NEUROTRANSMITTER AND BRAIN PARTS INVOLVED IN SCHIZOPHRENIA

Schizophrenia (SCZ) is a major debilitating, complex, and costly illness that strikes 1% of the world's population. It is characterized by three general types of symptoms: Atypical symptoms (aggressiveness, agitation, delusions, hallucinations), depressive symptoms (alogia, avolition, anhedonia, apathy), and cognitive symptoms (impaired attention, learning, memory). The etiology of SCZ has still not been fully understood. Alteration in various neurochemical systems such as dopamine, serotonin, norepinephrine, gamma-aminobutyric acid, and glutamate are involved in the pathophysiology of SCZ. The lack of understanding regarding the exact pathogenic process may be the likely a reason for the non-availability of effective treatment, which can prevent onset and progression of the SCZ. The tools of modern neuroscience, drawing from neuroanatomy, neurophysiology, brain imaging, and psychopharmacology, promise to provide a host of new insights into the etiology and treatment of SCZ. In this review, we will discuss the role of the various neurotransmitter concerned and brain parts exaggerated in the SCZ

True and False Memories: Neuropsychological and Neuropharmacological Approaches

Some recent studies have explored the false memory and its mechanisms. True memories depend on draw in the past, retrieve of the information, remember past events plus recombine (reorganize) them with new information to finally re-encode these elements creating a new memory. But, sometimes failures in this system lead to memory errors collaborating to false memory formation. This chapter will address new neuropsychological tools to evaluate true and false memory performance. Some neuropharmacological aspects as possible mechanisms of agonist and antagonist modulation of false memory will be discussed

Functional significance of central D1 receptors in cognition: beyond working memory

The role of dopamine D1 receptors in prefrontal cortex function, including working memory, is well acknowledged. However, relatively little is known about their role in other cognitive or emotional functions. We measured both D1 and D2 receptors in the brain using positron emission tomography in healthy subjects, with the aim of elucidating how regional D1 and D2 receptors are differentially involved in cognitive and emotional functions beyond working memory. We found an inverted U-shaped relation between prefrontal D1 receptor availability and Wisconsin Card Sorting Test performance, indicating that too little or too much D1 receptor stimulation impairs working memory or set shifting. In addition, variability of D1 receptor availability in the amygdala and striatum was related to individual differences in emotional responses and decision-making processes, respectively. These observations suggest that the variability of available D1 receptors might be associated with individual differences in brain functions that require phasic dopamine release. An interdisciplinary approach combining molecular imaging of dopamine neurotransmission with cognitive neuroscience and clinical psychiatry will provide new perspectives for understanding the neurobiology of neuropsychiatric disorders such as schizophrenia, addiction and Parkinson's disease, as well as novel therapeutics for cognitive impairments observed in them

Effects of Sulpiride on True and False Memories of Thematically Related Pictures and Associated Words in Healthy Volunteers

Episodic memory, working memory, emotional memory, and attention are subject to dopaminergic modulation. However, the potential role of dopamine on the generation of false memories is unknown. This study defined the role of the dopamine D-2 receptor on true and false recognition memories. Twenty-four young, healthy volunteers ingested a single dose of placebo or 400 mg oral sulpiride, a dopamine D-2-receptor antagonist, just before starting the recognition memory task in a randomized, double-blind, and placebo-controlled trial. The sulpiride group presented more false recognitions during visual and verbal processing than the placebo group, although both groups had the same indices of true memory. These findings demonstrate that dopamine D-2 receptors blockade in healthy volunteers can specifically increase the rate of false recognitions. The findings fit well the two-process view of causes of false memories, the activation/monitoring failures model.Univ Fed Sao Paulo, Dept Psychobiol, Sao Paulo, BrazilAssociacao Fundo Incent Pesquisa, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Physiol, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Psychobiol, Sao Paulo, BrazilWeb of Scienc

CNTRICS Final Task Selection: Long-term Memory

Long-term memory (LTM) is a multifactorial construct, composed of different stages of information processing and different cognitive operations that are mediated by distinct neural systems, some of which may be more responsible for the marked memory problems that limit the daily function of individuals with schizophrenia. From the outset of the CNTRICS initiative, this multidimensionality was appreciated, and an effort was made to identify the specific memory constructs and task paradigms that hold the most promise for immediate translational development. During the second CNTRICS meeting, the LTM group identified item encoding and retrieval and relational encoding and retrieval as key constructs. This article describes the process that the LTM group went through in the third and final CNTRICS meeting to select nominated tasks within the 2 LTM constructs and within a reinforcement learning construct that were judged most promising for immediate development. This discussion is followed by each nominating authors' description of their selected task paradigm, ending with some thoughts about future directions.Psycholog

Aging and functional reorganization of striatum- and Medial-Temporal Lobe-dependent memory systems

Bisherige Forschung hat zwischen zwei Gedächtnissystemen unterschieden: dem sog. deklarativen Gedächtnis (DG), welches sich durch die Fähigkeit vergangene Lebensereignisse bewusst zu erinnern auszeichnet und mit dem lobus temporalis medialis (MTL) in Verbindung steht, und dem prozeduralen Gedächtnis (PG), welches erlernte Fertigkeiten beinhaltet und mit dem Corpus striatum assoziiert ist. Weitere Studien haben ergeben, dass Alterung von neurologischen Schäden in beiden Systemen, erhöhter Aktivität im MTL und einer relativ geringeren Beeinträchtigung des PG begleitet ist. Hyperaktivität im MTL wurde dabei sowohl mit verbesserten als auch verschlechterten Gedächtnisleistungen in Verbindung gebracht. Die hier vorgelegte Dissertation befasst sich mit dem Einfluss von Alterung auf die Beziehungen zwischen o. g. Hirnnetzwerken und prozeduralen bzw. deklarativen Gedächtnisfähigkeiten. Studie I zeigte, dass Altersunterschiede in einer prozeduralen Gedächtnisaufgabe graduell im Verlaufe des Trainings entstehen und vmtl. mit negativen Einflüssen von Alterung auf den Übergang von PG zu DG in Zusammenhang stehen. Zwei striatal-dopaminerge genetische Polymorphismen, rs907094 auf DARPP-32 und VNTR auf DAT, wirkten sich dabei auf das DG älterer aber nicht jüngerer Erwachsener aus. In Studie II wurden Beeinträchtigungen im neuronalen Vorhersagefehler, einem neuronales Lernsignal im Striatum, in älteren Probanden gefunden. Studie III konnte teilweise intaktes PG in einer räumlichen Gedächtnisaufgabe demonstrieren, wobei der Polymorphismus rs17070145 auf WWC1, der sich auf Lanzeitpotenzierung im MTL auswirkt, diese Altersunterschiede modulierte. In Studie IV wurden neuronale Repräsentationen und Komputationen während einer räumlichen Gedächtnisaufgabe untersucht. Während jüngere Probanden in dieser Studie Anzeichen von MTL-basiertem DG zeigten, zeigten ältere Teilnehmer Evidenz von PG. Die neuronalen Signaturen älterer Erwachsener wurden jedoch am stärksten im MTL beobachtet.Previous research has distinguished between a declarative memory system that stores flexible representations and is subserved by the medial-temporal lobe (MTL) and a procedural memory system that expresses past experiences through skills and is based mainly on the striatum. Investigations into age-related changes in these memory systems indicated a complex pattern of neural degradation in both systems, elevated MTL activity as well as partially spared procedural memory functions in older adults. A literature review further suggests that MTL overactivity can be caused by factors which are either beneficial or detrimental for memory. The present dissertation investigated the effects of human aging on the relations of brain functions to declarative and procedural memory. In Study I, age differences in a procedural memory task gradually emerged over the course of training and were linked to negative effects of aging on the transition from procedural to declarative memory. In addition, this study showed that striatal dopaminergic genetic polymorphisms, rs907094 on DARPP-32 and VNTR on DAT, affected declarative knowledge in older but not younger adults. Study II indicated that prediction error signals in the human brain, a neural computation associated with striatal learning functions, were partially impaired in older adults. Study III demonstrated partially intact procedural memory in older adults in a spatial memory task, whereby age differences were modulated by a polymorphism influencing long-term potentiation in the MTL (rs17070145 on WWC1). Finally, Study IV showed hat that neural representations and computations subserving spatial memory qualitatively differed between younger and older adults. The performance and neural activation of younger adults showed unique properties of MTL-dependent declarative memory. Older adults, in contrast, showed behavioral and neural indications of procedural memory but the localization of the neural signatures peaked in the MTL