Trevor W. Robbins

Bio: Trevor W. Robbins is an academic researcher from University of Cambridge. The author has contributed to research in topics: Prefrontal cortex & Impulsivity. The author has an hindex of 231, co-authored 1137 publications receiving 164437 citations. Previous affiliations of Trevor W. Robbins include Centre national de la recherche scientifique & Massachusetts Institute of Technology.

A dimensional approach to modeling symptoms of neuropsychiatric disorders in the marmoset monkey

Abstract: Some patients suffering from the same neuropsychiatric disorder may have no overlapping symptoms whilst others may share symptoms common to other distinct disorders. Therefore, the Research Domain Criteria initiative recognises the need for better characterisation of the individual symptoms on which to focus symptom-based treatment strategies. Many of the disorders involve dysfunction within the prefrontal cortex (PFC) and so the marmoset, due to their highly developed PFC and small size, is an ideal species for studying the neurobiological basis of the behavioural dimensions that underlie these symptoms.Here we focus on a battery of tests that address dysfunction spanning the cognitive (cognitive inflexibility and working memory), negative valence (fear generalisation and negative bias) and positive valence (anhedonia) systems pertinent for understanding disorders such as ADHD, Schizophrenia, Anxiety, Depression and OCD. Parsing the separable prefrontal and striatal circuits and identifying the selective neurochemical modulation (serotonin vs dopamine) that underlie cognitive dysfunction have revealed counterparts in the clinical domain. Aspects of the negative valence system have been explored both at individual- (trait anxiety and genetic variation in serotonin transporter) and circuit-based levels enabling the understanding of generalisation processes, negative biases and differential responsiveness to SSRIs. Within the positive valence system, the combination of cardiovascular and behavioural measures provides a framework for understanding motivational, anticipatory and consummatory aspects of anhedonia and their neurobiological mechanisms. Together, the direct comparison of experimental findings in marmosets with clinical studies is proving an excellent translational model to address the behavioural dimensions and neurobiology of neuropsychiatric symptoms. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 328-353, 2017.

Effects of Excitotoxic Lesions of the Septum and Vertical Limb Nucleus of the Diagonal Band of Broca on Conditional Visual Discrimination: Relationship between Performance and Choline Acetyltransferase Activity in the Cingulate Cortex

Abstract: Four experiments examined the role of the cholinergic projections from the septum and vertical limb nucleus of the diagonal band of Broca (VDB) in acquisition and performance of a conditional visual discrimination. In experiments 1-3, excitotoxic lesions were made of the septum and VDB in rats using quisqualic acid, which resulted in significant reductions in ChAT activity in the hippocampus and cingulate cortex, but with no effects on cortical monoamines. In experiment 1, there were significant impairments in acquisition of the conditional discrimination, which did not result from motivational impairments. Experiment 2 repeated these results with lesion parameters, which produced variable effects on hippocampal and cingulate ChAT activity. Those rats with reductions in predominantly cingulate ChAT were most impaired in acquisition, but those with predominantly hippocampal reductions were relatively unimpaired. Experiment 3 showed that quisquate-induced lesions of the VDB, but not of the more caudal VDB and horizontal limb nucleus of the diagonal band, produced deficits, and a model incorporating the results of experiments 1-3 showed a highly significant correlation between errors of commission and cingulate cortical ChAT activity (r = -0.82, p < 0.001). Experiment 4 used the excitotoxin AMPA to lesion the VDB in rats pretrained on a modified form of the conditional discrimination task. In one subgroup of rats this excitotoxin produced profound and regionally selective reductions in ChAT activity. This subgroup was also impaired in relearning the discrimination to criterion. Again, there was a significant inverse relationship between the number of errors of commission made in relearning the discrimination and cingulate ChAT activity (r = -0.94, p < 0.001). These experiments suggest that excitotoxic lesions of the septum/VDB produce deficits in conditional discrimination learning and performance, and that the integrity of the projection to the cingulate cortex is more crucial than that to the hippocampus in this effect. Moreover, there is a close relationship between discrimination performance and cholinergic function in the cingulate cortex. In conjunction with other results, these data suggest that different aspects of cognition and memory are modulated by cholinergic activity in different cortical regions.

Distinguishing separable domains of cognition in human and animal studies: what separations are optimal for targeting interventions? A summary of recommendations from breakout group 2 at the measurement and treatment research to improve cognition in schizophrenia new approaches conference.

Abstract: At the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) New Approaches Conference, a discussion group focused on directions for future research that are critical to enhancing our understanding of the distinctions among key cognitive domains that have relevance for the development of cognition-enhancing interventions. One set of recommendations emphasizes the need for examining and optimizing the psychometric properties of relevant measurement paradigms from cognitive psychology and cognitive neuroscience. This step is critical to translating many notable advances in these basic fields into measures that would be appropriate for clinical trials. A second set of recommendations focuses on key directions for the development and application of animal models of cognitive processes that would greatly aid the discovery and preclinical testing of potential cognition-enhancing agents. As part of this process, the group noted several existing animal paradigms that have particular promise as measures in the key cognitive domains in schizophrenia identified by the MATRICS Neurocognition Committee.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Control of goal-directed and stimulus-driven attention in the brain

Abstract: We review evidence for partially segregated networks of brain areas that carry out different attentional functions. One system, which includes parts of the intraparietal cortex and superior frontal cortex, is involved in preparing and applying goal-directed (top-down) selection for stimuli and responses. This system is also modulated by the detection of stimuli. The other system, which includes the temporoparietal cortex and inferior frontal cortex, and is largely lateralized to the right hemisphere, is not involved in top-down selection. Instead, this system is specialized for the detection of behaviourally relevant stimuli, particularly when they are salient or unexpected. This ventral frontoparietal network works as a 'circuit breaker' for the dorsal system, directing attention to salient events. Both attentional systems interact during normal vision, and both are disrupted in unilateral spatial neglect.

An integrative theory of prefrontal cortex function

Abstract: ▪ Abstract The prefrontal cortex has long been suspected to play an important role in cognitive control, in the ability to orchestrate thought and action in accordance with internal goals. Its neural basis, however, has remained a mystery. Here, we propose that cognitive control stems from the active maintenance of patterns of activity in the prefrontal cortex that represent goals and the means to achieve them. They provide bias signals to other brain structures whose net effect is to guide the flow of activity along neural pathways that establish the proper mappings between inputs, internal states, and outputs needed to perform a given task. We review neurophysiological, neurobiological, neuroimaging, and computational studies that support this theory and discuss its implications as well as further issues to be addressed

Chapter 11 Working memory

Abstract: Publisher Summary This chapter focuses on the modern notion of short-term memory, called working memory. Working memory refers to the temporary maintenance of information that was just experienced or just retrieved from long-term memory but no longer exists in the external environment. These internal representations are short-lived, but can be maintained for longer periods of time through active rehearsal strategies, and can be subjected to various operations that manipulate the information in such a way that makes it useful for goal-directed behavior. Working memory is a system that is critically important in cognition and seems necessary in the course of performing many other cognitive functions, such as reasoning, language comprehension, planning, and spatial processing. This chapter demonstrates the functional importance of dopamine to working memory function in several ways. Elucidation of the cognitive and neural mechanisms underlying human working memory is an important focus of cognitive neuroscience and neurology for much of the past decade. One conclusion that arises from research is that working memory, a faculty that enables temporary storage and manipulation of information in the service of behavioral goals, can be viewed as neither a unitary, nor a dedicated system. Data from numerous neuropsychological and neurophysiological studies in animals and humans demonstrates that a network of brain regions, including the prefrontal cortex, is critical for the active maintenance of internal representations.