6 years.

PubMed

Gavriatopoulou, Maria; García-Sanz, Ramón; Kastritis, Efstathios; Morel, Pierre; Kyrtsonis, Marie-Christine; Michalis, Eurydiki; Kartasis, Zafiris; Leleu, Xavier; Palladini, Giovanni; Tedeschi, Alessandra; Gika, Dimitra; Merlini, Giampaolo; Sonneveld, Pieter; Dimopoulos, Meletios A

2017-01-26

In this phase 2 multicenter trial, we evaluated the efficacy of the combination of bortezomib, dexamethasone, and rituximab (BDR) in 59 previously untreated symptomatic patients with Waldenström macroglobulinemia (WM), most of which were of advanced age and with adverse prognostic factors. BDR consisted of a single 21-day cycle of bortezomib alone (1.3 mg/m 2 IV on days 1, 4, 8, and 11), followed by weekly IV bortezomib (1.6 mg/m 2 on days 1, 8, 15, and 22) for 4 additional 35-day cycles, with IV dexamethasone (40 mg) and IV rituximab (375 mg/m 2 ) on cycles 2 and 5, for a total treatment duration of 23 weeks. On intent to treat, 85% responded (3% complete response, 7% very good partial response, 58% partial response). After a minimum follow-up of 6 years, median progression-free survival was 43 months and median duration of response for patients with at least partial response was 64.5 months. Overall survival at 7 years was 66%. No patient had developed secondary myelodysplasia, whereas transformation to high-grade lymphoma occurred in 3 patients who had received chemoimmunotherapy after BDR. Thus, BDR is a very active, fixed-duration, chemotherapy-free regimen, inducing durable responses and with a favorable long-term toxicity profile (www.ClinicalTrials.gov #NCT00981708). © 2017 by The American Society of Hematology.

C&O Canal prism, with towpath (left) and fill under WM ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

C&O Canal prism, with towpath (left) and fill under WM roadbed (right), milepost 142 vicinity, looking southwest. - Western Maryland Railway, Cumberland Extension, Pearre to North Branch, from WM milepost 125 to 160, Pearre, Washington County, MD

Molecular Characterization of Watermelon Chlorotic Stunt Virus (WmCSV) from Palestine

PubMed Central

Ali-Shtayeh, Mohammed S.; Jamous, Rana M.; Mallah, Omar B.; Abu-Zeitoun, Salam Y.

2014-01-01

The incidence of watermelon chlorotic stunt disease and molecular characterization of the Palestinian isolate of Watermelon chlorotic stunt virus (WmCSV-[PAL]) are described in this study. Symptomatic leaf samples obtained from watermelon Citrullus lanatus (Thunb.), and cucumber (Cucumis sativus L.) plants were tested for WmCSV-[PAL] infection by polymerase chain reaction (PCR) and Rolling Circle Amplification (RCA). Disease incidence ranged between 25%–98% in watermelon fields in the studied area, 77% of leaf samples collected from Jenin were found to be mixed infected with WmCSV-[PAL] and SLCV. The full-length DNA-A and DNA-B genomes of WmCSV-[PAL] were amplified and sequenced, and the sequences were deposited in the GenBank. Sequence analysis of virus genomes showed that DNA-A and DNA-B had 97.6%–99.42% and 93.16%–98.26% nucleotide identity with other virus isolates in the region, respectively. Sequence analysis also revealed that the Palestinian isolate of WmCSV shared the highest nucleotide identity with an isolate from Israel suggesting that the virus was introduced to Palestine from Israel. PMID:24956181

Ibrutinib in Treating Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma in Patients With HIV Infection

ClinicalTrials.gov

2015-08-18

Adult B Acute Lymphoblastic Leukemia; Chronic Lymphocytic Leukemia; Cutaneous B-Cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; HIV Infection; Intraocular Lymphoma; Multicentric Angiofollicular Lymphoid Hyperplasia; Nodal Marginal Zone Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Plasma Cell Myeloma; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

The importance of the genomic landscape in Waldenström's Macroglobulinemia for targeted therapeutical interventions

PubMed Central

Sacco, Antonio; Fenotti, Adriano; Affò, Loredana; Bazzana, Stefano; Russo, Domenico; Presta, Marco; Malagola, Michele; Anastasia, Antonella; Motta, Marina; Patterson, Christopher J.; Rossi, Giuseppe; Imberti, Luisa; Treon, Steven P.; Ghobrial, Irene M.; Roccaro, Aldo M.

2017-01-01

The Literature has recently reported on the importance of genomics in the field of hematologic malignancies, including B-cell lymphoproliferative disorders such as Waldenström's Macrolgobulinemia (WM). Particularly, whole exome sequencing has led to the identification of the MYD88L265P and CXCR4C1013G somatic variants in WM, occurring in about 90% and 30% of the patients, respectively. Subsequently, functional studies have demonstrated their functional role in supporting WM pathogenesis and disease progression, both in vitro and in vivo, thus providing the pre-clinical evidences for extremely attractive targets for novel therapeutic interventions in WM. Of note, recent evidences have also approached and defined the transcriptome profiling of WM cells, revealing a signature that mirrors the somatic aberrations demonstrated within the tumor clone. A parallel research field has also reported on microRNAs (miRNAs), highlighting the oncogenic role of miRNA-155 in WM. In the present review, we focus on the latest reports on genomics and miRNAs in WM, providing an overview of the clinical relevance of the latest acquired knowledge about genomics and miRNA aberrations in WM. PMID:28423722

The importance of the genomic landscape in Waldenström's Macroglobulinemia for targeted therapeutical interventions.

PubMed

Sacco, Antonio; Fenotti, Adriano; Affò, Loredana; Bazzana, Stefano; Russo, Domenico; Presta, Marco; Malagola, Michele; Anastasia, Antonella; Motta, Marina; Patterson, Christopher J; Rossi, Giuseppe; Imberti, Luisa; Treon, Steven P; Ghobrial, Irene M; Roccaro, Aldo M

2017-05-23

The Literature has recently reported on the importance of genomics in the field of hematologic malignancies, including B-cell lymphoproliferative disorders such as Waldenström's Macrolgobulinemia (WM). Particularly, whole exome sequencing has led to the identification of the MYD88L265P and CXCR4C1013G somatic variants in WM, occurring in about 90% and 30% of the patients, respectively. Subsequently, functional studies have demonstrated their functional role in supporting WM pathogenesis and disease progression, both in vitro and in vivo, thus providing the pre-clinical evidences for extremely attractive targets for novel therapeutic interventions in WM. Of note, recent evidences have also approached and defined the transcriptome profiling of WM cells, revealing a signature that mirrors the somatic aberrations demonstrated within the tumor clone. A parallel research field has also reported on microRNAs (miRNAs), highlighting the oncogenic role of miRNA-155 in WM. In the present review, we focus on the latest reports on genomics and miRNAs in WM, providing an overview of the clinical relevance of the latest acquired knowledge about genomics and miRNA aberrations in WM.

A phase II trial on alpha-interferon (alpha IFN) effect in patients with monoclonal IgM gammopathy.

PubMed

Rotoli, B; De Renzo, A; Frigeri, F; Buffardi, S; Marcenò, R; Cavallaro, A M; Ruggeri, P; Liso, V; Musto, P; Andriani, A

1994-05-01

Waldenström's macroglobulinemia (WM) is an incurable disorder of B cells. Following occasional reports of response to alpha interferon (IFN) and in view of its effectiveness in hairy cell leukemia, we tested this agent in a relatively large group (n = 88) of patients who had an IgM monoclonal component (MC) greater than 10 g/l. Thirty eight patients had a MC > 30 g/l and were classified as Waldenström's macroglobulinemia (WM), while fifty had either WM in an early stage or an IgM monoclonal gammopathy of undeterminated significance (all of them operationally classified as IgM-MGUS). All patients received IFN 3 MU/day for one month and then 3 times/week. Response to treatment was mainly based on MC reduction in two consecutive determinations (> 50%: major response; 25-50%: minor response). Of 36 evaluable WM patients, 12 had a major and 6 a minor response; of 41 evaluable IgM-MGUS patients, 2 had a major and 6 a minor response. In WM patients with a major response, MC reduction was associated with disappearance of hyperviscosity symptoms, raised Hb level and reduced bone marrow lymphoplasmacytosis. At the dose used, tolerance was excellent in the majority of patients; only 15% withdrew from the study due to side effects. Although single cases and very small series have already been reported, no large study collecting quantitative data on the effects of alpha IFN in WM has been published so far. Our results suggest that IFN treatment is not indicated for patients with a low monoclonal component, while it is of clinical benefit in about 50% of patients with IgM > 30 g/l.

Chronic inflammatory demyelinating polyneuropathy in Waldenström's macroglobulinemia.

PubMed

Cassereau, J; Letournel, F; François, S; Dubas, F; Nicolas, G

2011-04-01

Waldenström's disease (WD) is frequently associated with a predominantly sensory neuropathy with a progressive course due to the monoclonal IgM activity against Myelin Associated Glycoprotein (MAG). However, neurolymphomatosis or chronic demyelinating inflammatory polyneuropathy (CDIP) may occur in some patients with WD. We report a case of Waldenström's macroglobulinemia in an adult male presenting with cranial nerve palsy and rapidly progressive asymmetric polyneuropathy. Intravenous IgM treatment that provided transient amelioration was followed by a relapse involving tetraparesis. Cerebrospinal fluid analysis, medullar magnetic resonance imaging, and electrophysiological studies led to equivocal findings suggesting the presence of either neurolymphomatosis or CIDP. Finally, sural nerve biopsy results supported the diagnosis of CIDP, which then received appropriate treatment. In patients with WD, the possible occurrence of CIDP should be investigated with a neuromuscular biopsy when other investigations are equivocal since the disease calls for a specific treatment. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Rituximab and Dexamethasone in Treating Patients With Low-Grade Non-Hodgkin Lymphoma

ClinicalTrials.gov

2017-04-14

Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Marginal Zone Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Marginal Zone Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

[Plasmapheresis--possible complications and their prevention].

PubMed

Seczyńska, Bozena; Sega, Aurelia; Nowak, Ilona; Fajfer, Izabela; Królikowski, Wiesław; Szczeklik, Wojciech

2011-01-01

Plasmapheresis it is a therapeutic method based on extracorporeal plasma exchange. First attempts at treatment with plasmapheresis date back to the beginning of the 20th century. However, it was first brought to clinical practice only in the 1950s as a way of treating Waldenstrom macroglobulinemia and in last decades a dynamic improvement in this method has been observed. At the moment plasmapheresis is used in the treatment of over 150 diseases. Like every invasive method, it may cause complications, which are due to anticoagulation, the use of replacement fluids, the technical part of the procedure, and the presence of intravenous catheters. The knowledge of potential complications and the way of preventing them by the medical staff help to avoid complications and to decrease their harmful effects.

Fludarabine Phosphate, Cyclophosphamide, Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Blood Cancer

ClinicalTrials.gov

2018-06-13

Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Acute Leukemia in Remission; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Acute Myeloid Leukemia With FLT3/ITD Mutation; Acute Myeloid Leukemia With Gene Mutations; Aplastic Anemia; B-Cell Non-Hodgkin Lymphoma; CD40 Ligand Deficiency; Chronic Granulomatous Disease; Chronic Leukemia in Remission; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Congenital Amegakaryocytic Thrombocytopenia; Congenital Neutropenia; Congenital Pure Red Cell Aplasia; Glanzmann Thrombasthenia; Immunodeficiency Syndrome; Myelodysplastic Syndrome; Myelofibrosis; Myeloproliferative Neoplasm; Paroxysmal Nocturnal Hemoglobinuria; Plasma Cell Myeloma; Polycythemia Vera; Recurrent Non-Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Severe Aplastic Anemia; Shwachman-Diamond Syndrome; Sickle Cell Disease; T-Cell Non-Hodgkin Lymphoma; Thalassemia; Waldenstrom Macroglobulinemia; Wiskott-Aldrich Syndrome

75 FR 1362 - WM Renewable Energy, L.L.C.; Notice of Filing

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-11

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket Nos. EL10-32-000, QF08-622-002] WM Renewable Energy, L.L.C.; Notice of Filing January 4, 2010. Take notice that on December 31, 2009, WM Renewable Energy, L.L.C. filed a petition for a declaratory order, pursuant to Rule 207(a)(2) of...

Non-invasive Glucose Measurements Using Wavelength Modulated Differential Photothermal Radiometry (WM-DPTR)

NASA Astrophysics Data System (ADS)

Guo, X.; Mandelis, A.; Zinman, B.

2012-11-01

Wavelength-modulated differential laser photothermal radiometry (WM-DPTR) is introduced for potential development of clinically viable non-invasive glucose biosensors. WM-DPTR features unprecedented glucose-specificity and sensitivity by combining laser excitation by two out-of-phase modulated beams at wavelengths near the peak and the baseline of a prominent and isolated mid-IR glucose absorption band. Measurements on water-glucose phantoms (0 to 300 mg/dl glucose concentration) demonstrate high sensitivity to meet wide clinical detection requirements ranging from hypoglycemia to hyperglycemia. The measurement results have been validated by simulations based on fully developed WM-DPTR theory. For sensitive and accurate glucose measurements, the key is the selection and tight control of the intensity ratio and the phase shift of the two laser beams.

Assessing Working Memory in Children: The Comprehensive Assessment Battery for Children - Working Memory (CABC-WM).

PubMed

Cabbage, Kathryn; Brinkley, Shara; Gray, Shelley; Alt, Mary; Cowan, Nelson; Green, Samuel; Kuo, Trudy; Hogan, Tiffany P

2017-06-12

The Comprehensive Assessment Battery for Children - Working Memory (CABC-WM) is a computer-based battery designed to assess different components of working memory in young school-age children. Working memory deficits have been identified in children with language-based learning disabilities, including dyslexia 1 , 2 and language impairment 3 , 4 , but it is not clear whether these children exhibit deficits in subcomponents of working memory, such as visuospatial or phonological working memory. The CABC-WM is administered on a desktop computer with a touchscreen interface and was specifically developed to be engaging and motivating for children. Although the long-term goal of the CABC-WM is to provide individualized working memory profiles in children, the present study focuses on the initial success and utility of the CABC-WM for measuring central executive, visuospatial, phonological loop, and binding constructs in children with typical development. Immediate next steps are to administer the CABC-WM to children with specific language impairment, dyslexia, and comorbid specific language impairment and dyslexia.

Detection of MYD88 L265P and WHIM-like CXCR4 mutation in patients with IgM monoclonal gammopathy related disease.

PubMed

Cao, Xin-Xin; Meng, Qi; Cai, Hao; He, Tian-Hua; Zhang, Cong-Li; Su, Wei; Sun, Jian; Li, Yue; Xu, Wei; Zhou, Dao-Bin; Li, Jian

2017-06-01

A broad spectrum of diseases are associated with IgM monoclonal gammopathy, including Waldenstrom macroglobulinemia (WM), various types of B cell non-Hodgkin's lymphoma (NHL), multiple myeloma (MM), primary amyloidosis (AL), and monoclonal gammopathy of undetermined significance (MGUS); these are called IgM monoclonal gammopathy related diseases (IgM-RD). We investigated MYD88 L265P and WHIM-like CXCR4 mutations in various IgM-RD. Patients with serum immunofixation electrophoresis confirmed IgM monoclonal gammopathy who had enough material for DNA extraction and presented between January 2008 and October 2016 at Peking Union Medical College Hospital were enrolled in this cohort. We performed real-time allele-specific-polymerase chain reaction and Sanger sequencing to explore the presence of MYD88 L265P and WHIM-like CXCR4 mutations. One hundred and twelve patients (64 male and 48 female patients) were included in this retrospective study. The median age at diagnosis was 62 years (range, 30-84 years). In total, 64 patients (57.1%) carried the MYD88 L265P mutation and 14 patients (12.5%) carried the CXCR4 WHIM-like mutation. We identified the MYD88 L265P somatic variant in cases with WM (39/42), MGUS (8/18), NHL (14/41, including 4/13 diffuse large B cell lymphoma (DLBCL), 1/8 mucosa-associated lymphoid tissue, 3/6 splenic marginal zone lymphoma (SMZL), 1/4 chronic lymphocytic leukemia, 2/3 nodal marginal zone lymphoma (NMZL), 1/2 mantle cell lymphoma, 1 Burkitt lymphoma, and 1 B cell NHL that could not be classified), primary AL (2/2), and IgM-PN (1/1). The mutation was absent in five patients with Cryoglobulinemia, two with primary cold agglutinin disease and one with MM. The CXCR4 WHIM-like mutation was present in 10/42 patients with WM, 3/41 with NHL (1 DLBCL, 1 SMZL, and 1 NMZL), and 1/18 patients with IgM MGUS. Among the patients with NHL, those with the mutated MYD88 L265P genotype were younger and had lower level of IgG and IgA than the patients with the

78 FR 56224 - Hydro Nelson, Ltd.; Hydro-WM, LLC; Notice of Transfer of Exemption

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-12

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 3401-049] Hydro Nelson, Ltd.; Hydro-WM, LLC; Notice of Transfer of Exemption 1. By documentation filed July 8, 2013 and supplemented on September 4, 2013, Hydro-WM, LLC informed the Commission that the exemption from licensing for the...

1. Historic American Buildings Survey Wm. H. Knowles Collection Original: ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. Historic American Buildings Survey Wm. H. Knowles Collection Original: Early 1860's Re-photo: January 1940 VIEW FROM NORTHWEST - Mission San Jose de Guadalupe, Mission & Washington Boulevards, Fremont, Alameda County, CA

3. Historic American Buildings Survey From Wm. H. Knowles Collection ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

3. Historic American Buildings Survey From Wm. H. Knowles Collection Copy from old print Original: Prior 1861 Re-photo: January 1940 VIEW FORM SOUTH - Mission San Rafael Archangel, San Rafael, Marin County, CA

Gemcitabine Hydrochloride, Carboplatin, Dexamethasone, and Rituximab in Treating Patients With Previously Treated Lymphoid Malignancies

ClinicalTrials.gov

2017-05-28

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

PFC Activity Pattern During Verbal WM Task in Healthy Male and Female Subjects: A NIRS Study.

PubMed

Gao, Chenyang; Zhang, Lei; Luo, Dewu; Liu, Dan; Gong, Hui

2016-01-01

Near-infrared spectroscopy (NIRS), as a non-invasive optical imaging method, has been widely used in psychology research. Working memory (WM) is an extensively researched psychological concept related to the temporary storage and processing of information. Many neuropsychological studies demonstrate that several brain areas of prefrontal cortex (PFC) are engaged during verbal WM tasks. The gender-based differences in WM remains under dispute. To better understand the active module and gender differences in PFC activity patterns during verbal WM tasks, we investigated the blood oxygenation changes of the PFC in 15 healthy subjects using a homemade multichannel continuous-wave NIRS instrument, while performing a verbal n-back task. We employed traditional activation and novel connectivity analyses simultaneously. Males had a higher level of oxygenation activity and connectivity in PFC than females. Only the results of females revealed a leftward lateralization in the 2-back task.

WM in Adolescence: What Is the Relationship With Emotional Regulation and Behavioral Outcomes?

PubMed

Malagoli, Chiara; Usai, Maria Carmen

2018-01-01

Adolescence is a fundamental transition phase, marked by physical, social, cognitive and emotional changes. At this stage in development two contrasting phenomena take place: brain changes cause a sensitivity to emotional aspects (Dahl, 2004); while also control processes register as well impressive improvements (e.g., Hooper et al., 2004; Best and Miller, 2010). The study is aimed to investigate the relationship between a core cognitive feature such as working memory (WM) (Diamond, 2013) and complex abilities such as emotion regulation (ER) and behavioral self-reported outcomes using a structural equation model approach. A sample of 227 typically developed adolescents between 14 and19 years of age (148 females; mean age in months 202.8, SD 18.57) participated in this study. The following tasks and self-reports were administered in a 45-min test session at school: Symmetry Span task (Kane et al., 2004). Reading Span task (Daneman and Carpenter, 1980), Mr. Cucumber (Case, 1985); Youth Self-Report (YSR, 11-18 years, Achenbach and Rescorla, 2001); Difficulties ER Scale (DERS, Gratz and Roemer, 2004; Italian version by Giromini et al., 2012). Results showed that difficulties in ER correlated with WM: high levels of ER difficulties are associated with low WM efficiency while no significant contributions of these predictors was observed on externalizing or internalizing symptoms. This study showed a significant relationship between self-reported difficulties in ER and WM, while no significant contribution of the considered predictors was showed on the outcomes, adding knowledge about how behavioral and emotional self-reported outcomes may relate to these processes.

Wm. Theodore de Bary: Asian Studies in the Core Curriculum.

ERIC Educational Resources Information Center

Turner, James S.

1991-01-01

Traces Asian studies' infusion into the curriculum at Columbia University. Attributes the program's development to Wm. Theodore de Bary's influence, including his translating and editing of primary sources. States his work continues to serve as basic texts in Japanese, Chinese, Indian, and Buddhist traditions. Discusses his views on scholarship,…

Alisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma

ClinicalTrials.gov

2018-04-10

Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Hepatosplenic T-Cell Lymphoma; Intraocular Lymphoma; Lymphomatous Involvement of Non-Cutaneous Extranodal Site; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Primary Cutaneous B-Cell Non-Hodgkin Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Recurrent Non-Hodgkin Lymphoma; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; T-Cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenstrom Macroglobulinemia

Disseminated Cryptococcal Disease in a Patient with Chronic Lymphocytic Leukemia on Ibrutinib.

PubMed

Okamoto, Koh; Proia, Laurie A; Demarais, Patricia L

2016-01-01

Cryptococcus is a unique environmental fungus that can cause disease most often in immunocompromised individuals with defective cell-mediated immunity. Chronic lymphocytic leukemia (CLL) is not known to be a risk factor for cryptococcal disease although cases have been described mainly in patients treated with agents that suppress cell-mediated immunity. Ibrutinib is a new biologic agent used for treatment of CLL, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. It acts by inhibiting Bruton's tyrosine kinase, a kinase downstream of the B-cell receptor critical for B-cell survival and proliferation. Ibrutinib use has not been associated previously with cryptococcal disease. However, recent evidence suggested that treatments aimed at blocking the function of Bruton's tyrosine kinase could pose a higher risk for cryptococcal infection in a mice model. Here, we report the first case of disseminated cryptococcal disease in a patient with CLL treated with ibrutinib. When evaluating possible infection in CLL patients receiving ibrutinib, cryptococcal disease, which could be life threatening if overlooked, could be considered.

DOWNSTREAM-WATER-LEVEL CONTROL TEST RESULTS ON THE WM LATERAL CANAL

USDA-ARS?s Scientific Manuscript database

On steep canals, distant downstream water-level control can be challenging. SacMan (Software for Automated Canal Management) was developed, in part, to test various distant downstream water level controllers. It was implemented on the WM canal of the Maricopa Stanfield Irrigation and Drainage Distri...

Wm. Lloyd Stackhouse & Robert E. Kinsman: A tale of two chiropractors

PubMed Central

Brown, Douglas M.

2013-01-01

This paper reviews the story of two childhood friends, Dr. Wm. Lloyd Stackhouse and Dr. Robert E. Kinsman, who attended the Canadian Memorial Chiropractic College (CMCC) together, graduated in 1953 to form an enduring partnership that included their immediate relatives, and to this day persists as a supportive tribe. PMID:23997249

78 FR 57105 - Wm. Wrigley Jr. Company; Filing of Color Additive Petition

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 73 [Docket No. FDA-2013-C-1008] Wm. Wrigley Jr. Company; Filing of Color Additive Petition AGENCY: Food and Drug... additive regulations be amended to expand the use of synthetic iron oxide to include soft and hard candy...

Wavelength-modulated differential photoacoustic radar imager (WM-DPARI): accurate monitoring of absolute hemoglobin oxygen saturation

PubMed Central

Choi, Sung Soo Sean; Lashkari, Bahman; Dovlo, Edem; Mandelis, Andreas

2016-01-01

Accurate monitoring of blood oxy-saturation level (SO2) in human breast tissues is clinically important for predicting and evaluating possible tumor growth at the site. In this work, four different non-invasive frequency-domain photoacoustic (PA) imaging modalities were compared for their absolute SO2 characterization capability using an in-vitro sheep blood circulation system. Among different PA modes, a new WM-DPAR imaging modality could estimate the SO2 with great accuracy when compared to a commercial blood gas analyzer. The developed WM-DPARI theory was further validated by constructing SO2 tomographic images of a blood-containing plastisol phantom. PMID:27446691

2C-R4WM Spectroscopy of Jet Cooled NO_3

NASA Astrophysics Data System (ADS)

Fukushima, Masaru; Ishiwata, Takashi; Hirota, Eizi

2016-06-01

We have generated NO_3 from pyrolysis of N_2O_5 following supersonic free jet expansion, and carried out two color resonant four wave mixing ( 2C-R4WM ) spectroscopy of the tilde{B} ^2E' - tilde{X} ^2A_2' electronic transition. One laser was fixed to pump NO_3 to a ro-vibronic level of the tilde{B} state, and the other laser ( probe ) was scanned across two levels of the tilde{X} ^2A_2' state lying at 1051 and 1492 cm-1, the ν_1 (a_1') and ν_3 (e') fundamentals, respectively. The 2C-R4WM spectra have unexpected back-ground signal of NO_3 ( stray signal due to experimental set-up is also detected ) similar to laser induced fluorescence ( LIF ) excitation spectrum of the 0-0 band, although the back-ground signal was not expected in considering the 2C-R4WM scheme. Despite the back-ground interference, we have observed two peaks at 1051.61 and 1055.29 cm-1 in the ν_1 region of the spectrum, and the frequencies agree with the two bands, 1051.2 and 1055.3 cm-1, of our relatively higher resolution dispersed fluorescence spectrum, the former of which has been assigned to the ν_1 fundamental. Band width of both peaks, ˜ 0.2 cm-1, is broader than twice the experimental spectral-resolution, 0.04 cm-1 ( because this experiment is double resonance spectroscopy ), and the 1051.61 cm-1 peak is attributed to a Q branch band head ( a line-like Q branch ) of the ν_1 fundamental. The other branches are suspected to be hidden in noise of the back-ground signal. The 1055.29 cm-1 peak is also attributed to a Q band head. The tilde{B} ^2E'1/2 ( J' = 3/2, K' = 1 ) - tilde{X} ^2A_2' ( N'' = 1, K'' = 0 ) ro-vibronic transition was used as the pump transition. The dump ( probe ) transition to both a_1' and e' vibronic levels are then allowed as perpendicular transition. Accordingly, it cannot be determined from present results whether the 1055.29 cm-1 band is attributed to a_1' or e' (ν_3), unfortunately. The 2C-R4WM spectrum of the 1492 cm-1 band region shows one Q head at 1499.79 cm

Factors predicting transformation of asymptomatic IgM monoclonal gammopathy.

PubMed

Greco, Antonino; Tedeschi, Alessandra; Varettoni, Marzia; Nichelatti, Michele; Paris, Laura; Ricci, Francesca; Vismara, Eleonora; Morra, Enrica

2011-02-01

We evaluated the risk of transformation of asymptomatic immunoglobulin (Ig) M monoclonal gammopathy (aIgM MG) into symptomatic lymphoproliferative disease in 287 patients all analyzed for bone marrow histopathology and immunophenotyping. This series included 201 patients with IgM MG of undetermined significance (IgM MGUS) and 86 with smoldering Waldenström's macroglobulinemia (sWM). After a median of 50 months (range, 12-322 months), 32 cases of aIgM-MG (11.1%) evolved into symptomatic malignant lymphoproliferative disease, as follows: symptomatic WM (n=26), non-Hodgkin lymphoma (n=6). The cumulative transformation percentage at 5 and 10 years was 8% and 19.5%, respectively. The parameters significantly correlated with evolution were, at univariate analysis, BM lymphoplasmacytic infiltration, high erythrocyte sedimentation rate, serum MC, serum IgM size, and serum IgA size. Among patients with aIgM-MG, those at high risk of evolution were patients with sWM, a distinct entity with serum IgM monoclonal protein≥3 g/dL and/or ≥10% bone marrow lymphoplasmacytic infiltration.

Deep-proteome mapping of WM-266-4 human metastatic melanoma cells: From oncogenic addiction to druggable targets

PubMed Central

Litou, Zoi I.; Konstandi, Ourania A.; Giannopoulou, Aikaterini F.; Anastasiadou, Ema; Voutsinas, Gerassimos E.; Tsangaris, George Th.; Stravopodis, Dimitrios J.

2017-01-01

Cutaneous melanoma is a malignant tumor of skin melanocytes that are pigment-producing cells located in the basal layer (stratum basale) of epidermis. Accumulation of genetic mutations within their oncogenes or tumor-suppressor genes compels melanocytes to aberrant proliferation and spread to distant organs of the body, thereby resulting in severe and/or lethal malignancy. Metastatic melanoma’s heavy mutational load, molecular heterogeneity and resistance to therapy necessitate the development of novel biomarkers and drug-based protocols that target key proteins involved in perpetuation of the disease. To this direction, we have herein employed a nano liquid chromatography-tandem mass spectrometry (nLC-MS/MS) proteomics technology to profile the deep-proteome landscape of WM-266-4 human metastatic melanoma cells. Our advanced melanoma-specific catalogue proved to contain 6,681 unique proteins, which likely constitute the hitherto largest single cell-line-derived proteomic collection of the disease. Through engagement of UNIPROT, DAVID, KEGG, PANTHER, INTACT, CYTOSCAPE, dbEMT and GAD bioinformatics resources, WM-266-4 melanoma proteins were categorized according to their sub-cellular compartmentalization, function and tumorigenicity, and successfully reassembled in molecular networks and interactomes. The obtained data dictate the presence of plastically inter-converted sub-populations of non-cancer and cancer stem cells, and also indicate the oncoproteomic resemblance of melanoma to glioma and lung cancer. Intriguingly, WM-266-4 cells seem to be subjected to both epithelial-to-mesenchymal (EMT) and mesenchymal-to-epithelial (MET) programs, with 1433G and ADT3 proteins being identified in the EMT/MET molecular interface. Oncogenic addiction of WM-266-4 cells to autocrine/paracrine signaling of IL17-, DLL3-, FGF(2/13)- and OSTP-dependent sub-routines suggests their critical contribution to the metastatic melanoma chemotherapeutic refractoriness. Interestingly, the

HCK is a survival determinant transactivated by mutated MYD88, and a direct target of ibrutinib.

PubMed

Yang, Guang; Buhrlage, Sara J; Tan, Li; Liu, Xia; Chen, Jie; Xu, Lian; Tsakmaklis, Nicholas; Chen, Jiaji G; Patterson, Christopher J; Brown, Jennifer R; Castillo, Jorge J; Zhang, Wei; Zhang, Xiaofeng; Liu, Shuai; Cohen, Philip; Hunter, Zachary R; Gray, Nathanael; Treon, Steven P

2016-06-23

Activating mutations in MYD88 are present in ∼95% of patients with Waldenström macroglobulinemia (WM), as well as other B-cell malignancies including activated B-cell (ABC) diffuse large B-cell lymphoma (DLBCL). In WM, mutated MYD88 triggers activation of Bruton tyrosine kinase (BTK). Ibrutinib, a pleiotropic kinase inhibitor that targets BTK, is highly active in patients with mutated MYD88. We observed that mutated MYD88 WM and ABC DLBCL cell lines, as well as primary WM cells show enhanced hematopoietic cell kinase (HCK) transcription and activation, and that HCK is activated by interleukin 6 (IL-6). Over-expression of mutated MYD88 triggers HCK and IL-6 transcription, whereas knockdown of HCK reduced survival and attenuated BTK, phosphoinositide 3-kinase/AKT, and mitogen-activated protein kinase/extracellular signal-regulated kinase signaling in mutated MYD88 WM and/or ABC DLBCL cells. Ibrutinib and the more potent HCK inhibitor A419259, blocked HCK activation and induced apoptosis in mutated MYD88 WM and ABC DLBCL cells. Docking and pull-down studies confirmed that HCK was a target of ibrutinib. Ibrutinib and A419259 also blocked adenosine triphosphate binding to HCK, whereas transduction of mutated MYD88 expressing WM cells with a mutated HCK gatekeeper greatly increased the half maximal effective concentration for ibrutinib and A419259. The findings support that HCK expression and activation is triggered by mutated MYD88, supports the growth and survival of mutated MYD88 WM and ABC DLBCL cells, and is a direct target of ibrutinib. HCK represents a novel target for therapeutic development in MYD88-mutated WM and ABC DLBCL, and possibly other diseases driven by mutated MYD88. © 2016 by The American Society of Hematology.

Donor Peripheral Stem Cell Transplant in Treating Patients With Hematolymphoid Malignancies

ClinicalTrials.gov

2016-11-17

Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Relapsing Chronic Myelogenous Leukemia; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

76 FR 72025 - Noise Compatibility Program Notice for W.M. Kellogg Airport, Battle Creek, MI

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-21

... for W.M. Kellogg Airport, Battle Creek, MI AGENCY: Federal Aviation Administration (FAA), DOT. ACTION... exposure maps submitted by the City of Battle Creek, Michigan for W.K. Kellogg Airport under the provisions... noise compatibility program that was submitted for W.K. Kellogg Airport under part 150 in conjunction...

The Seismic Broad Band Western Mediterranean (wm) Network and the Obs Fomar Pool: Current state and Obs activities.

NASA Astrophysics Data System (ADS)

Pazos, Antonio; Davila, Jose Martin; Buforn, Elisa; Bezzeghoud, Mourad; Harnafi, Mimoun; Mattesini, Mauricio; Caldeira, Bento; Hanka, Winfried; El Moudnib, Lahcen; Strollo, Angelo; Roca, Antoni; Lopez de Mesa, Mireya; Dahm, Torsten; Cabieces, Roberto

2016-04-01

The Western Mediterranean (WM) seismic network started in 1996 as an initiative of the Royal Spanish Navy Observatory (ROA) and the Universidad Complutense de Madrid (UCM), with the collaboration of the GeoForschungsZentrum (GFZ) of Potsdam. A first broad band seismic station (SFUC) was installed close to Cádiz (South Spain). Since then, additional stations have been installed in the Ibero-Moghrebian region. In 2005, the "WM" code was assigned by the FDSN and new partners were jointed: Evora University (UEVO, Portugal), the Scientifique Institute of Rabat (ISRABAT, Morocco), and GFZ. Now days, the WM network is composed by 15 BB stations, all of them with Streckaisen STS-2 or STS-2.5 sensors, Quanterra or Earthdata digitizers and SeiscomP. Most them have co-installed a permanent geodetic GPS stations, and some them also have an accelerometer. There are 10 stations deployed in Spanish territory (5 in the Iberian peninsula, 1 in Balearic islands and 4 in North Africa Spanish places) with VSAT or Internet communications, 2 in Portugal (one of them without real time), and 3 in Morocco (2 VSAT and 1 ADSL). Additionally, 2 more stations (one in South Spain and one in Morocco) will be installed along this year. Additionally ROA has deployed a permanent real time VBB (CMG-3T: 360s) station at the Alboran Island. Due to the fact that part of the seismic activity is located at marine areas, and also because of the poor geographic azimuthal coverage at some zones provided by the land stations (specially in the SW of the San Vicente Cape area), ROA and UCM have acquired six broad band "LOBSTERN" OBS, manufactured by KUM (Kiel, Germany), conforming the OBS FOMAR pool. Three of them with CMG-40T sensor and the other with Trillium 120. These OBS were deployed along the Gibraltar strait since January to November 2014 to study the microseismicity in the Gibraltar strait area. In September 2015 FOMAR network has been deployed in SW of the San Vicente Cape for 8 months as a part of

Molecular Pathways: Targeting the CXCR4-CXCL12 Axis--Untapped Potential in the Tumor Microenvironment.

PubMed

Scala, Stefania

2015-10-01

Evidence suggests that the CXC-chemokine receptor-4 pathway plays a role in cancer cell homing and metastasis, and thus represents a potential target for cancer therapy. The homeostatic microenvironment chemokine CXCL12 binds the CXCR4 and CXCR7 receptors, activating divergent signals on multiple pathways, such as ERK1/2, p38, SAPK/JNK, AKT, mTOR, and the Bruton tyrosine kinase (BTK). An activating mutation in CXCR4 is responsible for a rare disease, WHIM syndrome (warts, hypogammaglobulinemia, infections, and myelokathexis), and dominant CXCR4 mutations have also been reported in Waldenstrom macroglobulinemia. The CXCR4-CXCL12 axis regulates the hematopoietic stem cell niche--a property that has led to the approval of the CXCR4 antagonist plerixafor (AMD3100) for mobilization of hematopoietic precursors. In preclinical models, plerixafor has shown antimetastatic potential in vivo, offering proof of concept. Other antagonists are in preclinical and clinical development. Recent evidence demonstrates that inhibiting CXCR4 signaling restores sensitivity to CTLA-4 and PD-1 checkpoint inhibitors, creating a new line for investigation. Targeting the CXCR4-CXCL12 axis thus offers the possibility of affecting CXCR4-expressing primary tumor cells, modulating the immune response, or synergizing with other targeted anticancer therapies. ©2015 American Association for Cancer Research.

[Direct and indirect ion selective electrodes methods: the differences specified through a case of Waldenström's macroglobulinemia].

PubMed

Zelmat, Mohamed Sofiane

2015-01-01

Direct and indirect ion selective electrodes (ISEs) are two methods commonly used in biochemistry laboratories in order to measure the electrolytes such as sodium. In the clinical practice, it's the sodium concentration in plasma water -measured by direct ISE- which is important to consider as it is responsible of water movements between the liquid compartments. Knowing the difference between the two methods is important because there are situations leading to conflicting results between direct and indirect ISE, especially with sodium and inappropriate therapeutic decisions could be taken if the clinician is not aware of this difference. The increase and the decrease in plasma water volume are the situations that distort the results of the indirect ISE because this method, after a dilution step, does not take into account the real percentage of plasma water of the patient in the determination of the concentrations (leading for sodium to pseudohyponatremia, pseudonormonatremia or pseudohypernatremia). In the direct ISE, the sample is not diluted and the results are correct even if the volume of plasma water is modified. This article specifies the differences between the two techniques through a case of Waldenström's macroglobulinemia and proposes a course of action to follow for both of the biologist and the clinician.

Attention, working memory, and phenomenal experience of WM content: memory levels determined by different types of top-down modulation.

PubMed

Jacob, Jane; Jacobs, Christianne; Silvanto, Juha

2015-01-01

What is the role of top-down attentional modulation in consciously accessing working memory (WM) content? In influential WM models, information can exist in different states, determined by allocation of attention; placing the original memory representation in the center of focused attention gives rise to conscious access. Here we discuss various lines of evidence indicating that such attentional modulation is not sufficient for memory content to be phenomenally experienced. We propose that, in addition to attentional modulation of the memory representation, another type of top-down modulation is required: suppression of all incoming visual information, via inhibition of early visual cortex. In this view, there are three distinct memory levels, as a function of the top-down control associated with them: (1) Nonattended, nonconscious associated with no attentional modulation; (2) attended, phenomenally nonconscious memory, associated with attentional enhancement of the actual memory trace; (3) attended, phenomenally conscious memory content, associated with enhancement of the memory trace and top-down suppression of all incoming visual input.

Innovative Soft-Sided Waste Packaging System Implementation at a Small Department of Energy Environmental Restoration/Waste Management (ER/WM) Site

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

Wolf, J.

2002-02-28

Weiss Associates (WA) performs a broad range of environmental restoration/waste management (ER/WM) activities for the U.S. Department of Energy (DOE) at the former Laboratory for Energy-Related Health Research (LEHR), University of California, Davis (UC Davis). Over the last three years, the LEHR ER/WM program transitioned from a baseline packaging system of steel, 2.7 cubic meter (3.5-cubic yard) B-25 boxes to a 7.0 cubic meter (9.1-cubic yard) soft-sided container (Lift Liner) system. The transition increased efficiencies in processing, packaging, and storage, and when combined with decreased procurement costs, achieved a $402,000 cost savings (Table I). Additional disposal costs between $128,600 andmore » $182,600 were avoided by minimizing void space. Future cost savings by the end of fiscal year 2003 are projected between $250,640 and $1,003,360.« less

Wavelength-Modulated Differential Photoacoustic Spectroscopy (WM-DPAS): Theory of a High-Sensitivity Methodology for the Detection of Early-Stage Tumors in Tissues

NASA Astrophysics Data System (ADS)

Choi, S.; Mandelis, A.; Guo, X.; Lashkari, B.; Kellnberger, S.; Ntziachristos, V.

2015-06-01

In the field of medical diagnostics, biomedical photoacoustics (PA) is a non-invasive hybrid optical-ultrasonic imaging modality. Due to the unique hybrid capability of optical and acoustic imaging, PA imaging has risen to the frontiers of medical diagnostic procedures such as human breast cancer detection. While conventional PA imaging has been mainly carried out by a high-power pulsed laser, an alternative technology, the frequency domain biophotoacoustic radar (FD-PAR) is under intensive development. It utilizes a continuous wave optical source with the laser intensity modulated by a frequency-swept waveform for acoustic wave generation. The small amplitude of the generated acoustic wave is significantly compensated by increased signal-to-noise ratio (several orders of magnitude) using matched-filter and pulse compression correlation processing in a manner similar to radar systems. The current study introduces the theory of a novel FD-PAR modality for ultra-sensitive characterization of functional information for breast cancer imaging. The newly developed theory of wavelength-modulated differential PA spectroscopy (WM-DPAS) detection has been introduced to address angiogenesis and hypoxia monitoring, two well-known benchmarks of breast tumor formation. Based on the WM-DPAS theory, this modality efficiently suppresses background absorptions and is expected to detect very small changes in total hemoglobin concentration and oxygenation levels, thereby identifying pre-malignant tumors before they are anatomically apparent. An experimental system design for the WM-DPAS is presented and preliminary single-ended laser experimental results were obtained and compared to a limiting case of the developed theoretical formalism.

[Clinical study of TCM-WM on aplastic anemia complicated with hepatitis C].

PubMed

Liu, Q C; Zheng, B R; Zhang, C L

1995-04-01

The testing kit of second generation for serum anti-HCV was used in 82 cases of aplastic anemia (AA). The results showed that positive rate was 69.4% (43/62) in the patients of AA with transfusion, this was significantly higher than that in the patients of AA without transfusion. There was no difference of anti-HCV antibody positive rate between chronic AA and acute AA (P > 0.05), incidence rate of post-transfusion hepatitis C (PTHC) in AA was 33.9% (21/62), among which the incidence rate in acute and chronic AA were 68.8% (11/16) and 21.7% (10/46) respectively (P < 0.01). The anti-HCV positive patients were divided into two groups: PTHC and non-PTHC, there was no statistical difference of their transfusion volume, hemoglobin, white blood cell between these groups. Response rate of AA was lower in anti-HCV positive patients than that in negative patients (P < 0.05). Acute, icteric PTHC was predominant in patients with AA. The patients with AA complicated with PTHC was liable to bleed and be infected. PTHC has been an important complication in patients with AA. The better response was obtained by TCM-WM therapy in the patients.

Metastatic B-cell lymphoma masquerading as infectious retinitis and vasculitis.

PubMed

Say, Emil Anthony T; Knupp, Charles L; Gertsch, Kevin R; Chavala, Sai H

2012-06-01

Intraocular lymphoma is a rare ocular malignancy that may occur in the retina or the uvea. Retina or vitreoretinal lymphoma accounts for the majority of cases and is often secondary to diffuse large B-cell lymphoma. In the present study, a 66-year-old Caucasian male with a history of Waldenstrom's macroglobulinemia with diffuse large B-cell lymphoma, presented with blurred vision in the left eye one month following cycle 4 of an R-CHOP regimen. At the time of onset, the patient was being treated for bacterial pneumonia. Visual acuity was 20/25 in his right eye (OD) and 20/30 in the left (OS). Ophthalmologic examination showed intraretinal white infiltrates associated with hemorrhage in the superotemporal midperiphery of the retina and vitritis OS. Initial diagnostic considerations included infectious (cytomegalovirus retinitis, syphilis, toxoplasmosis, tuberculosis), inflammatory (retinal vasculitis associated with autoimmune disease or hypercoagulable states) or malignant (intraocular lymphoma) diseases. The patient did not respond to intravitreal injection of foscarnet and oral valgancyclovir. Systemic work-up and aqueous fluid biopsy were inconclusive. Diagnostic vitrectomy yielded inconclusive results and the patient continued to have progressive loss of vision. A repeat diagnostic vitrectomy with retinal and subretinal biopsy confirmed large B cells consistent with metastatic B-cell lymphoma. A concomitant PET/CT scan was performed that revealed bilateral new pulmonary nodules resulting in additional chemotherapy. Our case shows the diagnostic dilemmas in patients with systemic lymphoma and the possible role of concurrent systemic restaging in patients with ocular complaints, even when in systemic remission.

Lenalidomide After Donor Bone Marrow Transplant in Treating Patients With High-Risk Hematologic Cancers

ClinicalTrials.gov

2017-09-22

Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A; Adult Acute Promyelocytic Leukemia With PML-RARA; Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-Cell Lymphoma; Alkylating Agent-Related Acute Myeloid Leukemia; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Hepatosplenic T-Cell Lymphoma; Intraocular Lymphoma; Lymphomatous Involvement of Non-Cutaneous Extranodal Site; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Post-Transplant Lymphoproliferative Disorder; Primary Cutaneous B-Cell Non-Hodgkin Lymphoma; Prolymphocytic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Recurrent Non-Hodgkin Lymphoma; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Richter Syndrome; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; T-Cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenstrom Macroglobulinemia

Least Square Fast Learning Network for modeling the combustion efficiency of a 300WM coal-fired boiler.

PubMed

Li, Guoqiang; Niu, Peifeng; Wang, Huaibao; Liu, Yongchao

2014-03-01

This paper presents a novel artificial neural network with a very fast learning speed, all of whose weights and biases are determined by the twice Least Square method, so it is called Least Square Fast Learning Network (LSFLN). In addition, there is another difference from conventional neural networks, which is that the output neurons of LSFLN not only receive the information from the hidden layer neurons, but also receive the external information itself directly from the input neurons. In order to test the validity of LSFLN, it is applied to 6 classical regression applications, and also employed to build the functional relation between the combustion efficiency and operating parameters of a 300WM coal-fired boiler. Experimental results show that, compared with other methods, LSFLN with very less hidden neurons could achieve much better regression precision and generalization ability at a much faster learning speed. Copyright © 2013 Elsevier Ltd. All rights reserved.

Ibrutinib Inhibits Platelet Integrin αIIbβ3 Outside-In Signaling and Thrombus Stability But Not Adhesion to Collagen.

PubMed

Bye, Alexander P; Unsworth, Amanda J; Vaiyapuri, Sakthivel; Stainer, Alexander R; Fry, Michael J; Gibbins, Jonathan M

2015-11-01

Ibrutinib is an irreversible Bruton tyrosine kinase inhibitor approved for treatment of Waldenstrom macroglobulinemia, chronic lymphocytic leukemia, and mantle cell lymphoma that increases the risk of bleeding among patients. Platelets from ibrutinib-treated patients exhibit deficiencies in collagen-evoked signaling in suspension; however, the significance of this observation and how it relates to bleeding risk is unclear, as platelets encounter immobile collagen in vivo. We sought to clarify the effects of ibrutinib on platelet function to better understand the mechanism underlying bleeding risk. By comparing signaling in suspension and during adhesion to immobilized ligands, we found that the collagen signaling deficiency caused by ibrutinib is milder during adhesion to immobilized collagen. We also found that platelets in whole blood treated with ibrutinib adhered to collagen under arterial shear but formed unstable thrombi, suggesting that the collagen signaling deficiency caused by ibrutinib may not be the predominant cause of bleeding in vivo. However, clot retraction and signaling evoked by platelet adhesion to immobilized fibrinogen were also inhibited by ibrutinib, indicating that integrin αIIbβ3 outside-in signaling is also effected in addition to GPVI signaling. When ibrutinib was combined with the P2Y12 inhibitor, cangrelor, thrombus formation under arterial shear was inhibited additively. These findings suggest that (1) ibrutinib causes GPVI and integrin αIIbβ3 platelet signaling deficiencies that result in formation of unstable thrombi and may contribute toward bleeding observed in vivo and (2) combining ibrutinib with P2Y12 antagonists, which also inhibit thrombus stability, may have a detrimental effect on hemostasis. © 2015 American Heart Association, Inc.

Development of the Bruton's tyrosine kinase inhibitor ibrutinib for B cell malignancies.

PubMed

Gayko, Urte; Fung, Mann; Clow, Fong; Sun, Steven; Faust, Elizabeth; Price, Samiyeh; James, Danelle; Doyle, Margaret; Bari, Samina; Zhuang, Sen Hong

2015-11-01

Ibrutinib is a first-in-class oral covalent inhibitor of Bruton's tyrosine kinase that has demonstrated clinical benefit for many patients with B cell malignancies. Positive results in initial trials led the U.S. Food and Drug Administration to grant ibrutinib three breakthrough therapy designations for mantle cell lymphoma (MCL), del17p chronic lymphocytic leukemia (CLL), and Waldenström's macroglobulinemia (WM). Ibrutinib was approved for these three cancers within 14 months of the original U.S. approval. Additionally, ibrutinib is approved for patient subsets with MCL and/or CLL in >45 other countries. Via a unique mechanism of action, ibrutinib inhibits B cell signaling pathways that regulate the survival, proliferation, adhesion, and homing of cancerous cells. This marks a paradigm shift from the conventional cytotoxic chemotherapy approach to treating B cell malignancies. Ibrutinib continues to be evaluated across a range of B cell malignancies, either as single-agent therapy or in combination with other therapies, and continues to transform the lives of these patients. © 2015 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.

Study of ADCT-301 in Patients With Relapsed or Refractory Hodgkin and Non-Hodgkin Lymphoma

ClinicalTrials.gov

2018-05-07

Hodgkin Lymphoma; Non-Hodgkin Lymphoma; Burkitt's Lymphoma; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, Marginal Zone; Waldenstrom's Macroglobulinaemia; Lymphoma,T-cell Cutaneous; Lymphoma, T-Cell, Peripheral

Cellular immune responses against CT7 (MAGE-C1) and humoral responses against other cancer-testis antigens in multiple myeloma patients

PubMed Central

Lendvai, Nikoletta; Gnjatic, Sacha; Ritter, Erika; Mangone, Michael; Austin, Wayne; Reyner, Karina; Jayabalan, David; Niesvizky, Ruben; Jagannath, Sundar; Bhardwaj, Nina; Chen-Kiang, Selina; Old, Lloyd J.

2010-01-01

The type I melanoma antigen gene (MAGE) proteins CT7 (MAGE-C1) and MAGE-A3 are commonly expressed in multiple myeloma (MM), and their expression correlates with increased plasma cell proliferation and poor clinical outcome. They belong to the cancer-testis antigen (CTAg) group of tumor-associated proteins, some of which elicit spontaneous immune responses in cancer patients. CT7 and MAGE-A3 are promising antigenic targets for therapeutic tumor vaccines in myeloma; therefore, it is critical to determine if they are immunogenic in MM patients. We analyzed cellular and humoral immune responses against CTAgs in patients with plasma cell dyscrasias: MM, monoclonal gammopathy of undetermined significance (MGUS), and Waldenström's macroglobulinemia (WM). Bone marrow lymphocytes from two of four untreated MM patients exhibited CT7-specific cellular immune responses as measured by an autologous cellular immunity assay, the first such immune response to CT7 to be reported in cancer patients. Sera from 24 patients were screened by ELISA for humoral immune responses to CTAgs. Two patients with MM demonstrated positive titers, one for MAGE-A1 and the other for SSX1. These data demonstrate that CTAgs, particularly CT7, are immunogenic in MM patients and merit further exploration as targets of immunological therapy in MM. PMID:20108890

Cellular immune responses against CT7 (MAGE-C1) and humoral responses against other cancer-testis antigens in multiple myeloma patients.

PubMed

Lendvai, Nikoletta; Gnjatic, Sacha; Ritter, Erika; Mangone, Michael; Austin, Wayne; Reyner, Karina; Jayabalan, David; Niesvizky, Ruben; Jagannath, Sundar; Bhardwaj, Nina; Chen-Kiang, Selina; Old, Lloyd J; Cho, Hearn Jay

2010-01-29

The type I melanoma antigen gene (MAGE) proteins CT7 (MAGE-C1) and MAGE-A3 are commonly expressed in multiple myeloma (MM), and their expression correlates with increased plasma cell proliferation and poor clinical outcome. They belong to the cancer-testis antigen (CTAg) group of tumor-associated proteins, some of which elicit spontaneous immune responses in cancer patients. CT7 and MAGE-A3 are promising antigenic targets for therapeutic tumor vaccines in myeloma; therefore, it is critical to determine if they are immunogenic in MM patients. We analyzed cellular and humoral immune responses against CTAgs in patients with plasma cell dyscrasias: MM, monoclonal gammopathy of undetermined significance (MGUS), and Waldenström's macroglobulinemia (WM). Bone marrow lymphocytes from two of four untreated MM patients exhibited CT7-specific cellular immune responses as measured by an autologous cellular immunity assay, the first such immune response to CT7 to be reported in cancer patients. Sera from 24 patients were screened by ELISA for humoral immune responses to CTAgs. Two patients with MM demonstrated positive titers, one for MAGE-A1 and the other for SSX1. These data demonstrate that CTAgs, particularly CT7, are immunogenic in MM patients and merit further exploration as targets of immunological therapy in MM.

Is VEGF under-expressed in Indian children with Perthes disease?

PubMed

Tiwari, V; Poudel, R R; Khan, S A; Mehra, S; Chauhan, S S; Raje, A

2018-04-01

The role of vascular endothelial growth factor (VEGF) after ischaemic necrosis of the femoral head in Legg-Calve-Perthes disease (LCPD) has not been adequately studied in humans, especially in Indian population. Therefore, we aimed to evaluate the serum levels of VEGF-A in Indian children with various stages of LCPD and compare them with those of an age- and sex-matched control group of healthy children. In this case-control study, we enrolled 42 children (below 14 years age) suffering from LCPD and 21 age- and sex-matched healthy controls. Patients were classified radiographically according to Waldenstrom's classification. Serum VEGF-A was estimated by sandwich enzyme-linked immunosorbent assay technique. The serum values were compared between the patient group and the control group, as well as between the Waldenstrom subgroups. Results were expressed as means with ranges or median with interquartile range. The mean age in the patient as well as the control group was 9 years (range 4-13 years). The median value (interquartile range) of serum VEGF-A was 162.5 pg/ml (673.75 pg/ml) in the patient group and 652 pg/ml (190.5 pg/ml) in the control group (p = 0.013). When compared between lower Waldenstrom stages (initial stage + stage of fragmentation) and higher Waldenstrom stages (re-ossification stage + stage of healing), the mean values of serum VEGF-A were 464.7 pg/ml (range 0-2211 pg/ml) and 301.1 pg/ml (range 0-1910 pg/ml), respectively (p = 0.305). VEGF is under-expressed in Indian children suffering from LCPD. As VEGF acts as a key regulator of endochondral ossification, our finding may open new therapeutic approaches to the disease. Also, serum VEGF may act as a valuable marker for the follow-up of the disease. Our study also provides baseline data about serum VEGF-A levels in Indian cohort of LCPD patients. Future multi-centre studies are warranted with a larger sample size to fully appreciate the patho-physiological changes in VEGF

21 CFR 866.5550 - Immunoglobulin (light chain specific) immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... macroglobulinemia (increased production of large immunoglobulins), and connective tissue diseases such as rheumatoid arthritis or systemic lupus erythematosus. (b) Classification. Class II (performance standards). ...

21 CFR 866.5550 - Immunoglobulin (light chain specific) immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... macroglobulinemia (increased production of large immunoglobulins), and connective tissue diseases such as rheumatoid arthritis or systemic lupus erythematosus. (b) Classification. Class II (performance standards). ...

21 CFR 866.5550 - Immunoglobulin (light chain specific) immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... macroglobulinemia (increased production of large immunoglobulins), and connective tissue diseases such as rheumatoid arthritis or systemic lupus erythematosus. (b) Classification. Class II (performance standards). ...

21 CFR 866.5550 - Immunoglobulin (light chain specific) immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... macroglobulinemia (increased production of large immunoglobulins), and connective tissue diseases such as rheumatoid arthritis or systemic lupus erythematosus. (b) Classification. Class II (performance standards). ...

21 CFR 866.5550 - Immunoglobulin (light chain specific) immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... macroglobulinemia (increased production of large immunoglobulins), and connective tissue diseases such as rheumatoid arthritis or systemic lupus erythematosus. (b) Classification. Class II (performance standards). ...

Multi-parameter observations in the Ibero-Moghrebian region: the Western Mediterranean seismic network (WM) and ROA GPS geodynamic network

NASA Astrophysics Data System (ADS)

Pazos, Antonio; Martín Davila, José; Buforn, Elisa; Gárate Pasquín, Jorge; Catalán Morollón, Manuel; Hanka, Winfried; Udías, Agustín.; Benzzeghoud, Mourad; Harnafi, Mimoun

2010-05-01

The plate boundary between Eurasia and Africa plates crosses the called "Ibero-Maghrebian" region from the San Vicente Cape (SW Portugal) to Tunisia including the South of Iberia, Alboran Sea, and northern Morocco and Algeria. In this area, the convergence, with a low rate, is accommodated over a wide and diffuse deformation zone, characterized by a significant and widespread moderate seismic activity [Buforn et al., 1995], and the occurrence of large earthquakes is separated by long time intervals. Since more than hundred years ago San Fernando Naval Observatory (ROA), in collaboration with other Institutes, has deployed different geophysical and geodetic equipment in the Southern Spain - North-western Africa area in order to study this broad deformation zone. Currently a Broad Band seismic net (Western Mediterranean, WM net) is deployed, in collaboration with other institutions, around the Gulf of Cádiz and the Alboran sea, with stations in the South of Iberia and in North Africa (at Spanish places and Morocco), together with the seismic stations a permanent geodetic GPS net is co-installed at the same sites. Also, other geophysical instruments have been installed: a Satellite Laser Ranging (SLR) station at San Fernando Observatory Headquarter, a Geomagnetic Observatory in Cádiz bay area and some meteorological stations. These networks have been recently improved with the deployment of a new submarine and on-land geophysical observatory in the Alboran island (ALBO Observatory), where a permanent GPS, a meteorological station were installed on land and a permanent submarine observatory in 50 meters depth was also deploy in last October (with a broad band seismic sensor, a 3 C accelerometer and a DPG). This work shows the present status and the future plans of these networks and some results.

AR-42 in Treating Patients With Advanced or Relapsed Multiple Myeloma, Chronic Lymphocytic Leukemia, or Lymphoma

ClinicalTrials.gov

2017-02-21

Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

Urine protein electrophoresis test

MedlinePlus

Urine protein electrophoresis; UPEP; Multiple myeloma - UPEP; Waldenström macroglobulinemia - UPEP; Amyloidosis - UPEP ... special paper and apply an electric current. The proteins move and form visible bands. These reveal the ...

PP2B and ERK1/2 regulate hyaluronan synthesis of HT168 and WM35 human melanoma cell lines.

PubMed

Katona, Éva; Juhász, Tamás; Somogyi, Csilla Szűcs; Hajdú, Tibor; Szász, Csaba; Rácz, Kálmán; Kókai, Endre; Gergely, Pál; Zákány, Róza

2016-03-01

Hyaluronan (HA) is the major glycosaminoglycan component of the extracellular matrix in either normal or malignant tissues and it may affect proliferation, motility and differentiation of various cell types. Three isoforms of plasma membrane-bound hyaluronan synthases (HAS 1, 2 and 3) secrete and simultaneously bind pericellular HA. HAS enzymes are subjects of post-translational protein phosphorylation which is believed to regulate their enzymatic activity. In this study, we investigated the HA homeostasis of normal human epidermal melanocytes, HT168 and WM35 human melanoma cell lines and melanoma metastases. HAS2 and HAS3 were detected in all the samples, while the expression of HAS1 was not detectable in any case. Malignant tissue samples and melanoma cell lines contained extra- and intracellular HA abundantly but not normal melanocytes. Applying HA as a chemoattractant facilitated the migration of melanoma cells in Boyden chamber. The amount of HA was reduced upon the inhibition of calcineurin with cyclosporine A (CsA), while the inhibition of ERK1/2 with PD098059 elevated it in both cell lines. The signals of Ser/Thr phosphoproteins at 57 kD were stronger after CsA treatment, while a markedly weaker signal was detected upon inhibition of the MAPK pathway. Our results suggest opposing effects of the two investigated enzymes on the HA homeostasis of melanoma cells. We propose that the dephosphorylation of HAS enzymes targeted by PP2B augments HA production, while their phosphorylation by the activity of MAPK pathway reduces HA synthesis. As the expression of the HA receptor RHAMM was also significantly enhanced by PD098059, the MAPK pathway exerted a complex attenuating effect on HA signalling in the investigated melanoma cells. This observation suggests that the application of MAPK-ERK pathway inhibitors requires a careful therapeutic design in melanoma treatment.

PP2B and ERK1/2 regulate hyaluronan synthesis of HT168 and WM35 human melanoma cell lines

PubMed Central

KATONA, ÉVA; JUHÁSZ, TAMÁS; SOMOGYI, CSILLA SZŰCS; HAJDÚ, TIBOR; SZÁSZ, CSABA; RÁCZ, KÁLMÁN; KÓKAI, ENDRE; GERGELY, PÁL; ZÁKÁNY, RÓZA

2016-01-01

Hyaluronan (HA) is the major glycosaminoglycan component of the extracellular matrix in either normal or malignant tissues and it may affect proliferation, motility and differentiation of various cell types. Three isoforms of plasma membrane-bound hyaluronan synthases (HAS 1, 2 and 3) secrete and simultaneously bind pericellular HA. HAS enzymes are subjects of post-translational protein phosphorylation which is believed to regulate their enzymatic activity. In this study, we investigated the HA homeostasis of normal human epidermal melanocytes, HT168 and WM35 human melanoma cell lines and melanoma metastases. HAS2 and HAS3 were detected in all the samples, while the expression of HAS1 was not detectable in any case. Malignant tissue samples and melanoma cell lines contained extra- and intracellular HA abundantly but not normal melanocytes. Applying HA as a chemoattractant facilitated the migration of melanoma cells in Boyden chamber. The amount of HA was reduced upon the inhibition of calcineurin with cyclosporine A (CsA), while the inhibition of ERK1/2 with PD098059 elevated it in both cell lines. The signals of Ser/Thr phosphoproteins at 57 kD were stronger after CsA treatment, while a markedly weaker signal was detected upon inhibition of the MAPK pathway. Our results suggest opposing effects of the two investigated enzymes on the HA homeostasis of melanoma cells. We propose that the dephosphorylation of HAS enzymes targeted by PP2B augments HA production, while their phosphorylation by the activity of MAPK pathway reduces HA synthesis. As the expression of the HA receptor RHAMM was also significantly enhanced by PD098059, the MAPK pathway exerted a complex attenuating effect on HA signalling in the investigated melanoma cells. This observation suggests that the application of MAPK-ERK pathway inhibitors requires a careful therapeutic design in melanoma treatment. PMID:26717964

Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

ClinicalTrials.gov

2017-09-08

Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Secondary Myelofibrosis; Severe Combined Immunodeficiency; Severe Congenital Neutropenia; Shwachman-Diamond Syndrome; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Waldenstrom Macroglobulinemia; Wiskott-Aldrich Syndrome

Clinical and Pathologic Studies in Non-Hodgkin's Lymphoma Patients Receiving Antibody Treatment

ClinicalTrials.gov

2011-05-31

Lymphoma, Non-Hodgkin; Lymphomas: Non-Hodgkin; Lymphomas: Non-Hodgkin Cutaneous Lymphoma; Lymphomas: Non-Hodgkin Diffuse Large B-Cell; Lymphomas: Non-Hodgkin Follicular / Indolent B-Cell; Lymphomas: Non-Hodgkin Mantle Cell; Lymphomas: Non-Hodgkin Marginal Zone; Lymphomas: Non-Hodgkin Peripheral T-Cell; Lymphomas: Non-Hodgkin Waldenstr Macroglobulinemia

Study of BKM120 & Rituximab in Patients With Relapsed or Refractory Indolent B-Cell Lymphoma

ClinicalTrials.gov

2017-09-12

Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

Radiolabeled Monoclonal Antibody Plus Rituximab With and Without Filgrastim and Interleukin-11 in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

ClinicalTrials.gov

2015-11-04

Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

Genetically Engineered Lymphocytes, Cyclophosphamide, and Aldesleukin in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma or Indolent B-Cell Non-Hodgkin Lymphoma

ClinicalTrials.gov

2014-08-04

B-cell Chronic Lymphocytic Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

Arsenic Trioxide in Treating Patients With Relapsed or Refractory Lymphoma or Leukemia

ClinicalTrials.gov

2013-01-31

Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Prolymphocytic Leukemia; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

Understanding the role of mind wandering in stress-related working memory impairments.

PubMed

Banks, Jonathan B; Boals, Adriel

2017-08-01

Mind wandering has been identified as a possible cause for stress-related working memory (WM) task impairments following laboratory stressors. The current study attempted to induce mind wandering regarding negative, positive, or neutral events using an expressive writing task and examined the impact on WM task performance. We examined the role of mind wandering in understanding the impact of life stress on WM. Additionally, we explored the role of thought suppression on the relationship between mind wandering and WM. One hundred and fifty participants completed WM measures before (Time 1) and after (Time 2) the writing manipulation. The writing manipulation did not alter mind wandering or WM task performance. Time 1 WM predicted mind wandering during the Time 2 WM task, which subsequently predicted poorer Time 2 WM task performance. The impact of daily life stress on WM was mediated by mind wandering. Trait levels of thought suppression moderated the impact of mind wandering on WM. Specifically, higher levels of suppression resulted in stronger negative impact of mind wandering on WM task performance. Findings are discussed in terms of the impact of mind wandering on WM task performance.

Working Memory, Language Skills, and Autism Symptomatology

PubMed Central

Schuh, Jillian M.; Eigsti, Inge-Marie

2012-01-01

While many studies have reported working memory (WM) impairments in autism spectrum disorders, others do not. Sample characteristics, WM domain, and task complexity likely contribute to these discrepancies. Although deficits in visuospatial WM have been more consistently documented, there is much controversy regarding verbal WM in autism. The goal of the current study was to explore visuospatial and verbal WM in a well-controlled sample of children with high-functioning autism (HFA) and typical development. Individuals ages 9–17 with HFA (n = 18) and typical development (n = 18), were carefully matched on gender, age, IQ, and language, and were administered a series of standardized visuospatial and verbal WM tasks. The HFA group displayed significant impairment across WM domains. No differences in performance were noted across WM tasks for either the HFA or typically developing groups. Over and above nonverbal cognition, WM abilities accounted for significant variance in language skills and symptom severity. The current study suggests broad WM limitations in HFA. We further suggest that deficits in verbal WM are observed in more complex tasks, as well as in simpler tasks, such as phonological WM. Increased task complexity and linguistic demands may influence WM abilities. PMID:25379222

Bortezomib and Fludarabine With or Without Rituximab in Treating Patients With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia

ClinicalTrials.gov

2013-09-27

Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hematopoietic/Lymphoid Cancer; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

Donor Umbilical Cord Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

ClinicalTrials.gov

2015-12-18

Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Secondary Myelofibrosis; Splenic Marginal Zone Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; Waldenstrom Macroglobulinemia

High-Dose Busulfan and High-Dose Cyclophosphamide Followed By Donor Bone Marrow Transplant in Treating Patients With Leukemia, Myelodysplastic Syndrome, Multiple Myeloma, or Recurrent Hodgkin or Non-Hodgkin Lymphoma

ClinicalTrials.gov

2010-08-05

Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Secondary Myelodysplastic Syndromes; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

Memory processes of flight situation awareness: interactive roles of working memory capacity, long-term working memory, and expertise.

PubMed

Sohn, Young Woo; Doane, Stephanie M

2004-01-01

This research examined the role of working memory (WM) capacity and long-term working memory (LT-WM) in flight situation awareness (SA). We developed spatial and verbal measures of WM capacity and LT-WM skill and then determined the ability of these measures to predict pilot performance on SA tasks. Although both spatial measures of WM capacity and LT-WM skills were important predictors of SA performance, their importance varied as a function of pilot expertise. Spatial WM capacity was most predictive of SA performance for novices, whereas spatial LT-WM skill based on configurations of control flight elements (attitude and power) was most predictive for experts. Furthermore, evidence for an interactive role of WM and LT-WM mechanisms was indicated. Actual or potential applications of this research include cognitive analysis of pilot expertise and aviation training.

Parietal structure and function explain human variation in working memory biases of visual attention.

PubMed

Soto, David; Rotshtein, Pia; Kanai, Ryota

2014-04-01

Recent research indicates that human attention appears inadvertently biased by items that match the contents of working memory (WM). WM-biases can lead to attentional costs when the memory content matches goal-irrelevant items and to attentional benefits when it matches the sought target. Here we used functional and structural MRI data to determine the neural basis of human variation in WM biases. We asked whether human variation in WM-benefits and WM-costs merely reflects the process of attentional capture by the contents of WM or whether variation in WM biases may be associated with distinct forms of cognitive control over internal WM signals based on selection goals. Human ability to use WM contents to facilitate selection was positively correlated with gray matter volume in the left superior posterior parietal cortex (PPC), while the ability to overcome interference by WM-matching distracters was associated with the left inferior PPC in the anterior IPS. Functional activity in the left PPC, measured by functional MRI, also predicted the magnitude of WM-costs on selection. Both structure and function of left PPC mediate the expression of WM biases in human visual attention. Copyright © 2013 Elsevier Inc. All rights reserved.

Does Working Memory Impact Functional Outcomes in Individuals With ADHD: A Qualitative and Comprehensive Literature Review.

PubMed

Fried, Ronna; Abrams, Jessica; Hall, Anna; Feinberg, Leah; Pope, Amanda; Biederman, Joseph

2017-09-01

Working Memory (WM) is a domain of executive functioning often impaired in individuals with ADHD. Although assumed to cause difficulties across functioning, the scope of impairments from WM deficits in ADHD has not been investigated. The aim of this study was to examine outcomes associated with WM deficits in ADHD. We conducted a search of the scientific literature on WM deficits, and Freedom From Distractibility (FFD), in ADHD using PubMed and PsycInfo databases. The final sample included 11 controlled studies of WM/FFD deficits in ADHD with operationalized assessment of outcomes in academic, social, and emotional areas. WM assessment was divided into auditory-verbal memory (AVM) and spatial-visual memory (SWM). Seven studies examined WM deficits in academic functioning, eight studies assessed WM deficits in social functioning, and three assessed WM deficits in psychopathology. The majority of the literature suggests that WM deficits affect primarily academic functioning.

Investigation of Crimean-Congo Hemorrhagic Fever and Hemorrhagic Fever with Renal Syndrome in Greece

DTIC Science & Technology

1988-10-12

patients with rheumatoid arthritis (20 samples), with macroglobulinemia (3 samples), with pyrexia of unknown origin (41 samples) and from healthy...precomatose or comatose and 10 had renal failure with oliguria or anuria, requiring hemodialysis . The indication for dialysis in these patients was serum...against Hantaan vi- us and Crimean-Congo Hemorrhagic Fever respectively. Two hundred and two blood samples were aken from patients with disease resembling

Motor system contributions to verbal and non-verbal working memory.

PubMed

Liao, Diana A; Kronemer, Sharif I; Yau, Jeffrey M; Desmond, John E; Marvel, Cherie L

2014-01-01

Working memory (WM) involves the ability to maintain and manipulate information held in mind. Neuroimaging studies have shown that secondary motor areas activate during WM for verbal content (e.g., words or letters), in the absence of primary motor area activation. This activation pattern may reflect an inner speech mechanism supporting online phonological rehearsal. Here, we examined the causal relationship between motor system activity and WM processing by using transcranial magnetic stimulation (TMS) to manipulate motor system activity during WM rehearsal. We tested WM performance for verbalizable (words and pseudowords) and non-verbalizable (Chinese characters) visual information. We predicted that disruption of motor circuits would specifically affect WM processing of verbalizable information. We found that TMS targeting motor cortex slowed response times (RTs) on verbal WM trials with high (pseudoword) vs. low (real word) phonological load. However, non-verbal WM trials were also significantly slowed with motor TMS. WM performance was unaffected by sham stimulation or TMS over visual cortex (VC). Self-reported use of motor strategy predicted the degree of motor stimulation disruption on WM performance. These results provide evidence of the motor system's contributions to verbal and non-verbal WM processing. We speculate that the motor system supports WM by creating motor traces consistent with the type of information being rehearsed during maintenance.

Working memory operates over the same representations as attention

PubMed Central

Xie, Jiushu; Xia, Tiansheng; Mo, Lei

2017-01-01

A recent study observed a working memory (WM) Stroop effect with a magnitude equivalent to that of the classic Stroop effect, indicating that WM operates over the same representations as attention. However, more research is needed to examine this proposal. One unanswered question is whether the WM Stroop effect occurs when the WM item and the perceptual task do not have an overlapping response set. We addressed this question in Experiment 1 by conducting an attentional word-color task and a WM word-color task. The results showed that a WM Stroop effect also occurred in that condition, as a word that only indirectly evoked a color representation could interfere with the color judgement in both the attentional task and WM task. In Experiment 2, we used a classic Simon task and a WM Simon task to examine whether holding visuo-spatial information rather than verbal information in WM could interfere with perceptual judgment as well. We observed a WM Simon effect of equivalent magnitude to that of the classic Simon effect. The well-known stimulus-response compatibility effect also existed in the WM domain. The two experiments together demonstrated that WM operates over the same representations as attention, which sheds new light on the hypothesis that working memory is internally directed attention. PMID:28604840

Working memory, worry, and algebraic ability.

PubMed

Trezise, Kelly; Reeve, Robert A

2014-05-01

Math anxiety (MA)-working memory (WM) relationships have typically been examined in the context of arithmetic problem solving, and little research has examined the relationship in other math domains (e.g., algebra). Moreover, researchers have tended to examine MA/worry separate from math problem solving activities and have used general WM tasks rather than domain-relevant WM measures. Furthermore, it seems to have been assumed that MA affects all areas of math. It is possible, however, that MA is restricted to particular math domains. To examine these issues, the current research assessed claims about the impact on algebraic problem solving of differences in WM and algebraic worry. A sample of 80 14-year-old female students completed algebraic worry, algebraic WM, algebraic problem solving, nonverbal IQ, and general math ability tasks. Latent profile analysis of worry and WM measures identified four performance profiles (subgroups) that differed in worry level and WM capacity. Consistent with expectations, subgroup membership was associated with algebraic problem solving performance: high WM/low worry>moderate WM/low worry=moderate WM/high worry>low WM/high worry. Findings are discussed in terms of the conceptual relationship between emotion and cognition in mathematics and implications for the MA-WM-performance relationship. Copyright © 2013 Elsevier Inc. All rights reserved.

Emotional working memory in patients with major depressive disorder.

PubMed

Li, Mi; Feng, Lei; Liu, Xingwang; Zhang, Ming; Fu, Bingbing; Wang, Gang; Lu, Shengfu; Zhong, Ning; Hu, Bin

2018-05-01

Objective This study was performed to examine the working memory (WM) encoding and retrieval abilities in patients with major depressive disorder (MDD) and determine whether a mood-congruent memory effect is present. Methods The modified Sternberg WM paradigm with positive, negative, and neutral emotional pictures was used to investigate the WM abilities of 26 patients with MDD and 26 healthy controls (HCs). Results No significant difference in picture WM was found between the MDD and HC groups; however, the accuracy of picture position WM was significantly lower and the response time was significantly longer in the MDD than HC group, regardless of the picture or position WM. Additionally, in the MDD group, the accuracy of negative picture/position WM was significantly higher than that of positive picture/position WM. Conclusions These results suggest that in patients with MDD, spatial WM impairment was more severe than object WM. In addition, these patients' WM retrieval was impaired, resulting in a decrease in WM retrieval ability, which may be an important cause of the slow thought in patients with MDD. Moreover, patients with depression have a mood-congruent memory effect, which may be an important factor in the occurrence and maintenance of depression.

Working memory operates over the same representations as attention.

PubMed

Chen, Ke; Ye, Yanyan; Xie, Jiushu; Xia, Tiansheng; Mo, Lei

2017-01-01

A recent study observed a working memory (WM) Stroop effect with a magnitude equivalent to that of the classic Stroop effect, indicating that WM operates over the same representations as attention. However, more research is needed to examine this proposal. One unanswered question is whether the WM Stroop effect occurs when the WM item and the perceptual task do not have an overlapping response set. We addressed this question in Experiment 1 by conducting an attentional word-color task and a WM word-color task. The results showed that a WM Stroop effect also occurred in that condition, as a word that only indirectly evoked a color representation could interfere with the color judgement in both the attentional task and WM task. In Experiment 2, we used a classic Simon task and a WM Simon task to examine whether holding visuo-spatial information rather than verbal information in WM could interfere with perceptual judgment as well. We observed a WM Simon effect of equivalent magnitude to that of the classic Simon effect. The well-known stimulus-response compatibility effect also existed in the WM domain. The two experiments together demonstrated that WM operates over the same representations as attention, which sheds new light on the hypothesis that working memory is internally directed attention.

Mediating Effects of Working Memory in the Relation Between Rapid Automatized Naming and Chinese Reading Comprehension.

PubMed

Weng, Xiaoqian; Li, Guangze; Li, Rongbao

2016-08-01

This study examined the mediating role of working memory (WM) in the relation between rapid automatized naming (RAN) and Chinese reading comprehension. Three tasks assessing differentially visual and verbal components of WM were programmed by E-prime 2.0. Data collected from 55 Chinese college students were analyzed using correlations and hierarchical regression methods to determine the connection among RAN, reading comprehension, and WM components. Results showed that WM played a significant mediating role in the RAN-reading relation and that auditory WM made stronger contributions than visual WM. Taking into account of the multi-component nature of WM and the specificity of Chinese reading processing, this study discussed the mediating powers of the WM components, particularly auditory WM, further clarifying the possible components involved in the RAN-reading relation and thus providing some insight into the complicated Chinese reading process.

A preliminary study of the effects of working memory training on brain function.

PubMed

Stevens, Michael C; Gaynor, Alexandra; Bessette, Katie L; Pearlson, Godfrey D

2016-06-01

Working memory (WM) training improves WM ability in Attention-Deficit/Hyperactivity Disorder (ADHD), but its efficacy for non-cognitive ADHD impairments ADHD has been sharply debated. The purpose of this preliminary study was to characterize WM training-related changes in ADHD brain function and see if they were linked to clinical improvement. We examined 18 adolescents diagnosed with DSM-IV Combined-subtype ADHD before and after 25 sessions of WM training using a frequently employed approach (Cogmed™) using a nonverbal Sternberg WM fMRI task, neuropsychological tests, and participant- and parent-reports of ADHD symptom severity and associated functional impairment. Whole brain SPM8 analyses identified ADHD activation deficits compared to 18 non-ADHD control participants, then tested whether impaired ADHD frontoparietal brain activation would increase following WM training. Post hoc tests examined the relationships between neural changes and neurocognitive or clinical improvements. As predicted, WM training increased WM performance, ADHD clinical functioning, and WM-related ADHD brain activity in several frontal, parietal and temporal lobe regions. Increased left inferior frontal sulcus region activity was seen in all Encoding, Maintenance, and Retrieval Sternberg task phases. ADHD symptom severity improvements were most often positively correlated with activation gains in brain regions known to be engaged for WM-related executive processing; improvement of different symptom types had different neural correlates. The responsiveness of both amodal WM frontoparietal circuits and executive process-specific WM brain regions was altered by WM training. The latter might represent a promising, relatively unexplored treatment target for researchers seeking to optimize clinical response in ongoing ADHD WM training development efforts.

A parieto-medial temporal pathway for the strategic control over working memory biases in human visual attention.

PubMed

Soto, David; Greene, Ciara M; Kiyonaga, Anastasia; Rosenthal, Clive R; Egner, Tobias

2012-12-05

The contents of working memory (WM) can both aid and disrupt the goal-directed allocation of visual attention. WM benefits attention when its contents overlap with goal-relevant stimulus features, but WM leads attention astray when its contents match features of currently irrelevant stimuli. Recent behavioral data have documented that WM biases of attention may be subject to strategic cognitive control processes whereby subjects are able to either enhance or inhibit the influence of WM contents on attention. However, the neural mechanisms supporting cognitive control over WM biases on attention are presently unknown. Here, we characterize these mechanisms by combining human functional magnetic resonance imaging with a task that independently manipulates the relationship between WM cues and attention targets during visual search (with WM contents matching either search targets or distracters), as well as the predictability of this relationship (100 vs 50% predictability) to assess participants' ability to strategically enhance or inhibit WM biases on attention when WM contents reliably matched targets or distracter stimuli, respectively. We show that cues signaling predictable (> unpredictable) WM-attention relations reliably enhanced search performance, and that this strategic modulation of the interplay between WM contents and visual attention was mediated by a neuroanatomical network involving the posterior parietal cortex, the posterior cingulate, and medial temporal lobe structures, with responses in the hippocampus proper correlating with behavioral measures of strategic control of WM biases. Thus, we delineate a novel parieto-medial temporal pathway implementing cognitive control over WM biases to optimize goal-directed selection.

Working memory capacity of biological movements predicts empathy traits.

PubMed

Gao, Zaifeng; Ye, Tian; Shen, Mowei; Perry, Anat

2016-04-01

Working memory (WM) and empathy are core issues in cognitive and social science, respectively. However, no study so far has explored the relationship between these two constructs. Considering that empathy takes place based on the others' observed experiences, which requires extracting the observed dynamic scene into WM and forming a coherent representation, we hypothesized that a sub-type of WM capacity, i.e., WM for biological movements (BM), should predict one's empathy level. Therefore, WM capacity was measured for three distinct types of stimuli in a change detection task: BM of human beings (BM; Experiment 1), movements of rectangles (Experiment 2), and static colors (Experiment 3). The first two stimuli were dynamic and shared one WM buffer which differed from the WM buffer for colors; yet only the BM conveyed social information. We found that BM-WM capacity was positively correlated with both cognitive and emotional empathy, with no such correlations for WM capacity of movements of rectangles or of colors. Thus, the current study is the first to provide evidence linking a specific buffer of WM and empathy, and highlights the necessity for considering different WM capacities in future social and clinical research.

Aging of Cerebral White Matter

PubMed Central

Liu, Huan; Yang, Yuanyuan; Xia, Yuguo; Zhu, Wen; Leak, Rehana K.; Wei, Zhishuo; Wang, Jianyi; Hu, Xiaoming

2016-01-01

White matter (WM) occupies a large volume of the human cerebrum and is mainly composed of myelinated axons and myelin-producing glial cells. The myelinated axons within WM are the structural foundation for efficient neurotransmission between cortical and subcortical areas. Similar to neuron-enriched gray matter areas, WM undergoes a series of changes during the process of aging. WM malfunction can induce serious neurobehavioral and cognitive impairments. Thus, age-related changes in WM may contribute to the functional decline observed in the elderly. In addition, aged WM becomes more susceptible to neurological disorders, such as stroke, traumatic brain injury (TBI), and neurodegeneration. In this review, we summarize the structural and functional alterations of WM in natural aging and speculate on the underlying mechanisms. We also discuss how age-related WM changes influence the progression of various brain disorders, including ischemic and hemorrhagic stroke, TBI, Alzheimer’s disease, and Parkinson’s disease. Although the physiology of WM is still poorly understood relative to gray matter, WM is a rational therapeutic target for a number of neurological and psychiatric conditions. PMID:27865980

Working memory load modulates the neural response to other's pain: Evidence from an ERP study.

PubMed

Cui, Fang; Zhu, Xiangru; Luo, Yuejia; Cheng, Jiaping

2017-03-22

The present study investigated the time course of processing other's pain under different conditions of working memory (WM) load. Event-related potentials (ERPs) were recorded while the participants held two digits (low WM load) or six digits (high WM load) in WM and viewed pictures that showed others who were in painful or non-painful situations. Robust WM-load×Picture interactions were found for the N2 and LPP components. In the high WM-load condition, painful pictures elicited significantly larger amplitudes than non-painful pictures. In the low WM load condition, the difference between the painful and non-painful pictures was not significant. These ERP results indicate that WM load can influence both the early automatic N2 component and late cognitive LPP component. Compared with high WM load, low WM load reduced affective arousal and emotional sharing in response to other's pain and weakened the cognitive evaluation of task irrelevant stimuli. These findings are explained from the load theory perspective. Copyright © 2017 Elsevier B.V. All rights reserved.

A Comparison of Laboratory and Clinical Working Memory Tests and Their Prediction of Fluid Intelligence

PubMed Central

Shelton, Jill T.; Elliott, Emily M.; Hill, B. D.; Calamia, Matthew R.; Gouvier, Wm. Drew

2010-01-01

The working memory (WM) construct is conceptualized similarly across domains of psychology, yet the methods used to measure WM function vary widely. The present study examined the relationship between WM measures used in the laboratory and those used in applied settings. A large sample of undergraduates completed three laboratory-based WM measures (operation span, listening span, and n-back), as well as the WM subtests from the Wechsler Adult Intelligence Scale-III and the Wechsler Memory Scale-III. Performance on all of the WM subtests of the clinical batteries shared positive correlations with the lab measures; however, the Arithmetic and Spatial Span subtests shared lower correlations than the other WM tests. Factor analyses revealed that a factor comprising scores from the three lab WM measures and the clinical subtest, Letter-Number Sequencing (LNS), provided the best measurement of WM. Additionally, a latent variable approach was taken using fluid intelligence as a criterion construct to further discriminate between the WM tests. The results revealed that the lab measures, along with the LNS task, were the best predictors of fluid abilities. PMID:20161647

Motor system contributions to verbal and non-verbal working memory

PubMed Central

Liao, Diana A.; Kronemer, Sharif I.; Yau, Jeffrey M.; Desmond, John E.; Marvel, Cherie L.

2014-01-01

Working memory (WM) involves the ability to maintain and manipulate information held in mind. Neuroimaging studies have shown that secondary motor areas activate during WM for verbal content (e.g., words or letters), in the absence of primary motor area activation. This activation pattern may reflect an inner speech mechanism supporting online phonological rehearsal. Here, we examined the causal relationship between motor system activity and WM processing by using transcranial magnetic stimulation (TMS) to manipulate motor system activity during WM rehearsal. We tested WM performance for verbalizable (words and pseudowords) and non-verbalizable (Chinese characters) visual information. We predicted that disruption of motor circuits would specifically affect WM processing of verbalizable information. We found that TMS targeting motor cortex slowed response times (RTs) on verbal WM trials with high (pseudoword) vs. low (real word) phonological load. However, non-verbal WM trials were also significantly slowed with motor TMS. WM performance was unaffected by sham stimulation or TMS over visual cortex (VC). Self-reported use of motor strategy predicted the degree of motor stimulation disruption on WM performance. These results provide evidence of the motor system’s contributions to verbal and non-verbal WM processing. We speculate that the motor system supports WM by creating motor traces consistent with the type of information being rehearsed during maintenance. PMID:25309402

Effects of solar radiation on endurance exercise capacity in a hot environment.

PubMed

Otani, Hidenori; Kaya, Mitsuharu; Tamaki, Akira; Watson, Phillip; Maughan, Ronald J

2016-04-01

The present study investigated the effects of variations in solar radiation on endurance exercise capacity and thermoregulatory responses in a hot environment. Eight male volunteers performed four cycle exercise trials at 70 % maximum oxygen uptake until exhaustion in an environmental chamber maintained at 30 °C and 50 % relative humidity. Volunteers were tested under four solar radiation conditions: 800, 500, 250 and 0 W/m(2). Exercise time to exhaustion was less on the 800 W/m(2) trial (23 ± 4 min) than on all the other trials (500 W/m(2) 30 ± 7 min; P < 0.05, 250 W/m(2) 43 ± 10 min; P < 0.001, 0 W/m(2) 46 ± 10 min; P < 0.001), and on the 500 W/m(2) trial than the 250 W/m(2) (P < 0.05) and 0 W/m(2) (P < 0.01) trials. There were no differences in core (rectal) temperature, total sweat loss, heart rate, skin blood flow, cutaneous vascular conductance and percentage changes in plasma volume between trials (P > 0.05). Mean skin temperature was higher on the 800 W/m(2) trial than the 250 and 0 W/m(2) trials (P < 0.05), and on the 500 W/m(2) trial than the 0 W/m(2) trial (P < 0.05). The core-to-skin temperature gradient was narrower on the 800 W/m(2) trial than the 250 and 0 W/m(2) trials (P < 0.05). The present study demonstrates that endurance exercise capacity in a hot environment falls progressively as solar radiation increases.

Cognitive control over working memory biases of selection.

PubMed

Kiyonaga, Anastasia; Egner, Tobias; Soto, David

2012-08-01

Across many studies, researchers have found that representations in working memory (WM) can guide visual attention toward items that match the features of the WM contents. While some researchers have contended that this occurs involuntarily, others have suggested that the impact of WM contents on attention can be strategically controlled. Here, we varied the probability that WM items would coincide with either targets or distractors in a visual search task to examine (1) whether participants could intentionally enhance or inhibit the influence of WM items on attention and (2) whether cognitive control over WM biases would also affect access to the memory contents in a surprise recognition test. We found visual search to be faster when the WM item coincided with the search target, and this effect was enhanced when the memory item reliably predicted the location of the target. Conversely, visual search was slowed when the memory item coincided with a search distractor, and this effect was diminished, but not abolished, when the memory item was reliably associated with distractors. This strategic dampening of the influence of WM items on attention came at a price to memory, however, as participants were slowest to perform WM recognition tests on blocks in which the WM contents were consistently invalid. These results document that attentional capture by WM contents is partly, but not fully, malleable by top-down control, which appears to adjust the state of the WM contents to optimize search behavior. These data illustrate the role of cognitive control in modulating the strength of WM biases of selection, and they support a tight coupling between WM and attention.

The strategy and motivational influences on the beneficial effect of neurostimulation: a tDCS and fNIRS study

PubMed Central

Jones, Kevin T.; Gözenman, Filiz; Berryhill, Marian E.

2014-01-01

Working memory (WM) capacity falls along a spectrum with some people demonstrating higher and others lower WM capacity. Efforts to improve WM include applying transcranial direct current stimulation (tDCS), in which small amounts of current modulate the activity of underlying neurons and enhance cognitive function. However, not everyone benefits equally from a given tDCS protocol. Recent findings revealed tDCS-related WM benefits for individuals with higher working memory (WM) capacity. Here, we test two hypotheses regarding those with low WM capacity to see if they too would benefit under more optimal conditions. We tested whether supplying a WM strategy (Experiment 1) or providing greater extrinsic motivation through incentives (Experiment 2) would restore tDCS benefit to the low WM capacity group. We also employed functional near infrared spectroscopy to monitor tDCS-induced changes in neural activity. Experiment 1 demonstrated that supplying a WM strategy improved the high WM capacity participants’ accuracy and the amount of oxygenated blood levels following anodal tDCS, but it did not restore tDCS-linked WM benefits to the low WM capacity group. Experiment 2 demonstrated that financial motivation enhanced performance in both low and high WM capacity groups, especially after anodal tDCS. Here, only the low WM capacity participants showed a generalized increase in oxygenated blood flow across both low and high motivation conditions. These results indicate that ensuring that participants’ incentives are high may expand cognitive benefits associated with tDCS. This finding is relevant for translational work using tDCS in clinical populations, in which motivation can be a concern. PMID:25462798

A preliminary study of the effects of working memory training on brain function in Attention-Deficit/Hyperactivity Disorder

PubMed Central

Stevens, Michael C.; Gaynor, Alexandra; Bessette, Katie L.; Pearlson, Godfrey D.

2015-01-01

Working memory (WM) training improves WM ability in Attention-Deficit/Hyperactivity Disorder (ADHD), but its efficacy for non-cognitive ADHD impairments ADHD has been sharply debated. The purpose of this preliminary study was to characterize WM training-related changes in ADHD brain function and see if they were linked to clinical improvement. We examined 18 adolescents diagnosed with DSM-IV Combined-subtype ADHD before and after 25 sessions of WM training using a frequently employed approach (CogmedTM) using a nonverbal Sternberg WM fMRI task, neuropsychological tests, and participant- and parent-reports of ADHD symptom severity and associated functional impairment. Whole brain SPM8 analyses identified ADHD activation deficits compared to 18 non-ADHD control participants, then tested whether impaired ADHD frontoparietal brain activation would increase following WM training. Post hoc tests examined the relationships between neural changes and neurocognitive or clinical improvements. As predicted, WM training increased WM performance, ADHD clinical functioning, and WM-related ADHD brain activity in several frontal, parietal and temporal lobe regions. Increased left inferior frontal sulcus region activity was seen in all Encoding, Maintenance, and Retrieval Sternberg task phases. ADHD symptom severity improvements were most often positively correlated with activation gains in brain regions known to be engaged for WM-related executive processing; improvement of different symptom types had different neural correlates. The responsiveness of both amodal WM frontoparietal circuits and executive process-specific WM brain regions was altered by WM training. The latter might represent a promising, relatively unexplored treatment target for researchers seeking to optimize clinical response in ongoing ADHD WM training development efforts. PMID:26138580

Photodegradation of organophosphorus pesticides in honey medium.

PubMed

Yuan, Zhimin; Yao, Jun; Liu, Haijun; Han, Jun; Trebše, Polonca

2014-10-01

Honey can be polluted due to environmental pollution and misuse of beekeeping practices. In the present study, photodegradation experiments of organophosphorus pesticides (coumaphos, methyl parathion and fenitrothion) in honey medium were conducted using Atlas Suntest simulator CPS+ as a sunlight producer. Photodegradation experiments were conducted under three different intensities as 250W/m(2), 500W/m(2) and 750W/m(2) to evaluate the impact of sunlight intensity on removal of OPs in honey medium. Significant decreases of three OPs' concentrations were observed. Coumaphos showed the highest degradability, reaching a degradation percentage of 90 percent within 15min. After 1h irradiation, residual percentages of coumaphos were 6.62 percent for 250W/m(2), 3.48 percent for 500W/m(2) and 2.98 percent for 750W/m(2), respectively. Methyl parathion and fenitrothion also could be removed through photodegradation efficiently. After 1h irradiation, the residual percentages of methyl parathion and fenitrothion under 750W/m(2) sunlight irradiation were 26.89 percent and 16.70 percent, respectively. Intensity of sunlight showed a positive impact on removal of OPs in honey medium. The higher intensity, the lower residual percentage. Photodegradation of three OPs fitted well with pseudo-first order kinetics. Half-lives calculated from pseudo-first order kinetics were 17.61min (250W/m(2)), 16.67min (500W/m(2)) and 17.58min (750W/m(2)) for coumaphos, 57.62min (250W/m(2)), 34.13min (500W/m(2)) and 31.69min (750W/m(2)) for methyl parathion and 144.70min (250W/m(2)), 95.47min (500W/m(2)) and 22.57min (750W/m(2)) for fenitrothion, respectively. Most of the three OPs could dissipate in a short time under sunlight irradiation. Photodegradation could be accepted as an appropriate method for the removal of OPs in honey medium. Copyright © 2014 Elsevier Inc. All rights reserved.

Implicit working memory.

PubMed

Hassin, Ran R; Bargh, John A; Engell, Andrew D; McCulloch, Kathleen C

2009-09-01

Working Memory (WM) plays a crucial role in many high-level cognitive processes (e.g., reasoning, decision making, goal pursuit and cognitive control). The prevalent view holds that active components of WM are predominantly intentional and conscious. This conception is oftentimes expressed explicitly, but it is best reflected in the nature of major WM tasks: All of them are blatantly explicit. We developed two new WM paradigms that allow for an examination of the role of conscious awareness in WM. Results from five studies show that WM can operate unintentionally and outside of conscious awareness, thus suggesting that the current view should be expanded to include implicit WM.

Independent operation of implicit working memory under cognitive load.

PubMed

Ji, Eunhee; Lee, Kyung Min; Kim, Min-Shik

2017-10-01

Implicit working memory (WM) has been known to operate non-consciously and unintentionally. The current study investigated whether implicit WM is a discrete mechanism from explicit WM in terms of cognitive resource. To induce cognitive resource competition, we used a conjunction search task (Experiment 1) and imposed spatial WM load (Experiment 2a and 2b). Each trial was composed of a set of five consecutive search displays. The location of the first four displays appeared as per pre-determined patterns, but the fifth display could follow the same pattern or not. If implicit WM can extract the moving pattern of stimuli, response times for the fifth target would be faster when it followed the pattern compared to when it did not. Our results showed implicit WM can operate when participants are searching for the conjunction target and even while maintaining spatial WM information. These results suggest that implicit WM is independent from explicit spatial WM. Copyright © 2017. Published by Elsevier Inc.

Reduced contribution of executive functions in impaired working memory performance in mild traumatic brain injury patients.

PubMed

Kumar, Sanjay; Rao, Shobini L; Chandramouli, Bangalore A; Pillai, Shibu

2013-08-01

Mild traumatic brain injury (MTBI) is associated with often selective impairment of both working memory (WM) and the executive functions (EFs). Research indicates that one of the commonest deficits present in MTBI patients falls in the domain of WM. We aimed to investigate the role of EFs in WM impairment following MTBI. Performance on the tests of EFs and the verbal and visuo-spatial WM of 30 consecutive MTBI patients were compared with age/education/IQ matched 30 normal healthy control participants. Correlation between EFs and WM was studied separately for the MTBI and the control group. The MTBI and control group were tested on a range of EF tests and WM. The MTBI group was demonstrated impairment on verbal and visuo-spatial WM and category fluency tests only. Furthermore, the MTBI group had fewer significant correlations between the WM and EFs (5 out of 54 possible correlations) than in the control group (13 out of 54 possible correlations). We suggest that MTBI may lead to WM deficits as the contribution of executive processes to support the WM is diminished following MTBI. Such an understanding of the poor WM performance in MTBI patients will be helpful when planning appropriate strategies for cognitive rehabilitation. Copyright © 2013 Elsevier B.V. All rights reserved.

The contribution of working memory to divided attention.

PubMed

Santangelo, Valerio; Macaluso, Emiliano

2013-01-01

Previous studies have indicated that increasing working memory (WM) load can affect the attentional selection of signals originating from one object/location. Here we assessed whether WM load affects also the selection of multiple objects/locations (divided attention). Participants monitored either two object-categories (vs. one category; object-based divided attention) or two locations (vs. one location; space-based divided attention) while maintaining in WM either a variable number of objects (object-based WM load) or locations (space-based WM load). Behavioural results showed that WM load affected attentional performance irrespective of divided or focused attention. However, fMRI results showed that the activity associated with object-based divided attention increased linearly with increasing object-based WM load in the left and right intraparietal sulcus (IPS); while, in the same areas, activity associated with space-based divided attention was not affected by any type of WM load. These findings support the hypothesis that WM contributes to the maintenance of resource-demanding attentional sets in a domain-specific manner. Moreover, the dissociable impact of WM load on performance and brain activity suggests that increased IPS activation reflects a recruitment of additional, domain-specific processing resources that enable dual-task performance under conditions of high WM load and high attentional demand. Copyright © 2011 Wiley Periodicals, Inc.

Cross-Modal Decoding of Neural Patterns Associated with Working Memory: Evidence for Attention-Based Accounts of Working Memory

PubMed Central

Majerus, Steve; Cowan, Nelson; Péters, Frédéric; Van Calster, Laurens; Phillips, Christophe; Schrouff, Jessica

2016-01-01

Recent studies suggest common neural substrates involved in verbal and visual working memory (WM), interpreted as reflecting shared attention-based, short-term retention mechanisms. We used a machine-learning approach to determine more directly the extent to which common neural patterns characterize retention in verbal WM and visual WM. Verbal WM was assessed via a standard delayed probe recognition task for letter sequences of variable length. Visual WM was assessed via a visual array WM task involving the maintenance of variable amounts of visual information in the focus of attention. We trained a classifier to distinguish neural activation patterns associated with high- and low-visual WM load and tested the ability of this classifier to predict verbal WM load (high–low) from their associated neural activation patterns, and vice versa. We observed significant between-task prediction of load effects during WM maintenance, in posterior parietal and superior frontal regions of the dorsal attention network; in contrast, between-task prediction in sensory processing cortices was restricted to the encoding stage. Furthermore, between-task prediction of load effects was strongest in those participants presenting the highest capacity for the visual WM task. This study provides novel evidence for common, attention-based neural patterns supporting verbal and visual WM. PMID:25146374

Training working memory in older adults: Is there an advantage of using strategies?

PubMed

Borella, Erika; Carretti, Barbara; Sciore, Roberta; Capotosto, Emanuela; Taconnat, Laurence; Cornoldi, Cesare; De Beni, Rossana

2017-03-01

The purpose of the present study was to test the efficacy of a working memory (WM) training in elderly people, and to compare the effects of a WM training based on an adaptive procedure with one combining the same procedure with the use of a strategy, based on the construction of visual mental images. Eighteen older adults received training with a WM task (the WM group), another 18 received the same WM training and were also taught to use a visual imagery strategy (the WM + Strategy group), and another 18 served as active controls. Training-related gains in the WM (criterion) task and transfer effects on measures of verbal and visuospatial WM, short-term memory (STM), processing speed, and reasoning were considered. Training gains and transfer effects were also assessed after 6 months. After the training, both the trained groups performed better than the control group in the WM criterion task, and maintained these gains 6 months later; they also showed immediate transfer effects on processing speed. The two trained groups also outperformed the control group in the long term in the WM tasks, in one of the STM tasks (backward span task), and in the processing speed measure. Long-term large effect sizes were found for all the tasks involving memory processes in the WM + Strategy group, but only for the processing speed task in the WM group. Findings are discussed in terms of the benefits and limits of teaching older people a strategy in combination with an adaptive WM training. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

A single-base deletion in soybean flavonol synthase gene is associated with magenta flower color.

PubMed

Takahashi, Ryoji; Githiri, Stephen M; Hatayama, Kouta; Dubouzet, Emilyn G; Shimada, Norimoto; Aoki, Toshio; Ayabe, Shin-ichi; Iwashina, Tsukasa; Toda, Kyoko; Matsumura, Hisakazu

2007-01-01

The Wm locus of soybean [Glycine max (L.) Merr.] controls flower color. Dominant Wm and recessive wm allele of the locus produce purple and magenta flower, respectively. A putative full-length cDNA of flavonol synthase (FLS), gmfls1 was isolated by 5' RACE and end-to-end PCR from a cultivar Harosoy with purple flower (WmWm). Sequence analysis revealed that gmfls1 consisted of 1,208 nucleotides encoding 334 amino acids. It had 59-72% homology with FLS proteins of other plant species. Conserved dioxygenase domains A and B were found in the deduced polypeptide. Sequence comparison between Harosoy and Harosoy-wm (magenta flower mutant of Harosoy; wmwm) revealed that they differed by a single G deletion in the coding region of Harosoy-wm. The deletion changed the subsequent reading frame resulting in a truncated polypeptide consisting of 37 amino acids that lacked the dioxygenase domains A and B. Extracts of E. coli cells expressing gmfls1 of Harosoy catalyzed the formation of quercetin from dihydroquercetin, whereas cell extracts expressing gmfls1 of Harosoy-wm had no FLS activity. Genomic Southern analysis suggested the existence of three to four copies of the FLS gene in the soybean genome. CAPS analysis was performed to detect the single-base deletion. Harosoy and Clark (WmWm) exhibited longer fragments, while Harosoy-wm had shorter fragments due to the single-base deletion. The CAPS marker co-segregated with genotypes at Wm locus in a F(2) population segregating for the locus. Linkage mapping using SSR markers revealed that the Wm and gmfls1 were mapped at similar position in the molecular linkage group F. The above results strongly suggest that gmfls1 represents the Wm gene and that the single-base deletion may be responsible for magenta flower color.

Axial and radial diffusivity in preterm infants who have diffuse white matter changes on magnetic resonance imaging at term-equivalent age.

PubMed

Counsell, Serena J; Shen, Yuji; Boardman, James P; Larkman, David J; Kapellou, Olga; Ward, Philip; Allsop, Joanna M; Cowan, Frances M; Hajnal, Joseph V; Edwards, A David; Rutherford, Mary A

2006-02-01

Diffuse excessive high signal intensity (DEHSI) is observed in the majority of preterm infants at term-equivalent age on conventional MRI, and diffusion-weighted imaging has shown that apparent diffusion coefficient values are elevated in the white matter (WM) in DEHSI. Our aim was to obtain diffusion tensor imaging on preterm infants at term-equivalent age and term control infants to test the hypothesis that radial diffusivity was significantly different in the WM in preterm infants with DEHSI compared with both preterm infants with normal-appearing WM on conventional MRI and term control infants. Diffusion tensor imaging was obtained on 38 preterm infants at term-equivalent age and 8 term control infants. Values for axial (lambda1) and radial [(lambda2 + lambda3)/2] diffusivity were calculated in regions of interest positioned in the central WM at the level of the centrum semiovale, frontal WM, posterior periventricular WM, occipital WM, anterior and posterior portions of the posterior limb of the internal capsule, and the genu and splenium of the corpus callosum. Radial diffusivity was elevated significantly in the posterior portion of the posterior limb of the internal capsule and the splenium of the corpus callosum, and both axial and radial diffusivity were elevated significantly in the WM at the level of the centrum semiovale, the frontal WM, the periventricular WM, and the occipital WM in preterm infants with DEHSI compared with preterm infants with normal-appearing WM and term control infants. There was no significant difference between term control infants and preterm infants with normal-appearing WM in any region studied. These findings suggest that DEHSI represents an oligodendrocyte and/or axonal abnormality that is widespread throughout the cerebral WM.

Resource-sharing between internal maintenance and external selection modulates attentional capture by working memory content.

PubMed

Kiyonaga, Anastasia; Egner, Tobias

2014-01-01

It is unclear why and under what circumstances working memory (WM) and attention interact. Here, we apply the logic of the time-based resource-sharing (TBRS) model of WM (e.g., Barrouillet et al., 2004) to explore the mixed findings of a separate, but related, literature that studies the guidance of visual attention by WM contents. Specifically, we hypothesize that the linkage between WM representations and visual attention is governed by a time-shared cognitive resource that alternately refreshes internal (WM) and selects external (visual attention) information. If this were the case, WM content should guide visual attention (involuntarily), but only when there is time for it to be refreshed in an internal focus of attention. To provide an initial test for this hypothesis, we examined whether the amount of unoccupied time during a WM delay could impact the magnitude of attentional capture by WM contents. Participants were presented with a series of visual search trials while they maintained a WM cue for a delayed-recognition test. WM cues could coincide with the search target, a distracter, or neither. We varied both the number of searches to be performed, and the amount of available time to perform them. Slowing of visual search by a WM matching distracter-and facilitation by a matching target-were curtailed when the delay was filled with fast-paced (refreshing-preventing) search trials, as was subsequent memory probe accuracy. WM content may, therefore, only capture visual attention when it can be refreshed, suggesting that internal (WM) and external attention demands reciprocally impact one another because they share a limited resource. The TBRS rationale can thus be applied in a novel context to explain why WM contents capture attention, and under what conditions that effect should be observed.

Resource-sharing between internal maintenance and external selection modulates attentional capture by working memory content

PubMed Central

Kiyonaga, Anastasia; Egner, Tobias

2014-01-01

It is unclear why and under what circumstances working memory (WM) and attention interact. Here, we apply the logic of the time-based resource-sharing (TBRS) model of WM (e.g., Barrouillet et al., 2004) to explore the mixed findings of a separate, but related, literature that studies the guidance of visual attention by WM contents. Specifically, we hypothesize that the linkage between WM representations and visual attention is governed by a time-shared cognitive resource that alternately refreshes internal (WM) and selects external (visual attention) information. If this were the case, WM content should guide visual attention (involuntarily), but only when there is time for it to be refreshed in an internal focus of attention. To provide an initial test for this hypothesis, we examined whether the amount of unoccupied time during a WM delay could impact the magnitude of attentional capture by WM contents. Participants were presented with a series of visual search trials while they maintained a WM cue for a delayed-recognition test. WM cues could coincide with the search target, a distracter, or neither. We varied both the number of searches to be performed, and the amount of available time to perform them. Slowing of visual search by a WM matching distracter—and facilitation by a matching target—were curtailed when the delay was filled with fast-paced (refreshing-preventing) search trials, as was subsequent memory probe accuracy. WM content may, therefore, only capture visual attention when it can be refreshed, suggesting that internal (WM) and external attention demands reciprocally impact one another because they share a limited resource. The TBRS rationale can thus be applied in a novel context to explain why WM contents capture attention, and under what conditions that effect should be observed. PMID:25221499

Working Memory Encoding and False Memory in Schizophrenia and Bipolar Disorder in a Spatial Delayed Response Task

PubMed Central

Mayer, Jutta S.; Park, Sohee

2014-01-01

Working memory (WM) impairment is a core feature of schizophrenia, but the contributions of different WM components are not yet specified. Here, we investigated the potential role of inefficient encoding in reduced WM performance in patients with schizophrenia (PSZ). Twenty-eight PSZ, 16 patients with bipolar disorder (PBP), 16 unaffected and unmedicated relatives of PSZ (REL), and 29 demographically matched healthy controls (HC) performed a spatial delayed response task with either low or high WM demands. The demands on attentional selection were also manipulated by presenting distractor stimuli during encoding in some of the trials. After each trial, participants rated their level of response confidence. This allowed us to analyze different types of WM responses. WM was severely impaired in PSZ compared to HC; this reduction was mainly due to an increase in the amount of false memory responses (incorrect responses that were given with high confidence) rather than an increase in the amount of incorrect and not-confident responses. Although PBP showed WM impairments, they did not have increased false memory errors. In contrast, reduced WM in REL was also accompanied by an increase in false memory errors. The presentation of distractors led to a decline in WM performance, which was comparable across groups indicating that attentional selection was intact in PSZ. These findings suggest that inefficient WM encoding is responsible for impaired WM in schizophrenia and point to differential mechanisms underlying WM impairments in PSZ and PBP. PMID:22708888

Normative shifts of cortical mechanisms of encoding contribute to adult age differences in visual-spatial working memory.

PubMed

Störmer, Viola S; Li, Shu-Chen; Heekeren, Hauke R; Lindenberger, Ulman

2013-06-01

The capacity of visual-spatial working memory (WM) declines from early to late adulthood. Recent attempts at identifying neural correlates of WM capacity decline have focused on the maintenance phase of WM. Here, we investigate neural mechanisms during the encoding phase as another potential mechanism contributing to adult age differences in WM capacity. We used electroencephalography to track neural activity during encoding and maintenance on a millisecond timescale in 35 younger and 35 older adults performing a visual-spatial WM task. As predicted, we observed pronounced age differences in ERP indicators of WM encoding: Younger adults showed attentional selection during item encoding (N2pc component), but this selection mechanism was greatly attenuated in older adults. Conversely, older adults showed more pronounced signs of early perceptual stimulus processing (N1 component) than younger adults. The amplitude modulation of the N1 component predicted WM capacity in older adults, whereas the attentional amplitude modulation of the N2pc component predicted WM capacity in younger adults. Our findings suggest that adult age differences in mechanisms of WM encoding contribute to adult age differences in limits of visual-spatial WM capacity. Copyright © 2013 Elsevier Inc. All rights reserved.

Aging of cerebral white matter.

PubMed

Liu, Huan; Yang, Yuanyuan; Xia, Yuguo; Zhu, Wen; Leak, Rehana K; Wei, Zhishuo; Wang, Jianyi; Hu, Xiaoming

2017-03-01

White matter (WM) occupies a large volume of the human cerebrum and is mainly composed of myelinated axons and myelin-producing glial cells. The myelinated axons within WM are the structural foundation for efficient neurotransmission between cortical and subcortical areas. Similar to neuron-enriched gray matter areas, WM undergoes a series of changes during the process of aging. WM malfunction can induce serious neurobehavioral and cognitive impairments. Thus, age-related changes in WM may contribute to the functional decline observed in the elderly. In addition, aged WM becomes more susceptible to neurological disorders, such as stroke, traumatic brain injury (TBI), and neurodegeneration. In this review, we summarize the structural and functional alterations of WM in natural aging and speculate on the underlying mechanisms. We also discuss how age-related WM changes influence the progression of various brain disorders, including ischemic and hemorrhagic stroke, TBI, Alzheimer's disease, and Parkinson's disease. Although the physiology of WM is still poorly understood relative to gray matter, WM is a rational therapeutic target for a number of neurological and psychiatric conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

The Importance of Encoding-Related Neural Dynamics in the Prediction of Inter-Individual Differences in Verbal Working Memory Performance

PubMed Central

Majerus, Steve; Salmon, Eric; Attout, Lucie

2013-01-01

Studies of brain-behaviour interactions in the field of working memory (WM) have associated WM success with activation of a fronto-parietal network during the maintenance stage, and this mainly for visuo-spatial WM. Using an inter-individual differences approach, we demonstrate here the equal importance of neural dynamics during the encoding stage, and this in the context of verbal WM tasks which are characterized by encoding phases of long duration and sustained attentional demands. Participants encoded and maintained 5-word lists, half of them containing an unexpected word intended to disturb WM encoding and associated task-related attention processes. We observed that inter-individual differences in WM performance for lists containing disturbing stimuli were related to activation levels in a region previously associated with task-related attentional processing, the left intraparietal sulcus (IPS), and this during stimulus encoding but not maintenance; functional connectivity strength between the left IPS and lateral prefrontal cortex (PFC) further predicted WM performance. This study highlights the critical role, during WM encoding, of neural substrates involved in task-related attentional processes for predicting inter-individual differences in verbal WM performance, and, more generally, provides support for attention-based models of WM. PMID:23874935

The persistence of thought: evidence for a role of working memory in the maintenance of task-unrelated thinking.

PubMed

Levinson, Daniel B; Smallwood, Jonathan; Davidson, Richard J

2012-04-01

Tasks that tax working memory (WM) have consistently been found to decrease mind wandering. These findings may indicate that maintenance of mind wandering requires WM resources, such that mind wandering cannot persist when WM resources are being consumed by a task. An alternative explanation for these findings, however, is that mind wandering persists without the support of WM but is nonetheless decreased during any demanding task because good task performance requires that attention be restricted from task-unrelated thought (TUT). The present study tested these two competing theories by investigating whether individuals with greater WM resources mind-wander more during an undemanding task, as would be predicted only by the theory that WM supports TUT. We found that individuals with higher WM capacity reported more TUT in undemanding tasks, which suggests that WM enables the maintenance of mind wandering.

Diffusion tensor imaging assessment of brain white matter maturation during the first postnatal year.

PubMed

Provenzale, James M; Liang, Luxia; DeLong, David; White, Leonard E

2007-08-01

The purpose of this study was to use diffusion-weighted and diffusion tensor imaging to investigate the status of cerebral white matter (WM) at term gestation and the rate of WM maturation throughout the first year of life in healthy infants. Fifty-three children (35 boys) ranging in age from 1.5 weeks premature to 51.5 weeks (mean age, 22.9 weeks) underwent conventional MRI, diffusion imaging in three directions (b = 1,000 s/mm2), and diffusion tensor imaging with gradient encoding in six directions, all on a 1.5-T MRI system. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in three deep WM structures (posterior limb of internal capsule, genu, and splenium of corpus callosum) and two peripheral WM regions (associational WM underlying prefrontal and posterior parietal cortex) with a standard region of interest (44 +/- 4 cm2). ADC and FA were expressed as a percentage of corresponding values measured in a group of healthy young adults. Mean ADC and FA values for deep and peripheral WM were plotted against gestational age normalized to term. The data were fit best with a broken-line linear regression model with a breakpoint at 100 days. ADC and FA values at term were estimated according to the intercept of the initial linear period (before day 100) with day 0. The slope of the linear fits was used to determine the rate of WM maturation in both the early and the late (after day 100) periods. Multivariate analysis of variance tests were used to compare deep and peripheral WM structures at term and at representative early and late ages (days 30 and 200) and to compare rates of ADC and FA maturation in early and late periods within the first year. At term, peripheral WM was less mature than deep WM according to results of extrapolation of ADC and FA values in the first 100 days of life to day 0 (p < 0.01). Mean ADC and FA value (percentage of mean adult value) for peripheral WM were 1.32 x 10(-3) mm2/s (163%) and 0.16 (32%), respectively

Analysis of White Matter Damage in Patients with Multiple Sclerosis via a Novel In Vivo MR Method for Measuring Myelin, Axons, and G-Ratio.

PubMed

Hagiwara, A; Hori, M; Yokoyama, K; Nakazawa, M; Ueda, R; Horita, M; Andica, C; Abe, O; Aoki, S

2017-10-01

Myelin and axon volume fractions can now be estimated via MR imaging in vivo, as can the g-ratio, which equals the ratio of the inner to the outer diameter of a nerve fiber. The purpose of this study was to evaluate WM damage in patients with MS via this novel MR imaging technique. Twenty patients with relapsing-remitting MS with a combined total of 149 chronic plaques were analyzed. Myelin volume fraction was calculated based on simultaneous tissue relaxometry. Intracellular and CSF compartment volume fractions were quantified via neurite orientation dispersion and density imaging. Axon volume fraction and g-ratio were calculated by combining these measurements. Myelin and axon volume fractions and g-ratio were measured in plaques, periplaque WM, and normal-appearing WM. All metrics differed significantly across the 3 groups ( P < .001, except P = .027 for g-ratio between periplaque WM and normal-appearing WM). Those in plaques differed most from those in normal-appearing WM. The percentage changes in plaque and periplaque WM metrics relative to normal-appearing WM were significantly larger in absolute value for myelin volume fraction than for axon volume fraction and g-ratio ( P < .001, except P = .033 in periplaque WM relative to normal-appearing WM for comparison between myelin and axon volume fraction). In this in vivo MR imaging study, the myelin of WM was more damaged than axons in plaques and periplaque WM of patients with MS. Myelin and axon volume fractions and g-ratio may potentially be useful for evaluating WM damage in patients with MS. © 2017 by American Journal of Neuroradiology.

Investigating the influence of working memory capacity when driving behavior is combined with cognitive load: An LCT study of young novice drivers.

PubMed

Ross, Veerle; Jongen, Ellen M M; Wang, Weixin; Brijs, Tom; Brijs, Kris; Ruiter, Robert A C; Wets, Geert

2014-01-01

Distracted driving has received increasing attention in the literature due to potential adverse safety outcomes. An often posed solution to alleviate distraction while driving is hands-free technology. Interference by distraction can occur however at the sensory input (e.g., visual) level, but also at the cognitive level where hands-free technology induces working memory (WM) load. Active maintenance of goal-directed behavior in the presence of distraction depends on WM capacity (i.e., Lavie's Load theory) which implies that people with higher WM capacity are less susceptible to distractor interference. This study investigated the interaction between verbal WM load and WM capacity on driving performance to determine whether individuals with higher WM capacity were less affected by verbal WM load, leading to a smaller deterioration of driving performance. Driving performance of 46 young novice drivers (17-25 years-old) was measured with the lane change task (LCT). Participants drove without and with verbal WM load of increasing complexity (auditory-verbal response N-back task). Both visuospatial and verbal WM capacity were investigated. Dependent measures were mean deviation in the lane change path (MDEV), lane change initiation (LCI) and percentage of correct lane changes (PCL). Driving experience was included as a covariate. Performance on each dependent measure deteriorated with increasing verbal WM load. Meanwhile, higher WM capacity related to better LCT performance. Finally, for LCI and PCL, participants with higher verbal WM capacity were influenced less by verbal WM load. These findings entail that completely eliminating distraction is necessary to minimize crash risks among young novice drivers. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cross-Modal Decoding of Neural Patterns Associated with Working Memory: Evidence for Attention-Based Accounts of Working Memory.

PubMed

Majerus, Steve; Cowan, Nelson; Péters, Frédéric; Van Calster, Laurens; Phillips, Christophe; Schrouff, Jessica

2016-01-01

Recent studies suggest common neural substrates involved in verbal and visual working memory (WM), interpreted as reflecting shared attention-based, short-term retention mechanisms. We used a machine-learning approach to determine more directly the extent to which common neural patterns characterize retention in verbal WM and visual WM. Verbal WM was assessed via a standard delayed probe recognition task for letter sequences of variable length. Visual WM was assessed via a visual array WM task involving the maintenance of variable amounts of visual information in the focus of attention. We trained a classifier to distinguish neural activation patterns associated with high- and low-visual WM load and tested the ability of this classifier to predict verbal WM load (high-low) from their associated neural activation patterns, and vice versa. We observed significant between-task prediction of load effects during WM maintenance, in posterior parietal and superior frontal regions of the dorsal attention network; in contrast, between-task prediction in sensory processing cortices was restricted to the encoding stage. Furthermore, between-task prediction of load effects was strongest in those participants presenting the highest capacity for the visual WM task. This study provides novel evidence for common, attention-based neural patterns supporting verbal and visual WM. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Normal white matter microstructure in women long-term recovered from anorexia nervosa: A diffusion tensor imaging study.

PubMed

Bang, Lasse; Rø, Øyvind; Endestad, Tor

2018-01-01

Studies point to white matter (WM) microstructure alterations in both adolescent and adult patients with anorexia nervosa (AN). These include reduced fractional anisotropy in several WM fiber tracts, suggesting reduced WM integrity. The extent to which these alterations are reversible with recovery from AN is unclear. There is a paucity of research investigating the presence of WM microstructure alterations in recovered AN patients, and results are inconsistent. This study aimed to investigate the presence of WM microstructure alterations in women long-term recovered from AN. Twenty-one adult women who were recovered from AN for at least 1 year were compared to 21 adult comparison women. Participants were recruited via user-organizations for eating disorders, local advertisements, and online forums. Diffusion tensor imaging was used to compare WM microstructure between groups. Correlations between WM microstructure and clinical characteristics were also explored. There were no statistically significant between-group differences in WM microstructure. These null findings remained when employing liberal alpha level thresholds. Furthermore, there were no statistically significant correlations between WM microstructure and clinical characteristics. Our findings showed normal WM microstructure in long-term recovered patients, indicating the alterations observed during the acute phase are reversible. Given the paucity of research and inconsistent findings, future studies are warranted to determine the presence of WM microstructure alterations following recovery from AN. © 2017 Wiley Periodicals, Inc.

Timing and gender determine if acute pain impairs working memory performance.

PubMed

Hood, Anna; Pulvers, Kim; Spady, Thomas J

2013-11-01

The effects of pain on memory are complex, and little is known about the vulnerability of working memory (WM) performance when individuals complete a WM test while concurrently experiencing pain. Here, we subjected 78 healthy nonsmoking participants to either acute pain or a control condition while we administered a WM test. In this context, we also tested WM 20 minutes after pain in order to determine if timing of pain affected WM performance, and assessed objective and subjective measures of pain. We hypothesized that pain would impair WM performance during pain. Further, women's WM performance would be impaired more than men. Importantly, there was an interaction between gender and condition, with women exposed to pain experiencing impairments during but not after the cold pressor task. Our data imply that timing and gender are critically important in whether acute pain is costly to WM performance. Our findings have interesting clinical, professional, and educational implications, and understanding the influence of pain could help to improve the interpretation of WM tests in these diverse settings. Results of this study support the growing body of work that attests to the detrimental effect of pain on WM performance. Further, this study provides new evidence that concurrently experiencing cold pressor pain impairs WM in regularly menstruating women and women taking a contraceptive. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

Neural evidence of the strategic choice between working memory and episodic memory in prospective remembering.

PubMed

Lewis-Peacock, Jarrod A; Cohen, Jonathan D; Norman, Kenneth A

2016-12-01

Theories of prospective memory (PM) posit that it can be subserved either by working memory (WM) or episodic memory (EM). Testing and refining these multiprocess theories of PM requires a way of tracking participants' reliance on WM versus EM. Here we use multi-voxel pattern analysis (MVPA) to derive a trial-by-trial measure of WM use in prospective memory. We manipulated strategy demands by varying the degree of proactive interference (which impairs EM) and the memory load required to perform the secondary task (which impairs WM). For the condition in which participants were pushed to rely more on WM, our MVPA measures showed 1) greater WM use and 2) a trial-by-trial correlation between WM use and PM behavior. Finally, we also showed that MVPA measures of WM use are not redundant with other behavioral measures: in the condition in which participants were pushed more to rely on WM, using neural and behavioral measures together led to better prediction of PM accuracy than either measure on its own. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Working memory management and predicted utility

PubMed Central

Chatham, Christopher H.; Badre, David

2013-01-01

Given the limited capacity of working memory (WM), its resources should be allocated strategically. One strategy is filtering, whereby access to WM is granted preferentially to items with the greatest utility. However, reallocation of WM resources might be required if the utility of maintained information subsequently declines. Here, we present behavioral, computational, and neuroimaging evidence that human participants track changes in the predicted utility of information in WM. First, participants demonstrated behavioral costs when the utility of items already maintained in WM declined and resources should be reallocated. An adapted Q-learning model indicated that these costs scaled with the historical utility of individual items. Finally, model-based neuroimaging demonstrated that frontal cortex tracked the utility of items to be maintained in WM, whereas ventral striatum tracked changes in the utility of items maintained in WM to the degree that these items are no longer useful. Our findings suggest that frontostriatal mechanisms track the utility of information in WM, and that these dynamics may predict delays in the removal of information from WM. PMID:23882196

Dissociating effects of stimulus identity and load on working memory attentional guidance: lengthening encoding time eliminates the effect of load but not identity.

PubMed

Tsvetanov, Kamen A; Arvanitis, Theodoros N; Humphreys, Glyn W

2012-01-01

Effects of the identity and load of items in working memory (WM) on visual attention were examined. With a short interval between the WM item and a subsequent search task, there were effects of both load (slowed overall reaction times, RTs, in a WM condition relative to a mere repetition baseline) and identity (search RTs were affected by re-presentation of the item in WM in the search display). As the time to encode the initial display increased, the effects of load decreased while the effect of identity remained. The data indicate that the identity of stimuli in WM can affect the subsequent deployment of attention even when time is allowed for consolidation of the stimuli in WM, and that the WM effects are not causally related to the presence of cognitive load. The results are consistent with the identity of stimuli in WM modulating attention post the memory consolidation stage.

Familiarity enhances visual working memory for faces.

PubMed

Jackson, Margaret C; Raymond, Jane E

2008-06-01

Although it is intuitive that familiarity with complex visual objects should aid their preservation in visual working memory (WM), empirical evidence for this is lacking. This study used a conventional change-detection procedure to assess visual WM for unfamiliar and famous faces in healthy adults. Across experiments, faces were upright or inverted and a low- or high-load concurrent verbal WM task was administered to suppress contribution from verbal WM. Even with a high verbal memory load, visual WM performance was significantly better and capacity estimated as significantly greater for famous versus unfamiliar faces. Face inversion abolished this effect. Thus, neither strategic, explicit support from verbal WM nor low-level feature processing easily accounts for the observed benefit of high familiarity for visual WM. These results demonstrate that storage of items in visual WM can be enhanced if robust visual representations of them already exist in long-term memory.

Verbal and visuospatial working memory as predictors of children's reading ability.

PubMed

Pham, Andy V; Hasson, Ramzi M

2014-08-01

Children with reading difficulties often demonstrate weaknesses in working memory (WM). This research study explored the relation between two WM systems (verbal and visuospatial WM) and reading ability in a sample of school-aged children with a wide range of reading skills. Children (N = 157), ages 9-12, were administered measures of short-term memory, verbal WM, visuospatial WM, and reading measures (e.g., reading fluency and comprehension). Although results indicated that verbal WM was a stronger predictor in reading fluency and comprehension, visuospatial WM also significantly predicted reading skills, but provided more unique variance in reading comprehension than reading fluency. These findings suggest that visuospatial WM may play a significant role in higher level reading processes, particularly in reading comprehension, than previously thought. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Prospective memory and working memory: asymmetrical effects during frontal lobe TMS stimulation.

PubMed

Basso, Demis; Ferrari, Marcella; Palladino, Paola

2010-09-01

The role of working memory (WM) for the realization of an intended action (prospective memory, PM) has been debated in recent neuropsychological literature. The present study aimed to assess whether WM and PM share resources or are, alternatively, two distinct mechanisms. A verbal task was used, which manipulated the cognitive demand of both WM and PM dimensions on an event-based prospective task. Transcranial magnetic stimulation (TMS) was also employed to clarify the causal contribution of frontal areas previously related to WM, to the PM process. The prospective task required the participant to respond whenever a word appeared which had been presented before the beginning of the task. Two ongoing tasks were administered: an updating WM task (in two conditions of medium and high WM demands) and a lexical decision task (representing a low WM demand). In the first two experiments, higher PM demand affected WM only at higher loads, but the PM load effect was independent of WM, showing asymmetrical behavioural effects. In the third experiment, single pulse TMS was applied to left and right dorsolateral prefrontal cortices. When applied to the experimental sites, stimulation increased error rates of the PM task, while the effect was only marginal in the WM task. The effect was bilateral, since there was no difference between left and right stimulation sites. These findings demonstrated, from both behavioural and neurofunctional perspectives, that WM and PM processes are not based on the same memory system, but PM may require WM resources at high demand. Copyright 2010 Elsevier Ltd. All rights reserved.

What part of working memory is not working in ADHD? Short-term memory, the central executive and effects of reinforcement.

PubMed

Dovis, Sebastiaan; Van der Oord, Saskia; Wiers, Reinout W; Prins, Pier J M

2013-08-01

Deficits in Working Memory (WM) are related to symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD). In children with ADHD visuospatial WM is most impaired. WM is composed of Short-Term Memory (STM) and a Central Executive (CE). Therefore, deficits in either or both STM and the CE may account for WM impairments in children with ADHD. WM-component studies investigating this find deficits in both STM and the CE. However, recent studies show that not only cognitive deficits, but also motivational deficits give rise to the aberrant WM performance of children with ADHD. To date, the influence of these motivational deficits on the components of WM has not been investigated. This study examined the effects of a standard (feedback-only) and a high level of reinforcement (feedback + 10 euros) on the visuospatial WM-, visuospatial STM-, and the CE performance of 86 children with ADHD and 62 typically-developing controls. With standard reinforcement the STM, CE, and WM performance of children with ADHD was worse than that of controls. High reinforcement improved STM and WM performance more in children with ADHD than in controls, but was unable to normalize their performance. High reinforcement did not appear to improve the CE-related performance of children with ADHD and controls. Motivational deficits have a detrimental effect on both the visuospatial WM performance and the STM performance of children with ADHD. Aside from motivational deficits, both the visuospatial STM and the CE of children with ADHD are impaired, and give rise to their deficits in visuospatial WM.

Unilateral prefrontal direct current stimulation effects are modulated by working memory load and gender.

PubMed

Meiron, Oded; Lavidor, Michal

2013-05-01

Recent studies revealed that anodal transcranial direct current stimulation (tDCS) to the left dorsolateral prefrontal cortex (DLPFC) may improve verbal working memory (WM) performance in humans. In the present study, we evaluated executive attention, which is the core of WM capacity, considered to be significantly involved in tasks that require active maintenance of memory representations in interference-rich conditions, and is highly dependent on DLPFC function. We investigated verbal WM accuracy using a WM task that is highly sensitive to executive attention function. We were interested in how verbal WM accuracy may be affected by WM load, unilateral DLPFC stimulation, and gender, as previous studies showed gender-dependent brain activation during verbal WM tasks. We utilized a modified verbal n-Back task hypothesized to increase demands on executive attention. We examined "online" WM performance while participants received transcranial direct current stimulation (tDCS), and implicit learning performance in a post-stimulation WM task. Significant lateralized "online" stimulation effects were found only in the highest WM load condition revealing that males benefit from left DLPFC stimulation, while females benefit from right DLPFC stimulation. High WM load performance in the left DLPFC stimulation was significantly related to post-stimulation recall performance. Our findings support the idea that lateralized stimulation effects in high verbal WM load may be gender-dependent. Further, our post-stimulation results support the idea that increased left hemisphere activity may be important for encoding verbal information into episodic memory as well as for facilitating retrieval of context-specific targets from semantic memory. Copyright © 2013 Elsevier Inc. All rights reserved.

Guideline for the diagnosis, treatment and response criteria for Bing-Neel syndrome

PubMed Central

Minnema, Monique C.; Kimby, Eva; D’Sa, Shirley; Fornecker, Luc-Matthieu; Poulain, Stéphanie; Snijders, Tom J.; Kastritis, Efstathios; Kremer, Stéphane; Fitsiori, Aikaterini; Simon, Laurence; Davi, Frédéric; Lunn, Michael; Castillo, Jorge J.; Patterson, Christopher J.; Le Garff-Tavernier, Magali; Costopoulos, Myrto; Leblond, Véronique; Kersten, Marie-José; Dimopoulos, Meletios A.; Treon, Steven P.

2017-01-01

Bing Neel syndrome is a rare disease manifestation of Waldenström’s macroglobulinemia that results from infiltration of the central nervous system by malignant lymphoplasmacytic cells. In this guideline we describe the clinical symptoms, as well as the appropriate laboratory and radiological studies, that can aid in the diagnosis. The presentation of Bing Neel syndrome may be very diverse, and includes headaches, cognitive deficits, paresis, and psychiatric symptoms. The syndrome can present in patients with known Waldenström’s macroglobulinemia, even in the absence of systemic progression, but also in previously undiagnosed patients. Diagnostic work-up should include cerebral spinal fluid analysis with multiparameter flow cytometry to establish B-cell clonality, protein electrophoresis and immunofixation for the detection and classification of a monoclonal protein as well as molecular diagnostic testing for immunoglobulin gene rearrangement and mutated MYD88. MRI of the brain and spinal cord is also essential. The second challenge is to expand our knowledge of prognosis and treatment outcome. Prospective clinical trials on Bing Neel syndrome patients that employ uniform treatment along with appropriate laboratory cerebral spinal fluid assessments and standardized MRI protocols will be invaluable, constituting a significant step forward in delineating treatment outcome for this intriguing disease manifestation. PMID:27758817

White matter and schizophrenia: A meta-analysis of voxel-based morphometry and diffusion tensor imaging studies.

PubMed

Vitolo, Enrico; Tatu, Mona Karina; Pignolo, Claudia; Cauda, Franco; Costa, Tommaso; Ando', Agata; Zennaro, Alessandro

2017-12-30

Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) are the most implemented methodologies to detect alterations of both gray and white matter (WM). However, the role of WM in mental disorders is still not well defined. We aimed at clarifying the role of WM disruption in schizophrenia and at identifying the most frequently involved brain networks. A systematic literature search was conducted to identify VBM and DTI studies focusing on WM alterations in patients with schizophrenia compared to control subjects. We selected studies reporting the coordinates of WM reductions and we performed the anatomical likelihood estimation (ALE). Moreover, we labeled the WM bundles with an anatomical atlas and compared VBM and DTI ALE-scores of each significant WM tract. A total of 59 studies were eligible for the meta-analysis. WM alterations were reported in 31 and 34 foci with VBM and DTI methods, respectively. The most occurred WM bundles in both VBM and DTI studies and largely involved in schizophrenia were long projection fibers, callosal and commissural fibers, part of motor descending fibers, and fronto-temporal-limbic pathways. The meta-analysis showed a widespread WM disruption in schizophrenia involving specific cerebral circuits instead of well-defined regions. Copyright © 2017 Elsevier B.V. All rights reserved.

Parent ratings of working memory are uniquely related to performance-based measures of secondary memory but not primary memory.

PubMed

Ralph, Kathryn J; Gibson, Bradley S; Gondoli, Dawn M

2018-03-06

Existing evidence suggests that performance- and rating-based measures of working memory (WM) correlate poorly. Although some researchers have interpreted this evidence as suggesting that these measures may be assessing distinct cognitive constructs, another possibility is that rating-based measures are related to some but not all theoretically motivated performance-based measures. The current study distinguished between performance-based measures of primary memory (PM) and secondary memory (SM), and examined the relation between each of these components of WM and parent-ratings on the WM subscale of the Behavior Rating Inventory of Executive Function (BRIEF-WM). Because SM and BRIEF-WM scores have both been associated with group differences in attention-deficit/hyperactivity disorder (ADHD), it was hypothesized that SM scores would be uniquely related to parent-rated BRIEF-WM scores. Participants were a sample of 77 adolescents with and without an ADHD diagnosis, aged 11 to 15 years, from a midwestern school district. Participant scores on verbal and spatial immediate free recall tasks were used to estimate both PM and SM capacities. Partial correlation analyses were used to evaluate the extent to which estimates of PM and SM were uniquely related parent-rated BRIEF-WM scores. Both verbal and spatial SM scores were significantly related to parent-rated BRIEF-WM scores, when corresponding PM scores were controlled. Higher verbal and spatial SM scores were associated with less frequent parent-report of WM-related failures in their child's everyday life. However, neither verbal nor spatial PM scores significantly related to parent-rated BRIEF-WM scores, when corresponding SM scores were controlled. The current study suggested that previously observed low correlations between performance- and rating-based measures of WM may result from use of performance-based WM measures that do not capture the unique contributions of PM and SM components of WM.

Next-Generation Angular Distribution Models for Top-of-Atmosphere Radiative Flux Calculation from CERES Instruments: Validation

NASA Technical Reports Server (NTRS)

Su, W.; Corbett, J.; Eitzen, Z.; Liang, L.

2015-01-01

Radiative fluxes at the top of the atmosphere (TOA) from the Clouds and the Earth's Radiant Energy System (CERES) instrument are fundamental variables for understanding the Earth's energy balance and how it changes with time. TOA radiative fluxes are derived from the CERES radiance measurements using empirical angular distribution models (ADMs). This paper evaluates the accuracy of CERES TOA fluxes using direct integration and flux consistency tests. Direct integration tests show that the overall bias in regional monthly mean TOA shortwave (SW) flux is less than 0.2Wm(exp -2) and the RMSE is less than 1.1Wm(exp -2). The bias and RMSE are very similar between Terra and Aqua. The bias in regional monthly mean TOA LW fluxes is less than 0.5Wm(exp -2) and the RMSE is less than 0.8Wm(exp -)2 for both Terra and Aqua. The accuracy of the TOA instantaneous flux is assessed by performing tests using fluxes inverted from nadir- and oblique-viewing angles using CERES along-track observations and temporally and spatially matched MODIS observations, and using fluxes inverted from multi-angle MISR observations. The averaged TOA instantaneous SW flux uncertainties from these two tests are about 2.3% (1.9Wm(exp -2) over clear ocean, 1.6% (4.5Wm(exp -2) over clear land, and 2.0% (6.0Wm(exp -) over clear snow/ice; and are about 3.3% (9.0Wm(exp -2), 2.7% (8.4Wm(exp -2), and 3.7% (9.9Wm(exp -2) over ocean, land, and snow/ice under all-sky conditions. The TOA SW flux uncertainties are generally larger for thin broken clouds than for moderate and thick overcast clouds. The TOA instantaneous daytime LW flux uncertainties derived from the CERESMODIS test are 0.5% (1.5Wm(exp -2), 0.8% (2.4Wm(exp -2), and 0.7% (1.3Wm(exp -2) over clear ocean, land, and snow/ice; and are about 1.5% (3.5Wm(exp -2), 1.0% (2.9Wm(exp -2), and 1.1% (2.1Wm(exp -2) over ocean, land, and snow/ice under all-sky conditions. The TOA instantaneous nighttime LW flux uncertainties are about 0.5-1% (<2.0Wm(exp -2) for all

The generality of working memory capacity: a latent-variable approach to verbal and visuospatial memory span and reasoning.

PubMed

Kane, Michael J; Hambrick, David Z; Tuholski, Stephen W; Wilhelm, Oliver; Payne, Tabitha W; Engle, Randall W

2004-06-01

A latent-variable study examined whether verbal and visuospatial working memory (WM) capacity measures reflect a primarily domain-general construct by testing 236 participants in 3 span tests each of verbal WM. visuospatial WM, verbal short-term memory (STM), and visuospatial STM. as well as in tests of verbal and spatial reasoning and general fluid intelligence (Gf). Confirmatory' factor analyses and structural equation models indicated that the WM tasks largely reflected a domain-general factor, whereas STM tasks, based on the same stimuli as the WM tasks, were much more domain specific. The WM construct was a strong predictor of Gf and a weaker predictor of domain-specific reasoning, and the reverse was true for the STM construct. The findings support a domain-general view of WM capacity, in which executive-attention processes drive the broad predictive utility of WM span measures, and domain-specific storage and rehearsal processes relate more strongly to domain-specific aspects of complex cognition. ((c) 2004 APA, all rights reserved)

Working memory affects false memory production for emotional events.

PubMed

Mirandola, Chiara; Toffalini, Enrico; Ciriello, Alfonso; Cornoldi, Cesare

2017-01-01

Whereas a link between working memory (WM) and memory distortions has been demonstrated, its influence on emotional false memories is unclear. In two experiments, a verbal WM task and a false memory paradigm for negative, positive or neutral events were employed. In Experiment 1, we investigated individual differences in verbal WM and found that the interaction between valence and WM predicted false recognition, with negative and positive material protecting high WM individuals against false remembering; the beneficial effect of negative material disappeared in low WM participants. In Experiment 2, we lowered the WM capacity of half of the participants with a double task request, which led to an overall increase in false memories; furthermore, consistent with Experiment 1, the increase in negative false memories was larger than that of neutral or positive ones. It is concluded that WM plays a critical role in determining false memory production, specifically influencing the processing of negative material.

Effects of age, working memory, and word order on passive-sentence comprehension: evidence from a verb-final language.

PubMed

Sung, Jee Eun; Yoo, Jae Keun; Lee, Soo Eun; Eom, Bora

2017-06-01

The purpose of the current study was to investigate the effects of working-memory (WM) capacity on age-related changes in abilities to comprehend passive sentences when the word order was systematically manipulated. A total of 134 individuals participated in the study. The sentence-comprehension task consisted of the canonical and non-canonical word-order conditions. A composite measure of WM scores was used as an index of WM capacity. Participants exhibited worse performance on sentences with non-canonical word order than canonical word order. The two-way interaction between age and WM was significant, suggesting that WM effects were greater than age effects on the task. WM capacity effects on passive-sentence comprehension increased dramatically as people aged, suggesting that those who have larger WM capacity are less vulnerable to age-related changes in sentence-comprehension abilities. WM capacity may serve as a cognitive reserve associated with sentence-comprehension abilities for elderly adults.

Depressive thoughts limit working memory capacity in dysphoria.

PubMed

Hubbard, Nicholas A; Hutchison, Joanna L; Turner, Monroe; Montroy, Janelle; Bowles, Ryan P; Rypma, Bart

2016-01-01

Dysphoria is associated with persistence of attention on mood-congruent information. Longer time attending to mood-congruent information for dysphoric individuals (DIs) detracts from goal-relevant information processing and should reduce working memory (WM) capacity. Study 1 showed that DIs and non-DIs have similar WM capacities. Study 2 embedded depressive information into a WM task. Compared to non-DIs, DIs showed significantly reduced WM capacity for goal-relevant information in this task. Study 3 replicated results from Studies 1 and 2, and further showed that DIs had a significantly greater association between processing speed and recall on the depressively modified WM task compared to non-DIs. The presence of inter-task depressive information leads to DI-related decreased WM capacity. Results suggest dysphoria-related WM capacity deficits when depressive thoughts are present. WM capacity deficits in the presence of depressive thoughts are a plausible mechanism to explain day-to-day memory and concentration difficulties associated with depressed mood.

A new modified listening span task to enhance validity of working memory assessment for people with and without aphasia

PubMed Central

Ivanova, Maria V.; Hallowell, Brooke

2014-01-01

Deficits in working memory (WM) are an important subset of cognitive processing deficits associated with aphasia. However, there are serious limitations to research on WM in aphasia largely due to the lack of an established valid measure of WM impairment for this population. The aim of the current study was to address shortcomings of previous measures by developing and empirically evaluating a novel WM task with a sentence-picture matching processing component designed to circumvent confounds inherent in existing measures of WM in aphasia. The novel WM task was presented to persons with (n = 27) and without (n = 33) aphasia. Results demonstrated high concurrent validity of a novel WM task. Individuals with aphasia performed significantly worse on all conditions of the WM task compared to individuals without aphasia. Different patterns of performance across conditions were observed for the two groups. Additionally, WM capacity was significantly related to auditory comprehension abilities in individuals with mild aphasia but not those with moderate aphasia. Strengths of the novel WM task are that it allows for differential control for length versus complexity of verbal stimuli and indexing of the relative influence of each, minimizes metalinguistic requirements, enables control for complexity of processing components, allows participants to respond with simple gestures or verbally, and eliminates reading requirements. Results support the feasibility and validity of using a novel task to assess WM in individuals with and without aphasia. PMID:24986153

Isotropic non-white matter partial volume effects in constrained spherical deconvolution.

PubMed

Roine, Timo; Jeurissen, Ben; Perrone, Daniele; Aelterman, Jan; Leemans, Alexander; Philips, Wilfried; Sijbers, Jan

2014-01-01

Diffusion-weighted (DW) magnetic resonance imaging (MRI) is a non-invasive imaging method, which can be used to investigate neural tracts in the white matter (WM) of the brain. Significant partial volume effects (PVEs) are present in the DW signal due to relatively large voxel sizes. These PVEs can be caused by both non-WM tissue, such as gray matter (GM) and cerebrospinal fluid (CSF), and by multiple non-parallel WM fiber populations. High angular resolution diffusion imaging (HARDI) methods have been developed to correctly characterize complex WM fiber configurations, but to date, many of the HARDI methods do not account for non-WM PVEs. In this work, we investigated the isotropic PVEs caused by non-WM tissue in WM voxels on fiber orientations extracted with constrained spherical deconvolution (CSD). Experiments were performed on simulated and real DW-MRI data. In particular, simulations were performed to demonstrate the effects of varying the diffusion weightings, signal-to-noise ratios (SNRs), fiber configurations, and tissue fractions. Our results show that the presence of non-WM tissue signal causes a decrease in the precision of the detected fiber orientations and an increase in the detection of false peaks in CSD. We estimated 35-50% of WM voxels to be affected by non-WM PVEs. For HARDI sequences, which typically have a relatively high degree of diffusion weighting, these adverse effects are most pronounced in voxels with GM PVEs. The non-WM PVEs become severe with 50% GM volume for maximum spherical harmonics orders of 8 and below, and already with 25% GM volume for higher orders. In addition, a low diffusion weighting or SNR increases the effects. The non-WM PVEs may cause problems in connectomics, where reliable fiber tracking at the WM-GM interface is especially important. We suggest acquiring data with high diffusion-weighting 2500-3000 s/mm(2), reasonable SNR (~30) and using lower SH orders in GM contaminated regions to minimize the non-WM PVEs in CSD.

N-back versus Complex Span Working Memory Training.

PubMed

Blacker, Kara J; Negoita, Serban; Ewen, Joshua B; Courtney, Susan M

2017-12-01

Working memory (WM) is the ability to maintain and manipulate task-relevant information in the absence of sensory input. While its improvement through training is of great interest, the degree to which WM training transfers to untrained WM tasks (near transfer) and other untrained cognitive skills (far transfer) remains debated and the mechanism(s) underlying transfer are unclear. Here we hypothesized that a critical feature of dual n-back training is its reliance on maintaining relational information in WM. In Experiment 1, using an individual differences approach, we found evidence that performance on an n-back task was predicted by performance on a measure of relational WM (i.e., WM for vertical spatial relationships independent of absolute spatial locations); whereas the same was not true for a complex span WM task. In Experiment 2, we tested the idea that reliance on relational WM is critical to produce transfer from n-back but not complex span task training. Participants completed adaptive training on either a dual n-back task, a symmetry span task, or on a non-WM active control task. We found evidence of near transfer for the dual n-back group; however, far transfer to a measure of fluid intelligence did not emerge. Recording EEG during a separate WM transfer task, we examined group-specific, training-related changes in alpha power, which are proposed to be sensitive to WM demands and top-down modulation of WM. Results indicated that the dual n-back group showed significantly greater frontal alpha power after training compared to before training, more so than both other groups. However, we found no evidence of improvement on measures of relational WM for the dual n-back group, suggesting that near transfer may not be dependent on relational WM. These results suggest that dual n-back and complex span task training may differ in their effectiveness to elicit near transfer as well as in the underlying neural changes they facilitate.

The Effects of Home-Based Cognitive Training on Verbal Working Memory and Language Comprehension in Older Adulthood

PubMed Central

Payne, Brennan R.; Stine-Morrow, Elizabeth A. L.

2017-01-01

Effective language understanding is crucial to maintaining cognitive abilities and learning new information through adulthood. However, age-related declines in working memory (WM) have a robust negative influence on multiple aspects of language comprehension and use, potentially limiting communicative competence. In the current study (N = 41), we examined the effects of a novel home-based computerized cognitive training program targeting verbal WM on changes in verbal WM and language comprehension in healthy older adults relative to an active component-control group. Participants in the WM training group showed non-linear improvements in performance on trained verbal WM tasks. Relative to the active control group, WM training participants also showed improvements on untrained verbal WM tasks and selective improvements across untrained dimensions of language, including sentence memory, verbal fluency, and comprehension of syntactically ambiguous sentences. Though the current study is preliminary in nature, it does provide initial promising evidence that WM training may influence components of language comprehension in adulthood and suggests that home-based training of WM may be a viable option for probing the scope and limits of cognitive plasticity in older adults. PMID:28848421

The Effects of Home-Based Cognitive Training on Verbal Working Memory and Language Comprehension in Older Adulthood.

PubMed

Payne, Brennan R; Stine-Morrow, Elizabeth A L

2017-01-01

Effective language understanding is crucial to maintaining cognitive abilities and learning new information through adulthood. However, age-related declines in working memory (WM) have a robust negative influence on multiple aspects of language comprehension and use, potentially limiting communicative competence. In the current study ( N = 41), we examined the effects of a novel home-based computerized cognitive training program targeting verbal WM on changes in verbal WM and language comprehension in healthy older adults relative to an active component-control group. Participants in the WM training group showed non-linear improvements in performance on trained verbal WM tasks. Relative to the active control group, WM training participants also showed improvements on untrained verbal WM tasks and selective improvements across untrained dimensions of language, including sentence memory, verbal fluency, and comprehension of syntactically ambiguous sentences. Though the current study is preliminary in nature, it does provide initial promising evidence that WM training may influence components of language comprehension in adulthood and suggests that home-based training of WM may be a viable option for probing the scope and limits of cognitive plasticity in older adults.

The development of non-spatial working memory capacity during childhood and adolescence and the role of interference control: an N-Back task study.

PubMed

Schleepen, Tamara M J; Jonkman, Lisa M

2010-01-01

To investigate the role of interference control on the development of working memory (WM) capacity, 6-12-year-old children and adults performed an N-Back task with differing WM-load and interference control demands. Correlation analyses between flanker interference scores and WM-load levels showed that interference control was only required in the 2-back condition. While WM maintenance (1-back task) reached adult accuracy levels at age 10-12, the ability to maintain information in WM during distraction (2-back-task) displayed protracted maturation into adolescence. This is suggested to reflect yet immature connections between prefrontal and posterior association areas, respectively involved in interference control and WM storage.

Altered Development of White Matter in Youth at High Familial Risk for Bipolar Disorder: A Diffusion Tensor Imaging Study

ERIC Educational Resources Information Center

Versace, Amelia; Ladouceur, Cecile D.; Romero, Soledad; Birmaher, Boris; Axelson, David A.; Kupfer, David J.; Phillips, Mary L.

2010-01-01

Objective: To study white matter (WM) development in youth at high familial risk for bipolar disorder (BD). WM alterations are reported in youth and adults with BD. WM undergoes important maturational changes in adolescence. Age-related changes in WM microstructure using diffusion tensor imaging with tract-based spatial statistics in healthy…

Phonological and Visuospatial Working Memory in Autism Spectrum Disorders

ERIC Educational Resources Information Center

Macizo, P.; Soriano, M. F.; Paredes, N.

2016-01-01

We evaluated phonological and visuospatial working memory (WM) in autism spectrum disorders. Autistic children and typically developing children were compared. We used WM tasks that measured phonological and visuospatial WM up to the capacity limit of each children. Overall measures of WM did not show differences between autistic children and…

Verbal Working Memory and Language Production: Common Approaches to the Serial Ordering of Verbal Information

ERIC Educational Resources Information Center

Acheson, Daniel J.; MacDonald, Maryellen C.

2009-01-01

Verbal working memory (WM) tasks typically involve the language production architecture for recall; however, language production processes have had a minimal role in theorizing about WM. A framework for understanding verbal WM results is presented here. In this framework, domain-specific mechanisms for serial ordering in verbal WM are provided by…

Effects of task-irrelevant emotional stimuli on working memory processes in mild cognitive impairment.

PubMed

Berger, Christoph; Erbe, Anna-Katharina; Ehlers, Inga; Marx, Ivo; Hauenstein, Karlheinz; Teipel, Stefan

2015-01-01

Research suggests generally impaired cognitive control functions in working memory (WM) processes in amnestic mild cognitive impairment (MCI) and incipient Alzheimer's disease (AD). Little is known how emotional salience of task-irrelevant stimuli may modulate cognitive control of WM performance and neurofunctional activation in MCI and AD individuals. We investigated the impact of emotional task-irrelevant visual stimuli on cortical activation during verbal WM. Twelve AD/MCI individuals and 12 age-matched healthy individuals performed a verbal WM (nback-) task with task-irrelevant emotionally neutral and emotionally negative background pictures during fMRI measurement. AD/MCI individuals showed decreased WM performance compared with controls; both AD/MCI and control groups reacted slower during presentation of negative pictures, regardless of WM difficulty. The AD/MCI group showed increased activation in the left hemispheric prefrontal network, higher amygdala and less cerebellar activation with increasing WM task difficulty compared to healthy controls. Correlation analysis between neurofunctional activation and WM performance revealed a negative correlation between task sensitivity and activation in the dorsal anterior cingulum for the healthy controls but not for the AD/MCI group. Our data suggest compensatory activation in prefrontal cortex and amygdala, but also dysfunctional inhibition of distracting information in the AD/MCI group during higher WM task difficulty. Additionally, attentional processes affecting the correlation between WM performance and neurofunctional activation seem to be different between incipient AD and healthy aging.

Adaptive working-memory training benefits reading, but not mathematics in middle childhood.

PubMed

Karbach, Julia; Strobach, Tilo; Schubert, Torsten

2015-01-01

Working memory (WM) capacity is highly correlated with general cognitive ability and has proven to be an excellent predictor for academic success. Given that WM can be improved by training, our aim was to test whether WM training benefited academic abilities in elementary-school children. We examined 28 participants (mean age = 8.3 years, SD = 0.4) in a pretest-training-posttest-follow-up design. Over 14 training sessions, children either performed adaptive WM training (training group, n = 14) or nonadaptive low-level training (active control group, n = 14) on the same tasks. Pretest, posttest, and follow-up at 3 months after posttest included a neurocognitive test battery (WM, task switching, inhibition) and standardized tests for math and reading abilities. Adaptive WM training resulted in larger training gains than nonadaptive low-level training. The benefits induced by the adaptive training transferred to an untrained WM task and a standardized test for reading ability, but not to task switching, inhibition, or performance on a standardized math test. Transfer to the untrained WM task was maintained over 3 months. The analysis of individual differences revealed compensatory effects with larger gains in children with lower WM and reading scores at pretest. These training and transfer effects are discussed against the background of cognitive processing resulting from WM span training and the nature of the intervention.

Impaired Processing of Serial Order Determines Working Memory Impairments in Alzheimer's Disease.

PubMed

De Belder, Maya; Santens, Patrick; Sieben, Anne; Fias, Wim

2017-01-01

Working memory (WM) problems are commonly observed in Alzheimer's disease (AD), but the affected mechanisms leading to impaired WM are still insufficiently understood. The ability to efficiently process serial order in WM has been demonstrated to be fundamental to fluent daily life functioning. The decreased capability to mentally process serial position in WM has been put forward as the underlying explanation for generally compromised WM performance. Determine which mechanisms, such as order processing, are responsible for deficient WM functioning in AD. A group of AD patients (n = 32) and their partners (n = 25), assigned to the control group, were submitted to an extensive battery of neuropsychological and experimental tasks, assessing general cognitive state and functioning of several aspects related to serial order WM. The results revealed an impaired ability to bind item information to serial position within WM in AD patients compared to controls. It was additionally observed that AD patients experienced specific difficulties with directing spatial attention when searching for item information stored in WM. The processing of serial order and the allocation of attentional resources are both disrupted, explaining the generally reduced WM functioning in AD patients. Further studies should now clarify whether this observation could explain disease-related problems for other cognitive functions such as verbal expression, auditory comprehension, or planning.

A Randomized Control Trial of Working Memory Training With and Without Strategy Instruction: Effects on Young Children’s Working Memory and Comprehension

PubMed Central

Peng, Peng

2015-01-01

Researchers are increasingly interested in working memory (WM) training. However, it is unclear whether it strengthens comprehension in young children who are at risk for learning difficulties. We conducted a modest study of whether the training of verbal WM would improve verbal WM and passage listening comprehension, and whether training effects differed between two approaches: training with and without strategy instruction. A total of 58 first-grade children were randomly assigned to 3 groups: WM training with a rehearsal strategy, WM training without strategy instruction, and controls. Every member of the 2 training groups received a one-to-one, 35-minute session of verbal WM training on each of 10 consecutive school days, totaling 5.8 hours. Both training groups improved on trained verbal WM tasks, with the rehearsal group making greater gains. Without correction for multiple group comparisons, the rehearsal group made reliable improvements over controls on an untrained verbal WM task and on passage listening comprehension and listening retell measures. The no-strategy- instruction group outperformed controls on passage listening comprehension. When corrected for multiple contrasts, these group differences disappeared, but were associated with moderate-to-large effect sizes. Findings suggest—however tentatively—that brief but intensive verbal WM training may strengthen the verbal WM and comprehension performance of young children at risk. Necessary caveats and possible implications for theory and future research are discussed. PMID:26156961

Sex differences in verbal working memory performance emerge at very high loads of common neuroimaging tasks.

PubMed

Reed, Jessica L; Gallagher, Natalie M; Sullivan, Marie; Callicott, Joseph H; Green, Adam E

2017-04-01

Working memory (WM) supports a broad range of intelligent cognition and has been the subject of rich cognitive and neural characterization. However, the highest ranges of WM have not been fully characterized, especially for verbal information. Tasks developed to test multiple levels of WM demand (load) currently predominate brain-based WM research. These tasks are typically used at loads that allow most healthy participants to perform well, which facilitates neuroimaging data collection. Critically, however, high performance at lower loads may obscure differences that emerge at higher loads. A key question not yet addressed at high loads concerns the effect of sex. Thoroughgoing investigation of high-load verbal WM is thus timely to test for potential hidden effects, and to provide behavioral context for effects of sex observed in WM-related brain structure and function. We tested 111 young adults, matched on genotype for the WM-associated COMT-Val 108/158 Met polymorphism, on three classic WM tasks using verbal information. Each task was tested at four WM loads, including higher loads than those used in previous studies of sex differences. All tasks loaded on a single factor, enabling comparison of verbal WM ability at a construct level. Results indicated sex effects at high loads across tasks and within each task, such that males had higher accuracy, even among groups that were matched for performance at lower loads. Published by Elsevier Inc.

Altered brain activation and functional connectivity in working memory related networks in patients with type 2 diabetes: An ICA-based analysis

PubMed Central

Zhang, Yang; Lu, Shan; Liu, Chunlei; Zhang, Huimei; Zhou, Xuanhe; Ni, Changlin; Qin, Wen; Zhang, Quan

2016-01-01

Type 2 diabetes mellitus (T2DM) can cause multidimensional cognitive deficits, among which working memory (WM) is usually involved at an early stage. However, the neural substrates underlying impaired WM in T2DM patients are still unclear. To clarify this issue, we utilized functional magnetic resonance imaging (fMRI) and independent component analysis to evaluate T2DM patients for alterations in brain activation and functional connectivity (FC) in WM networks and to determine their associations with cognitive and clinical variables. Twenty complication-free T2DM patients and 19 matched healthy controls (HCs) were enrolled, and fMRI data were acquired during a block-designed 1-back WM task. The WM metrics of the T2DM patients showed no differences compared with those of the HCs, except for a slightly lower accuracy rate in the T2DM patients. Compared with the HCs, the T2DM patients demonstrated increased activation within their WM fronto-parietal networks, and activation strength was significantly correlated with WM performance. The T2DM patients also showed decreased FC within and between their WM networks. Our results indicate that the functional integration of WM sub-networks was disrupted in the complication-free T2DM patients and that strengthened regional activity in fronto-parietal networks may compensate for the WM impairment caused by T2DM. PMID:27021340

Working Memory Training in Typically Developing Children: A Meta-Analysis of the Available Evidence

ERIC Educational Resources Information Center

Sala, Giovanni; Gobet, Fernand

2017-01-01

The putative effectiveness of working memory (WM) training at enhancing cognitive and academic skills is still ardently debated. Several researchers have claimed that WM training fosters not only skills such as visuospatial WM and short-term memory (STM), but also abilities outside the domain of WM, such as fluid intelligence and mathematics.…

Improving Working Memory in Children with Attention-Deficit/Hyperactivity Disorder: The Separate and Combined Effects of Incentives and Stimulant Medication

ERIC Educational Resources Information Center

Strand, Michael T.; Hawk, Larry W., Jr.; Bubnik, Michelle; Shiels, Keri; Pelham, William E., Jr.; Waxmonsky, James G.

2012-01-01

Working memory (WM) is considered a core deficit in Attention-Deficit/Hyperactivity Disorder (ADHD), with numerous studies demonstrating impaired WM among children with ADHD. We tested the degree to which WM in children with ADHD was improved by performance-based incentives, an analog of behavioral intervention. In two studies, WM performance was…

The Influence of Working Memory on Reading and Creative Writing Processes in a Second Language.

ERIC Educational Resources Information Center

Abu-Rabia, Salim

2003-01-01

Investigates the working memory (WM) processing and storage functions; whether WM in writing follows the same process as in reading; and the influence of WM on creative writing. Focuses on high school students (n=47). Finds relationships between WM measures and reading and writing in English as a Second Language. Includes references. (CMK)

Children with low working memory and children with ADHD: same or different?

PubMed

Holmes, Joni; Hilton, Kerry A; Place, Maurice; Alloway, Tracy P; Elliott, Julian G; Gathercole, Susan E

2014-01-01

The purpose of this study was to compare working memory (WM), executive function, academic ability, and problem classroom behaviors in children aged 8-11 years who were either identified via routine screening as having low WM, or had been diagnosed with ADHD. Standardized assessments of WM, executive function and reading and mathematics were administered to 83 children with ADHD, 50 children with low WM and 50 typically developing children. Teachers rated problem behaviors on checklists measuring attention, hyperactivity/impulsivity, oppositional behavior, and difficulties associated with executive function in the classroom. The ADHD and low WM groups had highly similar WM and executive function profiles, but were distinguished in two key respects: children with ADHD had higher levels of rated and observed impulsive behavior, and children with low WM had slower response times. Possible mechanisms for these common and distinct deficits are discussed.

Stressing the mind: the effect of cognitive load and articulatory suppression on attentional guidance from working memory.

PubMed

Soto, David; Humphreys, Glyn W

2008-07-01

Four experiments explored the effect of cognitive load on the time course of top-down guidance of attention from working memory (WM). Observers had to search for a target presented among several distractors, with the target and distractor stimuli embedded inside different objects. On half of the trials, one of the distractor objects was cued by a matching item held in WM. When a single item was maintained in memory, search performance was impaired relative to a neutral baseline, where the memory and search displays did not match. These effects of WM on subsequent search were reduced by including a verbal suppression task during the WM and search displays, and by varying the WM load. The degree of competition for resources in WM is a key factor in determining the time course and magnitude of the interaction between WM and visual selection.

Expanding the mind's workspace: training and transfer effects with a complex working memory span task.

PubMed

Chein, Jason M; Morrison, Alexandra B

2010-04-01

In the present study, a novel working memory (WM) training paradigm was used to test the malleability of WM capacity and to determine the extent to which the benefits of this training could be transferred to other cognitive skills. Training involved verbal and spatial versions of a complex WM span task designed to emphasize simultaneous storage and processing requirements. Participants who completed 4 weeks of WM training demonstrated significant improvements on measures of temporary memory. These WM training benefits generalized to performance on the Stroop task and, in a novel finding, promoted significant increases in reading comprehension. The results are discussed in relation to the hypothesis that WM training affects domain-general attention control mechanisms and can thereby elicit far-reaching cognitive benefits. Implications include the use of WM training as a general tool for enhancing important cognitive skills.

Memory under pressure: secondary-task effects on contextual cueing of visual search.

PubMed

Annac, Efsun; Manginelli, Angela A; Pollmann, Stefan; Shi, Zhuanghua; Müller, Hermann J; Geyer, Thomas

2013-11-04

Repeated display configurations improve visual search. Recently, the question has arisen whether this contextual cueing effect (Chun & Jiang, 1998) is itself mediated by attention, both in terms of selectivity and processing resources deployed. While it is accepted that selective attention modulates contextual cueing (Jiang & Leung, 2005), there is an ongoing debate whether the cueing effect is affected by a secondary working memory (WM) task, specifically at which stage WM influences the cueing effect: the acquisition of configural associations (e.g., Travis, Mattingley, & Dux, 2013) versus the expression of learned associations (e.g., Manginelli, Langer, Klose, & Pollmann, 2013). The present study re-investigated this issue. Observers performed a visual search in combination with a spatial WM task. The latter was applied on either early or late search trials--so as to examine whether WM load hampers the acquisition of or retrieval from contextual memory. Additionally, the WM and search tasks were performed either temporally in parallel or in succession--so as to permit the effects of spatial WM load to be dissociated from those of executive load. The secondary WM task was found to affect cueing in late, but not early, experimental trials--though only when the search and WM tasks were performed in parallel. This pattern suggests that contextual cueing involves a spatial WM resource, with spatial WM providing a workspace linking the current search array with configural long-term memory; as a result, occupying this workspace by a secondary WM task hampers the expression of learned configural associations.

Working Memory Capacity Limits Motor Learning When Implementing Multiple Instructions

PubMed Central

Buszard, Tim; Farrow, Damian; Verswijveren, Simone J. J. M.; Reid, Machar; Williams, Jacqueline; Polman, Remco; Ling, Fiona Chun Man; Masters, Rich S. W.

2017-01-01

Although it is generally accepted that certain practice conditions can place large demands on working memory (WM) when performing and learning a motor skill, the influence that WM capacity has on the acquisition of motor skills remains unsubstantiated. This study examined the role of WM capacity in a motor skill practice context that promoted WM involvement through the provision of explicit instructions. A cohort of 90 children aged 8 to 10 years were assessed on measures of WM capacity and attention. Children who scored in the lowest and highest thirds on the WM tasks were allocated to lower WM capacity (n = 24) and higher WM capacity (n = 24) groups, respectively. The remaining 42 participants did not participate in the motor task. The motor task required children to practice basketball shooting for 240 trials in blocks of 20 shots, with pre- and post-tests occurring before and after the intervention. A retention test was administered 1 week after the post-test. Prior to every practice block, children were provided with five explicit instructions that were specific to the technique of shooting a basketball. Results revealed that the higher WM capacity group displayed consistent improvements from pre- to post-test and through to the retention test, while the opposite effect occurred in the lower WM capacity group. This implies that the explicit instructions had a negative influence on learning by the lower WM capacity children. Results are discussed in relation to strategy selection for dealing with instructions and the role of attention control. PMID:28878701

A meta-analysis of working memory impairments in survivors of moderate-to-severe traumatic brain injury.

PubMed

Dunning, Darren L; Westgate, Briony; Adlam, Anna-Lynne R

2016-10-01

To establish the magnitude of deficits in working memory (WM) and short-term memory (STM) in those with moderate-to-severe traumatic brain injury (TBI) relative to age-matched, healthy controls and to explore the moderating effects of time since injury and age at injury on these impairments. Twenty-one studies that compared the WM and/or STM abilities of individuals with at least a moderate TBI relative to healthy controls were included in a random effects meta-analysis. Measures used to examine memory performance were categorized by modality (visuospatial, verbal) and memory system (WM, STM). Individuals with TBI had significant deficits in verbal STM (Cohen's d = .41), visuospatial WM (Cohen's d = .69), and verbal WM (Cohen's d = .37) relative to controls. Greater decrements in verbal STM and verbal WM skills were associated with longer time postinjury. Larger deficits were observed in verbal WM abilities in individuals with older age at injury. Evidence for WM impairments following TBI is consistent with previous research. Larger verbal STM and verbal WM deficits were related to a longer time postinjury, suggesting that these aspects of memory do not "recover" over time and instead, individuals might show increased rates of cognitive decline. Age at injury was associated with the severity of verbal WM impairments, with larger deficits evident for injuries that occurred later in life. Further research needs to chart the long-term effects of TBI on WM and to compare the effects of injury on verbal relative to visuospatial memory. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

White matter pathology and disconnection in the frontal lobe in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

PubMed

Craggs, Lucinda J L; Yamamoto, Yumi; Ihara, Masafumi; Fenwick, Richard; Burke, Matthew; Oakley, Arthur E; Roeber, Sigrun; Duering, Marco; Kretzschmar, Hans; Kalaria, Raj N

2014-08-01

Magnetic resonance imaging indicates diffuse white matter (WM) changes are associated with cognitive impairment in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We examined whether the distribution of axonal abnormalities is related to microvascular pathology in the underlying WM. We used post-mortem brains from CADASIL subjects and similar age cognitively normal controls to examine WM axonal changes, microvascular pathology, and glial reaction in up to 16 different regions extending rostro-caudally through the cerebrum. Using unbiased stereological methods, we estimated length densities of affected axons immunostained with neurofilament antibody SMI32. Standard immunohistochemistry was used to assess amyloid precursor protein immunoreactivity per WM area. To relate WM changes to microvascular pathology, we also determined the sclerotic index (SI) in WM arterioles. The degree of WM pathology consistently scored higher across all brain regions in CADASIL subjects (P<0.01) with the WM underlying the primary motor cortex exhibiting the most severe change. SMI32 immunoreactive axons in CADASIL were invariably increased compared with controls (P<0.01), with most prominent axonal abnormalities observed in the frontal WM (P<0.05). The SIs of arterioles in CADASIL were increased by 25-45% throughout the regions assessed, with the highest change in the mid-frontal region (P=0.000). Our results suggest disruption of either cortico-cortical or subcortical-cortical networks in the WM of the frontal lobe that may explain motor deficits and executive dysfunction in CADASIL. Widespread WM axonal changes arise from differential stenosis and sclerosis of arterioles in the WM of CADASIL subjects, possibly affecting some axons of projection neurones connecting to targets in the subcortical structures. © 2013 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British

Interference within the Focus of Attention: Working Memory Tasks Reflect More than Temporary Maintenance

ERIC Educational Resources Information Center

Shipstead, Zach; Engle, Randall W.

2013-01-01

One approach to understanding working memory (WM) holds that individual differences in WM capacity arise from the amount of information a person can store in WM over short periods of time. This view is especially prevalent in WM research conducted with the visual arrays task. Within this tradition, many researchers have concluded that the average…

Improving working memory abilities in individuals with Down syndrome: a treatment case study

PubMed Central

Costa, Hiwet Mariam; Purser, Harry R. M.; Passolunghi, Maria Chiara

2015-01-01

Working memory (WM) skills of individuals with Down’s syndrome (DS) tend to be very poor compared to typically developing children of similar mental age. In particular, research has found that in individuals with DS visuo-spatial WM is better preserved than verbal WM. This study investigated whether it is possible to train short-term memory (STM) and WM abilities in individuals with DS. The cases of two teenage children are reported: EH, 17 years and 3 months, and AS, 15 years and 11 months. A school-based treatment targeting visuo-spatial WM was given to EH and AS for six weeks. Both prior to and after the treatment, they completed a set of assessments to measure WM abilities and their performance was compared with younger typically developing non-verbal mental age controls. The results showed that the trained participants improved their performance in some of the trained and non-trained WM tasks proposed, especially with regard to the tasks assessing visuo-spatial WM abilities. These findings are discussed on the basis of their theoretical, educational, and clinical implications. PMID:26441713

White matter tract covariance patterns predict age-declining cognitive abilities.

PubMed

Gazes, Yunglin; Bowman, F DuBois; Razlighi, Qolamreza R; O'Shea, Deirdre; Stern, Yaakov; Habeck, Christian

2016-01-15

Previous studies investigating the relationship of white matter (WM) integrity to cognitive abilities and aging have either focused on a global measure or a few selected WM tracts. Ideally, contribution from all of the WM tracts should be evaluated at the same time. However, the high collinearity among WM tracts precludes systematic examination of WM tracts simultaneously without sacrificing statistical power due to stringent multiple-comparison corrections. Multivariate covariance techniques enable comprehensive simultaneous examination of all WM tracts without being penalized for high collinearity among observations. In this study, Scaled Subprofile Modeling (SSM) was applied to the mean integrity of 18 major WM tracts to extract covariance patterns that optimally predicted four cognitive abilities (perceptual speed, episodic memory, fluid reasoning, and vocabulary) in 346 participants across ages 20 to 79years old. Using expression of the covariance patterns, age-independent effects of white matter integrity on cognition and the indirect effect of WM integrity on age-related differences in cognition were tested separately, but inferences from the indirect analyses were cautiously made given that cross-sectional data set was used in the analysis. A separate covariance pattern was identified that significantly predicted each cognitive ability after controlling for age except for vocabulary, but the age by WM covariance pattern interaction was not significant for any of the three abilities. Furthermore, each of the patterns mediated the effect of age on the respective cognitive ability. A distinct set of WM tracts was most influential in each of the three patterns. The WM covariance pattern accounting for fluid reasoning showed the most number of influential WM tracts whereas the episodic memory pattern showed the least number. Specific patterns of WM tracts make significant contributions to the age-related differences in perceptual speed, episodic memory, and

Does computerized working memory training with game elements enhance motivation and training efficacy in children with ADHD?

PubMed

Prins, Pier J M; Dovis, Sebastiaan; Ponsioen, Albert; ten Brink, Esther; van der Oord, Saskia

2011-03-01

This study examined the benefits of adding game elements to standard computerized working memory (WM) training. Specifically, it examined whether game elements would enhance motivation and training performance of children with ADHD, and whether it would improve training efficacy. A total of 51 children with ADHD aged between 7 and 12 years were randomly assigned to WM training in a gaming format or to regular WM training that was not in a gaming format. Both groups completed three weekly sessions of WM training. Children using the game version of the WM training showed greater motivation (i.e., more time training), better training performance (i.e., more sequences reproduced and fewer errors), and better WM (i.e., higher scores on a WM task) at post-training than children using the regular WM training. Results are discussed in terms of executive functions and reinforcement models of ADHD. It is concluded that WM training with game elements significantly improves the motivation, training performance, and working memory of children with ADHD. The findings of this study are encouraging and may have wide-reaching practical implications in terms of the role of game elements in the design and implementation of new intervention efforts for children with ADHD.

Affective bias in visual working memory is associated with capacity.

PubMed

Xie, Weizhen; Li, Huanhuan; Ying, Xiangyu; Zhu, Shiyou; Fu, Rong; Zou, Yingmin; Cui, Yanyan

2017-11-01

How does the affective nature of task stimuli modulate working memory (WM)? This study investigates whether WM maintains emotional information in a biased manner to meet the motivational principle of approaching positivity and avoiding negativity by retaining more approach-related positive content over avoidance-related negative content. This bias may exist regardless of individual differences in WM functionality, as indexed by WM capacity (overall bias hypothesis). Alternatively, this bias may be contingent on WM capacity (capacity-based hypothesis), in which a better WM system may be more likely to reveal an adaptive bias. In two experiments, participants performed change localisation tasks with emotional and non-emotional stimuli to estimate the number of items that they could retain for each of those stimuli. Although participants did not seem to remember one type of emotional content (e.g. happy faces) better than the other type of emotional content (e.g. sad faces), there was a significant correlation between WM capacity and affective bias. Specifically, participants with higher WM capacity for non-emotional stimuli (colours or line-drawing symbols) tended to maintain more happy faces over sad faces. These findings demonstrated the presence of a "built-in" affective bias in WM as a function of its systematic limitations, favouring the capacity-based hypothesis.

Neural circuit basis of visuo-spatial working memory precision: a computational and behavioral study.

PubMed

Almeida, Rita; Barbosa, João; Compte, Albert

2015-09-01

The amount of information that can be retained in working memory (WM) is limited. Limitations of WM capacity have been the subject of intense research, especially in trying to specify algorithmic models for WM. Comparatively, neural circuit perspectives have barely been used to test WM limitations in behavioral experiments. Here we used a neuronal microcircuit model for visuo-spatial WM (vsWM) to investigate memory of several items. The model assumes that there is a topographic organization of the circuit responsible for spatial memory retention. This assumption leads to specific predictions, which we tested in behavioral experiments. According to the model, nearby locations should be recalled with a bias, as if the two memory traces showed attraction or repulsion during the delay period depending on distance. Another prediction is that the previously reported loss of memory precision for an increasing number of memory items (memory load) should vanish when the distances between items are controlled for. Both predictions were confirmed experimentally. Taken together, our findings provide support for a topographic neural circuit organization of vsWM, they suggest that interference between similar memories underlies some WM limitations, and they put forward a circuit-based explanation that reconciles previous conflicting results on the dependence of WM precision with load. Copyright © 2015 the American Physiological Society.

Practice makes imperfect: Working memory training can harm recognition memory performance

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

Matzen, Laura E.; Trumbo, Michael C.; Haass, Michael J.

There is a great deal of debate concerning the benefits of working memory (WM) training and whether that training can transfer to other tasks. Although a consistent finding is that WM training programs elicit a short-term near-transfer effect (i.e., improvement in WM skills), results are inconsistent when considering persistence of such improvement and far transfer effects. In this study, we compared three groups of participants: a group that received WM training, a group that received training on how to use a mental imagery memory strategy, and a control group that received no training. Although the WM training group improved onmore » the trained task, their posttraining performance on nontrained WM tasks did not differ from that of the other two groups. In addition, although the imagery training group’s performance on a recognition memory task increased after training, the WM training group’s performance on the task decreased after training. Participants’ descriptions of the strategies they used to remember the studied items indicated that WM training may lead people to adopt memory strategies that are less effective for other types of memory tasks. Our results indicate that WM training may have unintended consequences for other types of memory performance.« less

Neural Mechanisms of Interference Control Underlie the Relationship Between Fluid Intelligence and Working Memory Span

PubMed Central

Burgess, Gregory C.; Gray, Jeremy R.; Conway, Andrew R. A.; Braver, Todd S.

2014-01-01

Fluid intelligence (gF) and working memory (WM) span predict success in demanding cognitive situations. Recent studies show that much of the variance in gF and WM span is shared, suggesting common neural mechanisms. This study provides a direct investigation of the degree to which shared variance in gF and WM span can be explained by neural mechanisms of interference control. We measured performance and fMRI activity in 102 participants during the n-back WM task, focusing on the selective activation effects associated with high-interference lure trials. Brain activity on these trials was correlated with gF, WM span, and task performance in core brain regions linked to WM and executive control, including bilateral dorsolateral PFC (middle frontal gyrus, BA9) and parietal cortex (inferior parietal cortex; BA 40/7). Interference-related performance and interference-related activity accounted for a significant proportion of the shared variance in gF and WM span. Path analyses indicate that interference control activity may affect gF through a common set of processes that also influence WM span. These results suggest that individual differences in interference control mechanisms are important for understanding the relationship between gF and WM span. PMID:21787103

The effects of working memory training on functional brain network efficiency.

PubMed

Langer, Nicolas; von Bastian, Claudia C; Wirz, Helen; Oberauer, Klaus; Jäncke, Lutz

2013-10-01

The human brain is a highly interconnected network. Recent studies have shown that the functional and anatomical features of this network are organized in an efficient small-world manner that confers high efficiency of information processing at relatively low connection cost. However, it has been unclear how the architecture of functional brain networks is related to performance in working memory (WM) tasks and if these networks can be modified by WM training. Therefore, we conducted a double-blind training study enrolling 66 young adults. Half of the subjects practiced three WM tasks and were compared to an active control group practicing three tasks with low WM demand. High-density resting-state electroencephalography (EEG) was recorded before and after training to analyze graph-theoretical functional network characteristics at an intracortical level. WM performance was uniquely correlated with power in the theta frequency, and theta power was increased by WM training. Moreover, the better a person's WM performance, the more their network exhibited small-world topology. WM training shifted network characteristics in the direction of high performers, showing increased small-worldness within a distributed fronto-parietal network. Taken together, this is the first longitudinal study that provides evidence for the plasticity of the functional brain network underlying WM. Copyright © 2013 Elsevier Ltd. All rights reserved.

Working memory deficits in developmental dyscalculia: The importance of serial order.

PubMed

Attout, Lucie; Majerus, Steve

2015-01-01

Although a number of studies suggests a link between working memory (WM) storage capacity of short-term memory and calculation abilities, the nature of verbal WM deficits in children with developmental dyscalculia (DD) remains poorly understood. We explored verbal WM capacity in DD by focusing on the distinction between memory for item information (the items to be retained) and memory for order information (the order of the items within a list). We hypothesized that WM for order could be specifically related to impaired numerical abilities given that recent studies suggest close interactions between the representation of order information in WM and ordinal numerical processing. We investigated item and order WM abilities as well as basic numerical processing abilities in 16 children with DD (age: 8-11 years) and 16 typically developing children matched on age, IQ, and reading abilities. The DD group performed significantly poorer than controls in the order WM condition but not in the item WM condition. In addition, the DD group performed significantly slower than the control group on a numerical order judgment task. The present results show significantly reduced serial order WM abilities in DD coupled with less efficient numerical ordinal processing abilities, reflecting more general difficulties in explicit processing of ordinal information.

Cognitive control during audiovisual working memory engages frontotemporal theta-band interactions.

PubMed

Daume, Jonathan; Graetz, Sebastian; Gruber, Thomas; Engel, Andreas K; Friese, Uwe

2017-10-03

Working memory (WM) maintenance of sensory information has been associated with enhanced cross-frequency coupling between the phase of low frequencies and the amplitude of high frequencies, particularly in medial temporal lobe (MTL) regions. It has been suggested that these WM maintenance processes are controlled by areas of the prefrontal cortex (PFC) via frontotemporal phase synchronisation in low frequency bands. Here, we investigated whether enhanced cognitive control during audiovisual WM as compared to visual WM alone is associated with increased low-frequency phase synchronisation between sensory areas maintaining WM content and areas from PFC. Using magnetoencephalography, we recorded neural oscillatory activity from healthy human participants engaged in an audiovisual delayed-match-to-sample task. We observed that regions from MTL, which showed enhanced theta-beta phase-amplitude coupling (PAC) during the WM delay window, exhibited stronger phase synchronisation within the theta-band (4-7 Hz) to areas from lateral PFC during audiovisual WM as compared to visual WM alone. Moreover, MTL areas also showed enhanced phase synchronisation to temporooccipital areas in the beta-band (20-32 Hz). Our results provide further evidence that a combination of long-range phase synchronisation and local PAC might constitute a mechanism for neuronal communication between distant brain regions and across frequencies during WM maintenance.

Tissue-Selective Salvage of the White Matter by Successful Endovascular Stroke Therapy.

PubMed

Kleine, Justus F; Kaesmacher, Mirjam; Wiestler, Benedikt; Kaesmacher, Johannes

2017-10-01

White matter (WM) is less vulnerable to ischemia than gray matter. In ischemic stroke caused by acute large-vessel occlusion, successful recanalization might therefore sometimes selectively salvage the WM, leading to infarct patterns confined to gray matter. This study examines occurrence, determinants, and clinical significance of such effects. Three hundred twenty-two patients with acute middle cerebral artery occlusion subjected to mechanical thrombectomy were included. Infarct patterns were categorized into WM - (sparing the WM) and WM + (involving WM). National Institutes of Health Stroke Scale-based measures of neurological outcome, including National Institutes of Health Stroke Scale improvement or National Institutes of Health Stroke Scale worsening, good functional midterm outcome (day 90-modified Rankin Scale score of ≤2), the occurrence of malignant swelling, and in-hospital mortality were predefined outcome measures. WM - infarcts occurred in 118 of 322 patients and were associated with successful recanalization and better collateral grades ( P <0.05). Shorter symptom-onset to recanalization times were also associated with WM - infarcts in univariate analysis, but not when adjusted for collateral grades. WM - infarcts were independently associated with good neurological outcome (adjusted odds ratio, 3.003; 95% confidence interval, 1.186-7.607; P =0.020) and good functional midterm outcome (adjusted odds ratio, 8.618; 95% confidence interval, 2.409-30.828; P =0.001) after correcting for potential confounders, including final infarct volume. Only 2.6% of WM - patients, but 20.5% of WM + patients exhibited neurological worsening, and none versus 12.8% developed malignant swelling ( P <0.001), contributing to lower mortality in this group (2.5% versus 10.3%; P =0.014). WM infarction commonly commences later than gray matter infarction after acute middle cerebral artery occlusion. Successful recanalization can therefore salvage completely the WM at risk in

The working memory stroop effect: when internal representations clash with external stimuli.

PubMed

Kiyonaga, Anastasia; Egner, Tobias

2014-08-01

Working memory (WM) has recently been described as internally directed attention, which implies that WM content should affect behavior exactly like an externally perceived and attended stimulus. We tested whether holding a color word in WM, rather than attending to it in the external environment, can produce interference in a color-discrimination task, which would mimic the classic Stroop effect. Over three experiments, the WM Stroop effect recapitulated core properties of the classic attentional Stroop effect, displaying equivalent congruency effects, additive contributions from stimulus- and response-level congruency, and susceptibility to modulation by the percentage of congruent and incongruent trials. Moreover, WM maintenance was inversely related to attentional demands during the WM delay between stimulus presentation and recall, with poorer memory performance following incongruent than congruent trials. Together, these results suggest that WM and attention rely on the same resources and operate over the same representations. © The Author(s) 2014.

Children with low working memory and children with ADHD: same or different?

PubMed Central

Holmes, Joni; Hilton, Kerry A.; Place, Maurice; Alloway, Tracy P.; Elliott, Julian G.; Gathercole, Susan E.

2014-01-01

The purpose of this study was to compare working memory (WM), executive function, academic ability, and problem classroom behaviors in children aged 8–11 years who were either identified via routine screening as having low WM, or had been diagnosed with ADHD. Standardized assessments of WM, executive function and reading and mathematics were administered to 83 children with ADHD, 50 children with low WM and 50 typically developing children. Teachers rated problem behaviors on checklists measuring attention, hyperactivity/impulsivity, oppositional behavior, and difficulties associated with executive function in the classroom. The ADHD and low WM groups had highly similar WM and executive function profiles, but were distinguished in two key respects: children with ADHD had higher levels of rated and observed impulsive behavior, and children with low WM had slower response times. Possible mechanisms for these common and distinct deficits are discussed. PMID:25538599

High intelligence prevents the negative impact of anxiety on working memory.

PubMed

Chuderski, Adam

2015-01-01

Using a large sample and the confirmatory factor analysis, the study investigated the relationships between anxiety, working memory (WM) and (fluid) intelligence. The study showed that the negative impact of anxiety on WM functioning diminishes with increasing intelligence, and that anxiety can significantly affect WM only in people below average intelligence. This effect could not be fully explained by the sheer differences in WM capacity (WMC), suggesting the importance of higher-level cognition in coping with anxiety. Although intelligence moderated the impact of anxiety on WM, it was only weakly related to anxiety. In contrast to previous studies, anxiety explained the substantial amount of WMC variance (17.8%) in less intelligent participants, but none of the variance in more intelligent ones. These results can be explained in terms of either increased motivation of intelligent but anxious people to cope with a WM task, or their ability to compensate decrements in WM.

“Distracters” Do Not Always Distract: Visual Working Memory for Angry Faces is Enhanced by Incidental Emotional Words

PubMed Central

Jackson, Margaret C.; Linden, David E. J.; Raymond, Jane E.

2012-01-01

We are often required to filter out distraction in order to focus on a primary task during which working memory (WM) is engaged. Previous research has shown that negative versus neutral distracters presented during a visual WM maintenance period significantly impair memory for neutral information. However, the contents of WM are often also emotional in nature. The question we address here is how incidental information might impact upon visual WM when both this and the memory items contain emotional information. We presented emotional versus neutral words during the maintenance interval of an emotional visual WM faces task. Participants encoded two angry or happy faces into WM, and several seconds into a 9 s maintenance period a negative, positive, or neutral word was flashed on the screen three times. A single neutral test face was presented for retrieval with a face identity that was either present or absent in the preceding study array. WM for angry face identities was significantly better when an emotional (negative or positive) versus neutral (or no) word was presented. In contrast, WM for happy face identities was not significantly affected by word valence. These findings suggest that the presence of emotion within an intervening stimulus boosts the emotional value of threat-related information maintained in visual WM and thus improves performance. In addition, we show that incidental events that are emotional in nature do not always distract from an ongoing WM task. PMID:23112782

Improving working memory in children with attention-deficit/hyperactivity disorder: the separate and combined effects of incentives and stimulant medication.

PubMed

Strand, Michael T; Hawk, Larry W; Bubnik, Michelle; Shiels, Keri; Pelham, William E; Waxmonsky, James G

2012-10-01

Working memory (WM) is considered a core deficit in Attention-Deficit/ Hyperactivity Disorder (ADHD), with numerous studies demonstrating impaired WM among children with ADHD. We tested the degree to which WM in children with ADHD was improved by performance-based incentives, an analog of behavioral intervention. In two studies, WM performance was assessed using a visuo-spatial n-back task. Study 1 compared children (ages 9-12 years) with ADHD-Combined type (n = 24) to a group of typically developing (TD) children (n = 32). Study 1 replicated WM deficits among children with ADHD. Incentives improved WM, particularly among children with ADHD. The provision of incentives reduced the ADHD-control group difference by approximately half but did not normalize WM. Study 2 examined the separate and combined effects of incentives and stimulant medication among 17 children with ADHD-Combined type. Both incentives and a moderate dose of long-acting methylphenidate (MPH; ~0.3 mg/kg t.i.d. equivalent) robustly improved WM relative to the no-incentive, placebo condition. The combination of incentives and medication improved WM significantly more than either incentives or MPH alone. These studies indicate that contingencies markedly improve WM among children with ADHD-Combined type, with effect sizes comparable to a moderate dose of stimulant medication. More broadly, this work calls attention to the role of motivation in studying cognitive deficits in ADHD and in testing multifactorial models of ADHD.

A yoga program for cognitive enhancement.

PubMed

Brunner, Devon; Abramovitch, Amitai; Etherton, Joseph

2017-01-01

Recent studies suggest that yoga practice may improve cognitive functioning. Although preliminary data indicate that yoga improves working memory (WM), high-resolution information about the type of WM subconstructs, namely maintenance and manipulation, is not available. Furthermore, the association between cognitive enhancement and improved mindfulness as a result of yoga practice requires empirical examination. The aim of the present study is to assess the impact of a brief yoga program on WM maintenance, WM manipulation and attentive mindfulness. Measures of WM (Digit Span Forward, Backward, and Sequencing, and Letter-Number Sequencing) were administered prior to and following 6 sessions of yoga (N = 43). Additionally, the Mindfulness Attention Awareness Scale was administered to examine the potential impact of yoga practice on mindfulness, as well as the relationships among changes in WM and mindfulness. Analyses revealed significant improvement from pre- to post- training assessment on both maintenance WM (Digit Span Forward) and manipulation WM (Digit Span Backward and Letter-Number Sequencing). No change was found on Digit Span Sequencing. Improvement was also found on mindfulness scores. However, no correlation was observed between mindfulness and WM measures. A 6-session yoga program was associated with improvement on manipulation and maintenance WM measures as well as enhanced mindfulness scores. Additional research is needed to understand the extent of yoga-related cognitive enhancement and mechanisms by which yoga may enhance cognition, ideally by utilizing randomized controlled trials and more comprehensive neuropsychological batteries.

Cognition-emotion interactions: patterns of change and implications for math problem solving

PubMed Central

Trezise, Kelly; Reeve, Robert A.

2014-01-01

Surprisingly little is known about whether relationships between cognitive and emotional states remain stable or change over time, or how different patterns of stability and/or change in the relationships affect problem solving abilities. Nevertheless, cross-sectional studies show that anxiety/worry may reduce working memory (WM) resources, and the ability to minimize the effects anxiety/worry is higher in individuals with greater WM capacity. To investigate the patterns of stability and/or change in cognition-emotion relations over time and their implications for problem solving, 126 14-year-olds’ algebraic WM and worry levels were assessed twice in a single day before completing an algebraic math problem solving test. We used latent transition analysis to identify stability/change in cognition-emotion relations, which yielded a six subgroup solution. Subgroups varied in WM capacity, worry, and stability/change relationships. Among the subgroups, we identified a high WM/low worry subgroup that remained stable over time and a high WM/high worry, and a moderate WM/low worry subgroup that changed to low WM subgroups over time. Patterns of stability/change in subgroup membership predicted algebraic test results. The stable high WM/low worry subgroup performed best and the low WM capacity-high worry “unstable across time” subgroup performed worst. The findings highlight the importance of assessing variations in cognition-emotion relationships over time (rather than assessing cognition or emotion states alone) to account for differences in problem solving abilities. PMID:25132830

A Randomized Control Trial of Working Memory Training With and Without Strategy Instruction: Effects on Young Children's Working Memory and Comprehension.

PubMed

Peng, Peng; Fuchs, Douglas

2017-01-01

Researchers are increasingly interested in working memory (WM) training. However, it is unclear whether it strengthens comprehension in young children who are at risk for learning difficulties. We conducted a modest study of whether the training of verbal WM would improve verbal WM and passage listening comprehension and whether training effects differed between two approaches: training with and without strategy instruction. A total of 58 first-grade children were randomly assigned to three groups: WM training with a rehearsal strategy, WM training without strategy instruction, and controls. Each member of the two training groups received a one-to-one, 35-min session of verbal WM training on each of 10 consecutive school days, totaling 5.8 hr. Both training groups improved on trained verbal WM tasks, with the rehearsal group making greater gains. Without correction for multiple group comparisons, the rehearsal group made reliable improvements over controls on an untrained verbal WM task and on passage listening comprehension and listening retell measures. The no-strategy-instruction group outperformed controls on passage listening comprehension. When corrected for multiple contrasts, these group differences disappeared but were associated with moderate to large effect sizes. Findings suggest-however tentatively-that brief but intensive verbal WM training may strengthen the verbal WM and comprehension performance of young children at risk. Necessary caveats and possible implications for theory and future research are discussed. © Hammill Institute on Disabilities 2015.

Disruption of IGF-1R signaling increases TRAIL-induced apoptosis: A new potential therapy for the treatment of melanoma

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

Karasic, Thomas B.; Hei, Tom K.; Ivanov, Vladimir N., E-mail: vni3@columbia.edu

2010-07-15

Resistance of cancer cells to apoptosis is dependent on a balance of multiple genetic and epigenetic mechanisms, which up-regulate efficacy of the surviving growth factor-receptor signaling pathways and suppress death-receptor signaling pathways. The Insulin-like Growth Factor-1 Receptor (IGF-1R) signaling pathway is highly active in metastatic melanoma cells by mediating downstream activation of PI3K-AKT and MAPK pathways and controlling general cell survival and proliferation. In the present study, we used human melanoma lines with established genotypes that represented different phases of cancer development: radial-growth-phase WM35, vertical-growth-phase WM793, metastatic LU1205 and WM9 [1]. All these lines have normal NRAS. WM35, WM793, LU1205more » and WM9 cells have mutated BRAF (V600E). WM35 and WM9 cells express normal PTEN, while in WM793 cells PTEN expression is down-regulated; finally, in LU1205 cells PTEN is inactivated by mutation. Cyclolignan picropodophyllin (PPP), a specific inhibitor of IGF-1R kinase activity, strongly down-regulated the basal levels of AKT activity in WM9 and in WM793 cells, modestly does so in LU1205, but has no effect on AKT activity in the early stage WM35 cells that are deficient in IGF-1R. In addition, PPP partially down-regulated the basal levels of active ERK1/2 in all lines used, highlighting the role of an alternative, non-BRAF pathway in MAPK activation. The final result of PPP treatment was an induction of apoptosis in WM793, WM9 and LU1205 melanoma cells. On the other hand, dose-dependent inhibition of IGF-1R kinase activity by PPP at a relatively narrow dose range (near 500 nM) has different effects on melanoma cells versus normal cells, inducing apoptosis in cancer cells and G2/M arrest of fibroblasts. To further enhance the pro-apoptotic effects of PPP on melanoma cells, we used a combined treatment of TNF-Related Apoptosis-Inducing Ligand (TRAIL) and PPP. This combination substantially increased death by

Early blindness alters the spatial organization of verbal working memory.

PubMed

Bottini, Roberto; Mattioni, Stefania; Collignon, Olivier

2016-10-01

Several studies suggest that serial order in working memory (WM) is grounded on space. For a list of ordered items held in WM, items at the beginning of the list are associated with the left side of space and items at the end of the list with the right side. This suggests that maintaining items in verbal WM is performed in strong analogy to writing these items down on a physical whiteboard for later consultation (The Mental Whiteboard Hypothesis). What drives this spatial mapping of ordered series in WM remains poorly understood. In the present study we tested whether visual experience is instrumental in establishing the link between serial order in WM and spatial processing. We tested early blind (EB), late blind (LB) and sighted individuals in an auditory WM task. Replicating previous studies, left-key responses were faster for early items in the list whereas later items facilitated right-key responses in the sighted group. The same effect was observed in LB individuals. In contrast, EB participants did not show any association between space and serial position in WM. These results suggest that early visual experience plays a critical role in linking ordered items in WM and spatial representations. The analogical spatial structure of WM may depend in part on the actual experience of using spatially organized devices (e.g., notes, whiteboards) to offload WM. These practices are largely precluded to EB individuals, who instead rely to mnemonic devices that are less spatially organized (e.g., recordings, vocal notes). The way we habitually organize information in the external world may bias the way we organize information in our WM. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hemispheric lateralization of verbal and spatial working memory during adolescence

PubMed Central

Nagel, Bonnie J.; Herting, Megan M.; Maxwell, Emily C.; Bruno, Richard; Fair, Damien

2013-01-01

Adult functional magnetic resonance imaging (fMRI) literature suggests that a left-right hemispheric dissociation may exist between verbal and spatial working memory (WM), respectively. However, investigation of this type has been obscured by incomparable verbal and spatial WM tasks and/or visual inspection at arbitrary thresholds as means to assess lateralization. Furthermore, it is unclear whether this hemispheric lateralization is present during adolescence, a time in which WM skills are improving, and whether there is a developmental association with laterality of brain functioning. This study used comparable verbal and spatial WM n-back tasks during fMRI and a bootstrap analysis approach to calculate lateralization indices (LI) across several thresholds to examine the potential of a left-right WM hemispheric dissociation in healthy adolescents. We found significant left hemispheric lateralization for verbal WM, most notably in the frontal and parietal lobes, as well as right hemisphere lateralization for spatial WM, seen in frontal and temporal cortices. Although no significant relationships were observed between LI and age or LI and performance, significant age-related patterns of brain activity were demonstrated during both verbal and spatial WM. Specifically, increased adolescent age was associated with less activity in the default mode brain network during verbal WM. In contrast, increased adolescent age was associated with greater activity in task-positive posterior parietal cortex during spatial working memory. Our findings highlight the importance of utilizing non-biased statistical methods and comparable tasks for determining patterns of functional lateralization. Our findings also suggest that, while a left-right hemispheric dissociation of verbal and spatial WM is apparent by early adolescence, age-related changes in functional activation during WM are also present. PMID:23511846

Poorer frontolimbic white matter integrity is associated with chronic cannabis use, FAAH genotype, and increased depressive and apathy symptoms in adolescents and young adults.

PubMed

Shollenbarger, Skyler G; Price, Jenessa; Wieser, Jon; Lisdahl, Krista

2015-01-01

The heaviest period of cannabis use coincides with ongoing white matter (WM) maturation. Further, cannabis-related changes may be moderated by FAAH genotype (rs324420). We examined the association between cannabis use and FAAH genotype on frontolimbic WM integrity in adolescents and emerging adults. We then tested whether observed WM abnormalities were linked with depressive or apathy symptoms. Participants included 37 cannabis users and 37 healthy controls (33 female; ages 18-25). Multiple regressions examined the independent and interactive effects of variables on WM integrity. Regular cannabis users demonstrated reduced WM integrity in the bilateral uncinate fasciculus (UNC) (MD, right: p = .009 and left: p = .009; FA, right: p = .04 and left: p = .03) and forceps minor (fMinor) (MD, p = .03) compared to healthy controls. Marginally reduced WM integrity in the cannabis users was found in the left anterior thalamic radiation (ATR) (FA, p = .08). Cannabis group ∗ FAAH genotype interaction predicted WM integrity in bilateral ATR (FA, right: p = .05 and left: p = .001) and fMinor (FA, p = .02). In cannabis users, poorer WM integrity was correlated with increased symptoms of depression and apathy in bilateral ATR and UNC. Consistent with prior findings, cannabis use was associated with reduced frontolimbic WM integrity. WM integrity was also moderated by FAAH genotype, in that cannabis-using FAAH C/C carriers and A carrying controls had reduced WM integrity compared to control C/C carriers. Observed frontolimbic white matter abnormalities were linked with increased depressive and apathy symptoms in the cannabis users.

Poorer frontolimbic white matter integrity is associated with chronic cannabis use, FAAH genotype, and increased depressive and apathy symptoms in adolescents and young adults

PubMed Central

Shollenbarger, Skyler G.; Price, Jenessa; Wieser, Jon; Lisdahl, Krista

2015-01-01

Background The heaviest period of cannabis use coincides with ongoing white matter (WM) maturation. Further, cannabis-related changes may be moderated by FAAH genotype (rs324420). We examined the association between cannabis use and FAAH genotype on frontolimbic WM integrity in adolescents and emerging adults. We then tested whether observed WM abnormalities were linked with depressive or apathy symptoms. Methods Participants included 37 cannabis users and 37 healthy controls (33 female; ages 18–25). Multiple regressions examined the independent and interactive effects of variables on WM integrity. Results Regular cannabis users demonstrated reduced WM integrity in the bilateral uncinate fasciculus (UNC) (MD, right: p = .009 and left: p = .009; FA, right: p = .04 and left: p = .03) and forceps minor (fMinor) (MD, p = .03) compared to healthy controls. Marginally reduced WM integrity in the cannabis users was found in the left anterior thalamic radiation (ATR) (FA, p = .08). Cannabis group ∗ FAAH genotype interaction predicted WM integrity in bilateral ATR (FA, right: p = .05 and left: p = .001) and fMinor (FA, p = .02). In cannabis users, poorer WM integrity was correlated with increased symptoms of depression and apathy in bilateral ATR and UNC. Conclusions Consistent with prior findings, cannabis use was associated with reduced frontolimbic WM integrity. WM integrity was also moderated by FAAH genotype, in that cannabis-using FAAH C/C carriers and A carrying controls had reduced WM integrity compared to control C/C carriers. Observed frontolimbic white matter abnormalities were linked with increased depressive and apathy symptoms in the cannabis users. PMID:26106535

Functional brain activation associated with working memory training and transfer.

PubMed

Clark, Cameron M; Lawlor-Savage, Linette; Goghari, Vina M

2017-09-15

While behavioural trials of working memory (WM) training have received much attention in recent years, a lesser explored parallel approach is functional neuroimaging. A small literature has suggested a complex time course for functional activation pattern changes following WM training (i.e. not simply increasing or decreasing due to training); however, no study to date has examined such neuroplastic effects in both the training task (dual n-back) and the fluid intelligence transfer task to which the training is purported to transfer (Raven's Matrices). This study investigated neural correlates of WM training in healthy young adults randomized to six weeks of WM training, or an active control condition (processing speed training) with a pre- and post-training fMRI design. Results indicated significant reductions in activation for the WM trained group in key WM-task related areas for trained WM tasks after training compared to the processing speed active control group. The same pattern of training related decreases in activation for the WM trained group was not observed for the transfer task, which is consistent with null results for all cognitive outcomes of the present trial. The observed pattern of results suggests that repetitive practice with a complex task does indeed lead to neuroplastic processes that very likely represent the reduced demand for attentional control while sub-components of the task become more routinized with practice. We suggest that future research investigate neural correlates of WM training in populations for which WM itself is impaired and/or behavioural trials of WM training have returned more promising results. Copyright © 2017 Elsevier B.V. All rights reserved.

Dasatinib in Treating Patients With Solid Tumors or Lymphomas That Are Metastatic or Cannot Be Removed By Surgery

ClinicalTrials.gov

2015-06-30

Immunoblastic Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-Cell Leukemia/Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IIIA Mycosis Fungoides and Sezary Syndrome; Stage IIIB Mycosis Fungoides and Sezary Syndrome; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-Cell Leukemia/Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Stage IVA Mycosis Fungoides and Sezary Syndrome; Stage IVB Mycosis Fungoides and Sezary Syndrome; T-Cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Hairy Cell Leukemia; Waldenstrom Macroglobulinemia

Deciphering the Adaptive Immune Response to Ovarian Cancer

DTIC Science & Technology

2014-10-01

of 10 mg/mL. Wells containing anti-CD3/ anti-CD28 coated beads (bead-to-cell ratio of 1:1) or human cytomegalovirus, Epstein - Barr virus , and...Waldenstrom’s Macroglobulinemia (MYD88L265P). CONCLUSION: Overall, this study is progressing on schedule and on budget. We have developed the...apart from T-cell–medi- ated control of virus -induced cancers (3). More obvious in humans is the influence of the immune system on cancer progression and

Working Memory and Consciousness: The Current State of Play

PubMed Central

Persuh, Marjan; LaRock, Eric; Berger, Jacob

2018-01-01

Working memory (WM), an important posit in cognitive science, allows one to temporarily store and manipulate information in the service of ongoing tasks. WM has been traditionally classified as an explicit memory system—that is, as operating on and maintaining only consciously perceived information. Recently, however, several studies have questioned this assumption, purporting to provide evidence for unconscious WM. In this article, we focus on visual working memory (VWM) and critically examine these studies as well as studies of unconscious perception that seem to provide indirect evidence for unconscious WM. Our analysis indicates that current evidence does not support an unconscious WM store, though we offer independent reasons to think that WM may operate on unconsciously perceived information. PMID:29551967

Mapping the Trajectory of Socioeconomic Disparity in Working Memory: Parental and Neighborhood Factors

PubMed Central

Hackman, Daniel A.; Betancourt, Laura M.; Gallop, Robert; Romer, Daniel; Brodsky, Nancy L.; Hurt, Hallam; Farah, Martha J.

2014-01-01

Working memory (WM) is positively correlated with socioeconomic status (SES). It is not clear, however, if SES predicts the rate of WM development over time nor whether SES effects are specific to family rather than neighborhood SES. A community sample of children (n = 316) enrolled between ages 10 and 13 completed four annual assessments of WM. Lower parental education, but not neighborhood disadvantage, was associated with worse WM performance. Neither measure of SES was associated with the rate of developmental change. Consequently the SES disparity in WM is not a developmental lag which narrows nor an accumulating effect that becomes more pronounced. Rather, the relation between family SES and WM originates earlier in childhood and is stable though adolescence. PMID:24779417

Working memory load can both improve and impair selective attention: evidence from the Navon paradigm.

PubMed

Ahmed, Lubna; de Fockert, Jan W

2012-10-01

Selective attention to relevant targets has been shown to depend on the availability of working memory (WM). Under conditions of high WM load, processing of irrelevant distractors is enhanced. Here we showed that this detrimental effect of WM load on selective attention efficiency is reversed when the task requires global- rather than local-level processing. Participants were asked to attend to either the local or the global level of a hierarchical Navon stimulus while keeping either a low or a high load in WM. In line with previous findings, during attention to the local level, distractors at the global level produced more interference under high than under low WM load. By contrast, loading WM had the opposite effect of improving selective attention during attention to the global level. The findings demonstrate that the impact of WM load on selective attention is not invariant, but rather is dependent on the level of the to-be-attended information.

Acute psychosocial stress and children's memory.

PubMed

de Veld, Danielle M J; Riksen-Walraven, J Marianne; de Weerth, Carolina

2014-07-01

We investigated whether children's performance on working memory (WM) and delayed retrieval (DR) tasks decreased after stress exposure, and how physiological stress responses related to performance under stress. About 158 children (83 girls; Mage = 10.61 years, SD = 0.52) performed two WM tasks (WM forward and WM backward) and a DR memory task first during a control condition, and 1 week later during a stress challenge. Salivary alpha-amylase (sAA) and cortisol were assessed during the challenge. Only WM backward performance declined over conditions. Correlations between physiological stress responses and performance within the stress challenge were present only for WM forward and DR. For WM forward, higher cortisol responses were related to better performance. For DR, there was an inverted U-shape relation between cortisol responses and performance, as well as a cortisol × sAA interaction, with concurrent high or low responses related to optimal performance. This emphasizes the importance of including curvilinear and interaction effects when relating physiology to memory.

Working Memory Load and Reminder Effect on Event-Based Prospective Memory of High- and Low-Achieving Students in Math.

PubMed

Chen, Youzhen; Lian, Rong; Yang, Lixian; Liu, Jianrong; Meng, Yingfang

The effects of working memory (WM) demand and reminders on an event-based prospective memory (PM) task were compared between students with low and high achievement in math. WM load (1- and 2-back tasks) was manipulated as a within-subject factor and reminder (with or without reminder) as a between-subject factor. Results showed that high-achieving students outperformed low-achieving students on all PM and n-back tasks. Use of a reminder improved PM performance and thus reduced prospective interference; the performance of ongoing tasks also improved for all students. Both PM and n-back performances in low WM load were better than in high WM load. High WM load had more influence on low-achieving students than on high-achieving students. Results suggest that low-achieving students in math were weak at PM and influenced more by high WM load. Thus, it is important to train these students to set up an obvious reminder for their PM and improve their WM.

EEG and Heart Rate Measures of Working Memory at 5 and 10 Months of Age

PubMed Central

Cuevas, Kimberly; Bell, Martha Ann; Marcovitch, Stuart; Calkins, Susan D.

2013-01-01

We recorded electroencephalogram (EEG; 6–9 Hz) and heart rate (HR) from infants at 5 and 10 months of age during baseline and performance on the looking A-not-B task of infant working memory (WM). Longitudinal baseline-to-task comparisons revealed WM-related increases in EEG power (all electrodes) and EEG coherence (medial frontal-occipital electrode pairs) at both ages. WM-related decreases in HR were only present at 5 months, and WM-related increases in EEG coherence became more localized by 10 months. Regression analyses revealed that baseline-to-task changes in psychophysiology accounted for variability in WM performance at 10, but not 5, months. HR and EEG power (medial frontal and lateral frontal electrodes) were unique predictors of variability in 10-month WM performance. These findings are discussed in relation to frontal lobe development, and represent the first comprehensive longitudinal analysis of age-related changes in the behavioral and psychophysiological correlates of WM. PMID:22148943

A pilot study of working memory and academic achievement in college students with ADHD.

PubMed

Gropper, Rachel J; Tannock, Rosemary

2009-05-01

To investigate working memory (WM), academic achievement, and their relationship in university students with attention-deficit/hyperactivity disorder (ADHD). Participants were university students with previously confirmed diagnoses of ADHD (n = 16) and normal control (NC) students (n = 30). Participants completed 3 auditory-verbal WM measures, 2 visual-spatial WM measures, and 1 control executive function task. Also, they self-reported grade point averages (GPAs) based on university courses. The ADHD group displayed significant weaknesses on auditory-verbal WM tasks and 1 visual-spatial task. They also showed a nonsignificant trend for lower GPAs. Within the entire sample, there was a significant relationship between GPA and auditory-verbal WM. WM impairments are evident in a subgroup of the ADHD population attending university. WM abilities are linked with, and thus may compromise, academic attainment. Parents and physicians are advised to counsel university-bound students with ADHD to contact the university accessibility services to provide them with academic guidance.

Evaluating relationships among clinical working memory assessment and inattentive and hyperactive/impulsive behaviors in a community sample of children.

PubMed

Colbert, Alison M; Bo, Jin

2017-07-01

This study examined relationships between inattentive and hyperactive/impulsive behaviors and working memory (WM) functioning, and the utility of WM in categorical diagnosis of ADHD versus considering ADHD symptoms on a continuum. The study included 50 male children (6-12 years). Inattentive and hyperactive/impulsive behaviors were measured by the Conners-3P parent report, and WM was assessed by the WISC-IV WM subtests and Working Memory Index (WMI). WISC-IV Arithmetic and Digit Span Backward were most consistently related to inattentive behaviors, and no WM measure was consistently related to ADHD hyperactive/impulsive behaviors. Arithmetic and Digit Span Backward also accounted for significant variance in inattentive behaviors and ADHD inattention symptoms, respectively. Neither the WMI nor the Arithmetic subtest correctly classified individuals diagnosed with ADHD. Measurement of inattentive behaviors on a continuum best characterized relationships between symptoms of ADHD and WM functioning; WM functioning did not have utility in categorical understanding of ADHD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Early auditory evoked potential is modulated by selective attention and related to individual differences in visual working memory capacity.

PubMed

Giuliano, Ryan J; Karns, Christina M; Neville, Helen J; Hillyard, Steven A

2014-12-01

A growing body of research suggests that the predictive power of working memory (WM) capacity for measures of intellectual aptitude is due to the ability to control attention and select relevant information. Crucially, attentional mechanisms implicated in controlling access to WM are assumed to be domain-general, yet reports of enhanced attentional abilities in individuals with larger WM capacities are primarily within the visual domain. Here, we directly test the link between WM capacity and early attentional gating across sensory domains, hypothesizing that measures of visual WM capacity should predict an individual's capacity to allocate auditory selective attention. To address this question, auditory ERPs were recorded in a linguistic dichotic listening task, and individual differences in ERP modulations by attention were correlated with estimates of WM capacity obtained in a separate visual change detection task. Auditory selective attention enhanced ERP amplitudes at an early latency (ca. 70-90 msec), with larger P1 components elicited by linguistic probes embedded in an attended narrative. Moreover, this effect was associated with greater individual estimates of visual WM capacity. These findings support the view that domain-general attentional control mechanisms underlie the wide variation of WM capacity across individuals.

Similarities and Differences Between Working Memory and Long-Term Memory: Evidence From the Levels-of-Processing Span Task

PubMed Central

Rose, Nathan S.; Myerson, Joel; Roediger, Henry L.; Hale, Sandra

2010-01-01

Two experiments compared the effects of depth of processing on working memory (WM) and long-term memory (LTM) using a levels-of-processing (LOP) span task, a newly developed WM span procedure that involves processing to-be-remembered words based on their visual, phonological, or semantic characteristics. Depth of processing had minimal effect on WM tests, yet subsequent memory for the same items on delayed tests showed the typical benefits of semantic processing. Although the difference in LOP effects demonstrates a dissociation between WM and LTM, we also found that the retrieval practice provided by recalling words on the WM task benefited long-term retention, especially for words initially recalled from supraspan lists. The latter result is consistent with the hypothesis that WM span tasks involve retrieval from secondary memory, but the LOP dissociation suggests the processes engaged by WM and LTM tests may differ. Therefore, similarities and differences between WM and LTM depend on the extent to which retrieval from secondary memory is involved and whether there is a match (or mismatch) between initial processing and subsequent retrieval, consistent with transfer-appropriate-processing theory. PMID:20192543

The many faces of working memory and short-term storage.

PubMed

Cowan, Nelson

2017-08-01

The topic of working memory (WM) is ubiquitous in research on cognitive psychology and on individual differences. According to one definition, it is a small amount of information kept in a temporary state of heightened accessibility; it is used in most types of communication and problem solving. Short-term storage has been defined as the passive (i.e., non-attention-based, nonstrategic) component of WM or, alternatively, as a passive store separate from an attention-based WM. Here I note that much confusion has been created by the use by various investigators of many, subtly different definitions of WM and short-term storage. The definitions are sometimes made explicit and sometimes implied. As I explain, the different definitions may have stemmed from the use of a wide variety of techniques to explore WM, along with differences in theoretical orientation. By delineating nine previously used definitions of WM and explaining how additional ones may emerge from combinations of these nine, I hope to improve scientific discourse on WM. The potential advantages of clarity about definitions of WM and short-term storage are illustrated with respect to several ongoing research controversies.

Considerations for the Optimization of Induced White Matter Injury Preclinical Models

PubMed Central

Ahmad, Abdullah Shafique; Satriotomo, Irawan; Fazal, Jawad; Nadeau, Stephen E.; Doré, Sylvain

2015-01-01

White matter (WM) injury in relation to acute neurologic conditions, especially stroke, has remained obscure until recently. Current advances in imaging technologies in the field of stroke have confirmed that WM injury plays an important role in the prognosis of stroke and suggest that WM protection is essential for functional recovery and post-stroke rehabilitation. However, due to the lack of a reproducible animal model of WM injury, the pathophysiology and mechanisms of this injury are not well studied. Moreover, producing selective WM injury in animals, especially in rodents, has proven to be challenging. Problems associated with inducing selective WM ischemic injury in the rodent derive from differences in the architecture of the brain, most particularly, the ratio of WM to gray matter in rodents compared to humans, the agents used to induce the injury, and the location of the injury. Aging, gender differences, and comorbidities further add to this complexity. This review provides a brief account of the techniques commonly used to induce general WM injury in animal models (stroke and non-stroke related) and highlights relevance, optimization issues, and translational potentials associated with this particular form of injury. PMID:26322013

Age-related white matter microstructural differences partly mediate age-related decline in processing speed but not cognition.

PubMed

Salami, Alireza; Eriksson, Johan; Nilsson, Lars-Göran; Nyberg, Lars

2012-03-01

Aging is associated with declining cognitive performance as well as structural changes in brain gray and white matter (WM). The WM deterioration contributes to a disconnection among distributed brain networks and may thus mediate age-related cognitive decline. The present diffusion tensor imaging (DTI) study investigated age-related differences in WM microstructure and their relation to cognition (episodic memory, visuospatial processing, fluency, and speed) in a large group of healthy subjects (n=287) covering 6 decades of the human life span. Age related decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) were observed across the entire WM skeleton as well as in specific WM tracts, supporting the WM degeneration hypothesis. The anterior section of the corpus callosum was more susceptible to aging compared to the posterior section, lending support to the anterior-posterior gradient of WM integrity in the corpus callosum. Finally, and of critical interest, WM integrity differences were found to mediate age-related reductions in processing speed but no significant mediation was found for episodic memory, visuospatial ability, or fluency. These findings suggest that compromised WM integrity is not a major contributing factor to declining cognitive performance in normal aging. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease. Copyright © 2011 Elsevier B.V. All rights reserved.

Working memory enhances visual perception: evidence from signal detection analysis.

PubMed

Soto, David; Wriglesworth, Alice; Bahrami-Balani, Alex; Humphreys, Glyn W

2010-03-01

We show that perceptual sensitivity to visual stimuli can be modulated by matches between the contents of working memory (WM) and stimuli in the visual field. Observers were presented with an object cue (to hold in WM or to merely attend) and subsequently had to identify a brief target presented within a colored shape. The cue could be re-presented in the display, where it surrounded either the target (on valid trials) or a distractor (on invalid trials). Perceptual identification of the target, as indexed by A', was enhanced on valid relative to invalid trials but only when the cue was kept in WM. There was minimal effect of the cue when it was merely attended and not kept in WM. Verbal cues were as effective as visual cues at modulating perceptual identification, and the effects were independent of the effects of target saliency. Matches to the contents of WM influenced perceptual sensitivity even under conditions that minimized competition for selecting the target. WM cues were also effective when targets were less likely to fall in a repeated WM stimulus than in other stimuli in the search display. There were no effects of WM on decisional criteria, in contrast to sensitivity. The findings suggest that reentrant feedback from WM can affect early stages of perceptual processing.

Impact of working memory load on cognitive control in trait anxiety: an ERP study.

PubMed

Qi, Senqing; Zeng, Qinghong; Luo, Yangmei; Duan, Haijun; Ding, Cody; Hu, Weiping; Li, Hong

2014-01-01

Whether trait anxiety is associated with a general impairment of cognitive control is a matter of debate. This study investigated whether and how experimentally manipulated working memory (WM) load modulates the relation between trait anxiety and cognitive control. This question was investigated using a dual-task design in combination with event-related potentials. Participants were required to remember either one (low WM load) or six letters (high WM load) while performing a flanker task. Our results showed that a high WM load disrupted participants' ability to overcome distractor interference and this effect was exacerbated for the high trait-anxious (HTA) group. This exacerbation was reflected by larger interference effects (i.e., incongruent minus congruent) on reaction times (RTs) and N2 amplitudes for the HTA group than for the low trait-anxious group under high WM load. The two groups, however, did not differ in their ability to inhibit task-irrelevant distractors under low WM load, as indicated by both RTs and N2 amplitudes. These findings underscore the significance of WM-related cognitive demand in contributing to the presence (or absence) of a general cognitive control deficit in trait anxiety. Furthermore, our findings show that when limited WM resources are depleted by high WM load, HTA individuals exhibit less efficient recruitments of cognitive control required for the inhibition of distractors, therefore resulting in a greater degree of response conflict.

Gender Differences in Verbal and Visuospatial Working Memory Performance and Networks.

PubMed

Zilles, David; Lewandowski, Mirjana; Vieker, Henning; Henseler, Ilona; Diekhof, Esther; Melcher, Tobias; Keil, Maria; Gruber, Oliver

2016-01-01

Working memory (WM) has been a matter of intensive basic and clinical research for some decades now. The investigation of WM function and dysfunction may facilitate the understanding of both physiological and pathological processes in the human brain. Though WM paradigms are widely used in neuroscientific and psychiatric research, conclusive knowledge about potential moderating variables such as gender is still missing. We used functional magnetic resonance imaging to investigate the effects of gender on verbal and visuospatial WM maintenance tasks in a large and homogeneous sample of young healthy subjects. We found significant gender effects on both the behavioral and neurofunctional level. Females exhibited disadvantages with a small effect size in both WM domains accompanied by stronger activations in a set of brain regions (including bilateral substantia nigra/ventral tegmental area and right Broca's area) independent of WM modality. As load and task difficulty effects have been shown for some of these regions, the stronger activations may reflect a slightly lower capacity of both WM domains in females. Males showed stronger bilateral intraparietal activations next to the precuneus which were specific for the visuospatial WM task. Activity in this specific region may be associated with visuospatial short-term memory capacity. These findings provide evidence for a slightly lower capacity in both WM modalities in females. © 2016 S. Karger AG, Basel.

Working memory as internal attention: toward an integrative account of internal and external selection processes.

PubMed

Kiyonaga, Anastasia; Egner, Tobias

2013-04-01

Working memory (WM) and attention have been studied as separate cognitive constructs, although it has long been acknowledged that attention plays an important role in controlling the activation, maintenance, and manipulation of representations in WM. WM has, conversely, been thought of as a means of maintaining representations to voluntarily guide perceptual selective attention. It has more recently been observed, however, that the contents of WM can capture visual attention, even when such internally maintained representations are irrelevant, and often disruptive, to the immediate external task. Thus, the precise relationship between WM and attention remains unclear, but it appears that they may bidirectionally impact one another, whether or not internal representations are consistent with the external perceptual goals. This reciprocal relationship seems, further, to be constrained by limited cognitive resources to handle demands in either maintenance or selection. We propose here that the close relationship between WM and attention may be best described as a give-and-take interdependence between attention directed toward either actively maintained internal representations (traditionally considered WM) or external perceptual stimuli (traditionally considered selective attention), underpinned by their shared reliance on a common cognitive resource. Put simply, we argue that WM and attention should no longer be considered as separate systems or concepts, but as competing and influencing one another because they rely on the same limited resource. This framework can offer an explanation for the capture of visual attention by irrelevant WM contents, as well as a straightforward account of the underspecified relationship between WM and attention.

Distinct structural alterations independently contributing to working memory deficits and symptomatology in paranoid schizophrenia.

PubMed

Zierhut, Kathrin C; Schulte-Kemna, Anna; Kaufmann, Jörn; Steiner, Johann; Bogerts, Bernhard; Schiltz, Kolja

2013-04-01

Schizophrenia is considered a brain disease with a quite heterogeneous clinical presentation. Studies in schizophrenia have yielded a wide array of correlations between structural and functional brain changes and clinical and cognitive symptoms. Reductions of grey matter volume (GMV) in the prefrontal and temporal cortex have been described which are crucial for the development of positive and negative symptoms and impaired working memory (WM). Associations between GMV reduction and positive and negative symptoms as well as WM impairment were assessed in schizophrenia patients (symptomatology in 34, WM in 26) and compared to healthy controls (36 total, WM in 26). GMV was determined by voxel-based morphometry and its relation to positive and negative symptoms as well as WM performance was assessed. In schizophrenia patients, reductions of GMV were evident in anterior cingulate cortex, ventrolateral prefrontal cortex (VLPFC), superior temporal cortex, and insula. GMV reductions in the superior temporal gyrus (STG) were associated with positive symptom severity as well as WM impairment. Furthermore, the absolute GMV of VLPFC was strongly related to negative symptoms. These predicted WM performance as well as processing speed. The present results support the assumption of two distinct pathomechanisms responsible for impaired WM in schizophrenia: (1) GMV reductions in the VLPFC predict the severity of negative symptoms. Increased negative symptoms in turn are associated with a slowing down of processing speed and predict an impaired WM. (2) GMV reductions in the temporal and mediofrontal cortex are involved in the development of positive symptoms and impair WM performance, too. Copyright © 2012 Elsevier Ltd. All rights reserved.

Working Memory as Internal Attention: Toward an Integrative Account of Internal and External Selection Processes

PubMed Central

Kiyonaga, Anastasia; Egner, Tobias

2012-01-01

Working memory (WM) and attention have been studied as separate cognitive constructs, although it has long been acknowledged that attention plays an important role in controlling the activation, maintenance, and manipulation of representations in WM. WM has, conversely, been thought of as a means of maintaining representations to voluntarily guide perceptual selective attention. It has more recently been observed, however, that the contents of WM can capture visual attention, even when such internally maintained representations are irrelevant, and often disruptive, to the immediate external task. Thus the precise relationship between WM and attention remains unclear, but it appears that they may bi-directionally impact one another, whether or not internal representations are consistent with external perceptual goals. This reciprocal relationship seems, further, to be constrained by limited cognitive resources to handle demands in either maintenance or selection. We propose here that the close relationship between WM and attention may be best described as a give-and-take interdependence between attention directed toward actively maintained internal representations (traditionally considered WM) versus external perceptual stimuli (traditionally considered selective attention), underpinned by their shared reliance on a common cognitive resource. Put simply, we argue that WM and attention should no longer be considered as separate systems or concepts, but as competing and impacting one another because they rely on the same limited resource. This framework can offer an explanation for the capture of visual attention by irrelevant WM contents, as well as a straightforward account of the underspecified relationship between WM and attention. PMID:23233157

Fractal dimension assessment of brain white matter structural complexity post stroke in relation to upper-extremity motor function

PubMed Central

Zhang, Luduan; Butler, Andrew J.; Sun, Chang-Kai; Sahgal, Vinod; Wittenberg, George F.; Yue, Guang H.

2008-01-01

Little is known about the association between brain white matter (WM) structure and motor function in humans. This study investigated complexity of brain WM interior shape as determined by magnetic resonance imaging (MRI) and its relationship with upper-extremity (UE) motor function in patients post stroke. We hypothesized that (1) the WM complexity would decrease following stroke, and (2) higher WM complexity in non-affected cortical areas would be related to greater UE motor function. Thirty-eight stroke patients (16 with left-hemisphere lesions) underwent MRI anatomical brain scans. Fractal dimension (FD), a quantitative shape metric, was applied onto skeletonized brain WM images to evaluate WM internal structural complexity. Wolf Motor Function Test (WMFT) and Fugl-Meyer Motor Assessment (FM) scores were measured to assess motor function of the affected limb. The WM complexity was lower in the stroke-affected hemisphere. The FD was associated with better motor function in two subgroups: with left-subcortical lesions, FD values of the lesion-free areas of the left hemisphere were associated with better FM scores; with right-cortical lesions, FD values of lesion-free regions were robustly associated with better WMFT scores. These findings suggest that greater residual WM complexity is associated with less impaired UE motor function, which is more robust in patients with right-hemisphere lesions. No correlations were found between lesion volume and WMFT or FM scores. This study addressed WM complexity in stroke patients and its relationship with UE motor function. Measurement of brain WM reorganization may be a sensitive correlate of UE function in people recovering from stroke. PMID:18590710

Frontal white matter changes and aggression in methamphetamine dependence.

PubMed

Lederer, Katharina; Fouche, Jean-Paul; Wilson, Don; Stein, Dan J; Uhlmann, Anne

2016-02-01

Chronic methamphetamine (MA) use can lead to white matter (WM) changes and increased levels of aggression. While previous studies have examined WM abnormalities relating to cognitive impairment, associations between WM integrity and aggression in MA dependence remain unclear. Diffusion Tensor Imaging (DTI) was used to investigate WM changes in 40 individuals with MA dependence and 40 matched healthy controls. A region of interest (ROI) approach using tract based spatial statistics (TBSS) in FSL was performed. We compared fractional anisotropy (FA), mean diffusivity (MD), parallel diffusivity (λ║) and perpendicular diffusivity (λ┴) in WM tracts of the frontal brain. A relationship of WM with aggression scores from the Buss & Perry Questionnaire was investigated. Mean scores for anger (p < 0.001), physical aggression (p = 0.032) and total aggression (p = 0.021) were significantly higher in the MA group relative to controls. ROI analysis showed increased MD (U = 439.5, p = 0.001) and λ┴ (U = 561.5, p = 0.021) values in the genu of the corpus callosum, and increased MD (U = 541.5, p = 0.012) values in the right cingulum in MA dependence. None of the WM changes were significantly associated with aggression scores. This study provides evidence of frontal WM changes and increased levels of aggression in individuals with MA dependence. The lack of significant associations between WM and aggressive behaviour may reflect methodological issues in measuring such behaviour, or may indicate that the neurobiology of aggression is not simply correlated with WM damage but is more complex.

Common capacity-limited neural mechanisms of selective attention and spatial working memory encoding

PubMed Central

Fusser, Fabian; Linden, David E J; Rahm, Benjamin; Hampel, Harald; Haenschel, Corinna; Mayer, Jutta S

2011-01-01

One characteristic feature of visual working memory (WM) is its limited capacity, and selective attention has been implicated as limiting factor. A possible reason why attention constrains the number of items that can be encoded into WM is that the two processes share limited neural resources. Functional magnetic resonance imaging (fMRI) studies have indeed demonstrated commonalities between the neural substrates of WM and attention. Here we investigated whether such overlapping activations reflect interacting neural mechanisms that could result in capacity limitations. To independently manipulate the demands on attention and WM encoding within one single task, we combined visual search and delayed discrimination of spatial locations. Participants were presented with a search array and performed easy or difficult visual search in order to encode one, three or five positions of target items into WM. Our fMRI data revealed colocalised activation for attention-demanding visual search and WM encoding in distributed posterior and frontal regions. However, further analysis yielded two patterns of results. Activity in prefrontal regions increased additively with increased demands on WM and attention, indicating regional overlap without functional interaction. Conversely, the WM load-dependent activation in visual, parietal and premotor regions was severely reduced during high attentional demand. We interpret this interaction as indicating the sites of shared capacity-limited neural resources. Our findings point to differential contributions of prefrontal and posterior regions to the common neural mechanisms that support spatial WM encoding and attention, providing new imaging evidence for attention-based models of WM encoding. PMID:21781193

Distributed and Dynamic Storage of Working Memory Stimulus Information in Extrastriate Cortex

PubMed Central

Sreenivasan, Kartik K.; Vytlacil, Jason; D'Esposito, Mark

2015-01-01

The predominant neurobiological model of working memory (WM) posits that stimulus information is stored via stable elevated activity within highly selective neurons. Based on this model, which we refer to as the canonical model, the storage of stimulus information is largely associated with lateral prefrontal cortex (lPFC). A growing number of studies describe results that cannot be fully explained by the canonical model, suggesting that it is in need of revision. In the present study, we directly test key elements of the canonical model. We analyzed functional MRI data collected as participants performed a task requiring WM for faces and scenes. Multivariate decoding procedures identified patterns of activity containing information about the items maintained in WM (faces, scenes, or both). While information about WM items was identified in extrastriate visual cortex (EC) and lPFC, only EC exhibited a pattern of results consistent with a sensory representation. Information in both regions persisted even in the absence of elevated activity, suggesting that elevated population activity may not represent the storage of information in WM. Additionally, we observed that WM information was distributed across EC neural populations that exhibited a broad range of selectivity for the WM items rather than restricted to highly selective EC populations. Finally, we determined that activity patterns coding for WM information were not stable, but instead varied over the course of a trial, indicating that the neural code for WM information is dynamic rather than static. Together, these findings challenge the canonical model of WM. PMID:24392897

Promoting the experimental dialogue between working memory and chunking: Behavioral data and simulation.

PubMed

Portrat, Sophie; Guida, Alessandro; Phénix, Thierry; Lemaire, Benoît

2016-04-01

Working memory (WM) is a cognitive system allowing short-term maintenance and processing of information. Maintaining information in WM consists, classically, in rehearsing or refreshing it. Chunking could also be considered as a maintenance mechanism. However, in the literature, it is more often used to explain performance than explicitly investigated within WM paradigms. Hence, the aim of the present paper was (1) to strengthen the experimental dialogue between WM and chunking, by studying the effect of acronyms in a computer-paced complex span task paradigm and (2) to formalize explicitly this dialogue within a computational model. Young adults performed a WM complex span task in which they had to maintain series of 7 letters for further recall while performing a concurrent location judgment task. The series to be remembered were either random strings of letters or strings containing a 3-letter acronym that appeared in position 1, 3, or 5 in the series. Together, the data and simulations provide a better understanding of the maintenance mechanisms taking place in WM and its interplay with long-term memory. Indeed, the behavioral WM performance lends evidence to the functional characteristics of chunking that seems to be, especially in a WM complex span task, an attentional time-based mechanism that certainly enhances WM performance but also competes with other processes at hand in WM. Computational simulations support and delineate such a conception by showing that searching for a chunk in long-term memory involves attentionally demanding subprocesses that essentially take place during the encoding phases of the task.

Focused, Unfocused, and Defocused Information in Working Memory

ERIC Educational Resources Information Center

Rerko, Laura; Oberauer, Klaus

2013-01-01

The study investigated the effect of selection cues in working memory (WM) on the fate of not-selected contents of WM. Experiments 1A and 1B showed that focusing on 1 cued item in WM does not impair memory for the remaining items. The nonfocused items are maintained in WM even when this is not required by the task. Experiments 2 and 3 showed that…

The complex interaction between anxiety and cognition: insight from spatial and verbal working memory

PubMed Central

Vytal, Katherine E.; Cornwell, Brian R.; Letkiewicz, Allison M.; Arkin, Nicole E.; Grillon, Christian

2013-01-01

Anxiety can be distracting, disruptive, and incapacitating. Despite problems with empirical replication of this phenomenon, one fruitful avenue of study has emerged from working memory (WM) experiments where a translational method of anxiety induction (risk of shock) has been shown to disrupt spatial and verbal WM performance. Performance declines when resources (e.g., spatial attention, executive function) devoted to goal-directed behaviors are consumed by anxiety. Importantly, it has been shown that anxiety-related impairments in verbal WM depend on task difficulty, suggesting that cognitive load may be an important consideration in the interaction between anxiety and cognition. Here we use both spatial and verbal WM paradigms to probe the effect of cognitive load on anxiety-induced WM impairment across task modality. Subjects performed a series of spatial and verbal n-back tasks of increasing difficulty (1, 2, and 3-back) while they were safe or at risk for shock. Startle reflex was used to probe anxiety. Results demonstrate that induced-anxiety differentially impacts verbal and spatial WM, such that low and medium-load verbal WM is more susceptible to anxiety-related disruption relative to high-load, and spatial WM is disrupted regardless of task difficulty. Anxiety impacts both verbal and spatial processes, as described by correlations between anxiety and performance impairment, albeit the effect on spatial WM is consistent across load. Demanding WM tasks may exert top-down control over higher-order cortical resources engaged by anxious apprehension, however high-load spatial WM may continue to experience additional competition from anxiety-related changes in spatial attention, resulting in impaired performance. By describing this disruption across task modalities, these findings inform current theories of emotion–cognition interactions and may facilitate development of clinical interventions that seek to target cognitive impairments associated with anxiety

Feeding untreated and pasteurized waste milk and bulk milk to calves: effects on calf performance, health status and antibiotic resistance of faecal bacteria.

PubMed

Aust, V; Knappstein, K; Kunz, H-J; Kaspar, H; Wallmann, J; Kaske, M

2013-12-01

Non-saleable milk (waste milk, WM) is contaminated with an undefined spectrum of potentially harmful pathogens and antimicrobial residues. The objective of this study was to determine the impact of feeding bulk milk (BM) or WM - both pasteurized or not - on calf performance, health and the antibiotic resistance of specific faecal bacteria. A total of 114 calves from a large-scale dairy were housed outdoors in individual hutches and were randomly assigned to one of four feeding groups. The calves were fed either WM, pasteurized WM (pWM), BM or pasteurized BM (pBM) from day 3 to 56 of life. Milk samples taken from the pasteurizer and calves' nipple buckets were investigated at regular intervals for total plate count and counts of thermoduric bacteria, coliforms and mastitis pathogens. Faecal samples were taken on days 2, 14, 28 and 56 of life from randomly selected calves of the WM, pWM and BM groups (each N = 8-9) and processed to obtain from each sample preferably two isolates of Escherichia (E.) coli and Enterococcus spp. respectively. Isolates were tested for their antimicrobial susceptibility to 25 antimicrobial agents by broth microdilution. Daily weight gain, milk and calf starter intake and health parameters did not differ significantly between the calves of the four feeding groups. The proportion of resistant E. coli isolates was significantly higher in calves fed WM and in calves fed pWM (most pronounced for cephalosporins) than in calves receiving BM. No differences in resistance were found for Enterococus spp. Thus, the concerns for selecting resistant faecal bacteria by feeding WM seem to be justified. Nonetheless, pasteurized WM of cows not treated with antimicrobials represents an acceptable feed for young calves. © 2012 Blackwell Verlag GmbH.

Implications of white matter damage in amyotrophic lateral sclerosis

PubMed Central

Zhou, Ting; Ahmad, Tina Khorshid; Gozda, Kiana; Truong, Jessica; Kong, Jiming; Namaka, Michael

2017-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, which involves the progressive degeneration of motor neurons. ALS has long been considered a disease of the grey matter; however, pathological alterations of the white matter (WM), including axonal loss, axonal demyelination and oligodendrocyte death, have been reported in patients with ALS. The present review examined motor neuron death as the primary cause of ALS and evaluated the associated WM damage that is guided by neuronal-glial interactions. Previous studies have suggested that WM damage may occur prior to the death of motor neurons, and thus may be considered an early indicator for the diagnosis and prognosis of ALS. However, the exact molecular mechanisms underlying early-onset WM damage in ALS have yet to be elucidated. The present review explored the detailed anatomy of WM and identified several pathological mechanisms that may be implicated in WM damage in ALS. In addition, it associated the pathophysiological alterations of WM, which may contribute to motor neuron death in ALS, with similar mechanisms of WM damage that are involved in multiple sclerosis (MS). Furthermore, the early detection of WM damage in ALS, using neuroimaging techniques, may lead to earlier therapeutic intervention, using immunomodulatory treatment strategies similar to those used in relapsing-remitting MS, aimed at delaying WM damage in ALS. Early therapeutic approaches may have the potential to delay motor neuron damage and thus prolong the survival of patients with ALS. The therapeutic interventions that are currently available for ALS are only marginally effective. However, early intervention with immunomodulatory drugs may slow the progression of WM damage in the early stages of ALS, thus delaying motor neuron death and increasing the life expectancy of patients with ALS. PMID:28791401

Acute and past subjective stress influence working memory and related neural substrates.

PubMed

Luettgau, Lennart; Schlagenhauf, Florian; Sjoerds, Zsuzsika

2018-05-28

Stress has been proposed to affect cognitive control capacities, including working memory (WM) maintenance. This effect may depend on variability in stress reactivity and past subjective stress. However, as most studies employed between-subjects designs, evidence for within-subject stress effects remains scarce. To understand the role of intra-individual stress effects on WM, we adopted a within-subject design to study how acute stress, variability in stress reactivity, and past subjective stress influence behavioral and neural WM mechanisms. Thirty-four healthy males performed a WM task during functional magnetic resonance imaging (fMRI) in a control versus acute stress condition following the Trier Social Stress Test, a validated psychosocial stressor method. We tested for stress effects on WM performance and related neural activation by associating them with individual acute stress responsivity and past subjective stress experience using retrospective self-report questionnaires. We found no evidence of an effect of acute stress or related stress-reactivity on intra-individual WM performance. However, past subjective stress negatively influenced acute stress-induced changes to WM. On the neural level, acute stress reduced WM-related activation in the dorsolateral prefrontal cortex (dlPFC). The observed negative influence of inter-individual variability in past subjective stress experience on changes in WM performance, suggests that past subjective stress might induce vulnerability for impairing effects of acute stress on cognitive functioning. Because acute stress reduced WM-related dlPFC activation while WM performance remained unaffected, acute stress might boost neural processing efficiency in this group of high performing healthy individuals. Our study suggests that measures of past subjective stress should be considered when studying and interpreting the effects of acute stress on cognition. Copyright © 2018. Published by Elsevier Ltd.

A new modified listening span task to enhance validity of working memory assessment for people with and without aphasia.

PubMed

Ivanova, Maria V; Hallowell, Brooke

2014-01-01

Deficits in working memory (WM) are an important subset of cognitive processing deficits associated with aphasia. However, there are serious limitations to research on WM in aphasia largely due to the lack of an established valid measure of WM impairment for this population. The aim of the current study was to address shortcomings of previous measures by developing and empirically evaluating a novel WM task with a sentence-picture matching processing component designed to circumvent confounds inherent in existing measures of WM in aphasia. The novel WM task was presented to persons with (n=27) and without (n=33) aphasia. Results demonstrated high concurrent validity of a novel WM task. Individuals with aphasia performed significantly worse on all conditions of the WM task compared to individuals without aphasia. Different patterns of performance across conditions were observed for the two groups. Additionally, WM capacity was significantly related to auditory comprehension abilities in individuals with mild aphasia but not those with moderate aphasia. Strengths of the novel WM task are that it allows for differential control for length versus complexity of verbal stimuli and indexing of the relative influence of each, minimizes metalinguistic requirements, enables control for complexity of processing components, allows participants to respond with simple gestures or verbally, and eliminates reading requirements. Results support the feasibility and validity of using a novel task to assess WM in individuals with and without aphasia. Readers will be able to (1) discuss the limitations of current working memory measures for individuals with aphasia; (2) describe how task design features of a new working memory task for people with aphasia address shortcomings of existing measures; (3) summarize the evidence supporting the validity of the novel working memory task. Copyright © 2014 Elsevier Inc. All rights reserved.

Working Memory for Serial Order Is Dysfunctional in Adults With a History of Developmental Dyscalculia: Evidence From Behavioral and Neuroimaging Data.

PubMed

Attout, Lucie; Salmon, Eric; Majerus, Steve

2015-01-01

Recent studies suggest that order working memory (WM) may be specifically associated with numerical abilities. This study explored behavioral performance and neural networks associated with verbal WM in adults with a history of developmental dyscalculia (DD). The DD group performed significantly poorer but with the same precision than the control group in order WM tasks and showed a lower activation of the right middle frontal gyrus during the order WM and the alphabetical order judgment tasks. This study suggests a persistent impairment in order WM in adults with DD, characterized by more general difficulties in controlled activation of order information.

Superior Intraparietal Sulcus Controls the Variability of Visual Working Memory Precision.

PubMed

Galeano Weber, Elena M; Peters, Benjamin; Hahn, Tim; Bledowski, Christoph; Fiebach, Christian J

2016-05-18

Limitations of working memory (WM) capacity depend strongly on the cognitive resources that are available for maintaining WM contents in an activated state. Increasing the number of items to be maintained in WM was shown to reduce the precision of WM and to increase the variability of WM precision over time. Although WM precision was recently associated with neural codes particularly in early sensory cortex, we have so far no understanding of the neural bases underlying the variability of WM precision, and how WM precision is preserved under high load. To fill this gap, we combined human fMRI with computational modeling of behavioral performance in a delayed color-estimation WM task. Behavioral results replicate a reduction of WM precision and an increase of precision variability under high loads (5 > 3 > 1 colors). Load-dependent BOLD signals in primary visual cortex (V1) and superior intraparietal sulcus (IPS), measured during the WM task at 2-4 s after sample onset, were modulated by individual differences in load-related changes in the variability of WM precision. Although stronger load-related BOLD increase in superior IPS was related to lower increases in precision variability, thus stabilizing WM performance, the reverse was observed for V1. Finally, the detrimental effect of load on behavioral precision and precision variability was accompanied by a load-related decline in the accuracy of decoding the memory stimuli (colors) from left superior IPS. We suggest that the superior IPS may contribute to stabilizing visual WM performance by reducing the variability of memory precision in the face of higher load. This study investigates the neural bases of capacity limitations in visual working memory by combining fMRI with cognitive modeling of behavioral performance, in human participants. It provides evidence that the superior intraparietal sulcus (IPS) is a critical brain region that influences the variability of visual working memory precision between and

Boosting Cognition: Effects of Multiple-Session Transcranial Direct Current Stimulation on Working Memory.

PubMed

Talsma, Lotte J; Kroese, Henryk A; Slagter, Heleen A

2017-04-01

Transcranial direct current stimulation (tDCS) is a promising tool for neurocognitive enhancement. Several studies have shown that just a single session of tDCS over the left dorsolateral pFC (lDLPFC) can improve the core cognitive function of working memory (WM) in healthy adults. Yet, recent studies combining multiple sessions of anodal tDCS over lDLPFC with verbal WM training did not observe additional benefits of tDCS in subsequent stimulation sessions nor transfer of benefits to novel WM tasks posttraining. Using an enhanced stimulation protocol as well as a design that included a baseline measure each day, the current study aimed to further investigate the effects of multiple sessions of tDCS on WM. Specifically, we investigated the effects of three subsequent days of stimulation with anodal (20 min, 1 mA) versus sham tDCS (1 min, 1 mA) over lDLPFC (with a right supraorbital reference) paired with a challenging verbal WM task. WM performance was measured with a verbal WM updating task (the letter n-back) in the stimulation sessions and several WM transfer tasks (different letter set n-back, spatial n-back, operation span) before and 2 days after stimulation. Anodal tDCS over lDLPFC enhanced WM performance in the first stimulation session, an effect that remained visible 24 hr later. However, no further gains of anodal tDCS were observed in the second and third stimulation sessions, nor did benefits transfer to other WM tasks at the group level. Yet, interestingly, post hoc individual difference analyses revealed that in the anodal stimulation group the extent of change in WM performance on the first day of stimulation predicted pre to post changes on both the verbal and the spatial transfer task. Notably, this relationship was not observed in the sham group. Performance of two individuals worsened during anodal stimulation and on the transfer tasks. Together, these findings suggest that repeated anodal tDCS over lDLPFC combined with a challenging WM task may

Positive affect improves working memory: implications for controlled cognitive processing.

PubMed

Yang, Hwajin; Yang, Sujin; Isen, Alice M

2013-01-01

This study examined the effects of positive affect on working memory (WM) and short-term memory (STM). Given that WM involves both storage and controlled processing and that STM primarily involves storage processing, we hypothesised that if positive affect facilitates controlled processing, it should improve WM more than STM. The results demonstrated that positive affect, compared with neutral affect, significantly enhanced WM, as measured by the operation span task. The influence of positive affect on STM, however, was weaker. These results suggest that positive affect enhances WM, a task that involves controlled processing, not just storage processing. Additional analyses of recall and processing times and accuracy further suggest that improved WM under positive affect is not attributable to motivational differences, but results instead from improved controlled cognitive processing.

The anterior-ventrolateral temporal lobe contributes to boosting visual working memory capacity for items carrying semantic information.

PubMed

Chiou, Rocco; Lambon Ralph, Matthew A

2018-04-01

Working memory (WM) is a buffer that temporarily maintains information, be it visual or auditory, in an active state, caching its contents for online rehearsal or manipulation. How the brain enables long-term semantic knowledge to affect the WM buffer is a theoretically significant issue awaiting further investigation. In the present study, we capitalise on the knowledge about famous individuals as a 'test-case' to study how it impinges upon WM capacity for human faces and its neural substrate. Using continuous theta-burst transcranial stimulation combined with a psychophysical task probing WM storage for varying contents, we provide compelling evidence that (1) faces (regardless of familiarity) continued to accrue in the WM buffer with longer encoding time, whereas for meaningless stimuli (colour shades) there was little increment; (2) the rate of WM accrual was significantly more efficient for famous faces, compared to unknown faces; (3) the right anterior-ventrolateral temporal lobe (ATL) causally mediated this superior WM storage for famous faces. Specifically, disrupting the ATL (a region tuned to semantic knowledge including person identity) selectively hinders WM accrual for celebrity faces while leaving the accrual for unfamiliar faces intact. Further, this 'semantically-accelerated' storage is impervious to disruption of the right middle frontal gyrus and vertex, supporting the specific and causative contribution of the right ATL. Our finding advances the understanding of the neural architecture of WM, demonstrating that it depends on interaction with long-term semantic knowledge underpinned by the ATL, which causally expands the WM buffer when visual content carries semantic information. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

The effectiveness of working memory training with individuals with intellectual disabilities - a meta-analytic review.

PubMed

Danielsson, Henrik; Zottarel, Valentina; Palmqvist, Lisa; Lanfranchi, Silvia

2015-01-01

Working memory (WM) training has been increasingly popular in the last years. Previous studies have shown that individuals with intellectual disabilities (ID) have low WM capacity and therefore would benefit by this type of intervention. The aim of this study was to investigate the effect of WM and cognitive training for individuals with ID. The effects reported in previous studies have varied and therefore a meta-analysis of articles in the major databases was conducted. Inclusion criteria included to have a pretest-posttest design with a training group and a control group and to have measures of WM or short-term memory. Ten studies with 28 comparisons were included. The results reveal a significant, but small, overall pretest-posttest effect size (ES) for WM training for individuals with ID compared to controls. A mixed WM approach, including both verbal and visuo-spatial components working mainly on strategies, was the only significant training type with a medium ES. The most commonly reported training type, visuo-spatial WM training, was performed in 60 percent of the included comparisons and had a non-significant ES close to zero. We conclude that even if there is an overall effect of WM training, a mixed WM approach appears to cause this effect. Given the few studies included and the different characteristics of the included studies, interpretations should be done with caution. However, different types of interventions appear to have different effects. Even if the results were promising, more studies are needed to better understand how to design an effective WM intervention for this group and to understand if, and how, these short-term effects remain over time and transfer to everyday activities.

The effectiveness of working memory training with individuals with intellectual disabilities – a meta-analytic review

PubMed Central

Danielsson, Henrik; Zottarel, Valentina; Palmqvist, Lisa; Lanfranchi, Silvia

2015-01-01

Working memory (WM) training has been increasingly popular in the last years. Previous studies have shown that individuals with intellectual disabilities (ID) have low WM capacity and therefore would benefit by this type of intervention. The aim of this study was to investigate the effect of WM and cognitive training for individuals with ID. The effects reported in previous studies have varied and therefore a meta-analysis of articles in the major databases was conducted. Inclusion criteria included to have a pretest–posttest design with a training group and a control group and to have measures of WM or short-term memory. Ten studies with 28 comparisons were included. The results reveal a significant, but small, overall pretest–posttest effect size (ES) for WM training for individuals with ID compared to controls. A mixed WM approach, including both verbal and visuo-spatial components working mainly on strategies, was the only significant training type with a medium ES. The most commonly reported training type, visuo-spatial WM training, was performed in 60 percent of the included comparisons and had a non-significant ES close to zero. We conclude that even if there is an overall effect of WM training, a mixed WM approach appears to cause this effect. Given the few studies included and the different characteristics of the included studies, interpretations should be done with caution. However, different types of interventions appear to have different effects. Even if the results were promising, more studies are needed to better understand how to design an effective WM intervention for this group and to understand if, and how, these short-term effects remain over time and transfer to everyday activities. PMID:26347692

Investigation of the influence of emotions on working memory capacity using ERP and ERSP.

PubMed

Zhang, Yuanyuan; Zhang, Gaoyan; Liu, Baolin

2017-08-15

Recent studies have reported that there are individual differences in working memory (WM), and that WM may be affected by emotions. To date, it remains controversial whether emotions impair or facilitate WM and whether there are individual differences in their effect on WM. In this study, three emotions (negative, neutral, and positive) were induced by a video database that was established according to the emotional stimuli habit of Chinese people. A change detection paradigm was used to examine the effect of emotions on the visual WM. Participants were divided into high- and low-capacity groups according to their WM capacity. The behavioral results revealed that both negative and positive emotions may enhance WM capacity in the high-capacity group compared with the neutral emotion. In contrast, an opposite effect was observed in the low-capacity group. Analysis of the contralateral delay activity and P300 components demonstrated significantly higher amplitudes in the high-capacity group following positive and negative emotions; the effects were opposite in the low-capacity group. The event-related spectral perturbation results demonstrated a more powerful event-related synchronization in the alpha-band (300-400ms) in the low-capacity group in positive and negative emotions; opposite results were observed in the high-capacity group. The consistence of the behavioral and electrophysiological results suggests interindividual differences in the impact of emotions on the WM capacity. Moreover, both positive and negative emotions can facilitate WM capacity in the high-capacity group, while they impair WM capacity in the low-capacity group. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Working memory updating and binding training: Bayesian evidence supporting the absence of transfer.

PubMed

De Simoni, Carla; von Bastian, Claudia C

2018-06-01

As working memory (WM) predicts a wide range of other abilities, it has become a popular target for training interventions. However, its effectiveness to elicit generalized cognitive benefits is still under debate. Previous research yielded inconsistent findings and focused only little on the mechanisms underlying transfer effects. To disentangle training effects on WM capacity and efficiency, we evaluated near transfer to untrained, structurally different WM tasks and far transfer to closely related abilities (i.e., reasoning, processing speed, task switching, and inhibitory control) in addition to process-specific effects on 3 WM mechanisms (i.e., focus switching, removal of WM contents, and interference resolution). We randomly assigned 197 young adults to 1 of 2 experimental groups (updating or item-to-context binding) or to an active control group practicing visual search tasks. Before and after 5 weeks of adaptive training, performance was assessed measuring each of the cognitive processes and abilities of interest with 4 tasks covering verbal-numerical and visual-spatial materials. Despite the relatively large sample size, large practice effects in the trained tasks, and at least moderate correlations between WM training tasks and transfer measures, we found consistent evidence for the absence of any training-induced improvements across all ranges of transfer and mechanisms. Instead, additional analyses of error patterns and self-reported strategy use indicated that WM training encouraged the development of stimulus-specific expertise and use of paradigm-specific strategies. Thus, the results suggest that the WM training interventions examined here enhanced neither WM capacity nor the WM mechanisms assumed to underlie transfer. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Comparison of Watermelon and Carbohydrate Beverage on Exercise-Induced Alterations in Systemic Inflammation, Immune Dysfunction, and Plasma Antioxidant Capacity

PubMed Central

Shanely, R. Andrew; Nieman, David C.; Perkins-Veazie, Penelope; Henson, Dru A.; Meaney, Mary P.; Knab, Amy M.; Cialdell-Kam, Lynn

2016-01-01

Consuming carbohydrate- and antioxidant-rich fruits during exercise as a means of supporting and enhancing both performance and health is of interest to endurance athletes. Watermelon (WM) contains carbohydrate, lycopene, l-citrulline, and l-arginine. WM may support exercise performance, augment antioxidant capacity, and act as a countermeasure to exercise-induced inflammation and innate immune changes. Trained cyclists (n = 20, 48 ± 2 years) participated in a randomized, placebo controlled, crossover study. Subjects completed two 75 km cycling time trials after either 2 weeks ingestion of 980 mL/day WM puree or no treatment. Subjects drank either WM puree containing 0.2 gm/kg carbohydrate or a 6% carbohydrate beverage every 15 min during the time trials. Blood samples were taken pre-study and pre-, post-, 1 h post-exercise. WM ingestion versus no treatment for 2-weeks increased plasma l-citrulline and l-arginine concentrations (p < 0.0125). Exercise performance did not differ between WM puree or carbohydrate beverage trials (p > 0.05), however, the rating of perceived exertion was greater during the WM trial (p > 0.05). WM puree versus carbohydrate beverage resulted in a similar pattern of increase in blood glucose, and greater increases in post-exercise plasma antioxidant capacity, l-citrulline, l-arginine, and total nitrate (all p < 0.05), but without differences in systemic markers of inflammation or innate immune function. Daily WM puree consumption fully supported the energy demands of exercise, and increased post-exercise blood levels of WM nutritional components (l-citrulline and l-arginine), antioxidant capacity, and total nitrate, but without an influence on post-exercise inflammation and changes in innate immune function. PMID:27556488

Comparison of Watermelon and Carbohydrate Beverage on Exercise-Induced Alterations in Systemic Inflammation, Immune Dysfunction, and Plasma Antioxidant Capacity.

PubMed

Shanely, R Andrew; Nieman, David C; Perkins-Veazie, Penelope; Henson, Dru A; Meaney, Mary P; Knab, Amy M; Cialdell-Kam, Lynn

2016-08-22

Consuming carbohydrate- and antioxidant-rich fruits during exercise as a means of supporting and enhancing both performance and health is of interest to endurance athletes. Watermelon (WM) contains carbohydrate, lycopene, l-citrulline, and l-arginine. WM may support exercise performance, augment antioxidant capacity, and act as a countermeasure to exercise-induced inflammation and innate immune changes. Trained cyclists (n = 20, 48 ± 2 years) participated in a randomized, placebo controlled, crossover study. Subjects completed two 75 km cycling time trials after either 2 weeks ingestion of 980 mL/day WM puree or no treatment. Subjects drank either WM puree containing 0.2 gm/kg carbohydrate or a 6% carbohydrate beverage every 15 min during the time trials. Blood samples were taken pre-study and pre-, post-, 1 h post-exercise. WM ingestion versus no treatment for 2-weeks increased plasma l-citrulline and l-arginine concentrations (p < 0.0125). Exercise performance did not differ between WM puree or carbohydrate beverage trials (p > 0.05), however, the rating of perceived exertion was greater during the WM trial (p > 0.05). WM puree versus carbohydrate beverage resulted in a similar pattern of increase in blood glucose, and greater increases in post-exercise plasma antioxidant capacity, l-citrulline, l-arginine, and total nitrate (all p < 0.05), but without differences in systemic markers of inflammation or innate immune function. Daily WM puree consumption fully supported the energy demands of exercise, and increased post-exercise blood levels of WM nutritional components (l-citrulline and l-arginine), antioxidant capacity, and total nitrate, but without an influence on post-exercise inflammation and changes in innate immune function.

Does Controlling for Temporal Parameters Change the Levels-of-Processing Effect in Working Memory?

PubMed Central

Loaiza, Vanessa M.; Camos, Valérie

2016-01-01

The distinguishability between working memory (WM) and long-term memory has been a frequent and long-lasting source of debate in the literature. One recent method of identifying the relationship between the two systems has been to consider the influence of long-term memory effects, such as the levels-of-processing (LoP) effect, in WM. However, the few studies that have examined the LoP effect in WM have shown divergent results. This study examined the LoP effect in WM by considering a theoretically meaningful methodological aspect of the LoP span task. Specifically, we fixed the presentation duration of the processing component a priori because such fixed complex span tasks have shown differences when compared to unfixed tasks in terms of recall from WM as well as the latent structure of WM. After establishing a fixed presentation rate from a pilot study, the LoP span task presented memoranda in red or blue font that were immediately followed by two processing words that matched the memoranda in terms of font color or semantic relatedness. On presentation of the processing words, participants made deep or shallow processing decisions for each of the memoranda before a cue to recall them from WM. Participants also completed delayed recall of the memoranda. Results indicated that LoP affected delayed recall, but not immediate recall from WM. These results suggest that fixing temporal parameters of the LoP span task does not moderate the null LoP effect in WM, and further indicate that WM and long-term episodic memory are dissociable on the basis of LoP effects. PMID:27152126

Structural development of human brain white matter from mid-fetal to perinatal stage

NASA Astrophysics Data System (ADS)

Ouyang, Austin; Yu, Qiaowen; Mishra, Virendra; Chalak, Lina; Jeon, Tina; Sivarajan, Muraleedharan; Jackson, Greg; Rollins, Nancy; Liu, Shuwei; Huang, Hao

2015-03-01

The structures of developing human brain white matter (WM) tracts can be effectively quantified by DTI-derived metrics, including fractional anisotropy (FA), mean, axial and radial diffusivity (MD, AD and RD). However, dynamics of WM microstructure during very early developmental period from mid-fetal to perinatal stage is unknown. It is difficult to accurately measure microstructural properties of these WM tracts due to severe contamination from cerebrospinal fluid (CSF). In this study, high resolution DTI of fetal brains at mid-fetal stage (20 weeks of gestation or 20wg), 19 brains in the middle of 3rd trimester (35wg) and 17 brains around term (40wg) were acquired. We established first population-averaged DTI templates at these three time points and extracted WM skeleton. 16 major WM tracts in limbic, projection, commissural and association tract groups were traced with DTI tractography in native space. The WM skeleton in the template space was inversely transformed back to the native space for measuring core WM microstructures of each individual tract. Continuous microstructural enhancement and volumetric increase of WM tracts were found from 20wg to 40wg. The microstructural enhancement from FA measurement is decelerated in late 3rd trimester compared to mid-fetal to middle 3rd trimester, while volumetric increase of prefrontal WM tracts is accelerated. The microstructural enhancement from 35wg to 40wg is heterogeneous among different tract groups with microstructures of association tracts undergoing most dramatic change. Besides decreases of RD indicating active myelination, the decrease of AD for most WM tracts during late 3rd trimester suggests axonal packing process.

A framework for understanding waste management studies in construction.

PubMed

Lu, Weisheng; Yuan, Hongping

2011-06-01

During the past decades, construction and demolition (C&D) waste issues have received increasing attention from both practitioners and researchers around the world. A plethora of research relating to C&D waste management (WM) has been published in scholarly journals. However, a comprehensive understanding of the C&D WM research is somehow absent in spite of its proliferation. The aim of this paper is to develop a framework that helps readers understand the C&D WM research as archived in selected journals. Papers under the topic of C&D WM are retrieved based on a set of rigorous procedures. The information of these papers is then analyzed with the assistance of the Qualitative Social Research (QSR) software package NVivo. A framework for understanding C&D WM research is created based on the analytic results. By following the framework, a bibliometric analysis of research in C&D WM is presented, followed by an in-depth literature analysis. It is found that C&D generation, reduction, and recycling are the three major topics in the discipline of C&D WM. Future research is recommended to (a) investigate C&D waste issues in wider scopes including design, maintenance and demolition, (b) develop a unified measurement for waste generation so that WM performance can be compared across various economies, and (c) enhance effectiveness of WM approaches (e.g. waste charging scheme) based on new WM concepts (e.g. Extended Producer Responsibility). In addition to the above research findings, the approach for producing the research framework can be useful references for other studies which attempt to understand the research of a given discipline. Copyright © 2011 Elsevier Ltd. All rights reserved.

Does Controlling for Temporal Parameters Change the Levels-of-Processing Effect in Working Memory?

PubMed

Loaiza, Vanessa M; Camos, Valérie

2016-01-01

The distinguishability between working memory (WM) and long-term memory has been a frequent and long-lasting source of debate in the literature. One recent method of identifying the relationship between the two systems has been to consider the influence of long-term memory effects, such as the levels-of-processing (LoP) effect, in WM. However, the few studies that have examined the LoP effect in WM have shown divergent results. This study examined the LoP effect in WM by considering a theoretically meaningful methodological aspect of the LoP span task. Specifically, we fixed the presentation duration of the processing component a priori because such fixed complex span tasks have shown differences when compared to unfixed tasks in terms of recall from WM as well as the latent structure of WM. After establishing a fixed presentation rate from a pilot study, the LoP span task presented memoranda in red or blue font that were immediately followed by two processing words that matched the memoranda in terms of font color or semantic relatedness. On presentation of the processing words, participants made deep or shallow processing decisions for each of the memoranda before a cue to recall them from WM. Participants also completed delayed recall of the memoranda. Results indicated that LoP affected delayed recall, but not immediate recall from WM. These results suggest that fixing temporal parameters of the LoP span task does not moderate the null LoP effect in WM, and further indicate that WM and long-term episodic memory are dissociable on the basis of LoP effects.

Common neural substrates for visual working memory and attention.

PubMed

Mayer, Jutta S; Bittner, Robert A; Nikolić, Danko; Bledowski, Christoph; Goebel, Rainer; Linden, David E J

2007-06-01

Humans are severely limited in their ability to memorize visual information over short periods of time. Selective attention has been implicated as a limiting factor. Here we used functional magnetic resonance imaging to test the hypothesis that this limitation is due to common neural resources shared by visual working memory (WM) and selective attention. We combined visual search and delayed discrimination of complex objects and independently modulated the demands on selective attention and WM encoding. Participants were presented with a search array and performed easy or difficult visual search in order to encode one or three complex objects into visual WM. Overlapping activation for attention-demanding visual search and WM encoding was observed in distributed posterior and frontal regions. In the right prefrontal cortex and bilateral insula blood oxygen-level-dependent activation additively increased with increased WM load and attentional demand. Conversely, several visual, parietal and premotor areas showed overlapping activation for the two task components and were severely reduced in their WM load response under the condition with high attentional demand. Regions in the left prefrontal cortex were selectively responsive to WM load. Areas selectively responsive to high attentional demand were found within the right prefrontal and bilateral occipital cortex. These results indicate that encoding into visual WM and visual selective attention require to a high degree access to common neural resources. We propose that competition for resources shared by visual attention and WM encoding can limit processing capabilities in distributed posterior brain regions.

Impact of Working Memory Load on Cognitive Control in Trait Anxiety: An ERP Study

PubMed Central

Qi, Senqing; Zeng, Qinghong; Luo, Yangmei; Duan, Haijun; Ding, Cody; Hu, Weiping; Li, Hong

2014-01-01

Whether trait anxiety is associated with a general impairment of cognitive control is a matter of debate. This study investigated whether and how experimentally manipulated working memory (WM) load modulates the relation between trait anxiety and cognitive control. This question was investigated using a dual-task design in combination with event-related potentials. Participants were required to remember either one (low WM load) or six letters (high WM load) while performing a flanker task. Our results showed that a high WM load disrupted participants' ability to overcome distractor interference and this effect was exacerbated for the high trait-anxious (HTA) group. This exacerbation was reflected by larger interference effects (i.e., incongruent minus congruent) on reaction times (RTs) and N2 amplitudes for the HTA group than for the low trait-anxious group under high WM load. The two groups, however, did not differ in their ability to inhibit task-irrelevant distractors under low WM load, as indicated by both RTs and N2 amplitudes. These findings underscore the significance of WM-related cognitive demand in contributing to the presence (or absence) of a general cognitive control deficit in trait anxiety. Furthermore, our findings show that when limited WM resources are depleted by high WM load, HTA individuals exhibit less efficient recruitments of cognitive control required for the inhibition of distractors, therefore resulting in a greater degree of response conflict. PMID:25369121

Abnormal brain white matter network in young smokers: a graph theory analysis study.

PubMed

Zhang, Yajuan; Li, Min; Wang, Ruonan; Bi, Yanzhi; Li, Yangding; Yi, Zhang; Liu, Jixin; Yu, Dahua; Yuan, Kai

2018-04-01

Previous diffusion tensor imaging (DTI) studies had investigated the white matter (WM) integrity abnormalities in some specific fiber bundles in smokers. However, little is known about the changes in topological organization of WM structural network in young smokers. In current study, we acquired DTI datasets from 58 male young smokers and 51 matched nonsmokers and constructed the WM networks by the deterministic fiber tracking approach. Graph theoretical analysis was used to compare the topological parameters of WM network (global and nodal) and the inter-regional fractional anisotropy (FA) weighted WM connections between groups. The results demonstrated that both young smokers and nonsmokers had small-world topology in WM network. Further analysis revealed that the young smokers exhibited the abnormal topological organization, i.e., increased network strength, global efficiency, and decreased shortest path length. In addition, the increased nodal efficiency predominately was located in frontal cortex, striatum and anterior cingulate gyrus (ACG) in smokers. Moreover, based on network-based statistic (NBS) approach, the significant increased FA-weighted WM connections were mainly found in the PFC, ACG and supplementary motor area (SMA) regions. Meanwhile, the network parameters were correlated with the nicotine dependence severity (FTND) scores, and the nodal efficiency of orbitofrontal cortex was positive correlation with the cigarette per day (CPD) in young smokers. We revealed the abnormal topological organization of WM network in young smokers, which may improve our understanding of the neural mechanism of young smokers form WM topological organization level.

Meta-QTL for resistance to white mold in common bean

PubMed Central

Vasconcellos, Renato C. C.; Oraguzie, O. Blessing; Soler, Alvaro; Arkwazee, Haidar; Myers, James R.; Ferreira, Juan J.; Song, Qijian; McClean, Phil; Miklas, Phillip N.

2017-01-01

White mold, caused by the fungus Sclerotinia sclerotiorum (Lib.) de Bary, is a major disease that limits common bean production and quality worldwide. The host-pathogen interaction is complex, with partial resistance in the host inherited as a quantitative trait with low to moderate heritability. Our objective was to identify meta-QTL conditioning partial resistance to white mold from individual QTL identified across multiple populations and environments. The physical positions for 37 individual QTL were identified across 14 recombinant inbred bi-parental populations (six new, three re-genotyped, and five from the literature). A meta-QTL analysis of the 37 QTL was conducted using the genetic linkage map of Stampede x Red Hawk population as the reference. The 37 QTL condensed into 17 named loci (12 previously named and five new) of which nine were defined as meta-QTL WM1.1, WM2.2, WM3.1, WM5.4, WM6.2, WM7.1, WM7.4, WM7.5, and WM8.3. The nine meta-QTL had confidence intervals ranging from 0.65 to 9.41 Mb. Candidate genes shown to express under S. sclerotiorum infection in other studies, including cell wall receptor kinase, COI1, ethylene responsive transcription factor, peroxidase, and MYB transcription factor, were found within the confidence interval for five of the meta-QTL. The nine meta-QTL are recommended as potential targets for MAS for partial resistance to white mold in common bean. PMID:28199342

Working memory retrieval as a decision process

PubMed Central

Pearson, Benjamin; Raškevičius, Julius; Bays, Paul M.; Pertzov, Yoni; Husain, Masud

2014-01-01

Working memory (WM) is a core cognitive process fundamental to human behavior, yet the mechanisms underlying it remain highly controversial. Here we provide a new framework for understanding retrieval of information from WM, conceptualizing it as a decision based on the quality of internal evidence. Recent findings have demonstrated that precision of WM decreases with memory load. If WM retrieval uses a decision process that depends on memory quality, systematic changes in response time distribution should occur as a function of WM precision. We asked participants to view sample arrays and, after a delay, report the direction of change in location or orientation of a probe. As WM precision deteriorated with increasing memory load, retrieval time increased systematically. Crucially, the shape of reaction time distributions was consistent with a linear accumulator decision process. Varying either task relevance of items or maintenance duration influenced memory precision, with corresponding shifts in retrieval time. These results provide strong support for a decision-making account of WM retrieval based on noisy storage of items. Furthermore, they show that encoding, maintenance, and retrieval in WM need not be considered as separate processes, but may instead be conceptually unified as operations on the same noise-limited, neural representation. PMID:24492597

Early Auditory Evoked Potential Is Modulated by Selective Attention and Related to Individual Differences in Visual Working Memory Capacity

PubMed Central

Giuliano, Ryan J.; Karns, Christina M.; Neville, Helen J.; Hillyard, Steven A.

2015-01-01

A growing body of research suggests that the predictive power of working memory (WM) capacity for measures of intellectual aptitude is due to the ability to control attention and select relevant information. Crucially, attentional mechanisms implicated in controlling access to WM are assumed to be domain-general, yet reports of enhanced attentional abilities in individuals with larger WM capacities are primarily within the visual domain. Here, we directly test the link between WM capacity and early attentional gating across sensory domains, hypothesizing that measures of visual WM capacity should predict an individual’s capacity to allocate auditory selective attention. To address this question, auditory ERPs were recorded in a linguistic dichotic listening task, and individual differences in ERP modulations by attention were correlated with estimates of WM capacity obtained in a separate visual change detection task. Auditory selective attention enhanced ERP amplitudes at an early latency (ca. 70–90 msec), with larger P1 components elicited by linguistic probes embedded in an attended narrative. Moreover, this effect was associated with greater individual estimates of visual WM capacity. These findings support the view that domain-general attentional control mechanisms underlie the wide variation of WM capacity across individuals. PMID:25000526

Altered white matter and cortical structure in neonates with antenatally diagnosed isolated ventriculomegaly.

PubMed

Lockwood Estrin, G; Kyriakopoulou, V; Makropoulos, A; Ball, G; Kuhendran, L; Chew, A; Hagberg, B; Martinez-Biarge, M; Allsop, J; Fox, M; Counsell, S J; Rutherford, M A

2016-01-01

Ventriculomegaly (VM) is the most common central nervous system abnormality diagnosed antenatally, and is associated with developmental delay in childhood. We tested the hypothesis that antenatally diagnosed isolated VM represents a biological marker for altered white matter (WM) and cortical grey matter (GM) development in neonates. 25 controls and 21 neonates with antenatally diagnosed isolated VM had magnetic resonance imaging at 41.97(± 2.94) and 45.34(± 2.14) weeks respectively. T2-weighted scans were segmented for volumetric analyses of the lateral ventricles, WM and cortical GM. Diffusion tensor imaging (DTI) measures were assessed using voxel-wise methods in WM and cortical GM; comparisons were made between cohorts. Ventricular and cortical GM volumes were increased, and WM relative volume was reduced in the VM group. Regional decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) were demonstrated in WM of the VM group compared to controls. No differences in cortical DTI metrics were observed. At 2 years, neurodevelopmental delays, especially in language, were observed in 6/12 cases in the VM cohort. WM alterations in isolated VM cases may be consistent with abnormal development of WM tracts involved in language and cognition. Alterations in WM FA and MD may represent neural correlates for later neurodevelopmental deficits.

Auditory Discrimination Learning: Role of Working Memory.

PubMed

Zhang, Yu-Xuan; Moore, David R; Guiraud, Jeanne; Molloy, Katharine; Yan, Ting-Ting; Amitay, Sygal

2016-01-01

Perceptual training is generally assumed to improve perception by modifying the encoding or decoding of sensory information. However, this assumption is incompatible with recent demonstrations that transfer of learning can be enhanced by across-trial variation of training stimuli or task. Here we present three lines of evidence from healthy adults in support of the idea that the enhanced transfer of auditory discrimination learning is mediated by working memory (WM). First, the ability to discriminate small differences in tone frequency or duration was correlated with WM measured with a tone n-back task. Second, training frequency discrimination around a variable frequency transferred to and from WM learning, but training around a fixed frequency did not. The transfer of learning in both directions was correlated with a reduction of the influence of stimulus variation in the discrimination task, linking WM and its improvement to across-trial stimulus interaction in auditory discrimination. Third, while WM training transferred broadly to other WM and auditory discrimination tasks, variable-frequency training on duration discrimination did not improve WM, indicating that stimulus variation challenges and trains WM only if the task demands stimulus updating in the varied dimension. The results provide empirical evidence as well as a theoretic framework for interactions between cognitive and sensory plasticity during perceptual experience.

Planning sentences while doing other things at the same time: effects of concurrent verbal and visuospatial working memory load.

PubMed

Klaus, Jana; Mädebach, Andreas; Oppermann, Frank; Jescheniak, Jörg D

2017-04-01

This study investigated to what extent advance planning during sentence production is affected by a concurrent cognitive load. In two picture-word interference experiments in which participants produced subject-verb-object sentences while ignoring auditory distractor words, we assessed advance planning at a phonological (lexeme) and at an abstract-lexical (lemma) level under visuospatial or verbal working memory (WM) load. At the phonological level, subject and object nouns were found to be activated before speech onset with concurrent visuospatial WM load, but only subject nouns were found to be activated with concurrent verbal WM load, indicating a reduced planning scope as a function of type of WM load (Experiment 1). By contrast, at the abstract-lexical level, subject and object nouns were found to be activated regardless of type of concurrent load (Experiment 2). In both experiments, sentence planning had a more detrimental effect on concurrent verbal WM task performance than on concurrent visuospatial WM task performance. Overall, our results suggest that advance planning at the phonological level is more affected by a concurrently performed verbal WM task than advance planning at the abstract-lexical level. Also, they indicate an overlap of resources allocated to phonological planning in speech production and verbal WM.

Working memory retrieval as a decision process.

PubMed

Pearson, Benjamin; Raskevicius, Julius; Bays, Paul M; Pertzov, Yoni; Husain, Masud

2014-02-03

Working memory (WM) is a core cognitive process fundamental to human behavior, yet the mechanisms underlying it remain highly controversial. Here we provide a new framework for understanding retrieval of information from WM, conceptualizing it as a decision based on the quality of internal evidence. Recent findings have demonstrated that precision of WM decreases with memory load. If WM retrieval uses a decision process that depends on memory quality, systematic changes in response time distribution should occur as a function of WM precision. We asked participants to view sample arrays and, after a delay, report the direction of change in location or orientation of a probe. As WM precision deteriorated with increasing memory load, retrieval time increased systematically. Crucially, the shape of reaction time distributions was consistent with a linear accumulator decision process. Varying either task relevance of items or maintenance duration influenced memory precision, with corresponding shifts in retrieval time. These results provide strong support for a decision-making account of WM retrieval based on noisy storage of items. Furthermore, they show that encoding, maintenance, and retrieval in WM need not be considered as separate processes, but may instead be conceptually unified as operations on the same noise-limited, neural representation.

Infiltration pattern in a regolith-fractured bedrock profile: field observation of a dye stain pattern

NASA Astrophysics Data System (ADS)

Kim, Jae Gon; Lee, Gyoo Ho; Lee, Jin-Soo; Chon, Chul-Min; Kim, Tack Hyun; Ha, Kyoochul

2006-02-01

We examined the infiltration pattern of water in a regolith-bedrock profile consisting of two overburdens (OB1 and OB2), a buried rice paddy soil (PS), two texturally distinctive weathered materials (WM1 and WM2) and a fractured sedimentary rock (BR), using a Brilliant Blue FCF dye tracer. A black-coloured coating in conducting fractures in WM1, WM2 and BR was analysed by X-ray diffraction and scanning electron microscopy. The dye tracer penetrated to greater than 2 m depth in the profile. The macropore flow and saturated interflow were the major infiltration patterns in the profile. Macropore flow and saturated interflow were observed along fractures in WM1, WM2 and BR and at the dipping interfaces of PS-WM1, PS-WM2 and PS-BR respectively. Heterogeneous matrix flow occurred in upper overburden (OB1) and PS. Compared with OB1, the coarser textured OB2 acted as a physical barrier for vertical flow of water. The PS with low bulk density and many fine roots was another major conducting route of water in the profile. Manganese oxide and iron oxide were positively identified in the black coating material and had low crystallinity and high surface area, indicating their high reactivity with conducting contaminants.

Effects of visual working memory on brain information processing of irrelevant auditory stimuli.

PubMed

Qu, Jiagui; Rizak, Joshua D; Zhao, Lun; Li, Minghong; Ma, Yuanye

2014-01-01

Selective attention has traditionally been viewed as a sensory processing modulator that promotes cognitive processing efficiency by favoring relevant stimuli while inhibiting irrelevant stimuli. However, the cross-modal processing of irrelevant information during working memory (WM) has been rarely investigated. In this study, the modulation of irrelevant auditory information by the brain during a visual WM task was investigated. The N100 auditory evoked potential (N100-AEP) following an auditory click was used to evaluate the selective attention to auditory stimulus during WM processing and at rest. N100-AEP amplitudes were found to be significantly affected in the left-prefrontal, mid-prefrontal, right-prefrontal, left-frontal, and mid-frontal regions while performing a high WM load task. In contrast, no significant differences were found between N100-AEP amplitudes in WM states and rest states under a low WM load task in all recorded brain regions. Furthermore, no differences were found between the time latencies of N100-AEP troughs in WM states and rest states while performing either the high or low WM load task. These findings suggested that the prefrontal cortex (PFC) may integrate information from different sensory channels to protect perceptual integrity during cognitive processing.

Predictors of the relationships between nutritional supplement use and weight-modification goals of U.S. Army soldiers.

PubMed

Austin, Krista G; Carvey, Christina E; Farina, Emily K; Lieberman, Harris R

2013-08-01

U.S. Army Soldiers must meet body weight and composition standards and consequently may use nutritional supplements (NS) purported to assist in weight modification (WM). Nutritional supplements are dietary supplements (DS) and foods intended to supplement the diet. This study assessed relationships between NS use, demographic characteristics, health-related behaviors, and WM goals among U.S. Army personnel. Participants (N = 990) self-reported NS use, categorized as energy drinks, sport nutrition products, or DS, and WM goal (lose, gain, or maintain) was ascertained by survey. DS were subcategorized as health, weight-loss, weight-gain, or other DS. Chi-square and logistic regression were used to assess relationships between predictors, NS use, and WM goal. Most respondents (70.3% ± 1.7%) consumed some NS; however, overall NS use was not related to WM goal. Significant relationships were observed between predictors (tobacco use, age, body-mass index, fitness score, general health, and eating habits) and both WM goal and NS use. Respondents attempting to lose or maintain weight were less likely to consume energy drinks and weight-gain DS. WM goal is related to multiple health behaviors including tobacco use, physical fitness score, and self-perception of health and eating behavior. NS are consumed in this population regardless of WM goal.

Auditory Discrimination Learning: Role of Working Memory

PubMed Central

Zhang, Yu-Xuan; Moore, David R.; Guiraud, Jeanne; Molloy, Katharine; Yan, Ting-Ting; Amitay, Sygal

2016-01-01

Perceptual training is generally assumed to improve perception by modifying the encoding or decoding of sensory information. However, this assumption is incompatible with recent demonstrations that transfer of learning can be enhanced by across-trial variation of training stimuli or task. Here we present three lines of evidence from healthy adults in support of the idea that the enhanced transfer of auditory discrimination learning is mediated by working memory (WM). First, the ability to discriminate small differences in tone frequency or duration was correlated with WM measured with a tone n-back task. Second, training frequency discrimination around a variable frequency transferred to and from WM learning, but training around a fixed frequency did not. The transfer of learning in both directions was correlated with a reduction of the influence of stimulus variation in the discrimination task, linking WM and its improvement to across-trial stimulus interaction in auditory discrimination. Third, while WM training transferred broadly to other WM and auditory discrimination tasks, variable-frequency training on duration discrimination did not improve WM, indicating that stimulus variation challenges and trains WM only if the task demands stimulus updating in the varied dimension. The results provide empirical evidence as well as a theoretic framework for interactions between cognitive and sensory plasticity during perceptual experience. PMID:26799068

Distinct mechanisms for the impact of distraction and interruption on working memory in aging

PubMed Central

Clapp, Wesley C; Gazzaley, Adam

2010-01-01

Interference is known to negatively impact the ability to maintain information in working memory (WM), an effect that is exacerbated with aging. Here, we explore how distinct sources of interference, i.e., distraction (stimuli to-be-ignored) and interruption (stimuli requiring attention), differentially influence WM in younger and older adults. EEG was recorded while participants engaged in three versions of a delayed-recognition task: no interference, a distracting stimulus, and an interrupting stimulus presented during WM maintenance. Behaviorally, both types of interference negatively impacted WM accuracy in older adults significantly more than younger adults (with a larger deficit for interruptions). N170 latency measures revealed that the degree of processing both distractors and interruptors predicted WM accuracy in both populations. However, while WM impairments could be explained by excessive attention to distractors by older adults (a suppression deficit), impairment induced by interruption were not clearly mediated by age-related increases in attention to interruptors. These results suggest that distinct underlying mechanisms mediate the impact of different types of external interference on WM in normal aging. PMID:20144492

Comparable mechanisms of working memory interference by auditory and visual motion in youth and aging

PubMed Central

Mishra, Jyoti; Zanto, Theodore; Nilakantan, Aneesha; Gazzaley, Adam

2013-01-01

Intrasensory interference during visual working memory (WM) maintenance by object stimuli (such as faces and scenes), has been shown to negatively impact WM performance, with greater detrimental impacts of interference observed in aging. Here we assessed age-related impacts by intrasensory WM interference from lower-level stimulus features such as visual and auditory motion stimuli. We consistently found that interference in the form of ignored distractions and secondary task i nterruptions presented during a WM maintenance period, degraded memory accuracy in both the visual and auditory domain. However, in contrast to prior studies assessing WM for visual object stimuli, feature-based interference effects were not observed to be significantly greater in older adults. Analyses of neural oscillations in the alpha frequency band further revealed preserved mechanisms of interference processing in terms of post-stimulus alpha suppression, which was observed maximally for secondary task interruptions in visual and auditory modalities in both younger and older adults. These results suggest that age-related sensitivity of WM to interference may be limited to complex object stimuli, at least at low WM loads. PMID:23791629

The modulation of perceptual selection by working memory is dependent on the focus of spatial attention.

PubMed

Pan, Yi; Soto, David

2010-07-09

Recent research suggests that visual selection can be automatically biased to those stimuli matching the contents of working memory (WM). However, a complete functional account of the interplay between WM and attention remains to be established. In particular, the boundary conditions of the WM effect on selection are unclear. Here, the authors investigate the influence of the focus of spatial attention (i.e., diffused vs. focused) by assessing the effect of spatial precues on attentional capture by WM. Experiments 1 and 2 showed that relative to a neutral condition without memory-matching stimuli, the presence of a memory distractor can trigger attentional capture despite being entirely irrelevant for the attention task but this happened only when the item was actively maintained in WM and not when it was merely repeated. Experiments 3a, 3b and 3c showed that attentional capture by WM can be modulated by endogenous spatial pre-cueing of the incoming target of selection. The authors conclude that WM-driven capture of visual selection is dependent on the focus of spatial attention. Copyright 2009 Elsevier Ltd. All rights reserved.

The role of working memory in inferential sentence comprehension.

PubMed

Pérez, Ana Isabel; Paolieri, Daniela; Macizo, Pedro; Bajo, Teresa

2014-08-01

Existing literature on inference making is large and varied. Trabasso and Magliano (Discourse Process 21(3):255-287, 1996) proposed the existence of three types of inferences: explicative, associative and predictive. In addition, the authors suggested that these inferences were related to working memory (WM). In the present experiment, we investigated whether WM capacity plays a role in our ability to answer comprehension sentences that require text information based on these types of inferences. Participants with high and low WM span read two narratives with four paragraphs each. After each paragraph was read, they were presented with four true/false comprehension sentences. One required verbatim information and the other three implied explicative, associative and predictive inferential information. Results demonstrated that only the explicative and predictive comprehension sentences required WM: participants with high verbal WM were more accurate in giving explanations and also faster at making predictions relative to participants with low verbal WM span; in contrast, no WM differences were found in the associative comprehension sentences. These results are interpreted in terms of the causal nature underlying these types of inferences.

Benefits of training working memory in amnestic mild cognitive impairment: specific and transfer effects.

PubMed

Carretti, Barbara; Borella, Erika; Fostinelli, Silvia; Zavagnin, Michela

2013-04-01

A growing number of studies are attempting to understand how effective cognitive interventions may be for patients with amnestic mild cognitive impairment (aMCI), particularly in relation to their memory problems. The present study aimed to explore the benefits of a working memory (WM) training program in aMCI patients. Patients (N = 20) were randomly assigned to two training programs: the experimental group practiced with a verbal WM task, while the active control group conducted educational activities on memory. Results showed that the aMCI patients completing the WM training obtained specific gains in the task trained with some transfer effects on other WM measures (visuospatial WM) and on processes involved in or related to WM, e.g. fluid intelligence (the Cattell test) and long-term memory. This was not the case for the aMCI control group, who experienced only a very limited improvement. This pilot study suggests that WM training could be a valuable method for improving cognitive performance in aMCI patients, possibly delaying the onset of Alzheimer's disease.

Iodine I 131 Tositumomab and Fludarabine Phosphate in Treating Older Patients Who Are Undergoing an Autologous or Syngeneic Stem Cell Transplant for Relapsed or Refractory Non-Hodgkin's Lymphoma

ClinicalTrials.gov

2014-08-04

Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

Age, sex, and performance influence the visuospatial working memory network in childhood.

PubMed

Spencer-Smith, Megan; Ritter, Barbara Catherine; Mürner-Lavanchy, Ines; El-Koussy, Marwan; Steinlin, Maja; Everts, Regula

2013-01-01

This study describes the influence of age, sex, and working memory (WM) performance on the visuospatial WM network. Thirty-nine healthy children (7-12 years) completed a dot location functional magnetic resonance imaging (fMRI) task. Percent signal change measured the intensity and laterality indices measured the asymmetry of activation in frontal and parietal brain regions. Old children showed greater intensity of activation in parietal regions than young children but no differences in lateralization were observed. Intensity of activation was similar across sex and WM performance groups. Girls and high WM performers showed more right-sided lateralization of parietal regions than boys and low WM performers.

Dorsolateral Prefrontal Cortex GABA Concentration in Humans Predicts Working Memory Load Processing Capacity.

PubMed

Yoon, Jong H; Grandelis, Anthony; Maddock, Richard J

2016-11-16

The discovery of neural mechanisms of working memory (WM) would significantly enhance our understanding of complex human behaviors and guide treatment development for WM-related impairments found in neuropsychiatric conditions and aging. Although the dorsolateral prefrontal cortex (DLPFC) has long been considered critical for WM, we still know little about the neural elements and pathways within the DLPFC that support WM in humans. In this study, we tested whether an individual's DLPFC gamma-aminobutryic acid (GABA) content predicts individual differences in WM task performance using a novel behavioral approach. Twenty-three healthy adults completed a task that measured the unique contribution of major WM components (memory load, maintenance, and distraction resistance) to performance. This was done to address the possibility that components have differing GABA dependencies and the failure to parse WM into components would lead to missing true associations with GABA. The subjects then had their DLPFC GABA content measured by single-voxel proton magnetic spectroscopy. We found that individuals with lower DLPFC GABA showed greater performance degradation with higher load, accounting for 31% of variance, p (corrected) = 0.015. This relationship was component, neurochemical, and brain region specific. DLPFC GABA content did not predict performance sensitivity to other components tested; DLPFC glutamate + glutamine and visual cortical GABA content did not predict load sensitivity. These results confirm the involvement of DLPFC GABA in WM load processing in humans and implicate factors controlling DLPFC GABA content in the neural mechanisms of WM and its impairments. This study demonstrated for the first time that the amount of gamma-aminobutryic acid (GABA), the major inhibitory neurotransmitter of the brain, in an individual's prefrontal cortex predicts working memory (WM) task performance. Given that WM is required for many of the most characteristic cognitive and

Chronic spatial working memory deficit associated with the superior longitudinal fasciculus: a study using voxel-based lesion-symptom mapping and intraoperative direct stimulation in right prefrontal glioma surgery.

PubMed

Kinoshita, Masashi; Nakajima, Riho; Shinohara, Harumichi; Miyashita, Katsuyoshi; Tanaka, Shingo; Okita, Hirokazu; Nakada, Mitsutoshi; Hayashi, Yutaka

2016-10-01

OBJECTIVE Although the right prefrontal region is regarded as a silent area, chronic deficits of the executive function, including working memory (WM), could occur after resection of a right prefrontal glioma. This may be overlooked by postoperative standard examinations, and the disabilities could affect the patient's professional life. The right prefrontal region is a part of the frontoparietal network and is subserved by the superior longitudinal fasciculus (SLF); however, the role of the SLF in spatial WM is unclear. This study investigated a persistent spatial WM deficit in patients who underwent right prefrontal glioma resection, and evaluated the relationship between the spatial WM deficit and the SLF. METHODS Spatial WM was examined in 24 patients who underwent prefrontal glioma resection (right, n = 14; left, n = 10) and in 14 healthy volunteers using a spatial 2-back task during the long-term postoperative period. The neural correlates of spatial WM were evaluated using lesion mapping and voxel-based lesion-symptom mapping. In addition, the spatial 2-back task was performed during surgery under direct subcortical electrical stimulation in 2 patients with right prefrontal gliomas. RESULTS Patients with a right prefrontal lesion had a significant chronic spatial WM deficit. Voxel-based lesion-symptom mapping analysis revealed a significant correlation between spatial WM deficit and the region that overlapped the first and second segments of the SLF (SLF I and SLF II). Two patients underwent awake surgery and had difficulties providing the correct responses in the spatial 2-back task with direct subcortical electrical stimulation on the SLF I, which was preserved and confirmed by postoperative diffusion tensor imaging tractography. These patients exhibited no spatial WM deficits during the postoperative immediate and long-term periods. CONCLUSIONS Spatial WM deficits may persist in patients who undergo resection of the tumor located in the right prefrontal

Neural Correlates of Visual Short-term Memory Dissociate between Fragile and Working Memory Representations.

PubMed

Vandenbroucke, Annelinde R E; Sligte, Ilja G; de Vries, Jade G; Cohen, Michael X; Lamme, Victor A F

2015-12-01

Evidence is accumulating that the classic two-stage model of visual STM (VSTM), comprising iconic memory (IM) and visual working memory (WM), is incomplete. A third memory stage, termed fragile VSTM (FM), seems to exist in between IM and WM [Vandenbroucke, A. R. E., Sligte, I. G., & Lamme, V. A. F. Manipulations of attention dissociate fragile visual STM from visual working memory. Neuropsychologia, 49, 1559-1568, 2011; Sligte, I. G., Scholte, H. S., & Lamme, V. A. F. Are there multiple visual STM stores? PLoS One, 3, e1699, 2008]. Although FM can be distinguished from IM using behavioral and fMRI methods, the question remains whether FM is a weak expression of WM or a separate form of memory with its own neural signature. Here, we tested whether FM and WM in humans are supported by dissociable time-frequency features of EEG recordings. Participants performed a partial-report change detection task, from which individual differences in FM and WM capacity were estimated. These individual FM and WM capacities were correlated with time-frequency characteristics of the EEG signal before and during encoding and maintenance of the memory display. FM capacity showed negative alpha correlations over peri-occipital electrodes, whereas WM capacity was positively related, suggesting increased visual processing (lower alpha) to be related to FM capacity. Furthermore, FM capacity correlated with an increase in theta power over central electrodes during preparation and processing of the memory display, whereas WM did not. In addition to a difference in visual processing characteristics, a positive relation between gamma power and FM capacity was observed during both preparation and maintenance periods of the task. On the other hand, we observed that theta-gamma coupling was negatively correlated with FM capacity, whereas it was slightly positively correlated with WM. These data show clear differences in the neural substrates of FM versus WM and suggest that FM depends more on

Dynamical Origin of the Effective Storage Capacity in the Brain's Working Memory

NASA Astrophysics Data System (ADS)

Bick, Christian; Rabinovich, Mikhail I.

2009-11-01

The capacity of working memory (WM), a short-term buffer for information in the brain, is limited. We suggest a model for sequential WM that is based upon winnerless competition amongst representations of available informational items. Analytical results for the underlying mathematical model relate WM capacity and relative lateral inhibition in the corresponding neural network. This implies an upper bound for WM capacity, which is, under reasonable neurobiological assumptions, close to the “magical number seven.”

SMARTweave Sensors for Assessing Ballistic Damage: A Feasibility Study.

DTIC Science & Technology

1998-05-01

in transition from ARL, Watertown, MA, to the Rodman Materials Research Laboratory, Aberdeen Proving Ground (APG), MD. ii Acknowledgments The authors...BERMAN A FRYDMAN T LI W MCINTOSH E SZYMANSKI AMSRL WM MC T HYNES 4600 AMSRL WM MD W ROY 4600 AMSRL WM ME R ADLER 4600 AMSRL WM T W MORRISON 309 AMSRL...that the Materials Division was in transition from ARL, Watertown, MA, to the Rodman Materials Research Laboratory, Aberdeen Proving Ground (APG), MD

Strengthening Superconductivity in Macro-Arrays of Nanoclusters and Nanostructures

DTIC Science & Technology

2015-02-11

general approach for creating superconducting wires based on CNT conducting cores, coated by layered superconductors; • Develop cost-effective...wire 0.5 mm diameter Thermal conductivity 6600 Wm-1K-1 (SWNT) [37] 3600 Wm-1K-1 (SWNT) [35] 640 Wm-1K-1 wet-spun CNT fibers [4] 3320 Wm-1K... conductivity , which can improve thermal stability and enhance heat dissipation of MgB2 wire. Being one-dimensional nanostructures, they can act as

Concurrent white and gray matter degeneration of disease-specific networks in early-stage Alzheimer's disease and behavioral variant frontotemporal dementia.

PubMed

Steketee, Rebecca M E; Meijboom, Rozanna; de Groot, Marius; Bron, Esther E; Niessen, Wiro J; van der Lugt, Aad; van Swieten, John C; Smits, Marion

2016-07-01

This study investigates regional coherence between white matter (WM) microstructure and gray matter (GM) volume and perfusion measures in Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) using a correlational approach. WM-GM coherence, compared with controls, was stronger between cingulum WM and frontotemporal GM in AD, and temporoparietal GM in bvFTD. In addition, in AD compared with controls, coherence was stronger between inferior fronto-occipital fasciculus WM microstructure and occipital GM perfusion. In this first study assessing regional WM-GM coherence in AD and bvFTD, we show that WM microstructure and GM volume and perfusion measures are coherent, particularly in regions implicated in AD and bvFTD pathology. This indicates concurrent degeneration in disease-specific networks. Our methodology allows for the detection of incipient abnormalities that go undetected in conventional between-group analyses. Copyright © 2016 Elsevier Inc. All rights reserved.

Central Executive Dysfunction and Deferred Prefrontal Processing in Veterans with Gulf War Illness.

PubMed

Hubbard, Nicholas A; Hutchison, Joanna L; Motes, Michael A; Shokri-Kojori, Ehsan; Bennett, Ilana J; Brigante, Ryan M; Haley, Robert W; Rypma, Bart

2014-05-01

Gulf War Illness is associated with toxic exposure to cholinergic disruptive chemicals. The cholinergic system has been shown to mediate the central executive of working memory (WM). The current work proposes that impairment of the cholinergic system in Gulf War Illness patients (GWIPs) leads to behavioral and neural deficits of the central executive of WM. A large sample of GWIPs and matched controls (MCs) underwent functional magnetic resonance imaging during a varied-load working memory task. Compared to MCs, GWIPs showed a greater decline in performance as WM-demand increased. Functional imaging suggested that GWIPs evinced separate processing strategies, deferring prefrontal cortex activity from encoding to retrieval for high demand conditions. Greater activity during high-demand encoding predicted greater WM performance. Behavioral data suggest that WM executive strategies are impaired in GWIPs. Functional data further support this hypothesis and suggest that GWIPs utilize less effective strategies during high-demand WM.

Working Memory Updating Training Improves Mathematics Performance in Middle School Students With Learning Difficulties.

PubMed

Zhang, Hongxia; Chang, Lei; Chen, Xiaoying; Ma, Liang; Zhou, Renlai

2018-01-01

Working memory (WM) deficit is considered the key cause of learning difficulties (LDs). Studies have shown that WM is plastic and thus can be improved through training. This positive effect is transferable to fluid intelligence and academic performance. This study investigated whether WM updating ability and academic performance in children with LDs could be improved through WM updating training and explored the effects of this training on the children's brain activity. We used a running memory task lasting approximately 40 min per day for 28 days to train a group of 23 children with LDs (TLDs group). We also selected two control groups of 22 children with LDs (CLDs group) and 20 children without LDs (normal control [NC] group). The behavioral results of a pretest indicated that WM updating ability and academic performance in the TLDs and CLDs groups were significantly lower than those in the NC group before training. Compared with the CLDs group, the TLDs group exhibited significant performance improvement in a 2-back WM task, as well as in mathematical ability. Event-related potentials (ERPs) results suggested that the amplitudes of N160 (representative of visual recognition) and P300 (representative of updating processing, which is a valid index for updating WM) in the TLDs and CLDs groups were markedly lower than those in the NC group before training. In the TLDs group, these two components increased considerably after training, approaching levels similar to those in the NC group. The results of this study suggest that WM updating training can improve WM updating ability in children with LDs and the training effect can transfer to mathematical performance in such children. Furthermore, the participants' brain activity levels can exhibit positive changes. This article provides experimental evidence that WM updating training could mitigate the symptoms of LDs to a certain degree.

Discourse comprehension in autism spectrum disorder: Effects of working memory load and common ground.

PubMed

Schuh, Jillian M; Eigsti, Inge-Marie; Mirman, Daniel

2016-12-01

Pragmatic language impairments are nearly universal in autism spectrum disorders (ASD). Discourse requires that we monitor information that is shared or mutually known, called "common ground." While many studies have examined the role of Theory of Mind (ToM) in such impairments, few have examined working memory (WM). Common ground impairments in ASD could reflect limitations in both WM and ToM. This study explored common ground use in youth ages 8-17 years with high-functioning ASD (n = 13) and typical development (n = 22); groups did not differ on age, gender, IQ, or standardized language. We tracked participants' eye movements while they performed a discourse task in which some information was known only to the participant (e.g., was privileged; a manipulation of ToM). In addition, the amount of privileged information varied (a manipulation of WM). All participants were slower to fixate the target when considering privileged information, and this effect was greatest during high WM load trials. Further, the ASD group was more likely to fixate competing (non-target) shapes. Predictors of fixation patterns included ASD symptomatology, language ability, ToM, and WM. Groups did not differ in ToM. Individuals with better WM fixated the target more rapidly, suggesting an association between WM capacity and efficient discourse. In addition to ToM knowledge, WM capacity constrains common ground representation and impacts pragmatic skills in ASD. Social impairments in ASD are thus associated with WM capacity, such that deficits in domain-general, nonsocial processes such as WM exert an influence during complex social interactions. Autism Res 2016, 9: 1340-1352. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

A framework for understanding waste management studies in construction

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

Lu Weisheng, E-mail: wilsonlu@hku.hk; Yuan Hongping, E-mail: hp.yuan@polyu.edu.hk

2011-06-15

During the past decades, construction and demolition (C and D) waste issues have received increasing attention from both practitioners and researchers around the world. A plethora of research relating to C and D waste management (WM) has been published in scholarly journals. However, a comprehensive understanding of the C and D WM research is somehow absent in spite of its proliferation. The aim of this paper is to develop a framework that helps readers understand the C and D WM research as archived in selected journals. Papers under the topic of C and D WM are retrieved based on amore » set of rigorous procedures. The information of these papers is then analyzed with the assistance of the Qualitative Social Research (QSR) software package NVivo. A framework for understanding C and D WM research is created based on the analytic results. By following the framework, a bibliometric analysis of research in C and D WM is presented, followed by an in-depth literature analysis. It is found that C and D generation, reduction, and recycling are the three major topics in the discipline of C and D WM. Future research is recommended to (a) investigate C and D waste issues in wider scopes including design, maintenance and demolition, (b) develop a unified measurement for waste generation so that WM performance can be compared across various economies, and (c) enhance effectiveness of WM approaches (e.g. waste charging scheme) based on new WM concepts (e.g. Extended Producer Responsibility). In addition to the above research findings, the approach for producing the research framework can be useful references for other studies which attempt to understand the research of a given discipline.« less

A Spiking Working Memory Model Based on Hebbian Short-Term Potentiation

PubMed Central

Fiebig, Florian

2017-01-01

A dominant theory of working memory (WM), referred to as the persistent activity hypothesis, holds that recurrently connected neural networks, presumably located in the prefrontal cortex, encode and maintain WM memory items through sustained elevated activity. Reexamination of experimental data has shown that prefrontal cortex activity in single units during delay periods is much more variable than predicted by such a theory and associated computational models. Alternative models of WM maintenance based on synaptic plasticity, such as short-term nonassociative (non-Hebbian) synaptic facilitation, have been suggested but cannot account for encoding of novel associations. Here we test the hypothesis that a recently identified fast-expressing form of Hebbian synaptic plasticity (associative short-term potentiation) is a possible mechanism for WM encoding and maintenance. Our simulations using a spiking neural network model of cortex reproduce a range of cognitive memory effects in the classical multi-item WM task of encoding and immediate free recall of word lists. Memory reactivation in the model occurs in discrete oscillatory bursts rather than as sustained activity. We relate dynamic network activity as well as key synaptic characteristics to electrophysiological measurements. Our findings support the hypothesis that fast Hebbian short-term potentiation is a key WM mechanism. SIGNIFICANCE STATEMENT Working memory (WM) is a key component of cognition. Hypotheses about the neural mechanism behind WM are currently under revision. Reflecting recent findings of fast Hebbian synaptic plasticity in cortex, we test whether a cortical spiking neural network model with such a mechanism can learn a multi-item WM task (word list learning). We show that our model can reproduce human cognitive phenomena and achieve comparable memory performance in both free and cued recall while being simultaneously compatible with experimental data on structure, connectivity, and

Working memory binding and episodic memory formation in aging, mild cognitive impairment, and Alzheimer's dementia.

PubMed

van Geldorp, Bonnie; Heringa, Sophie M; van den Berg, Esther; Olde Rikkert, Marcel G M; Biessels, Geert Jan; Kessels, Roy P C

2015-01-01

Recent studies indicate that in both normal and pathological aging working memory (WM) performance deteriorates, especially when associations have to be maintained. However, most studies typically do not assess the relationship between WM and episodic memory formation. In the present study, we examined WM and episodic memory formation in normal aging and in patients with early Alzheimer's disease (mild cognitive impairment, MCI; and Alzheimer's dementia, AD). In the first study, 26 young adults (mean age 29.6 years) were compared to 18 middle-aged adults (mean age 52.2 years) and 25 older adults (mean age 72.8 years). We used an associative delayed-match-to-sample WM task, which requires participants to maintain two pairs of faces and houses presented on a computer screen for short (3 s) or long (6 s) maintenance intervals. After the WM task, an unexpected subsequent associative memory task was administered (two-alternative forced choice). In the second study, 27 patients with AD and 19 patients with MCI were compared to 25 older controls, using the same paradigm as that in Experiment 1. Older adults performed worse than both middle-aged and young adults. No effect of delay was observed in the healthy adults, and pairs that were processed during long maintenance intervals were not better remembered in the subsequent memory task. In the MCI and AD patients, longer maintenance intervals hampered the task performance. Also, both patient groups performed significantly worse than controls on the episodic memory task as well as the associative WM task. Aging and AD present with a decline in WM binding, a finding that extends similar results in episodic memory. Longer delays in the WM task did not affect episodic memory formation. We conclude that WM deficits are found when WM capacity is exceeded, which may occur during associative processing.

Diagnostic Validity of an Automated Probabilistic Tractography in Amnestic Mild Cognitive Impairment

PubMed Central

Jung, Won Sang; Um, Yoo Hyun; Kang, Dong Woo; Lee, Chang Uk; Woo, Young Sup; Bahk, Won-Myong

2018-01-01

Objective Although several prior works showed the white matter (WM) integrity changes in amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease, it is still unclear the diagnostic accuracy of the WM integrity measurements using diffusion tensor imaging (DTI) in discriminating aMCI from normal controls. The aim of this study is to explore diagnostic validity of whole brain automated probabilistic tractography in discriminating aMCI from normal controls. Methods One hundred-two subjects (50 aMCI and 52 normal controls) were included and underwent DTI scans. Whole brain WM tracts were reconstructed with automated probabilistic tractography. Fractional anisotropy (FA) and mean diffusivity (MD) values of the memory related WM tracts were measured and compared between the aMCI and the normal control groups. In addition, the diagnostic validities of these WM tracts were evaluated. Results Decreased FA and increased MD values of memory related WM tracts were observed in the aMCI group compared with the control group. Among FA and MD value of each tract, the FA value of left cingulum angular bundle showed the highest area under the curve (AUC) of 0.85 with a sensitivity of 88.2%, a specificity of 76.9% in differentiating MCI patients from control subjects. Furthermore, the combination FA values of WM integrity measures of memory related WM tracts showed AUC value of 0.98, a sensitivity of 96%, a specificity of 94.2%. Conclusion Our results with good diagnostic validity of WM integrity measurements suggest DTI might be promising neuroimaging tool for early detection of aMCI and AD patients. PMID:29739127

Similarity, not complexity, determines visual working memory performance.

PubMed

Jackson, Margaret C; Linden, David E J; Roberts, Mark V; Kriegeskorte, Nikolaus; Haenschel, Corinna

2015-11-01

A number of studies have shown that visual working memory (WM) is poorer for complex versus simple items, traditionally accounted for by higher information load placing greater demands on encoding and storage capacity limits. Other research suggests that it may not be complexity that determines WM performance per se, but rather increased perceptual similarity between complex items as a result of a large amount of overlapping information. Increased similarity is thought to lead to greater comparison errors between items encoded into WM and the test item(s) presented at retrieval. However, previous studies have used different object categories to manipulate complexity and similarity, raising questions as to whether these effects are simply due to cross-category differences. For the first time, here the relationship between complexity and similarity in WM using the same stimulus category (abstract polygons) are investigated. The authors used a delayed discrimination task to measure WM for 1-4 complex versus simple simultaneously presented items and manipulated the similarity between the single test item at retrieval and the sample items at encoding. WM was poorer for complex than simple items only when the test item was similar to 1 of the encoding items, and not when it was dissimilar or identical. The results provide clear support for reinterpretation of the complexity effect in WM as a similarity effect and highlight the importance of the retrieval stage in governing WM performance. The authors discuss how these findings can be reconciled with current models of WM capacity limits. (c) 2015 APA, all rights reserved).

Self-initiated encoding facilitates object working memory in schizophrenia: implications for the etiology of working memory deficit.

PubMed

Kim, Jejoong; Park, Sohee; Shin, Yong-Wook; Jin Lee, Kyung; Kwon, Jun Soo

2006-02-15

Working memory (WM) deficit is present in a majority of patients with schizophrenia but it is unclear which components of WM are impaired. Past studies suggest that encoding may be compromised. One important determinant of encoding is the deployment of selective attention to the target stimulus. In addition, attention and encoding are modulated by motivational factors. In this study, we investigated the effects of self-initiated encoding (i.e., voluntary attention) on WM. 19 patients with schizophrenia and 19 matched control subjects participated in visual WM and control tasks. Encoding was manipulated by asking subjects to select from two face targets and memorize 1) one of the two identical faces (Non-preference condition), 2) one that is marked (Non-choice condition), and 3) one they prefer (Preference condition). WM accuracy for both location (spatial) and identity (object) was measured. Overall, patients with schizophrenia were less accurate and slower than the control subjects but the deficit was greater for object WM. However, patients were more accurate in object WM when they selected a preferred face as their target during encoding (preference condition) compared with the other two conditions. This effect was not significant for spatial WM. These results suggest that voluntary, self-initiated attention may facilitate object encoding especially if the selection of the target involves affective choice, and that attention may play different roles in encoding 'what' versus 'where' in WM. Since encoding affects all forms of memory, these results may have a more general implication for memory.

Will working memory training generalize to improve off-task behavior in children with attention-deficit/hyperactivity disorder?

PubMed

Green, Chloe T; Long, Debra L; Green, David; Iosif, Ana-Maria; Dixon, J Faye; Miller, Meghan R; Fassbender, Catherine; Schweitzer, Julie B

2012-07-01

Computerized working memory and executive function training programs designed to target specific impairments in executive functioning are becoming increasingly available, yet how well these programs generalize to improve functional deficits in disorders, such as attention-deficit/hyperactivity disorder (ADHD), beyond the training context is not well-established. The aim of this study was to examine the extent to which working memory (WM) training in children with ADHD would diminish a core dysfunctional behavior associated with the disorder, "off-task" behavior during academic task performance. The effect of computerized WM training (adaptive) was compared to a placebo condition (nonadaptive) in a randomized, double-blind, placebo-controlled design in 26 children (18 males; age, 7 to 14 years old) diagnosed with ADHD. Participants completed the training in approximately 25 sessions. The Restricted Academic Situations Task (RAST) observational system was used to assess aspects of off-task behavior during the completion of an academic task. Traditional measures of ADHD symptoms (Conners' Parent Rating Scale) and WM ability (standardized WM tests) were also collected. WM training led to significant reductions in off-task ADHD-associated behavior on the RAST system and improvement on WM tests. There were no significant differences between groups in improvement on parent rating scales. Findings lend insight into the generalizability of the effects of WM training and the relation between deficits in WM and off-task behavioral components of ADHD. These preliminary data suggest WM training may provide a mechanism for indirectly altering academic performance in children with ADHD.

Feasibility of Home-Based Computerized Working Memory Training With Children and Adolescents With Sickle Cell Disease.

PubMed

Hardy, Steven J; Hardy, Kristina K; Schatz, Jeffrey C; Thompson, Amanda L; Meier, Emily R

2016-09-01

Children with sickle cell disease (SCD) are at increased risk for neurocognitive deficits, yet the literature describing interventions to ameliorate these problems and promote academic achievement is limited. We evaluated the feasibility and preliminary efficacy of a home-based computerized working memory (WM) training intervention (Cogmed) in children with SCD. Youth with SCD between the age of 7 and 16 years completed an initial neuropsychological assessment; those with WM deficits were loaned an iPad on which they accessed Cogmed at home. Participants were instructed to work on Cogmed 5 days each week for 5 weeks (25 training sessions). We examined Cogmed usage characteristics and change on WM assessment scores following the intervention. Of the 21 participants (M age = 11.38, SD = 2.78; Mdn age = 10.00, interquartile range [IQR] = 5.00; 52% female) screened, 60% exhibited WM deficits (n = 12) and received the intervention and 50% (n = 6) completed Cogmed. The mean number of sessions completed was 15.83 (SD = 7.73; Mdn = 17.00, IQR = 16.00); females were more likely to complete Cogmed, χ(2) (1) = 6.00, P = 0.01. Participants who reported lower SCD-related pain impact completed more sessions (r = 0.71, P = 0.01). Children who completed Cogmed exhibited improvements in verbal WM, visuospatial short-term memory, and visuospatial WM. Initial findings suggest Cogmed is associated with WM improvement in youth with SCD; however, adherence was lower than expected. Home-based WM interventions may ameliorate SCD-related WM deficits but strategies are needed to address barriers to program completion. © 2016 Wiley Periodicals, Inc.

How working memory enables fluid reasoning.

PubMed

Dehn, Milton J

2017-01-01

The strong relation between fluid reasoning (Gf) and working memory (WM) is well established. Gf depends on WM to hold necessary information in a span of awareness until the reasoning task is completed. The influence of time constraints on the Gf-WM relation indicates that the abilities to control attention and inhibit interference may be the underlying traits that account for the Gf-WM relation. Neuroanatomy also explains the interrelations among these cognitive processes. Neuroimaging (fMRI) studies have confirmed that the same regions of the prefrontal cortex (PFC) are active during Gf and WM functioning. The dorsolateral prefrontal cortex (dPFC) is also a critical structure for attention functions and inhibition.

Abnormal Functional Activation and Connectivity in the Working Memory Network in Early-Onset Schizophrenia

ERIC Educational Resources Information Center

Kyriakopoulos, Marinos; Dima, Danai; Roiser, Jonathan P.; Corrigall, Richard; Barker, Gareth J.; Frangou, Sophia

2012-01-01

Objective: Disruption within the working memory (WM) neural network is considered an integral feature of schizophrenia. The WM network, and the dorsolateral prefrontal cortex (DLPFC) in particular, undergo significant remodeling in late adolescence. Potential interactions between developmental changes in the WM network and disease-related…

Quantitative T2 mapping of white matter: applications for ageing and cognitive decline

NASA Astrophysics Data System (ADS)

Knight, Michael J.; McCann, Bryony; Tsivos, Demitra; Dillon, Serena; Coulthard, Elizabeth; Kauppinen, Risto A.

2016-08-01

In MRI, the coherence lifetime T2 is sensitive to the magnetic environment imposed by tissue microstructure and biochemistry in vivo. Here we explore the possibility that the use of T2 relaxometry may provide information complementary to that provided by diffusion tensor imaging (DTI) in ageing of healthy controls (HC), Alzheimer’s disease (AD) and mild cognitive impairment (MCI). T2 and diffusion MRI metrics were quantified in HC and patients with MCI and mild AD using multi-echo MRI and DTI. We used tract-based spatial statistics (TBSS) to evaluate quantitative MRI parameters in white matter (WM). A prolonged T2 in WM was associated with AD, and able to distinguish AD from MCI, and AD from HC. Shorter WM T2 was associated with better cognition and younger age in general. In no case was a reduction in T2 associated with poorer cognition. We also applied principal component analysis, showing that WM volume changes independently of  T2, MRI diffusion indices and cognitive performance indices. Our data add to the evidence that age-related and AD-related decline in cognition is in part attributable to WM tissue state, and much less to WM quantity. These observations suggest that WM is involved in AD pathology, and that T2 relaxometry is a potential imaging modality for detecting and characterising WM in cognitive decline and dementia.

Functional brain organization of working memory in adolescents varies in relation to family income and academic achievement.

PubMed

Finn, Amy S; Minas, Jennifer E; Leonard, Julia A; Mackey, Allyson P; Salvatore, John; Goetz, Calvin; West, Martin R; Gabrieli, Christopher F O; Gabrieli, John D E

2017-09-01

Working memory (WM) capacity reflects executive functions associated with performance on a wide range of cognitive tasks and education outcomes, including mathematics achievement, and is associated with dorsolateral prefrontal and parietal cortices. Here we asked if family income is associated with variation in the functional brain organization of WM capacity among adolescents, and whether that variation is associated with performance on a statewide test of academic achievement in mathematics. Participants were classified into higher-income and lower-income groups based on family income, and performed a WM task with a parametric manipulation of WM load (N-back task) during functional magnetic resonance imaging (fMRI). Behaviorally, the higher-income group had greater WM capacity and higher mathematics achievement scores. Neurally, the higher-income group showed greater activation as a function of WM load in bilateral prefrontal, parietal, and other regions, although the lower-income group exhibited greater activation at the lowest load. Both groups exhibited positive correlations between parietal activations and mathematics achievement scores, but only the higher-income group exhibited a positive correlation between prefrontal activations and mathematics scores. Most of these findings were maintained when higher- and lower-income groups were matched on WM task performance or nonverbal IQ. Findings indicate that the functional neural architecture of WM varies with family income and is associated with education measures of mathematics achievement. © 2016 John Wiley & Sons Ltd.

Frontal and parietal theta burst TMS impairs working memory for visual-spatial conjunctions

PubMed Central

Morgan, Helen M.; Jackson, Margaret C.; van Koningsbruggen, Martijn G.; Shapiro, Kimron L.; Linden, David E.J.

2013-01-01

In tasks that selectively probe visual or spatial working memory (WM) frontal and posterior cortical areas show a segregation, with dorsal areas preferentially involved in spatial (e.g. location) WM and ventral areas in visual (e.g. object identity) WM. In a previous fMRI study [1], we showed that right parietal cortex (PC) was more active during WM for orientation, whereas left inferior frontal gyrus (IFG) was more active during colour WM. During WM for colour-orientation conjunctions, activity in these areas was intermediate to the level of activity for the single task preferred and non-preferred information. To examine whether these specialised areas play a critical role in coordinating visual and spatial WM to perform a conjunction task, we used theta burst transcranial magnetic stimulation (TMS) to induce a functional deficit. Compared to sham stimulation, TMS to right PC or left IFG selectively impaired WM for conjunctions but not single features. This is consistent with findings from visual search paradigms, in which frontal and parietal TMS selectively affects search for conjunctions compared to single features, and with combined TMS and functional imaging work suggesting that parietal and frontal regions are functionally coupled in tasks requiring integration of visual and spatial information. Our results thus elucidate mechanisms by which the brain coordinates spatially segregated processing streams and have implications beyond the field of working memory. PMID:22483548

Multimodal Imaging Evidence for Axonal and Myelin Deterioration in Amnestic Mild Cognitive Impairment

PubMed Central

Gold, Brian T.; Jiang, Yang; Powell, David K.; Smith, Charles D.

2012-01-01

White matter (WM) microstructural declines have been demonstrated in Alzheimer’s disease and amnestic mild cognitive impairment (aMCI). However, the pattern of WM microstructural changes in aMCI after controlling for WM atrophy is unknown. Here, we address this issue through joint consideration of aMCI alterations in fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity, as well as macrostructural volume in WM and gray matter compartments. Participants were 18 individuals with aMCI and 24 healthy seniors. Voxelwise analyses of diffusion tensor imaging data was carried out using tract-based spatial statistics (TBSS) and voxelwise analyses of high-resolution structural data was conducted using voxel based morphometry. After controlling for WM atrophy, the main pattern of TBSS findings indicated reduced fractional anisotropy with only small alterations in mean diffusivity/radial diffusivity/axial diffusivity. These WM microstructural declines bordered and/or were connected to gray matter structures showing volumetric declines. However, none of the potential relationships between WM integrity and volume in connected gray matter structures was significant, and adding fractional anisotropy information improved the classificatory accuracy of aMCI compared to the use of hippocampal atrophy alone. These results suggest that WM microstructural declines provide unique information not captured by atrophy measures that may aid the magnetic resonance imaging contribution to aMCI detection. PMID:22460327

Lie construction affects information storage under high memory load condition.

PubMed

Liu, Yuqiu; Wang, Chunjie; Jiang, Haibo; He, Hongjian; Chen, Feiyan

2017-01-01

Previous studies indicate that lying consumes cognitive resources, especially working memory (WM) resources. Considering the dual functions that WM might play in lying: holding the truth-related information and turning the truth into lies, the present study examined the relationship between the information storage and processing in the lie construction. To achieve that goal, a deception task based on the old/new recognition paradigm was designed, which could manipulate two levels of WM load (low-load task using 4 items and high-load task using 6 items) during the deception process. The analyses based on the amplitude of the contralateral delay activity (CDA), a proved index of the number of representations being held in WM, showed that the CDA amplitude was lower in the deception process than that in the truth telling process under the high-load condition. In contrast, under the low-load condition, no CDA difference was found between the deception and truth telling processes. Therefore, we deduced that the lie construction and information storage compete for WM resources; when the available WM resources cannot meet this cognitive demand, the WM resources occupied by the information storage would be consumed by the lie construction.

Negative emotional experiences arouse rumination and affect working memory capacity.

PubMed

Curci, Antonietta; Lanciano, Tiziana; Soleti, Emanuela; Rimé, Bernard

2013-10-01

Following an emotional experience, individuals are confronted with the persistence of ruminative thoughts that disturb the undertaking of other activities. In the present study, we experimentally tested the idea that experiencing a negative emotion triggers a ruminative process that drains working memory (WM) resources normally devoted to other tasks. Undergraduate participants of high versus low WM capacity were administered the operation-word memory span test (OSPAN) as a measure of availability of WM resources preceding and following the presentation of negative emotional versus neutral material. Rumination was assessed immediately after the second OSPAN session and at a 24-hr delay. Results showed that both the individual's WM capacity and the emotional valence of the material influenced WM performance and the persistence of ruminative thoughts. Following the experimental induction, rumination mediated the relationship between the negative emotional state and the concomitant WM performance. Based on these results, we argue that ruminative processes deplete WM resources, making them less available for concurrent tasks; in addition, rumination tends to persist over time. These findings have implications for the theoretical modeling of the long-term effects of emotions in both daily life and clinical contexts.

Controlling Working Memory Operations by Selective Gating: The Roles of Oscillations and Synchrony

PubMed Central

Dipoppa, Mario; Szwed, Marcin; Gutkin, Boris S.

2016-01-01

Working memory (WM) is a primary cognitive function that corresponds to the ability to update, stably maintain, and manipulate short-term memory (ST M) rapidly to perform ongoing cognitive tasks. A prevalent neural substrate of WM coding is persistent neural activity, the property of neurons to remain active after having been activated by a transient sensory stimulus. This persistent activity allows for online maintenance of memory as well as its active manipulation necessary for task performance. WM is tightly capacity limited. Therefore, selective gating of sensory and internally generated information is crucial for WM function. While the exact neural substrate of selective gating remains unclear, increasing evidence suggests that it might be controlled by modulating ongoing oscillatory brain activity. Here, we review experiments and models that linked selective gating, persistent activity, and brain oscillations, putting them in the more general mechanistic context of WM. We do so by defining several operations necessary for successful WM function and then discussing how such operations may be carried out by mechanisms suggested by computational models. We specifically show how oscillatory mechanisms may provide a rapid and flexible active gating mechanism for WM operations. PMID:28154616

Retrospective Attention Interacts with Stimulus Strength to Shape Working Memory Performance.

PubMed

Wildegger, Theresa; Humphreys, Glyn; Nobre, Anna C

2016-01-01

Orienting attention retrospectively to selective contents in working memory (WM) influences performance. A separate line of research has shown that stimulus strength shapes perceptual representations. There is little research on how stimulus strength during encoding shapes WM performance, and how effects of retrospective orienting might vary with changes in stimulus strength. We explore these questions in three experiments using a continuous-recall WM task. In Experiment 1 we show that benefits of cueing spatial attention retrospectively during WM maintenance (retrocueing) varies according to stimulus contrast during encoding. Retrocueing effects emerge for supraliminal but not sub-threshold stimuli. However, once stimuli are supraliminal, performance is no longer influenced by stimulus contrast. In Experiments 2 and 3 we used a mixture-model approach to examine how different sources of error in WM are affected by contrast and retrocueing. For high-contrast stimuli (Experiment 2), retrocues increased the precision of successfully remembered items. For low-contrast stimuli (Experiment 3), retrocues decreased the probability of mistaking a target with distracters. These results suggest that the processes by which retrospective attentional orienting shape WM performance are dependent on the quality of WM representations, which in turn depends on stimulus strength during encoding.

Lie construction affects information storage under high memory load condition

PubMed Central

Liu, Yuqiu; Wang, Chunjie; Jiang, Haibo; He, Hongjian; Chen, Feiyan

2017-01-01

Previous studies indicate that lying consumes cognitive resources, especially working memory (WM) resources. Considering the dual functions that WM might play in lying: holding the truth-related information and turning the truth into lies, the present study examined the relationship between the information storage and processing in the lie construction. To achieve that goal, a deception task based on the old/new recognition paradigm was designed, which could manipulate two levels of WM load (low-load task using 4 items and high-load task using 6 items) during the deception process. The analyses based on the amplitude of the contralateral delay activity (CDA), a proved index of the number of representations being held in WM, showed that the CDA amplitude was lower in the deception process than that in the truth telling process under the high-load condition. In contrast, under the low-load condition, no CDA difference was found between the deception and truth telling processes. Therefore, we deduced that the lie construction and information storage compete for WM resources; when the available WM resources cannot meet this cognitive demand, the WM resources occupied by the information storage would be consumed by the lie construction. PMID:28727794

Interference Impacts Working Memory in Mild Cognitive Impairment

PubMed Central

Aurtenetxe, Sara; García-Pacios, Javier; del Río, David; López, María E.; Pineda-Pardo, José A.; Marcos, Alberto; Delgado Losada, Maria L.; López-Frutos, José M.; Maestú, Fernando

2016-01-01

Mild cognitive impairment (MCI) is considered a transitional stage between healthy aging and dementia, specifically Alzheimer's disease (AD). The most common cognitive impairment of MCI includes episodic memory loss and difficulties in working memory (WM). Interference can deplete WM, and an optimal WM performance requires an effective control of attentional resources between the memoranda and the incoming stimuli. Difficulties in handling interference lead to forgetting. However, the interplay between interference and WM in MCI is not well-understood and needs further investigation. The current study investigated the effect of interference during a WM task in 20 MCIs and 20 healthy elder volunteers. Participants performed a delayed match-to-sample paradigm which consisted in two interference conditions, distraction and interruption, and one control condition without any interference. Results evidenced a disproportionate impact of interference on the WM performance of MCIs, mainly in the presence of interruption. These findings demonstrate that interference, and more precisely interruption, is an important proxy for memory-related deficits in MCI. Thus, the current findings reveal novel evidence regarding the causes of WM forgetting in MCI patients, associated with difficulties in the mechanisms of attentional control. PMID:27790082

Practice-related improvement in working memory is modulated by changes in processing external interference.

PubMed

Berry, Anne S; Zanto, Theodore P; Rutman, Aaron M; Clapp, Wesley C; Gazzaley, Adam

2009-09-01

Working memory (WM) performance is impaired by the presence of external interference. Accordingly, more efficient processing of intervening stimuli with practice may lead to enhanced WM performance. To explore the role of practice on the impact that interference has on WM performance, we studied young adults with electroencephalographic (EEG) recordings as they performed three motion-direction, delayed-recognition tasks. One task was presented without interference, whereas two tasks introduced different types of interference during the interval of memory maintenance: distractors and interruptors. Distractors were to be ignored, whereas interruptors demanded attention based on task instructions for a perceptual discrimination. We show that WM performance was disrupted by both types of interference, but interference-induced disruption abated across a single experimental session through rapid learning. WM accuracy and response time improved in a manner that was correlated with changes in early neural measures of interference processing in visual cortex (i.e., P1 suppression and N1 enhancement). These results suggest practice-related changes in processing interference exert a positive influence on WM performance, highlighting the importance of filtering irrelevant information and the dynamic interactions that exist between neural processes of perception, attention, and WM during learning.

Working memory training using EEG neurofeedback in normal young adults.

PubMed

Xiong, Shi; Cheng, Chen; Wu, Xia; Guo, Xiaojuan; Yao, Li; Zhang, Jiacai

2014-01-01

Recent studies have shown that working memory (WM) performance can be improved by intensive and adaptive computerized training. Here, we explored the WM training effect using Electroencephalography (EEG) neurofeedback (NF) in normal young adults. In the first study, we identified the EEG features related to WM in normal young adults. The receiver operating characteristic (ROC) curve showed that the power ratio of the theta-to-alpha rhythms in the anterior-parietal region, accurately classified a high percentage of the EEG trials recorded during WM and fixation control (FC) tasks. Based on these results, a second study aimed to assess the training effects of the theta-to-alpha ratio and tested the hypothesis that up-regulating the power ratio can improve working memory behavior. Our results demonstrated that these normal young adults succeeded in improving their WM performance with EEG NF, and the pre- and post-test evaluations also indicated that WM performance increase in experimental group was significantly greater than control groups. In summary, our findings provided preliminarily evidence that WM performance can be improved through learned regulation of the EEG power ratio using EEG NF.

Contextual knowledge reduces demands on working memory during reading.

PubMed

Miller, Lisa M Soederberg; Cohen, Jason A; Wingfield, Arthur

2006-09-01

An experiment is reported in which young, middle-aged, and older adults read and recalled ambiguous texts either with or without the topic title that supplied contextual knowledge. Within each of the age groups, the participants were divided into those with high or low working memory (WM) spans, with available WM capacity further manipulated by the presence or absence of an auditory target detection task concurrent with the reading task. Differences in reading efficiency (reading time per proposition recalled) between low WM span and high WM span groups were greater among readers who had access to contextual knowledge relative to those who did not, suggesting that contextual knowledge reduces demands on WM capacity. This position was further supported by the finding that increased age and attentional demands, two factors associated with reduced WM capacity, exaggerated the benefits of contextual knowledge on reading efficiency. The relative strengths of additional potential predictors of reading efficiency (e.g., interest, effort, and memory beliefs), along with knowledge, WM span, and age, are reported. Findings showed that contextual knowledge was the strongest predictor of reading efficiency even after controlling for the effects of all of the other predictors.

Gesture Imitation in Schizophrenia

PubMed Central

Matthews, Natasha; Gold, Brian J.; Sekuler, Robert; Park, Sohee

2013-01-01

Recent evidence suggests that individuals with schizophrenia (SZ) are impaired in their ability to imitate gestures and movements generated by others. This impairment in imitation may be linked to difficulties in generating and maintaining internal representations in working memory (WM). We used a novel quantitative technique to investigate the relationship between WM and imitation ability. SZ outpatients and demographically matched healthy control (HC) participants imitated hand gestures. In Experiment 1, participants imitated single gestures. In Experiment 2, they imitated sequences of 2 gestures, either while viewing the gesture online or after a short delay that forced the use of WM. In Experiment 1, imitation errors were increased in SZ compared with HC. Experiment 2 revealed a significant interaction between imitation ability and WM. SZ produced more errors and required more time to imitate when that imitation depended upon WM compared with HC. Moreover, impaired imitation from WM was significantly correlated with the severity of negative symptoms but not with positive symptoms. In sum, gesture imitation was impaired in schizophrenia, especially when the production of an imitation depended upon WM and when an imitation entailed multiple actions. Such a deficit may have downstream consequences for new skill learning. PMID:21765171

Enhancing Working Memory Training with Transcranial Direct Current Stimulation.

PubMed

Au, Jacky; Katz, Benjamin; Buschkuehl, Martin; Bunarjo, Kimberly; Senger, Thea; Zabel, Chelsea; Jaeggi, Susanne M; Jonides, John

2016-09-01

Working memory (WM) is a fundamental cognitive ability that supports complex thought but is limited in capacity. Thus, WM training interventions have become very popular as a means of potentially improving WM-related skills. Another promising intervention that has gained increasing traction in recent years is transcranial direct current stimulation (tDCS), a noninvasive form of brain stimulation that can modulate cortical excitability and temporarily increase brain plasticity. As such, it has the potential to boost learning and enhance performance on cognitive tasks. This study assessed the efficacy of tDCS to supplement WM training. Sixty-two participants were randomized to receive either right prefrontal, left prefrontal, or sham stimulation with concurrent visuospatial WM training over the course of seven training sessions. Results showed that tDCS enhanced training performance, which was strikingly preserved several months after training completion. Furthermore, we observed stronger effects when tDCS was spaced over a weekend break relative to consecutive daily training, and we also demonstrated selective transfer in the right prefrontal group to nontrained tasks of visual and spatial WM. These findings shed light on how tDCS may be leveraged as a tool to enhance performance on WM-intensive learning tasks.

White matter volume loss in amyotrophic lateral sclerosis: A meta-analysis of voxel-based morphometry studies.

PubMed

Chen, Guangxiang; Zhou, Baiwan; Zhu, Hongyan; Kuang, Weihong; Bi, Feng; Ai, Hua; Gu, Zhongwei; Huang, Xiaoqi; Lui, Su; Gong, Qiyong

2018-04-20

Structural neuroimaging studies of white matter (WM) volume in amyotrophic lateral sclerosis (ALS) using voxel-based morphometry (VBM) have yielded inconsistent findings. This study aimed to perform a quantitative voxel-based meta-analysis using effect-size signed differential mapping (ES-SDM) to establish a statistical consensus between published studies for WM volume alterations in ALS. The pooled meta-analysis revealed significant WM volume losses in the bilateral supplementary motor areas (SMAs), bilateral precentral gyri (PGs), left middle cerebellar peduncle and right cerebellum in patients with ALS, involving the corticospinal tract (CST), interhemispheric fibers, subcortical arcuate fibers, projection fibers to the striatum and cortico-ponto-cerebellar tract. The meta-regression showed that the ALS functional rating scale-revised (ALSFRS-R) was positively correlated with decreased WM volume in the bilateral SMAs, whereas illness duration was negatively correlated with WM volume reduction in the right SMA. This study provides a thorough profile of WM volume loss in ALS and robust evidence that ALS is a multisystem neurodegenerative disease that involves a variety of subcortical WM tracts extending beyond motor cortex involvement. Copyright © 2018 Elsevier Inc. All rights reserved.

Training spatial-simultaneous working memory in individuals with Down syndrome.

PubMed

Lanfranchi, Silvia; Pulina, Francesca; Carretti, Barbara; Mammarella, Irene C

2017-05-01

Recent studies have suggested that the spatial-simultaneous component of working memory (WM), which is involved when stimuli are presented simultaneously, is selectively impaired in individuals with Down syndrome (DS). The main objective of the present study was to examine whether WM performance can be enhanced in individuals with DS by analyzing the immediate and maintenance effects of a training program. For this purpose, 61 individuals with DS were randomly assigned to three groups: one trained on simultaneous components of visuospatial WM; one serving as an active control group, that completed activities on vocabulary; and one serving as a passive control group, that only attended the pre- and post-test and follow-up assessments. The efficacy of the training was analyzed in terms of specific (spatial-simultaneous WM tasks), near transfer (spatial-sequential and verbal WM tasks), far transfer (spatial abilities, everyday competences), and maintenance effects (with a follow-up at 1 month). The results showed an overall significant effect on the WM on the group receiving the training. The benefit was generally specific, however, with some transfer to other WM tasks, but only in the immediate (post-test) assessment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Disentangling Working Memory Functioning in Mood States of Bipolar Disorder: A Systematic Review

PubMed Central

Soraggi-Frez, Carolina; Santos, Flávia H.; Albuquerque, Pedro B.; Malloy-Diniz, Leandro F.

2017-01-01

Working memory (WM) deficits are often reported in patients with Bipolar Disorder (BD). However, it is not clear about the nature of these WM deficits (update or serial order processes) and their association with each BD states (euthymic, mania, and depressive). This review investigated the association between BD patient's states and the functioning of WM components. For this purpose, we carried out a systematic review fulfilling a search in the databases Medline, Scopus, SciELO, and Web of Science using specific terms in the abstracts of the articles that generated 212 outcomes in the restricted period from 2005 to 2016. Twenty-three papers were selected, completely read, and analyzed using PICOS strategy. The mood episodes predicted deficits in different components of WM in BD patients (the phonological loop or visuospatial sketchpad) and were associated with different WM processes (updating and serial recall). Lower cognitive scores persist even in remission of symptoms. This result suggests that WM deficit apparently is stage-independent in BD patients. Furthermore, findings suggest that the neutral point on Hedonic Detector component of WM could be maladjusted by BD. PMID:28491042

Controlling Working Memory Operations by Selective Gating: The Roles of Oscillations and Synchrony.

PubMed

Dipoppa, Mario; Szwed, Marcin; Gutkin, Boris S

2016-01-01

Working memory (WM) is a primary cognitive function that corresponds to the ability to update, stably maintain, and manipulate short-term memory (ST M) rapidly to perform ongoing cognitive tasks. A prevalent neural substrate of WM coding is persistent neural activity , the property of neurons to remain active after having been activated by a transient sensory stimulus. This persistent activity allows for online maintenance of memory as well as its active manipulation necessary for task performance. WM is tightly capacity limited. Therefore, selective gating of sensory and internally generated information is crucial for WM function. While the exact neural substrate of selective gating remains unclear, increasing evidence suggests that it might be controlled by modulating ongoing oscillatory brain activity. Here, we review experiments and models that linked selective gating, persistent activity, and brain oscillations, putting them in the more general mechanistic context of WM. We do so by defining several operations necessary for successful WM function and then discussing how such operations may be carried out by mechanisms suggested by computational models. We specifically show how oscillatory mechanisms may provide a rapid and flexible active gating mechanism for WM operations.

Shape and color conjunction stimuli are represented as bound objects in visual working memory.

PubMed

Luria, Roy; Vogel, Edward K

2011-05-01

The integrated object view of visual working memory (WM) argues that objects (rather than features) are the building block of visual WM, so that adding an extra feature to an object does not result in any extra cost to WM capacity. Alternative views have shown that complex objects consume additional WM storage capacity so that it may not be represented as bound objects. Additionally, it was argued that two features from the same dimension (i.e., color-color) do not form an integrated object in visual WM. This led some to argue for a "weak" object view of visual WM. We used the contralateral delay activity (the CDA) as an electrophysiological marker of WM capacity, to test those alternative hypotheses to the integrated object account. In two experiments we presented complex stimuli and color-color conjunction stimuli, and compared performance in displays that had one object but varying degrees of feature complexity. The results supported the integrated object account by showing that the CDA amplitude corresponded to the number of objects regardless of the number of features within each object, even for complex objects or color-color conjunction stimuli. Copyright © 2010 Elsevier Ltd. All rights reserved.

The Development of Verbal and Visual Working Memory Processes: A Latent Variable Approach

ERIC Educational Resources Information Center

Koppenol-Gonzalez, Gabriela V.; Bouwmeester, Samantha; Vermunt, Jeroen K.

2012-01-01

Working memory (WM) processing in children has been studied with different approaches, focusing on either the organizational structure of WM processing during development (factor analytic) or the influence of different task conditions on WM processing (experimental). The current study combined both approaches, aiming to distinguish verbal and…

Inventory of File gdas1.t06z.sfluxgrbf06.grib2

Science.gov Websites

hour ave Visible Diffuse Downward Solar Flux [W/m^2] 036 surface NBDSF 0-6 hour ave Near IR Beam Downward Solar Flux [W/m^2] 037 surface NDDSF 0-6 hour ave Near IR Diffuse Downward Solar Flux [W/m^2] 038

Inventory of File gfs.t06z.sfluxgrbf06.grib2

Science.gov Websites

hour ave Visible Diffuse Downward Solar Flux [W/m^2] 036 surface NBDSF 0-6 hour ave Near IR Beam Downward Solar Flux [W/m^2] 037 surface NDDSF 0-6 hour ave Near IR Diffuse Downward Solar Flux [W/m^2] 038

Yttrium Y 90 Ibritumomab Tiuxetan, Fludarabine, Radiation Therapy, and Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

ClinicalTrials.gov

2017-04-17

B-cell Chronic Lymphocytic Leukemia; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

Daily variability in working memory is coupled with negative affect: the role of attention and motivation.

PubMed

Brose, Annette; Schmiedek, Florian; Lövdén, Martin; Lindenberger, Ulman

2012-06-01

Across days, individuals experience varying levels of negative affect, control of attention, and motivation. We investigated whether this intraindividual variability was coupled with daily fluctuations in working memory (WM) performance. In 100 days, 101 younger individuals worked on a spatial N-back task and rated negative affect, control of attention, and motivation. Results showed that individuals differed in how reliably WM performance fluctuated across days, and that subjective experiences were primarily linked to performance accuracy. WM performance was lower on days with higher levels of negative affect, reduced control of attention, and reduced task-related motivation. Thus, variables that were found to predict WM in between-subjects designs showed important relationships to WM at the within-person level. In addition, there was shared predictive variance among predictors of WM. Days with increased negative affect and reduced performance were also days with reduced control of attention and reduced motivation to work on tasks. These findings are in line with proposed mechanisms linking negative affect and cognitive performance.

Working memory is related to perceptual processing: a case from color perception.

PubMed

Allen, Elizabeth C; Beilock, Sian L; Shevell, Steven K

2011-07-01

We explored the relation between individual differences in working memory (WM) and color constancy, the phenomenon of color perception that allows us to perceive the color of an object as relatively stable under changes in illumination. Successive color constancy (measured by first viewing a colored surface under a particular illumination and later recalling it under a new illumination) was better for higher WM individuals than for lower WM individuals. Moreover, the magnitude of this WM difference depended on how much contextual information was available in the scene, which typically improves color constancy. By contrast, simple color memory, measured by viewing and recalling a colored surface under the same illumination, showed no significant relation to WM. This study reveals a relation between WM and a low-level perceptual process not previously thought to operate within the confines of attentional control, and it provides a first account of the individual differences in color constancy known about for decades.

Frontal white matter damage impairs response inhibition in children following traumatic brain injury.

PubMed

Lipszyc, Jonathan; Levin, Harvey; Hanten, Gerri; Hunter, Jill; Dennis, Maureen; Schachar, Russell

2014-05-01

Inhibition, the ability to suppress inappropriate cognitions or behaviors, can be measured using computer tasks and questionnaires. Inhibition depends on the frontal cortex, but the role of the underlying white matter (WM) is unclear. We assessed the specific impact of frontal WM damage on inhibition in 29 children with moderate-to-severe traumatic brain injury (15 with and 14 without frontal WM damage), 21 children with orthopedic injury, and 29 population controls. We used the Stop Signal Task to measure response inhibition, the Behavior Rating Inventory of Executive Function to assess everyday inhibition, and T2 fluid-attenuated inversion recovery magnetic resonance imaging to identify lesions. Children with frontal WM damage had impaired response inhibition compared with all other groups and poorer everyday inhibition than the orthopedic injury group. Frontal WM lesions most often affected the superior frontal gyrus. These results provide evidence for the critical role of frontal WM in inhibition.

Quantity not quality: The relationship between fluid intelligence and working memory capacity

PubMed Central

Fukuda, Keisuke; Vogel, Edward; Mayr, Ulrich; Awh, Edward

2010-01-01

A key motivation for understanding capacity in working memory (WM) is its relationship with fluid intelligence. Recent evidence has suggested a 2-factor model that distinguishes between the number of representations that can be maintained in WM and the resolution of those representations. To determine how these factors relate to fluid intelligence, we conducted an exploratory factor analysis on multiple number-limited and resolution-limited measures of WM ability. The results strongly supported the 2-factor model, with fully orthogonal factors accounting for performance in the number-limited and resolution-limited conditions. Furthermore, the reliable relationship between WM capacity and fluid intelligence was exclusively supported by the number factor (r = .66), while the resolution factor made no reliable contribution (r = −.05). Thus, the relationship between WM capacity and standard measures of fluid intelligence is mediated by the number of representations that can be simultaneously maintained in WM rather than by the precision of those representations. PMID:21037165

Refreshing memory traces: thinking of an item improves retrieval from visual working memory.

PubMed

Souza, Alessandra S; Rerko, Laura; Oberauer, Klaus

2015-03-01

This article provides evidence that refreshing, a hypothetical attention-based process operating in working memory (WM), improves the accessibility of visual representations for recall. "Thinking of", one of several concurrently active representations, is assumed to refresh its trace in WM, protecting the representation from being forgotten. The link between refreshing and WM performance, however, has only been tenuously supported by empirical evidence. Here, we controlled which and how often individual items were refreshed in a color reconstruction task by presenting cues prompting participants to think of specific WM items during the retention interval. We show that the frequency with which an item is refreshed improves recall of this item from visual WM. Our study establishes a role of refreshing in recall from visual WM and provides a new method for studying the impact of refreshing on the amount of information we can keep accessible for ongoing cognition. © 2014 New York Academy of Sciences.

Attentional capture by working memory contents.

PubMed

Pan, Yi

2010-06-01

There has been controversy on whether working memory (WM) contents automatically guide attention. The present study tried to replicate the effect of WM-based attentional capture using an adaption of Downing's (2000) paradigm, in which WM and attentional capture were combined. Subjects were presented with an attention display containing two objects, one of which could be precued by a matching item being held in WM. As measured by a probe discrimination task, the memory-matching object had a privileged status to capture attention regardless of the stimulus onset asynchronies between the memory cue and the attention display, even when there was absolutely no benefit for subjects to bias attention in favour of the memory match. These results suggest that WM contents guide attention in an involuntary manner. The implications of current findings for understanding of WM effects on visual selection are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

Effects of a working memory training program in preschoolers with symptoms of attention-deficit/hyperactivity disorder.

PubMed

Capodieci, Agnese; Gola, Maria Laura; Cornoldi, Cesare; Re, Anna Maria

2018-02-01

Preschoolers with attention-deficit/hyperactivity disorder (ADHD) have been found to exhibit impairments on neuropsychological measures of working memory (WM). As WM is an important predictor of future learning abilities, early intervention could help to prevent severe problems. The purpose of this research was to ascertain the efficacy of an intervention for training WM in 5-year-old children with symptoms of ADHD. Thirty-four children with symptoms of ADHD were randomly divided into two groups: One was assigned to the WM training condition, and the other continued normal class activities. The training was provided at school in small groups that also included typically developing children. The trained group showed a significant improvement in tasks measuring their WM and other controlled processes at conclusion of study, whereas no significant improvement was found in the control group. We concluded that early intervention on WM may be effective in children with symptoms of ADHD.

Working memory contributes to elevated motor activity in adults with ADHD: an examination of the role of central executive and storage/rehearsal processes.

PubMed

Hudec, Kristen L; Alderson, R Matt; Kasper, Lisa J; Patros, Connor H G

2014-05-01

The relationship between working memory (WM) and objectively measured motor activity was examined in adults with ADHD and healthy controls (HCs). Thirty-five adults (ADHD = 20, HC = 15) were grouped using self-report and collateral-report measures in addition to a semistructured clinical interview. All participants completed control conditions with minimal WM demands, and separate phonological (PH) and visuospatial (VS) WM tasks with recall demands ranging from four to seven stimuli. The ADHD group exhibited significantly more motor activity relative to the HC group, and both groups exhibited greater activity during PH and VS WM tasks, relative to control conditions. Finally, the central executive (CE) and PH storage/rehearsal subsystems were associated with large-magnitude between-group differences in activity. Findings suggest that increased demands on WM, particularly the CE and PH storage/rehearsal, contribute to ADHD-related hyperactivity, though a portion of excessive motor activity in adults with ADHD may occur independently of WM demands.

Externally induced frontoparietal synchronization modulates network dynamics and enhances working memory performance.

PubMed

Violante, Ines R; Li, Lucia M; Carmichael, David W; Lorenz, Romy; Leech, Robert; Hampshire, Adam; Rothwell, John C; Sharp, David J

2017-03-14

Cognitive functions such as working memory (WM) are emergent properties of large-scale network interactions. Synchronisation of oscillatory activity might contribute to WM by enabling the coordination of long-range processes. However, causal evidence for the way oscillatory activity shapes network dynamics and behavior in humans is limited. Here we applied transcranial alternating current stimulation (tACS) to exogenously modulate oscillatory activity in a right frontoparietal network that supports WM. Externally induced synchronization improved performance when cognitive demands were high. Simultaneously collected fMRI data reveals tACS effects dependent on the relative phase of the stimulation and the internal cognitive processing state. Specifically, synchronous tACS during the verbal WM task increased parietal activity, which correlated with behavioral performance. Furthermore, functional connectivity results indicate that the relative phase of frontoparietal stimulation influences information flow within the WM network. Overall, our findings demonstrate a link between behavioral performance in a demanding WM task and large-scale brain synchronization.

Relation between working memory and self-regulation capacities and the level of social skills acquisition in people with moderate intellectual disability.

PubMed

Dučić, Bojan; Gligorović, Milica; Kaljača, Svetlana

2018-03-01

Social competence deficit is one of the main characteristics of intellectual disability. The aim of this paper is to determine the influence of working memory (WM) and self-regulation (SR) on social skills in persons with moderate intellectual disability (MID). The sample included 41 participants with MID, aged 14-21. Memorizing animals and maze tasks were used for WM assessment. SR skills were assessed by the Behavioral Multitask Batteries. Social skills were rated by the Socialization subscale from the Adaptive Behavior Assessment System II, which consists of two parts. Social skills part could mainly be predicted from SR scores (β = -.441), followed by WM (β = .390) and IQ score (β = .382). Only WM score (β = .494) had a predictive value for Leisure time part. As WM had a greater influence on social skills, incorporating WM training into programmes for improving social skills in persons with MID should be considered. © 2017 John Wiley & Sons Ltd.

Agreement processing and attraction errors in aging: evidence from subject-verb agreement in German.

PubMed

Reifegerste, Jana; Hauer, Franziska; Felser, Claudia

2017-11-01

Effects of aging on lexical processing are well attested, but the picture is less clear for grammatical processing. Where age differences emerge, these are usually ascribed to working-memory (WM) decline. Previous studies on the influence of WM on agreement computation have yielded inconclusive results, and work on aging and subject-verb agreement processing is lacking. In two experiments (Experiment 1: timed grammaticality judgment, Experiment 2: self-paced reading + WM test), we investigated older (OA) and younger (YA) adults' susceptibility to agreement attraction errors. We found longer reading latencies and judgment reaction times (RTs) for OAs. Further, OAs, particularly those with low WM scores, were more accepting of sentences with attraction errors than YAs. OAs showed longer reading latencies for ungrammatical sentences, again modulated by WM, than YAs. Our results indicate that OAs have greater difficulty blocking intervening nouns from interfering with the computation of agreement dependencies. WM can modulate this effect.

Physicochemical and sensory properties of chicken nuggets with washed mechanically deboned chicken meat: Research note.

PubMed

Perlo, F; Bonato, P; Teira, G; Fabre, R; Kueider, S

2006-04-01

The effects of different proportions (0%, 10%, 20%, 30%, 40%) of washed mechanically deboned chicken meat (WM) as a substitute for hand deboned chicken meat, on the physicochemical and sensory characteristics of chicken nuggets were evaluated. The addition of WM increased fat content, but it was only significant (P<0.05) when 40% of WM was added, whereas the protein content was significantly (P<0.05) reduced as from 20%. Significant differences (P<0.05) were found in L(*), a(*) and b(*) values with different proportions of WM, however, these differences were evidently not discerned as shown by the no significant differences (P>0.05) in ΔE(*) color scores. The addition of WM did not affect (P>0.05) sensory attributes of chicken nuggets. From a technical viewpoint, up to 40% WM could be incorporated into nugget formulation instead of hand deboned chicken meat without affecting sensory attributes of the product. Minor changes in composition were observed but they were probably not detrimental to the product.

Two Equals One: Two Human Actions During Social Interaction Are Grouped as One Unit in Working Memory.

PubMed

Ding, Xiaowei; Gao, Zaifeng; Shen, Mowei

2017-09-01

Every day, people perceive other people performing interactive actions. Retaining these actions of human agents in working memory (WM) plays a pivotal role in a normal social life. However, whether the semantic knowledge embedded in the interactive actions has a pervasive impact on the storage of the actions in WM remains unknown. In the current study, we investigated two opposing hypotheses: (a) that WM stores the interactions individually (the individual-storage hypothesis) and (b) that WM stores the interactions as chunks (the chunk-storage hypothesis). We required participants to memorize a set of individual actions while ignoring the underlying social interactions. We found that although the social-interaction aspect was task irrelevant, the interactive actions were stored in WM as chunks that were not affected by memory load (Experiments 1 and 2); however, inverting the human actions vertically abolished this chunking effect (Experiment 3). These results suggest that WM automatically and efficiently used semantic knowledge about interactive actions to store them and support the chunk-storage hypothesis.

Central Executive Dysfunction and Deferred Prefrontal Processing in Veterans with Gulf War Illness

PubMed Central

Hubbard, Nicholas A.; Hutchison, Joanna L.; Motes, Michael A.; Shokri-Kojori, Ehsan; Bennett, Ilana J.; Brigante, Ryan M.; Haley, Robert W.; Rypma, Bart

2015-01-01

Gulf War Illness is associated with toxic exposure to cholinergic disruptive chemicals. The cholinergic system has been shown to mediate the central executive of working memory (WM). The current work proposes that impairment of the cholinergic system in Gulf War Illness patients (GWIPs) leads to behavioral and neural deficits of the central executive of WM. A large sample of GWIPs and matched controls (MCs) underwent functional magnetic resonance imaging during a varied-load working memory task. Compared to MCs, GWIPs showed a greater decline in performance as WM-demand increased. Functional imaging suggested that GWIPs evinced separate processing strategies, deferring prefrontal cortex activity from encoding to retrieval for high demand conditions. Greater activity during high-demand encoding predicted greater WM performance. Behavioral data suggest that WM executive strategies are impaired in GWIPs. Functional data further support this hypothesis and suggest that GWIPs utilize less effective strategies during high-demand WM. PMID:25767746

Selective visual working memory in fear of spiders: the role of automaticity and material-specificity.

PubMed

Reinecke, Andrea; Becker, Eni S; Rinck, Mike

2009-12-01

Following cognitive models of anxiety, biases occur if threat processing is automatic versus strategic. Therefore, most of these models predict attentional bias, but not explicit memory bias. We suggest dividing memory into the highly automatic working memory (WM) component versus long-term memory when investigating bias in anxiety. WM for threat has rarely been investigated although its main function is stimulus monitoring, particularly important in anxiety. We investigated WM for spiders in spider fearfuls (SFs) versus non-anxious controls (NACs). In Experiment 1 (23 SFs/24 NACs), we replicated an earlier WM study, reducing strategic processing options. This led to stronger group differences and, thus, clearer WM threat biases. There were no group differences in Experiment 2 (18 SFs/19 NACs), using snakes instead of spiders to test whether WM biases are material-specific. This article supports cognitive models of anxiety in that biases are more likely to occur when reducing strategic processing. However, it contradicts the assumption that explicit memory biases are not characteristic of anxiety.

Numerical investigation of the thermal behavior of heated natural composite materials

NASA Astrophysics Data System (ADS)

Qasim, S. M.; Mohammed, F. Abbas; Hashim, R.

2015-11-01

In the present work numerical investigation was carried out for laminar natural convection heat transfer from natural composite material (NCM). Three types of natural materials such as seed dates, egg shells, and feathers are mixed separately with polyester resin. Natural materials are added with different volume fraction (10%, 20%, and 30%) are heated with different heat flux (1078W/m2, 928W/m2, 750W/m2, 608W/m2, and 457W/m2) at (vertical, inclined, and horizontal) position. Continuity and Navier-Stocks equations are solved numerically in three dimensions using ANSYS FLUENT package 12.1 software commercial program. Numerical results showed the temperature distribution was affected for all types at volume fraction 30% and heat flux is 1078 W/m2, for different position. So, shows that the plumes and temperature behavior are affected by the air and the distance from heat source. Numerical results showed acceptable agreement with the experimental previous results.

A selective egocentric topographical working memory deficit in the early stages of Alzheimer's disease: a preliminary study.

PubMed

Bianchini, F; Di Vita, A; Palermo, L; Piccardi, L; Blundo, C; Guariglia, C

2014-12-01

The aim of this study was to determine whether an egocentric topographical working memory (WM) deficit is present in the early stages of Alzheimer's disease (AD) with respect to other forms of visuospatial WM. Further, we would investigate whether this deficit could be present in patients having AD without topographical disorientation (TD) signs in everyday life assessed through an informal interview to caregivers. Seven patients with AD and 20 healthy participants performed the Walking Corsi Test and the Corsi Block-Tapping Test. The former test requires memorizing a sequence of places by following a path and the latter is a well-known visuospatial memory task. Patients with AD also performed a verbal WM test to exclude the presence of general WM impairments. Preliminary results suggest that egocentric topographical WM is selectively impaired, with respect to visuospatial and verbal WM, even without TD suggesting an important role of this memory in the early stages of AD. © The Author(s) 2014.

Working memory is related to perceptual processing: A case from color perception

PubMed Central

Allen, Elizabeth C.; Beilock, Sian L.; Shevell, Steven K.

2011-01-01

We explored the relation between individual differences in working memory (WM) and color constancy, the phenomenon of color perception that allows us to perceive the color of an object as relatively stable under changes in illumination. Successive color constancy (measured by first viewing a colored surface under a particular illumination and later recalling it under a new illumination) was better for higher-WM individuals than for lower-WM individuals. Moreover, the magnitude of this WM difference depended on how much contextual information was available in the scene, which typically improves color constancy. By contrast, simple color memory, measured by viewing and recalling a colored surface under the same illumination, showed no significant relation to WM. This study reveals a relation between WM and a low-level perceptual process not previously thought to operate within the confines of attentional control, and provides a first account of the individual differences in color constancy known about for decades. PMID:21480748

Analogous Mechanisms of Selection and Updating in Declarative and Procedural Working Memory: Experiments and a Computational Model

ERIC Educational Resources Information Center

Oberauer, Klaus; Souza, Alessandra S.; Druey, Michel D.; Gade, Miriam

2013-01-01

The article investigates the mechanisms of selecting and updating representations in declarative and procedural working memory (WM). Declarative WM holds the objects of thought available, whereas procedural WM holds representations of what to do with these objects. Both systems consist of three embedded components: activated long-term memory, a…

Blockade of IP[subscript 3]-Mediated SK Channel Signaling in the Rat Medial Prefrontal Cortex Improves Spatial Working Memory

ERIC Educational Resources Information Center

Brennan, Avis R.; Dolinsky, Beth; Vu, Mai-Anh T.; Stanley, Marion; Yeckel, Mark F.; Arnsten, Amy F. T.

2008-01-01

Planning and directing thought and behavior require the working memory (WM) functions of prefrontal cortex. WM is compromised by stress, which activates phosphatidylinositol (PI)-mediated IP[subscript 3]-PKC intracellular signaling. PKC overactivation impairs WM operations and in vitro studies indicate that IP[subscript 3] receptor (IP[subscript…

75 FR 6018 - Environmental Management Site-Specific Advisory Board, Hanford

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-05

... in the Draft Tank Closure (TC) and Waste Management (WM) Environmental Impact Statement (EIS) Overview of the Draft TC and WM EIS findings by other stakeholder groups Discussion of HAB member comments on the TC and WM EIS Development of HAB advice principles Adjourn Public Participation: The meeting...

Successful Training of Filtering Mechanisms in Multiple Object Tracking Does Not Transfer to Filtering Mechanisms in a Visual Working Memory Task: Behavioral and Electrophysiological Evidence

ERIC Educational Resources Information Center

Arend, Anna M.; Zimmer, Hubert D.

2012-01-01

In this training study, we aimed to selectively train participants' filtering mechanisms to enhance visual working memory (WM) efficiency. The highly restricted nature of visual WM capacity renders efficient filtering mechanisms crucial for its successful functioning. Filtering efficiency in visual WM can be measured via the lateralized change…

‘Activity-silent’ working memory in prefrontal cortex: a dynamic coding framework

PubMed Central

Stokes, Mark G.

2015-01-01

Working memory (WM) provides the functional backbone to high-level cognition. Maintenance in WM is often assumed to depend on the stationary persistence of neural activity patterns that represent memory content. However, accumulating evidence suggests that persistent delay activity does not always accompany WM maintenance but instead seems to wax and wane as a function of the current task relevance of memoranda. Furthermore, new methods for measuring and analysing population-level patterns show that activity states are highly dynamic. At first glance, these dynamics seem at odds with the very nature of WM. How can we keep a stable thought in mind while brain activity is constantly changing? This review considers how neural dynamics might be functionally important for WM maintenance. PMID:26051384

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.

Age differences in behavioral and neural correlates of proactive interference: Disentangling the role of overall working memory performance.

PubMed

Loosli, Sandra V; Rahm, Benjamin; Unterrainer, Josef M; Mader, Irina; Weiller, Cornelius; Kaller, Christoph P

2016-02-15

Reliable performance in working memory (WM) critically depends on the ability to resist proactive interference (PI) from previously relevant WM contents. Both WM performance and PI susceptibility are subject to cognitive decline at older adult age. However, the behavioral and neural processes underlying these co-evolving developmental changes and their potential interdependencies are not yet understood. Here, we investigated PI using a recent-probes WM paradigm and functional MRI in a cross-sectional sample of younger (n=18, 10 female, 23.4 ± 2.7 years) and older adults (n=18, 10 female, 70.2 ± 2.7 years). As expected, older adults showed lower WM performance and higher PI susceptibility than younger adults. Resolution of PI activated a mainly bilateral frontal network across all participants. Significant interactions with age indicated reduced neural activation in older adults for PI resolution. A second analysis in a selection of younger and older adults (n=12 each) with matched WM performance also revealed significant differences in PI between both age groups and - on a descriptive level - again a hypo-activation of the older adults' PI network. But the differential effect of age on the neural PI effects did not reach significance in this smaller sample most likely to the reduced statistical power. However, given the highly similar patterns in both the overall and the WM-matched samples, we propose that the hypo-activation of the PI network in the older adults may not be attributable to age-related differences in overall WM performance, hence suggesting that higher PI susceptibility in older adult age does not directly depend on their lower WM performance. Copyright © 2015 Elsevier Inc. All rights reserved.

Minimal RED cell pairs markedly improve electrode kinetics and power production in microbial reverse electrodialysis cells.

PubMed

Cusick, Roland D; Hatzell, Marta; Zhang, Fang; Logan, Bruce E

2013-12-17

Power production from microbial reverse electrodialysis cell (MRC) electrodes is substantially improved compared to microbial fuel cells (MFCs) by using ammonium bicarbonate (AmB) solutions in multiple RED cell pair stacks and the cathode chamber. Reducing the number of RED membranes pairs while maintaining enhanced electrode performance could help to reduce capital costs. We show here that using only a single RED cell pair (CP), created by operating the cathode in concentrated AmB, dramatically increased power production normalized to cathode area from both acetate (Acetate: from 0.9 to 3.1 W/m(2)-cat) and wastewater (WW: 0.3 to 1.7 W/m(2)), by reducing solution and charge transfer resistances at the cathode. A second RED cell pair increased RED stack potential and reduced anode charge transfer resistance, further increasing power production (Acetate: 4.2 W/m(2); WW: 1.9 W/m(2)). By maintaining near optimal electrode power production with fewer membranes, power densities normalized to total membrane area for the 1-CP (Acetate: 3.1 W/m(2)-mem; WW: 1.7 W/m(2)) and 2-CP (Acetate: 1.3 W/m(2)-mem; WW: 0.6 W/m(2)) reactors were much higher than previous MRCs (0.3-0.5 W/m(2)-mem with acetate). While operating at peak power, the rate of wastewater COD removal, normalized to reactor volume, was 30-50 times higher in 1-CP and 2-CP MRCs than that in a single chamber MFC. These findings show that even a single cell pair AmB RED stack can significantly enhance electrical power production and wastewater treatment.

Cinnamon users with prediabetes have a better fasting working memory: a cross-sectional function study.

PubMed

Wahlqvist, Mark L; Lee, Meei-Shyuan; Lee, Jiunn-Tay; Hsu, Chih-Cheng; Chou, Yu-Ching; Fang, Wen-Hui; Liu, Hsiao-Yu; Xiu, Lili; Andrews, Zane B

2016-04-01

Working memory (WM) is impaired in prediabetes. We hypothesized that culinary herbs and spices may decrease insulin resistance (IR) and improve WM in prediabetes. Healthy people aged ≥60 years with prediabetes (fasting blood glucose 100-125 mg/dL) (47 men and 46 women) whose food and culinary herb intakes were established with a food frequency questionnaire had body composition assessed and fasting glucose and insulin measured. Working memory and Mini-Mental State Examination (MMSE) were assessed on the same occasion. The contributions to associations between WM and diet, body fat, and IR were estimated by linear regression. Compared with nonusers, cinnamon users had significantly less frequent physical activity (2.9 vs. 4.4 times per week) and more often used fresh ginger (93.3% vs. 64.1%) and ginger in cooking (60.0% vs. 32.1%). Cinnamon users also had a better WM (2.9 vs. 2.5, P < .001). Cinnamon had a significant effect (users were 0.446 higher), but not ginger or curry usage, in predicting WM. For sociodemographic variables, only education (years) was significant in predicting WM (β = 0.065). Other significant determinants of WM were total fat mass (kilograms) (β = -0.024) and MMSE (β = 0.075). After adjustment for age and sex, cinnamon use, education, and MMSE remained significant individual predictors. In the final model, in which all variables listed were adjusted simultaneously, cinnamon users still had a significantly higher WM than nonusers. Cinnamon usage is associated with a better WM, not accounted for by dietary quality or IR, in untreated prediabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

White Matter Abnormalities Correlating with Memory and Depression in Heroin Users under Methadone Maintenance Treatment

PubMed Central

Lin, Wei-Che; Chou, Kun-Hsien; Chen, Chien-Chih; Huang, Chu-Chung; Chen, Hsiu-Ling; Lu, Cheng-Hsien; Li, Shau-Hsuan; Wang, Ya-Ling; Cheng, Yu-Fan; Lin, Ching-Po

2012-01-01

Methadone maintenance treatment (MMT) has elevated rates of co-morbid memory deficit and depression that are associated with higher relapse rates for substance abuse. White matter (WM) disruption in MMT patients have been reported but their impact on these co-morbidities is unknown. This study aimed to investigate changes in WM integrity of MMT subjects using diffusion tensor image (DTI), and their relationship with history of heroin and methadone use in treated opiate-dependent individuals. The association between WM integrity changes from direct group comparisons and the severity of memory deficit and depression was also investigated. Differences in WM integrity between 35 MMT patients and 23 healthy controls were evaluated using DTI with tract-based spatial statistical analysis. Differences in DTI indices correlated with diminished memory function, Beck Depression Inventory, duration of heroin use and MMT, and dose of heroin and methadone administration. Changes in WM integrity were found in several WM regions, including the temporal and frontal lobes, pons, cerebellum, and cingulum bundles. The duration of MMT was associated with declining DTI indices in the superior longitudinal fasciculus and para-hippocampus. MMT patients had more memory and emotional deficits than healthy subjects. Worse scores in both depression and memory functions were associated with altered WM integrity in the superior longitudinal fasciculus, para-hippocampus, and middle cerebellar peduncle in MMT. Patients on MMT also had significant WM differences in the reward circuit and in depression- and memory-associated regions. Correlations among decreased DTI indices, disease severity, and accumulation effects of methadone suggest that WM alterations may be involved in the psychopathology and pathophysiology of co-morbidities in MMT. PMID:22496768

Reduced Frontal Activations at High Working Memory Load in Mild Cognitive Impairment: Near-Infrared Spectroscopy.

PubMed

Yeung, Michael K; Sze, Sophia L; Woo, Jean; Kwok, Timothy; Shum, David H K; Yu, Ruby; Chan, Agnes S

2016-01-01

Some functional magnetic resonance imaging studies have reported altered activations in the frontal cortex during working memory (WM) performance in individuals with mild cognitive impairment (MCI), but the findings have been mixed. The objective of the present study was to utilize near-infrared spectroscopy (NIRS), an alternative imaging technique, to examine neural processing during WM performance in individuals with MCI. Twenty-six older adults with MCI (7 males; mean age 69.15 years) were compared with 26 age-, gender-, handedness-, and education-matched older adults with normal cognition (NC; 7 males; mean age 68.87 years). All of the participants undertook an n-back task with a low (i.e., 0-back) and a high (i.e., 2-back) WM load condition while their prefrontal dynamics were recorded by a 16-channel NIRS system. Although behavioral results showed that the two groups had comparable task performance, neuroimaging results showed that the MCI group, unlike the NC group, did not exhibit significantly increased frontal activations bilaterally when WM load increased. Compared to the NC group, the MCI group had similar frontal activations at low load (p > 0.05 on all channels) but reduced activations at high load (p < 0.05 on 4 channels), thus failing to demonstrate WM-related frontal activations (p < 0.05 on 9 channels). In addition, we found a positive correlation between the left WM-related frontal activations and WM ability primarily in the NC group (rs = 0.42, p = 0.035), suggesting a relationship between frontal hypoactivation and WM difficulties. The present findings suggest the presence of frontal dysfunction that is dependent on WM load in individuals with MCI. © 2016 S. Karger AG, Basel.

Working memory in pregnant women: Relation to estrogen and antepartum depression.

PubMed

Hampson, Elizabeth; Phillips, Shauna-Dae; Duff-Canning, Sarah J; Evans, Kelly L; Merrill, Mia; Pinsonneault, Julia K; Sadée, Wolfgang; Soares, Claudio N; Steiner, Meir

2015-08-01

This article is part of a Special Issue "Estradiol and cognition". Subjective changes in concentration and memory are commonly reported by women during the second or third trimesters of pregnancy, but the nature of the problem is poorly understood. We hypothesized that these self-reports might reflect difficulties in working memory (WM). It was further hypothesized that antepartum depression (depression arising during pregnancy) may play an etiological role, either on its own or due to secondary changes in endocrine function or sleep. Using WM tasks that emphasized executive control processes mediated by the prefrontal cortex (PFC) we compared pregnant women tested at 34-36 weeks of gestation (n = 28) with age- and education-matched non-pregnant controls (n = 26). All pregnant women were screened for depression. Evidence of a WM disturbance was found, and was evident only among pregnant women showing depressive symptoms. In contrast, pregnant women who were not depressed showed WM performance that equalled, or even significantly exceeded, non-pregnant controls. No significant differences were observed on control tests of other cognitive functions. Multiple regression revealed that serum estradiol concentrations, along with severity of depressive affect but not sleep disruption, significantly predicted variation in the WM scores. In agreement with studies of estradiol and WM in other contexts, higher estradiol was associated with better WM, while higher levels of depressive symptoms predicted poorer WM. We conclude that memory disturbance during gestation might not be as widespread as commonly believed, but can be seen among women experiencing antepartum depression. The high level of WM performance found in healthy, non-depressed, pregnant women is discussed from an adaptationist perspective. Copyright © 2015 Elsevier Inc. All rights reserved.

Music practice is associated with development of working memory during childhood and adolescence.

PubMed

Bergman Nutley, Sissela; Darki, Fahimeh; Klingberg, Torkel

2014-01-07

Practicing a musical instrument is associated with cognitive benefits and structural brain changes in correlational and interventional trials; however, the effect of musical training on cognition during childhood is still unclear. In this longitudinal study of child development we analyzed the association between musical practice and performance on reasoning, processing speed and working memory (WM) during development. Subjects (n = 352) between the ages of 6 and 25 years participated in neuropsychological assessments and neuroimaging investigations (n = 64) on two or three occasions, 2 years apart. Mixed model regression showed that musical practice had an overall positive association with WM capacity (visuo-spatial WM, F = 4.59, p = 0.033, verbal WM, F = 9.69, p = 0.002), processing speed, (F = 4.91, p = 0.027) and reasoning (Raven's progressive matrices, F = 28.34, p < 0.001) across all three time points, after correcting for the effect of parental education and other after school activities. Music players also had larger gray matter volume in the temporo-occipital and insular cortex (p = 0.008), areas previously reported to be related to musical notation reading. The change in WM between the time points was proportional to the weekly hours spent on music practice for both WM tests (VSWM, β = 0.351, p = 0.003, verbal WM, β = 0.261, p = 0.006) but this was not significant for reasoning ability (β = 0.021, p = 0.090). These effects remained when controlling for parental education and other after school activities. In conclusion, these results indicate that music practice positively affects WM development and support the importance of practice for the development of WM during childhood and adolescence.

Convergence and divergence across construction methods for human brain white matter networks: an assessment based on individual differences.

PubMed

Zhong, Suyu; He, Yong; Gong, Gaolang

2015-05-01

Using diffusion MRI, a number of studies have investigated the properties of whole-brain white matter (WM) networks with differing network construction methods (node/edge definition). However, how the construction methods affect individual differences of WM networks and, particularly, if distinct methods can provide convergent or divergent patterns of individual differences remain largely unknown. Here, we applied 10 frequently used methods to construct whole-brain WM networks in a healthy young adult population (57 subjects), which involves two node definitions (low-resolution and high-resolution) and five edge definitions (binary, FA weighted, fiber-density weighted, length-corrected fiber-density weighted, and connectivity-probability weighted). For these WM networks, individual differences were systematically analyzed in three network aspects: (1) a spatial pattern of WM connections, (2) a spatial pattern of nodal efficiency, and (3) network global and local efficiencies. Intriguingly, we found that some of the network construction methods converged in terms of individual difference patterns, but diverged with other methods. Furthermore, the convergence/divergence between methods differed among network properties that were adopted to assess individual differences. Particularly, high-resolution WM networks with differing edge definitions showed convergent individual differences in the spatial pattern of both WM connections and nodal efficiency. For the network global and local efficiencies, low-resolution and high-resolution WM networks for most edge definitions consistently exhibited a highly convergent pattern in individual differences. Finally, the test-retest analysis revealed a decent temporal reproducibility for the patterns of between-method convergence/divergence. Together, the results of the present study demonstrated a measure-dependent effect of network construction methods on the individual difference of WM network properties. © 2015 Wiley

Working memory load and distraction: dissociable effects of visual maintenance and cognitive control.

PubMed

Konstantinou, Nikos; Beal, Eleanor; King, Jean-Remi; Lavie, Nilli

2014-10-01

We establish a new dissociation between the roles of working memory (WM) cognitive control and visual maintenance in selective attention as measured by the efficiency of distractor rejection. The extent to which focused selective attention can prevent distraction has been shown to critically depend on the level and type of load involved in the task. High perceptual load that consumes perceptual capacity leads to reduced distractor processing, whereas high WM load that reduces WM ability to exert priority-based executive cognitive control over the task results in increased distractor processing (e.g., Lavie, Trends in Cognitive Sciences, 9(2), 75-82, 2005). WM also serves to maintain task-relevant visual representations, and such visual maintenance is known to recruit the same sensory cortices as those involved in perception (e.g., Pasternak & Greenlee, Nature Reviews Neuroscience, 6(2), 97-107, 2005). These findings led us to hypothesize that loading WM with visual maintenance would reduce visual capacity involved in perception, thus resulting in reduced distractor processing-similar to perceptual load and opposite to WM cognitive control load. Distractor processing was assessed in a response competition task, presented during the memory interval (or during encoding; Experiment 1a) of a WM task. Loading visual maintenance or encoding by increased set size for a memory sample of shapes, colors, and locations led to reduced distractor response competition effects. In contrast, loading WM cognitive control with verbal rehearsal of a random letter set led to increased distractor effects. These findings confirm load theory predictions and provide a novel functional distinction between the roles of WM maintenance and cognitive control in selective attention.

Working Memory Ability Predicts Trajectories of Early Alcohol Use in Adolescents: The Mediational Role of Impulsivity

PubMed Central

Khurana, Atika; Romer, Dan; Betancourt, Laura M.; Brodsky, Nancy L.; Giannetta, Joan M.; Hurt, Hallam

2012-01-01

Aims 1) To evaluate the role of pre-existing weakness in working memory ability (WM) as a risk factor for early alcohol use as mediated by different forms of impulsivity. 2) To assess the adverse effects of progressive alcohol use on variations in WM over time. Design, Setting and Participants A community sample of 358 adolescents [48% males, Meanage(baseline) = 11.4± 0.87 years] from a longitudinal cohort design, assessed annually over four consecutive years with less than 6% attrition. Measurements Repeated assessments were conducted for the following key variables: WM (based on performance on four separate tasks), frequency of alcohol use (AU), and three forms of impulsivity, namely sensation seeking (SS), acting-without-thinking (AWT) and delay discounting (DD). Latent growth curve modeling procedures were used to identify individual trajectories of change for all key variables. Findings Weakness in WM (at baseline) significantly predicted both concurrent alcohol use and increased frequency of use over the four waves (p <.05). This effect was entirely mediated by two forms of impulsivity, AWT and DD, both of which were characterized by underlying weakness in WM. No individual variation was observed in the slopes of WM, which suggests that individual variations in alcohol use were not associated with changes in WM in our early adolescent sample. Conclusions Early adolescent alcohol use may be a consequence of (pre-existing) weaknesses in working memory (WM) rather than a cause of it. Efforts to reduce early alcohol use should consider the distinct roles of different impulsivity dimensions, in addition to WM, as potential targets of intervention. PMID:23033972

The Weight Management Dietetics Practice Group collecting outcomes mentoring program

USDA-ARS?s Scientific Manuscript database

The is a newsletter article for the Academy of Nutrition and Dietetics (AND), Weight Management Dietetics Practice Group (WM DPG). The article presents the ‘Collecting Outcomes Mentoring Program’ for 2017 that is managed by the Research Section of the WM DPG. Dietitians in the WM DGP are provided wi...

The Contribution of Working Memory to Fluid Reasoning: Capacity, Control, or Both?

ERIC Educational Resources Information Center

Chuderski, Adam; Necka, Edward

2012-01-01

Fluid reasoning shares a large part of its variance with working memory capacity (WMC). The literature on working memory (WM) suggests that the capacity of the focus of attention responsible for simultaneous maintenance and integration of information within WM, as well as the effectiveness of executive control exerted over WM, determines…

Development of a Handbook for Educators: Addressing Working Memory Capacity in Elementary Students

ERIC Educational Resources Information Center

Fernandez, Julie Marie

2013-01-01

Working Memory (WM) refers to a brain system that provides temporary storage and manipulation of the information necessary for complex cognitive tasks such as language comprehension, learning, and reasoning. WM also requires the simultaneous storage and processing of information. WM is directly related to academic performance in the classroom.…

The Extent of Working Memory Deficits Associated with Williams Syndrome: Exploration of Verbal and Spatial Domains and Executively Controlled Processes

ERIC Educational Resources Information Center

Rhodes, Sinead M.; Riby, Deborah M.; Fraser, Emma; Campbell, Lorna Elise

2011-01-01

The present study investigated verbal and spatial working memory (WM) functioning in individuals with the neuro-developmental disorder Williams syndrome (WS) using WM component tasks. While there is strong evidence of WM impairments in WS, previous research has focused on short-term memory and has neglected assessment of executive components of…

Working Memory Is (Almost) Perfectly Predicted by "g"

ERIC Educational Resources Information Center

Colom, Roberto; Rebollo, Irene; Palacios, Antonio; Juan-Espinosa, Manuel; Kyllonen, Patrick C.

2004-01-01

This article analyzes if working memory (WM) is especially important to understand "g." WM comprises the functions of focusing attention, conscious rehearsal, and transformation and mental manipulation of information, while "g" reflects the component variance that is common to all tests of ability. The centrality of WM in individual differences in…

Computer Simulations of Developmental Change: The Contributions of Working Memory Capacity and Long-Term Knowledge

ERIC Educational Resources Information Center

Jones, Gary; Gobet, Fernand; Pine, Julian M.

2008-01-01

Increasing working memory (WM) capacity is often cited as a major influence on children's development and yet WM capacity is difficult to examine independently of long-term knowledge. A computational model of children's nonword repetition (NWR) performance is presented that independently manipulates long-term knowledge and WM capacity to determine…

Dopamine, Working Memory, and Training Induced Plasticity: Implications for Developmental Research

ERIC Educational Resources Information Center

Soderqvist, Stina; Bergman Nutley, Sissela; Peyrard-Janvid, Myriam; Matsson, Hans; Humphreys, Keith; Kere, Juha; Klingberg, Torkel

2012-01-01

Cognitive deficits and particularly deficits in working memory (WM) capacity are common features in neuropsychiatric disorders. Understanding the underlying mechanisms through which WM capacity can be improved is therefore of great importance. Several lines of research indicate that dopamine plays an important role not only in WM function but also…

On the Capacity of Attention: Its Estimation and Its Role in Working Memory and Cognitive Aptitudes

ERIC Educational Resources Information Center

Cowan, N.; Elliott, E.M.; Scott Saults, J.; Morey, C.C.; Mattox, S.; Hismjatullina, A.; Conway, A.R.A.

2005-01-01

Working memory (WM) is the set of mental processes holding limited information in a temporarily accessible state in service of cognition. We provide a theoretical framework to understand the relation between WM and aptitude measures. The WM measures that have yielded high correlations with aptitudes include separate storage-and-processing task…

A Randomized Control Trial of Working Memory Training with and without Strategy Instruction: Effects on Young Children's Working Memory and Comprehension

ERIC Educational Resources Information Center

Peng, Peng; Fuchs, Douglas

2017-01-01

Researchers are increasingly interested in working memory (WM) training. However, it is unclear whether it strengthens comprehension in young children who are at risk for learning difficulties. We conducted a modest study of whether the training of verbal WM would improve verbal WM and passage listening comprehension and whether training effects…

Assessing White Matter Microstructure in Brain Regions with Different Myelin Architecture Using MRI.

PubMed

Groeschel, Samuel; Hagberg, Gisela E; Schultz, Thomas; Balla, Dávid Z; Klose, Uwe; Hauser, Till-Karsten; Nägele, Thomas; Bieri, Oliver; Prasloski, Thomas; MacKay, Alex L; Krägeloh-Mann, Ingeborg; Scheffler, Klaus

2016-01-01

We investigate how known differences in myelin architecture between regions along the cortico-spinal tract and frontal white matter (WM) in 19 healthy adolescents are reflected in several quantitative MRI parameters that have been proposed to non-invasively probe WM microstructure. In a clinically feasible scan time, both conventional imaging sequences as well as microstructural MRI parameters were assessed in order to quantitatively characterise WM regions that are known to differ in the thickness of their myelin sheaths, and in the presence of crossing or parallel fibre organisation. We found that diffusion imaging, MR spectroscopy (MRS), myelin water fraction (MWF), Magnetization Transfer Imaging, and Quantitative Susceptibility Mapping were myelin-sensitive in different ways, giving complementary information for characterising WM microstructure with different underlying fibre architecture. From the diffusion parameters, neurite density (NODDI) was found to be more sensitive than fractional anisotropy (FA), underlining the limitation of FA in WM crossing fibre regions. In terms of sensitivity to different myelin content, we found that MWF, the mean diffusivity and chemical-shift imaging based MRS yielded the best discrimination between areas. Multimodal assessment of WM microstructure was possible within clinically feasible scan times using a broad combination of quantitative microstructural MRI sequences. By assessing new microstructural WM parameters we were able to provide normative data and discuss their interpretation in regions with different myelin architecture, as well as their possible application as biomarker for WM disorders.

Reorganization of functional brain networks mediates the improvement of cognitive performance following real-time neurofeedback training of working memory.

PubMed

Zhang, Gaoyan; Yao, Li; Shen, Jiahui; Yang, Yihong; Zhao, Xiaojie

2015-05-01

Working memory (WM) is essential for individuals' cognitive functions. Neuroimaging studies indicated that WM fundamentally relied on a frontoparietal working memory network (WMN) and a cinguloparietal default mode network (DMN). Behavioral training studies demonstrated that the two networks can be modulated by WM training. Different from the behavioral training, our recent study used a real-time functional MRI (rtfMRI)-based neurofeedback method to conduct WM training, demonstrating that WM performance can be significantly improved after successfully upregulating the activity of the target region of interest (ROI) in the left dorsolateral prefrontal cortex (Zhang et al., [2013]: PloS One 8:e73735); however, the neural substrate of rtfMRI-based WM training remains unclear. In this work, we assessed the intranetwork and internetwork connectivity changes of WMN and DMN during the training, and their correlations with the change of brain activity in the target ROI as well as with the improvement of post-training behavior. Our analysis revealed an "ROI-network-behavior" correlation relationship underlying the rtfMRI training. Further mediation analysis indicated that the reorganization of functional brain networks mediated the effect of self-regulation of the target brain activity on the improvement of cognitive performance following the neurofeedback training. The results of this study enhance our understanding of the neural basis of real-time neurofeedback and suggest a new direction to improve WM performance by regulating the functional connectivity in the WM related networks. © 2014 Wiley Periodicals, Inc.

Gray Matter-White Matter De-Differentiation on Brain Computed Tomography Predicts Brain Death Occurrence.

PubMed

Vigneron, C; Labeye, V; Cour, M; Hannoun, S; Grember, A; Rampon, F; Cotton, F

2016-01-01

Previous studies have shown that a loss of distinction between gray matter (GM) and white matter (WM) on unenhanced CT scans was predictive of poor outcome after cardiac arrest. The aim of this study was to identify a marker/predictor of imminent brain death. In this retrospective study, 15 brain-dead patients after anoxia and cardiac arrest were included. Patients were paired (1:1) with normal control subjects. Only patients' unenhanced CT scans performed before brain death and during the 24 hours after initial signs were analyzed. WM and GM densities were measured in predefined regions of interest (basal ganglia level, centrum semi-ovale level, high convexity level, brainstem level). At each level, GM and WM density and GM/WM ratio for brain-dead patients and normal control subjects were compared using the Wilcoxon signed-rank test. At each level, a lower GM/WM ratio and decreased GM and WM densities were observed in brain-dead patients' CT scans when compared with normal control subject CT scans. A cut-off value of 1.21 at the basal ganglia level was identified, below which brain death systematically occurred. GM/WM dedifferentiation on unenhanced CT scan is measurable before the occurrence of brain death, highlighting its importance in brain death prediction. The mechanism of GM/WM differentiation loss could be explained by the lack of oxygen caused by ischemia initially affecting the mitochondrial system. Copyright © 2016 Elsevier Inc. All rights reserved.

Frontal and parietal theta burst TMS impairs working memory for visual-spatial conjunctions.

PubMed

Morgan, Helen M; Jackson, Margaret C; van Koningsbruggen, Martijn G; Shapiro, Kimron L; Linden, David E J

2013-03-01

In tasks that selectively probe visual or spatial working memory (WM) frontal and posterior cortical areas show a segregation, with dorsal areas preferentially involved in spatial (e.g. location) WM and ventral areas in visual (e.g. object identity) WM. In a previous fMRI study [1], we showed that right parietal cortex (PC) was more active during WM for orientation, whereas left inferior frontal gyrus (IFG) was more active during colour WM. During WM for colour-orientation conjunctions, activity in these areas was intermediate to the level of activity for the single task preferred and non-preferred information. To examine whether these specialised areas play a critical role in coordinating visual and spatial WM to perform a conjunction task, we used theta burst transcranial magnetic stimulation (TMS) to induce a functional deficit. Compared to sham stimulation, TMS to right PC or left IFG selectively impaired WM for conjunctions but not single features. This is consistent with findings from visual search paradigms, in which frontal and parietal TMS selectively affects search for conjunctions compared to single features, and with combined TMS and functional imaging work suggesting that parietal and frontal regions are functionally coupled in tasks requiring integration of visual and spatial information. Our results thus elucidate mechanisms by which the brain coordinates spatially segregated processing streams and have implications beyond the field of working memory. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

Differential distribution of neurons in the gyral white matter of the human cerebral cortex.

PubMed

García-Marín, V; Blazquez-Llorca, L; Rodriguez, J R; Gonzalez-Soriano, J; DeFelipe, J

2010-12-01

The neurons in the cortical white matter (WM neurons) originate from the first set of postmitotic neurons that migrates from the ventricular zone. In particular, they arise in the subplate that contains the earliest cells generated in the telencephalon, prior to the appearance of neurons in gray matter cortical layers. These cortical WM neurons are very numerous during development, when they are thought to participate in transient synaptic networks, although many of these cells later die, and relatively few cells survive as WM neurons in the adult. We used light and electron microscopy to analyze the distribution and density of WM neurons in various areas of the adult human cerebral cortex. Furthermore, we examined the perisomatic innervation of these neurons and estimated the density of synapses in the white matter. Finally, we examined the distribution and neurochemical nature of interneurons that putatively innervate the somata of WM neurons. From the data obtained, we can draw three main conclusions: first, the density of WM neurons varies depending on the cortical areas; second, calretinin-immunoreactive neurons represent the major subpopulation of GABAergic WM neurons; and, third, the somata of WM neurons are surrounded by both glutamatergic and GABAergic axon terminals, although only symmetric axosomatic synapses were found. By contrast, both symmetric and asymmetric axodendritic synapses were observed in the neuropil. We discuss the possible functional implications of these findings in terms of cortical circuits. © 2010 Wiley-Liss, Inc.

Delay Discounting of Losses in Alcohol Use Disorders and Antisocial Psychopathology: Effects of a Working Memory Load.

PubMed

Gerst, Kyle R; Gunn, Rachel L; Finn, Peter R

2017-10-01

Alcohol use disorders (AUDs) are associated with increased discounting of delayed rewards and reduced executive working memory (eWM) capacity. This association is amplified when comorbid with antisocial psychopathology (AP). Furthermore, recent studies suggest that reduced WM capacity is associated with disinhibited decisions reflected by increased impulsive decision making on the delay discounting of rewards task. While discounting of delayed rewards is well studied, the discounting of delayed losses has received significantly less experimental attention. The current study investigated (i) the rate of discounting of delayed losses in individuals with AUD only (n = 61), AUD with comorbid AP (n = 79) and healthy controls (n = 64); (ii) the relationship between eWM capacity and discounting of delayed losses; and (iii) the effect of a WM load on discounting of delayed losses. Discounting performance was assessed using a computerized discounting of delayed losses task. Results showed that the AUD-only and AUD-AP groups had higher rates of discounting of delayed losses and lower eWM capacity compared to the control groups. Lower individual eWM capacity was associated with increased discounting of delayed losses. However, WM load did not increase discounting rates overall. These results support the hypothesis that greater discounting of delayed losses is associated with AUD and comorbid AP problems and lower individual eWM capacity. Copyright © 2017 by the Research Society on Alcoholism.

Working memory, perceptual priming, and the perception of hierarchical forms: opposite effects of priming and working memory without memory refreshing.

PubMed

Kim, Jeong-Im; Humphreys, Glyn W

2010-08-01

Previous research has shown that stimuli held in working memory (WM) can influence spatial attention. Using Navon stimuli, we explored whether and how items in WM affect the perception of visual targets at local and global levels in compound letters. Participants looked for a target letter presented at a local or global level while holding a regular block letter as a memory item. An effect of holding the target's identity in WM was found. When memory items and targets were the same, performance was better than in a neutral condition when the memory item did not appear in the hierarchical letter (a benefit from valid cuing). When the memory item matched the distractor in the hierarchical stimulus, performance was worse than in the neutral baseline (a cost on invalid trials). These effects were greatest when the WM cue matched the global level of the hierarchical stimulus, suggesting that WM biases attention to the global level of form. Interestingly, in a no-memory priming condition, target perception was faster in the invalid condition than in the neutral baseline, reversing the effect in the WM condition. A further control experiment ruled out the effects of WM being due to participants' refreshing their memory from the hierarchical stimulus display. The data show that information in WM biases the selection of hierarchical forms, whereas priming does not. Priming alters the perceptual processing of repeated stimuli without biasing attention.

Long-term effects of interference on short-term memory performance in the rat

PubMed Central

Missaire, Mégane; Fraize, Nicolas; Joseph, Mickaël Antoine; Hamieh, Al Mahdy; Parmentier, Régis; Marighetto, Aline; Salin, Paul Antoine; Malleret, Gaël

2017-01-01

A distinction has always been made between long-term and short-term memory (also now called working memory, WM). The obvious difference between these two kinds of memory concerns the duration of information storage: information is supposedly transiently stored in WM while it is considered durably consolidated into long-term memory. It is well acknowledged that the content of WM is erased and reset after a short time, to prevent irrelevant information from proactively interfering with newly stored information. In the present study, we used typical WM radial maze tasks to question the brief lifespan of spatial WM content in rodents. Groups of rats were submitted to one of two different WM tasks in a radial maze: a WM task involving the repetitive presentation of a same pair of arms expected to induce a high level of proactive interference (PI) (HIWM task), or a task using a different pair in each trial expected to induce a low level of PI (LIWM task). Performance was effectively lower in the HIWM group than in LIWM in the final trial of each training session, indicative of a “within-session/short-term” PI effect. However, we also observed a different “between-session/long-term” PI effect between the two groups: while performance of LIWM trained rats remained stable over days, the performance of HIWM rats dropped after 10 days of training, and this impairment was visible from the very first trial of the day, hence not attributable to within-session PI. We also showed that a 24 hour-gap across training sessions known to allow consolidation processes to unfold, was a necessary and sufficient condition for the long-term PI effect to occur. These findings suggest that in the HIWM task, WM content was not entirely reset between training sessions and that, in specific conditions, WM content can outlast its purpose by being stored more permanently, generating a long-term deleterious effect of PI. The alternative explanation is that WM content could be transferred and

Long-term effects of interference on short-term memory performance in the rat.

PubMed

Missaire, Mégane; Fraize, Nicolas; Joseph, Mickaël Antoine; Hamieh, Al Mahdy; Parmentier, Régis; Marighetto, Aline; Salin, Paul Antoine; Malleret, Gaël

2017-01-01

A distinction has always been made between long-term and short-term memory (also now called working memory, WM). The obvious difference between these two kinds of memory concerns the duration of information storage: information is supposedly transiently stored in WM while it is considered durably consolidated into long-term memory. It is well acknowledged that the content of WM is erased and reset after a short time, to prevent irrelevant information from proactively interfering with newly stored information. In the present study, we used typical WM radial maze tasks to question the brief lifespan of spatial WM content in rodents. Groups of rats were submitted to one of two different WM tasks in a radial maze: a WM task involving the repetitive presentation of a same pair of arms expected to induce a high level of proactive interference (PI) (HIWM task), or a task using a different pair in each trial expected to induce a low level of PI (LIWM task). Performance was effectively lower in the HIWM group than in LIWM in the final trial of each training session, indicative of a "within-session/short-term" PI effect. However, we also observed a different "between-session/long-term" PI effect between the two groups: while performance of LIWM trained rats remained stable over days, the performance of HIWM rats dropped after 10 days of training, and this impairment was visible from the very first trial of the day, hence not attributable to within-session PI. We also showed that a 24 hour-gap across training sessions known to allow consolidation processes to unfold, was a necessary and sufficient condition for the long-term PI effect to occur. These findings suggest that in the HIWM task, WM content was not entirely reset between training sessions and that, in specific conditions, WM content can outlast its purpose by being stored more permanently, generating a long-term deleterious effect of PI. The alternative explanation is that WM content could be transferred and stored

The Differential Role of Verbal and Spatial Working Memory in the Neural Basis of Arithmetic

PubMed Central

Demir, Özlem Ece; Prado, Jérôme; Booth, James R.

2014-01-01

We examine the relations of verbal and spatial WM ability to the neural bases of arithmetic in school-age children. We independently localize brain regions subserving verbal versus spatial representations. For multiplication, higher verbal WM ability is associated with greater recruitment of the left temporal cortex, identified by the verbal localizer. For multiplication and subtraction, higher spatial WM ability is associated with greater recruitment of right parietal cortex, identified by the spatial localizer. Depending on their WM ability, children engage different neural systems that manipulate different representations to solve arithmetic problems. PMID:25144257

In search of the focus of attention in working memory: 13 years of the retro-cue effect.

PubMed

Souza, Alessandra S; Oberauer, Klaus

2016-10-01

The concept of attention has a prominent place in cognitive psychology. Attention can be directed not only to perceptual information, but also to information in working memory (WM). Evidence for an internal focus of attention has come from the retro-cue effect: Performance in tests of visual WM is improved when attention is guided to the test-relevant contents of WM ahead of testing them. The retro-cue paradigm has served as a test bed to empirically investigate the functions and limits of the focus of attention in WM. In this article, we review the growing body of (behavioral) studies on the retro-cue effect. We evaluate the degrees of experimental support for six hypotheses about what causes the retro-cue effect: (1) Attention protects representations from decay, (2) attention prioritizes the selected WM contents for comparison with a probe display, (3) attended representations are strengthened in WM, (4) not-attended representations are removed from WM, (5) a retro-cue to the retrieval target provides a head start for its retrieval before decision making, and (6) attention protects the selected representation from perceptual interference. The extant evidence provides support for the last four of these hypotheses.

The use of standardised short-term and working memory tests in aphasia research: a systematic review

PubMed Central

Murray, Laura; Salis, Christos; Martin, Nadine; Dralle, Jenny

2017-01-01

Impairments of short-term and working memory (STM, WM), both verbal and non-verbal, are ubiquitous in aphasia. Increasing interest in assessing STM and WM in aphasia research and clinical practice as well as a growing evidence base of STM/WM treatments for aphasia warrant an understanding of the range of standardised STM/WM measures that have been utilised in aphasia. To date, however, no previous systematic review has focused on aphasia. Accordingly, the goals of this systematic review were: (1) to identify standardised tests of STM and WM utilised in the aphasia literature, (2) to evaluate critically the psychometric strength of these tests, and (3) to appraise critically the quality of the investigations utilising these tests. Results revealed that a very limited number of standardised tests, in the verbal and non-verbal domains, had robust psychometric properties. Standardisation samples to elicit normative data were often small, and most measures exhibited poor validity and reliability properties. Studies using these tests inconsistently documented demographic and aphasia variables essential to interpreting STM/WM test outcomes. In light of these findings, recommendations are provided to foster, in the future, consistency across aphasia studies and confidence in STM/WM tests as assessment and treatment outcome measures. PMID:27143500

Behavioral and Neural Markers of Flexible Attention over Working Memory in Aging

PubMed Central

Mok, Robert M.; Myers, Nicholas E.; Wallis, George; Nobre, Anna Christina

2016-01-01

Working memory (WM) declines as we age and, because of its fundamental role in higher order cognition, this can have highly deleterious effects in daily life. We investigated whether older individuals benefit from flexible orienting of attention within WM to mitigate cognitive decline. We measured magnetoencephalography (MEG) in older adults performing a WM precision task with cues during the maintenance period that retroactively predicted the location of the relevant items for performance (retro-cues). WM performance of older adults significantly benefitted from retro-cues. Whereas WM maintenance declined with age, retro-cues conferred strong attentional benefits. A model-based analysis revealed an increase in the probability of recalling the target, a lowered probability of retrieving incorrect items or guessing, and an improvement in memory precision. MEG recordings showed that retro-cues induced a transient lateralization of alpha (8–14 Hz) and beta (15–30 Hz) oscillatory power. Interestingly, shorter durations of alpha/beta lateralization following retro-cues predicted larger cueing benefits, reinforcing recent ideas about the dynamic nature of access to WM representations. Our results suggest that older adults retain flexible control over WM, but individual differences in control correspond to differences in neural dynamics, possibly reflecting the degree of preservation of control in healthy aging. PMID:26865653

Is refreshing in working memory impaired in older age? Evidence from the retro-cue paradigm.

PubMed

Loaiza, Vanessa M; Souza, Alessandra S

2018-04-10

Impairments in refreshing have been suggested as one source of working memory (WM) deficits in older age. Retro-cues provide an important method of investigating this question: a retro-cue guides attention to one WM item, thereby arguably refreshing it and increasing its accessibility compared with a no-cue baseline. In contrast to the refreshing deficit hypothesis, intact retro-cue benefits have been found in older adults. Refreshing, however, is assumed to boost not one but several WM representations when sequentially applied to them. Hence, intact refreshing requires the flexible switching of attention among WM items. So far, it remains an open question whether older adults show this flexibility. Here, we investigated whether older adults can use multiple cues to sequentially refresh WM representations. Younger and older adults completed a continuous-color delayed-estimation task, in which the number of retro-cues (0, 1, or 2) presented during the retention interval was manipulated. The results showed a similar retro-cue benefit for younger and older adults, even in the two-cue condition in which participants had to switch attention between items to refresh representations in WM. These findings suggest that the capacity to use cues to refresh information in visual WM may be preserved with age. © 2018 New York Academy of Sciences.

Synaptic efficacy shapes resource limitations in working memory.

PubMed

Krishnan, Nikhil; Poll, Daniel B; Kilpatrick, Zachary P

2018-06-01

Working memory (WM) is limited in its temporal length and capacity. Classic conceptions of WM capacity assume the system possesses a finite number of slots, but recent evidence suggests WM may be a continuous resource. Resource models typically assume there is no hard upper bound on the number of items that can be stored, but WM fidelity decreases with the number of items. We analyze a neural field model of multi-item WM that associates each item with the location of a bump in a finite spatial domain, considering items that span a one-dimensional continuous feature space. Our analysis relates the neural architecture of the network to accumulated errors and capacity limitations arising during the delay period of a multi-item WM task. Networks with stronger synapses support wider bumps that interact more, whereas networks with weaker synapses support narrower bumps that are more susceptible to noise perturbations. There is an optimal synaptic strength that both limits bump interaction events and the effects of noise perturbations. This optimum shifts to weaker synapses as the number of items stored in the network is increased. Our model not only provides a circuit-based explanation for WM capacity, but also speaks to how capacity relates to the arrangement of stored items in a feature space.

Behavioral and Neural Markers of Flexible Attention over Working Memory in Aging.

PubMed

Mok, Robert M; Myers, Nicholas E; Wallis, George; Nobre, Anna Christina

2016-04-01

Working memory (WM) declines as we age and, because of its fundamental role in higher order cognition, this can have highly deleterious effects in daily life. We investigated whether older individuals benefit from flexible orienting of attention within WM to mitigate cognitive decline. We measured magnetoencephalography (MEG) in older adults performing a WM precision task with cues during the maintenance period that retroactively predicted the location of the relevant items for performance (retro-cues). WM performance of older adults significantly benefitted from retro-cues. Whereas WM maintenance declined with age, retro-cues conferred strong attentional benefits. A model-based analysis revealed an increase in the probability of recalling the target, a lowered probability of retrieving incorrect items or guessing, and an improvement in memory precision. MEG recordings showed that retro-cues induced a transient lateralization of alpha (8-14 Hz) and beta (15-30 Hz) oscillatory power. Interestingly, shorter durations of alpha/beta lateralization following retro-cues predicted larger cueing benefits, reinforcing recent ideas about the dynamic nature of access to WM representations. Our results suggest that older adults retain flexible control over WM, but individual differences in control correspond to differences in neural dynamics, possibly reflecting the degree of preservation of control in healthy aging. © The Author 2016. Published by Oxford University Press.

Action Video Game Experience Related to Altered Large-Scale White Matter Networks.

PubMed

Gong, Diankun; Ma, Weiyi; Gong, Jinnan; He, Hui; Dong, Li; Zhang, Dan; Li, Jianfu; Luo, Cheng; Yao, Dezhong

2017-01-01

With action video games (AVGs) becoming increasingly popular worldwide, the cognitive benefits of AVG experience have attracted continuous research attention over the past two decades. Research has repeatedly shown that AVG experience can causally enhance cognitive ability and is related to neural plasticity in gray matter and functional networks in the brain. However, the relation between AVG experience and the plasticity of white matter (WM) network still remains unclear. WM network modulates the distribution of action potentials, coordinating the communication between brain regions and acting as the framework of neural networks. And various types of cognitive deficits are usually accompanied by impairments of WM networks. Thus, understanding this relation is essential in assessing the influence of AVG experience on neural plasticity and using AVG experience as an interventional tool for impairments of WM networks. Using graph theory, this study analyzed WM networks in AVG experts and amateurs. Results showed that AVG experience is related to altered WM networks in prefrontal networks, limbic system, and sensorimotor networks, which are related to cognitive control and sensorimotor functions. These results shed new light on the influence of AVG experience on the plasticity of WM networks and suggested the clinical applicability of AVG experience.

An Example-Based Multi-Atlas Approach to Automatic Labeling of White Matter Tracts

PubMed Central

Yoo, Sang Wook; Guevara, Pamela; Jeong, Yong; Yoo, Kwangsun; Shin, Joseph S.; Mangin, Jean-Francois; Seong, Joon-Kyung

2015-01-01

We present an example-based multi-atlas approach for classifying white matter (WM) tracts into anatomic bundles. Our approach exploits expert-provided example data to automatically classify the WM tracts of a subject. Multiple atlases are constructed to model the example data from multiple subjects in order to reflect the individual variability of bundle shapes and trajectories over subjects. For each example subject, an atlas is maintained to allow the example data of a subject to be added or deleted flexibly. A voting scheme is proposed to facilitate the multi-atlas exploitation of example data. For conceptual simplicity, we adopt the same metrics in both example data construction and WM tract labeling. Due to the huge number of WM tracts in a subject, it is time-consuming to label each WM tract individually. Thus, the WM tracts are grouped according to their shape similarity, and WM tracts within each group are labeled simultaneously. To further enhance the computational efficiency, we implemented our approach on the graphics processing unit (GPU). Through nested cross-validation we demonstrated that our approach yielded high classification performance. The average sensitivities for bundles in the left and right hemispheres were 89.5% and 91.0%, respectively, and their average false discovery rates were 14.9% and 14.2%, respectively. PMID:26225419