Article
Neurosciences
Kyle Duffer, Zachary S. Gillis, Sara E. Morrison
Summary: When a Pavlovian cue is presented separately from its associated reward, some animals will acquire a sign tracking response while others will acquire a goal tracking response. Previous studies have shown that excitations in the nucleus accumbens encode the vigor of these behaviors. However, the signaling of inhibitory cue responses in the nucleus accumbens during Pavlovian conditioning and their relationship with reward devaluation and dopamine release remain unknown.
Article
Behavioral Sciences
Elizabeth Bien, Kyle Smith
Summary: This study examined sex differences in sign-tracking behavior and sensitivity to reward devaluation. The results showed no differences in the acquisition and ultimate levels of sign-tracking between males and females. Additionally, there were no sex differences in sign-tracking levels and learning speed following reward devaluation.
BEHAVIOURAL BRAIN RESEARCH
(2023)
Article
Behavioral Sciences
Ankit Sood, Jocelyn M. Richard
Summary: Accurate mental representations of expected outcome value are crucial for goal-directed behavior. Both instrumental and Pavlovian settings can be used to study goal-directed behavior, and outcome devaluation can affect behavioral responses in Pavlovian conditioning. Studies suggest that male and female rats may differ in their Pavlovian-conditioned responses, but this interpretation is complicated by the distinct types of Pavlovian responses exhibited by female and male rats.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2023)
Article
Behavioral Sciences
Cristina E. Maria-Rios, Christopher J. Fitzpatrick, Francesca N. Czesak, Jonathan D. Morrow
Summary: When a neutral stimulus is repeatedly paired with an appetitive reward, two types of conditioned approach responses may develop: sign-tracking, directed towards the cue, and goal-tracking, directed towards the reward location. Sign-tracking is sensitive to incentive value, while goal-tracking is responsive to predictive value. Sign-tracking rats were more sensitive to manipulations of incentive value, while goal-tracking rats were more responsive to changes in cue predictive value. Sign-tracking was sensitive to outcome devaluation, while goal-tracking was not. The results suggest different rules of reinforcement learning for sign- and goal-tracking.
NEUROBIOLOGY OF LEARNING AND MEMORY
(2023)
Article
Neurosciences
Alexa Brown, Nadia Chaudhri
Summary: This study reveals that fear extinction retrieval and reinstatement of drug seeking are mediated by the influence of prelimbic (PL) and infralimbic (IL) cortices on the paraventricular nucleus of the thalamus (PVT). These findings are crucial for understanding the role of conditioning and contextual processing in behavioral responses.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2023)
Article
Neurosciences
Nicole L. Jenni, Nicola Symonds, Stan B. Floresco
Summary: This series of experiments examined the role of the medial subregion of the orbitofrontal cortex (mOFC) in Pavlovian conditioned approach, conditioned reinforcement, extinction, and cue-induced reinstatement of food-seeking behavior. The results revealed that mOFC inactivation had varied effects on these behaviors.
PSYCHOPHARMACOLOGY
(2023)
Article
Neurosciences
Aqilah M. McCane, Meredyth A. Wegener, Mojdeh Faraji, Maria T. Rivera-Garcia, Kathryn G. Wallin-Miller, Vincent D. Costa, Bita Moghaddam
Summary: The study found that reward-guided associative learning in adolescent male rats is encoded differently by midbrain dopamine neurons in two different conditioning paradigms. Adolescent neurons show a muted reward response during operant conditioning but a significantly larger reward response during Pavlovian conditioning, indicating a different valuation of reward by adolescent neurons when it is not gated by action.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Merridee J. Lefner, Claire E. Stelly, Kaitlyn M. Fonzi, Hector Zurita, Matthew J. Wanat
Summary: Dopamine's control over behavior in Pavlovian tasks depends upon one's prior training experience and the information signaled by the cues.
PSYCHOPHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Sina Kohne, Esther K. Diekhof
Summary: During adolescence, gonadal hormones have an impact on brain maturation and behavior. A study was conducted to investigate the influence of 17 beta-estradiol and testosterone on reinforcement learning in male and female adolescents. The results showed that 17 beta-estradiol was correlated with an enhanced ability to speed up responses for reward in both sexes, while testosterone was primarily correlated with the ability to wait for higher reward in males.
Article
Behavioral Sciences
Sandford Zeng, Elin F. B. McLaughlin, Aishwarya Ramesh, Sara E. Morrison
Summary: Adolescence is a period of increased risk-taking behavior. Adolescents show less cue-reactivity to reward-related cues compared to adults. Adolescents make more risky choices and fewer optimal choices in a rodent gambling task. Adolescent risk-taking behavior is less likely to be driven by reward-related cues compared to adults.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2023)
Article
Neurosciences
Patricia Gasalla, Denise Manahan-Vaughan, Dominic Michael Dwyer, Jeremy Hall, Marta Mendez-Couz
Summary: Recent studies have found that Cacna1c +/- heterozygous animals with impaired Cav 1.2 L-type voltage-gated calcium channels show difficulties in aversive forms of learning, but the role of these channels in extinction of appetitive associations is understudied. In this study, Cacna1c +/- male rats and their wild-type littermates were evaluated in an appetitive Pavlovian conditioning task to examine extinction learning and associated changes in the brain. The results showed that Cacna1c +/- animals adapted their responses during appetitive extinction and renewal, with distinct neural activation patterns observed in different brain regions. These findings provide novel evidence of brain plasticity in Cacna1c +/- rats after appetitive extinction and renewal. This study contributes to understanding the role of Cav 1.2 L-type voltage-gated calcium channels in neuropsychiatric disorders.
Article
Behavioral Sciences
Dong-Hee Kim, Bo-Ryoung Choi, Yong-Jae Jeon, Yoon-Sun Jang, Jung-Soo Han
Summary: Research indicates that midbrain dopamine neurons and lateral habenula neurons play crucial roles in appetitive extinction. The study found higher activity levels of LHb neurons in the paired-CS-alone group, while VTA and SNc activity was significantly higher in the paired-paired group. Additionally, lesions in the LHb decelerated the decline in conditioned food-cup responses, highlighting the crucial role of LHb in appetitive extinction.
BEHAVIOURAL BRAIN RESEARCH
(2021)
Article
Psychology
Rodrigo Sosa
Summary: Inhibition is a phenomenon in which an agent prevents or suppresses a behavioral state that would otherwise occur. Associative learning studies have extensively examined how experiences shape inhibitory behavioral tendencies, with a focus on different levels of analysis to understand how individuals implement learning from negative associations.
PSYCHOLOGICAL REVIEW
(2022)
Article
Neurosciences
Anne K. Baker, Lauren C. Ericksen, Vincent Koppelmans, Brian J. Mickey, Katherine T. Martucci, Jon-Kar Zubieta, Tiffany M. Love
Summary: There is a reciprocal relationship between chronic pain and reward processing. This study found that males with chronic pain exhibited reduced anticipatory responses to reward in the striatum compared to control males, while no significant sex differences were observed among female patients. These findings highlight the importance of considering sex as a factor of interest in future studies on reward processing in the context of chronic pain.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Neurosciences
Eva R. Pool, David Munoz Tord, Sylvain Delplanque, Yoann Stussi, Donato Cereghetti, Patrik Vuilleumier, David Sander
Summary: Different subregions of the ventral striatum play distinct roles in the motivational and hedonic components of reward processing. Understanding the neural mechanisms underlying the interplay between pavlovian incentive and hedonic processes is crucial for comprehending compulsive reward-seeking behaviors such as addiction, binge eating, or gambling.
JOURNAL OF NEUROSCIENCE
(2022)
Meeting Abstract
Oncology
J. Kellogg Parsons, Peter A. Pinto, Howard L. Parnes, Christian P. Pavlovich, Edward M. Uchio, Mike Minh Nguyen, Hyung Lae Kim, James L. Gulley, Houssein Abdul Sater, Christina Jamieson, Chiu-Hsieh Hsu, Malgorzata E. Wojtowicz, Jeffrey Schlom, Renee Nicole Donahue, Sara Centuori, Shania Bailey, Julie E. Bauman, H. H. Chow
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Meeting Abstract
Oncology
Emerson A. Lim, Michael Thomas Schweizer, Kim N. Chi, Rahul Raj Aggarwal, Neeraj Agarwal, James L. Gulley, Edward F. Attiyeh, James Greger, Shujian Wu, Pharavee Jaiprasart, John Loffredo, Nibedita Bandyopadhyay, Hong Xie, Aaron Richard Hansen
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Medicine, Research & Experimental
Youji Hong, Yvette Robbins, Xinping Yang, Wojciech K. Mydlarz, Anastasia Sowers, James B. Mitchell, James L. Gulley, Jeffrey Schlom, Sofia R. Gameiro, Cem Sievers, Clint T. Allen
Summary: This study demonstrates that local administration of a tumor-targeted IL-12 antibody fusion protein can achieve potent immune control of established tumors with low doses to avoid systemic toxicity. The treatment leads to reinvigoration and proliferation of exhausted T lymphocytes, induction of Th1 immunity, and a decrease in regulatory T cells and suppressive myeloid cells. Single-cell analysis also reveals similar IL-12 receptor expression patterns in human head and neck carcinomas.
Article
Immunology
Megan E. Hansen, Ralph Mangusan, Kathryn Lurain, Thomas Odeny, Jomy George, Crystal Lu, Maura Manion, Anaida Widell, Irene Ekwede, Denise Whitby, James L. Gulley, Sameer S. Kadri, Jason M. Elinoff, Amisha Barochia, Parizad Torabi-Parizi, Thomas S. Uldrick, Robert Yarchoan, Ramya Ramaswami
Summary: This retrospective study examined the clinical data of HIV and KAD patients admitted to the ICU. The results showed that the majority of patients had well controlled HIV, and a proportion of patients were diagnosed with additional KADs upon admission. Critical illness did not prevent some patients from receiving KAD-directed therapy in the ICU.
Article
Oncology
Arun Rajan, Jhanelle E. Gray, Siddhartha Devarakonda, Ruemu Birhiray, Borys Korchin, Erika Menius, Renee N. Donahue, Jeffrey Schlom, James L. Gulley
Summary: CV301 in combination with PD-1 inhibitors is safe and clinically active in advanced NSCLC patients, without an increased frequency or severity of immune-related adverse events.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Review
Oncology
Mary Helen Barcellos-Hoff, James L. Gulley
Summary: Despite the increasing number of TGFI3 inhibitors tested in cancer patients, there has been no clinical benefit achieved yet. The main obstacle to effective TGFI3 inhibition is the diverse mechanisms by which TGFI3 promotes tumor growth. TGFI3 is involved in regulating DNA repair and immune suppression, which can be used to synergize genotoxic therapy and immunotherapy for the benefit of cancer patients.
CLINICAL CANCER RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Cody J. Peer, Keith T. Schmidt, Oluwatobi Arisa, William J. Richardson, Koosha Paydary, Daniel A. Goldstein, James L. Gulley, William D. Figg, Mark J. Ratain
Summary: Atezolizumab, a humanized monoclonal antibody against PD-L1, was approved in 2016. Standard dose regimens result in high plasma concentrations, indicating the need for alternative dosing strategies to reduce exposure burden.
JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Oncology
Alexander Spira, Michael S. Wertheim, Edward J. Kim, Benjamin Tan, Heinz-Josef Lenz, Petros Nikolinakos, Patricia L. Rich, Genevieve Jehl, Andreas Machl, Rena Ito, James L. Gulley, Scott Kopetz
Summary: A phase I study on bintrafusp alfa in heavily pretreated patients with colorectal cancer showed promising early signs of clinical efficacy and manageable safety profile.
Article
Oncology
Margaret E. Gatti-Mays, Nicholas P. Tschernia, Julius Strauss, Ravi A. Madan, Fatima H. Karzai, Marijo Bilusic, Jason Redman, Houssein Abdul Sater, Charalampos S. Floudas, Nicole J. Toney, Renee N. Donahue, Caroline Jochems, Jennifer L. Marte, Deneise Francis, Sheri McMahon, Elizabeth Lamping, Lisa Cordes, Jeffrey Schlom, James L. Gulley
Summary: The results of this study showed that biweekly NHS-IL12 treatment was safe for patients with advanced cancers. NHS-IL12 is a first-in-class fusion protein used in this trial. Patients received NHS-IL12 every two weeks, and the results demonstrated stable disease status for the patients.
Article
Oncology
Emerson A. Lim, Michael T. Schweizer, Kim N. Chi, Rahul Aggarwal, Neeraj Agarwal, James Gulley, Edward Attiyeh, James Greger, Shujian Wu, Pharavee Jaiprasart, John Loffredo, Nibedita Bandyopadhyay, Hong Xie, Aaron R. Hansen
Summary: PSMA expression is maintained in all stages of prostate cancer. In a phase 1 study, a bispecific antibody targeting PSMA-expressing tumor cells and CD3-expressing T cells showed manageable cytokine release syndrome and temporary decline in PSA in patients with metastatic castration-resistant prostate cancer. Treatment-related deaths and radiographic responses were not observed. PSMA is a potential therapeutic target for T-cell redirection in prostate cancer.
CLINICAL GENITOURINARY CANCER
(2023)
Article
Oncology
Michael B. Atkins, Paolo A. Ascierto, David Feltquate, James L. Gulley, Douglas B. Johnson, Nikhil Khushalani, Jeffrey Sosman, Timonthy A. Yap, Harriet Kluger, Ryan J. Sullivan, Hussein Tawbi
Summary: Immunotherapy alone does not work for all tumors, so combining it with signal transduction inhibitors, such as antiangiogenic therapies, can enhance its effectiveness. Combination therapies with immunotherapy have shown improved antitumor activity in various solid tumor settings and have received regulatory approval for the treatment of several types of cancer. However, many patients still experience progression after combination treatment, highlighting the need for new strategies to address resistance to immunotherapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Oncology
Ryan Chang, James L. Gulley, Lawrence Fong
Summary: Immunotherapies, such as immune checkpoint inhibitors and cellular therapies, have revolutionized cancer treatment, but the development of successful cancer vaccines remains challenging. Only two vaccines have shown improved survival in advanced disease: sipuleucel-T and talimogene laherparepvec, which target specific antigens and utilize tumors in situ to prime responses. In this review, we examine the challenges and opportunities in developing therapeutic cancer vaccines.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Obstetrics & Gynecology
Lindsey R. Hammerslag, Rachel E. Campbell-Baier, Caitlin A. Otter, Ana Lopez-De Fede, Jheramy P. Smith, L. Angel Whittington, Larry J. Humble, Eddy R. Myers, Susan R. Kennedy, Jeffery C. Talbert, William S. Pearson
Summary: This study examines the association between prenatal syphilis screening rates and sexually transmitted infection history or patient characteristics in three states with high rates of congenital syphilis. The results show that previous sexually transmitted infections and continuous Medicaid enrollment before pregnancy are associated with higher rates of syphilis screening. However, Medicaid claims alone do not fully capture the patients' sexually transmitted infection history. The overall screening rates are lower than expected, especially in the third trimester, and there are disparities in early screening for non-Hispanic Black women compared to non-Hispanic White women.
AMERICAN JOURNAL OF OBSTETRICS & GYNECOLOGY MFM
(2023)
Article
Medicine, Research & Experimental
Jason M. Redman, Jay Friedman, Yvette Robbins, Cem Sievers, Xinping Yang, Wiem Lassoued, Andrew Sinkoe, Antonios Papanicolau-Sengos, Chyi-Chia Lee, Jennifer L. Marte, Evrim Turkbey, Wojtek Mydlarz, Arjun Joshi, Nyall R. London, Matthew Pierce, Rodney Taylor, Steven Hong, Andy Nguyen, Patrick Soon-Shiong, Jeffrey Schlom, James L. Gulley, Clint T. Allen
Summary: Neoadjuvant immunotherapy with dual PD-L1 and TGF-beta blockade can safely enhance tumor antigen-specific immunity and improve survival rate in patients with HPV-unrelated HNSCC. Myeloid cell infiltration in the tumor microenvironment may play a crucial role in enhancing antitumor immune response.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Meeting Abstract
Oncology
J. L. Gulley, A. Bayliffe, R. Donahue, Y. T. Tsai, K. Liu, M. Katraggada, J. Hsu, L. L. Siu, E. J. Wherry, R. Chopra, J. Schlom, Z. Su
EUROPEAN JOURNAL OF CANCER
(2022)