The Section on Neurophysiology studies the functional organization of the frontal cortex and the neural network underlying symbolically guided actions. Our research analyzes: (1) the role of the frontal cortex in the mapping of symbols to actions, (2) the orientation of attentional resources by the frontal lobe, and (3) the mechanisms of abstract response strategies and their implementation by frontal-lobe networks. In this report, these three topics are taken up, in turn. (1) Although the symbolic guidance of action is not always recognized as an important issue in mental health research, making decisions based on symbols is a fundamental feature of life, and diseases such as schizophrenia, attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, and others result, at least in part, from inappropriate selection and control of actions. In symbolic mapping, the choice of an action depends on the behavioral context provided by a symbol. This is the basis for learning the meaning of most words, linking meaning to speech, and for the wide variety of symbol- and signal-guided behavior that underlies the most advanced human behavior. The work on this project has shown that symbolically guided action depends upon the proper functioning of specific parts of the frontal cortex, hippocampal system and basal ganglia. In the past year, the highlights of progress in this field include: (a) the finding that learning related activity changes occur later in both putamen and premotor cortex than in the hippocampus (Buch, Brasted, and Wise, 2004 abstract); (b) the demonstration that the one-trial learning of symbolic associations is subserved by Hebbian mechanisms (Brasted, Bussey, Murray, and Wise, 2005); and (c) the dramatic finding that the putamen, a part of the basal ganglia, retains the information needed for learning longer during the learning process than does the premotor cortex. (2) We have dispelled the common misconception that the main function of the prefrontal cortex is the maintenance of sensory information in short-term, working memory. We found that attentional signals predominate over memory signals in the dorsolateral prefrontal cortex, contrary to the prevailing theory (Lebedev, Messinger, Kralik, and Wise, 2004). (3) We discovered that neural signals in prefrontal cortex underlie an advanced cognitive behavior, the use of abstract response strategies (Genevesio, Brasted, Mitz, and Wise, 2005). In this research, we found that separate populations of neurons in prefrontal encode previous and future goals, the starting materials and end products of a neural computation. This separation is important to many daily life activities. If the distinction between accomplished and pending goals cannot be maintained, a previous goal might be repeated inappropriately because it is wrongly represented as a future goal. Such perseverative behavior is a well-known concomitant of prefrontal dysfunction. Furthermore, if prefrontal cortex cannot maintain a representation of a particular goal as accomplished, this could result in compulsive checking, which is one prominent symptom type of obsessive-compulsive disorder. Conversely, if a future goal was wrongly construed as a past one, that goal will not be achieved or even attempted, as in certain forms of dementia that result in failures of omission. Difficulties with such monitoring have been reported in normal aging, in patients with schizophrenia, and in patients with Alzheimer?s dementia. One possible explanation for these failures could be that, as shown in our research, the previous and futures goals involve the same type of information. Given that fact, the only way to distinguish previous and future goals is to encode them in separate neuronal population, and this is what we found. Our past work on abstract response strategies has also lead to a review article that provides original insights into an important mental health disorder. In Lebedev et al. (2001), we reported that separate prefrontal networks encoded response goals based on perceptual reports versus relatively automatic sensory-motor guidance. This paper captured the attention of the organizers of a meeting on psychogenic movement disorders. Psychogenic movement disorders are a common problem presenting to neurologists and psychiatrists, estimated to be 5-20% of patient visits, depending upon the nature of the practice. Patients present with problems of gait difficulties, tremors, jerks, abnormal postures and clumsiness. Currently, the etiology and pathophysiology these disorders remain unknown. Our fundamental research contributed to a much improved understanding of the nature of psychogenic movement disorders. According to some recent models of decision, choice and action, distinct neural networks accumulate evidence in favor of making a potential movement. Voluntary movements arise when one of these networks reaches its threshold for producing an output. Sluggish operations in these networks could prevent an intended movement or make one difficult. Hyperactive networks might generate unintended movements. Other networks operate through similar mechanisms to """"""""veto"""""""" movements, and hyperactive operations in these networks could also prevent intended movements. Taken together with the idea that people might be aware of some of the """"""""evidence"""""""" for making or vetoing a movement, but not all of it, these models provide useful insights into psychogenic movement disorders, and provide a neurobiological basis for discussing these disorders with patients and their families. Our contribution will appear later this year in a book entitled """"""""Psychogenic Movement Disorders: Psychobiology and Treatment of a Functional Disorder"""""""" (M. Hallett, S. Fahn, J. Jankovic, A. E. Lang, C. R. Cloniger and S. C. Yudofsky eds., Lippincott, Williams and Wilkins). Our research has been thus directed at understanding symbolically guided actions, the division of labor within the frontal lobe, and the role of the frontal lobe in applying abstract response strategies in health, so that physicians, therapists, and other health care specialists can improve treatments for people who have disabilities in all of these key areas of mental health.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH001092-27
Application #
7135771
Study Section
(LSN)
Project Start
Project End
Budget Start
Budget End
Support Year
27
Fiscal Year
2005
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Nougaret, Simon; Genovesio, Aldo (2018) Learning the meaning of new stimuli increases the cross-correlated activity of prefrontal neurons. Sci Rep 8:11680
Marcos, Encarni; Nougaret, Simon; Tsujimoto, Satoshi et al. (2018) Outcome Modulation Across Tasks in the Primate Dorsolateral Prefrontal Cortex. Neuroscience 371:96-105
Marcos, Encarni; Tsujimoto, Satoshi; Genovesio, Aldo (2016) Event- and time-dependent decline of outcome information in the primate prefrontal cortex. Sci Rep 6:25622
Marcos, Encarni; Genovesio, Aldo (2016) Determining Monkey Free Choice Long before the Choice Is Made: The Principal Role of Prefrontal Neurons Involved in Both Decision and Motor Processes. Front Neural Circuits 10:75
Genovesio, Aldo; Cirillo, Rossella; Tsujimoto, Satoshi et al. (2015) Automatic comparison of stimulus durations in the primate prefrontal cortex: the neural basis of across-task interference. J Neurophysiol 114:48-56
Genovesio, Aldo; Tsujimoto, Satoshi; Navarra, Giulia et al. (2014) Autonomous encoding of irrelevant goals and outcomes by prefrontal cortex neurons. J Neurosci 34:1970-8
Tsujimoto, Satoshi; Genovesio, Aldo; Wise, Steven P (2012) Neuronal activity during a cued strategy task: comparison of dorsolateral, orbital, and polar prefrontal cortex. J Neurosci 32:11017-31
Genovesio, Aldo; Tsujimoto, Satoshi; Wise, Steven P (2012) Encoding goals but not abstract magnitude in the primate prefrontal cortex. Neuron 74:656-62
Genovesio, Aldo; Tsujimoto, Satoshi; Wise, Steven P (2011) Prefrontal cortex activity during the discrimination of relative distance. J Neurosci 31:3968-80
Tsujimoto, Satoshi; Genovesio, Aldo; Wise, Steven P (2011) Comparison of strategy signals in the dorsolateral and orbital prefrontal cortex. J Neurosci 31:4583-92

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