A neural network model of adaptively timed reinforcement learning and hippocampal dynamics

A neural model is described of how adaptively timed reinforcement learning occurs. The adaptive timing circuit is suggested to exist in the hippocampus, and to involve convergence of dentate granule cells on CA3 pyramidal cells, and NMDA receptors. This circuit forms part of a model neural system for the coordinated control of recognition learning, reinforcement learning, and motor learning, whose properties clarify how an animal can learn to acquire a delayed reward. Behavioral and neural data are summarized in support of each processing stage of the system. The relevant anatomical sites are in thalamus, neocortex, hippocampus, hypothalamus, amygdala, and cerebellum. Cerebellar influences on motor learning are distinguished from hippocampal influences on adaptive timing of reinforcement learning. The model simulates how damage to the hippocampal formation disrupts adaptive timing, eliminates attentional blocking, and causes symptoms of medial temporal amnesia. It suggests how normal acquisition of subcortical emotional conditioning can occur after cortical ablation, even though extinction of emotional conditioning is retarded by cortical ablation. The model simulates how increasing the duration of an unconditioned stimulus increases the amplitude of emotional conditioning, but does not change adaptive timing; and how an increase in the intensity of a conditioned stimulus "speeds up the clock", but an increase in the intensity of an unconditioned stimulus does not. Computer simulations of the model fit parametric conditioning data, including a Weber law property and an inverted U property. Both primary and secondary adaptively timed conditioning are simulated, as are data concerning conditioning using multiple interstimulus intervals (ISIs), gradually or abruptly changing ISis, partial reinforcement, and multiple stimuli that lead to time-averaging of responses. Neurobiologically testable predictions are made to facilitate further tests of the model.Air Force Office of Scientific Research (90-0175, 90-0128); Defense Advanced Research Projects Agency (90-0083); National Science Foundation (IRI-87-16960); Office of Naval Research (N00014-91-J-4100

The hippocampus and cerebellum in adaptively timed learning, recognition, and movement

The concepts of declarative memory and procedural memory have been used to distinguish two basic types of learning. A neural network model suggests how such memory processes work together as recognition learning, reinforcement learning, and sensory-motor learning take place during adaptive behaviors. To coordinate these processes, the hippocampal formation and cerebellum each contain circuits that learn to adaptively time their outputs. Within the model, hippocampal timing helps to maintain attention on motivationally salient goal objects during variable task-related delays, and cerebellar timing controls the release of conditioned responses. This property is part of the model's description of how cognitive-emotional interactions focus attention on motivationally valued cues, and how this process breaks down due to hippocampal ablation. The model suggests that the hippocampal mechanisms that help to rapidly draw attention to salient cues could prematurely release motor commands were not the release of these commands adaptively timed by the cerebellum. The model hippocampal system modulates cortical recognition learning without actually encoding the representational information that the cortex encodes. These properties avoid the difficulties faced by several models that propose a direct hippocampal role in recognition learning. Learning within the model hippocampal system controls adaptive timing and spatial orientation. Model properties hereby clarify how hippocampal ablations cause amnesic symptoms and difficulties with tasks which combine task delays, novelty detection, and attention towards goal objects amid distractions. When these model recognition, reinforcement, sensory-motor, and timing processes work together, they suggest how the brain can accomplish conditioning of multiple sensory events to delayed rewards, as during serial compound conditioning.Air Force Office of Scientific Research (F49620-92-J-0225, F49620-86-C-0037, 90-0128); Advanced Research Projects Agency (ONR N00014-92-J-4015); Office of Naval Research (N00014-91-J-4100, N00014-92-J-1309, N00014-92-J-1904); National Institute of Mental Health (MH-42900

Jean-Paul Sartre's concept of freedom.

Thesis (M.A.)--Boston UniversityThe purpose of this thesis is to present an exposition and interpretation of Jean-Paul Sartre's concept of freedom, as expressed in his major philosophical writings. This purpose calls for a consideration of the relationship between freedom and some of Sartre's other basic ontological concepts. The "other" concepts are those relating specifically to Sartre's theory of consciousness. To explore and make explicit the fundamental structures of consciousness is to take the front door into an understanding of Sartre's concept of freedom. Chapter II shows that the meaning of Sartre's concept of freedom widely diverges from various traditional and popular interpretations of freedom. It is concluded that the term freedom is intimately bound up with Sartre's conception of consciousness and that a consciousness which is free is, first, free because no determining motives affect the activities of consciousness and, second, consciousness is able to choose the "motives" which it pleases. In Chapter III it is learned that the cardinal activity of consciousness is its intentionality, that consciousness is always consciousness of something. The distinction is made between reflective and pre-reflective consciousness. It is further indicated in this chapter Sartre's rejection of a transcendental unifying and individualizing Ego and his replacement of it with a transcendent Ego, which, for Sartre, becomes an object for consciousness like any other object. In Chapter IV Sartre's ontology is developed by an analysis of all that which is not consciousness, or in Sartre's terminology, a being-in-itself. The in-it self is any transcendent object and its being is characterized by a massive, full identity with itself; being-in-itself is self-consistent, uncreated, and neither passivity nor activity. In Chapter V consciousness is identified with being-for-itself. Being-for-itself is empty of content, must make itself be, is its own nothingness, and introduces negations and temporality into the world. Consciousness will never be what it lacks, for its being lies outside, at a distance, and beyond; it is defined as not being that being. Ontologically speaking, man's being is nothingness. Chapter VI identifies Sartre's notion of freedom with the being of consciousness. Thus one meaning of Sartre's notion of freedom takes on an ontological dimension; man is freedom. The other meaning of freedom is assigned to the necessary activity of consciousness. This activity is characterized by the necessary, unceasing, yet interminable, desire of consciousness to choose or assume its own being, its essence. It has been objected by Wilfrid Desan that Sartre has made freedom itself into the essence of man. This thesis concludes, however, that only in defining freedom has Sartre made freedom an essence. Even in this sense, Sartre has made freedom an essence only if one is willing to identify man's ontological "condition" with the traditional notion of a fundamental "nature" of man. Desan further objects that Sartre's notion of "absolute" freedom results in a contradiction since absolute means unlimited, and Sartre's freedom is limited by freedom itself. The thesis concludes that this contradiction may be avoided by simply refraining from calling Sartre's concept of freedom "absolute" and accepting, along with Sartre, the existential condition that freedom is limited by one thing, namely, freedom itself. A final critical evaluation is made concerning the unavoidable conflict between Sartre's philosophy and philosophizing. It is asserted that this conflict is a conflict between fact and definition. It is the conflict between the fact of freedom and Sartre's definition of this fact

\u3cem\u3eDe Novo\u3c/em\u3e [PSI\u3csup\u3e+\u3c/sup\u3e] Prion Formation Involves Multiple Pathways to Form Infectious Oligomers

Prion and other neurodegenerative diseases are associated with misfolded protein assemblies called amyloid. Research has begun to uncover common mechanisms underlying transmission of amyloids, yet how amyloids form in vivo is still unclear. Here, we take advantage of the yeast prion, [PSI +], to uncover the early steps of amyloid formation in vivo. [PSI +] is the prion form of the Sup35 protein. While [PSI +] formation is quite rare, the prion can be greatly induced by overexpression of the prion domain of the Sup35 protein. This de novo induction of [PSI +] shows the appearance of fluorescent cytoplasmic rings when the prion domain is fused with GFP. Our current work shows that de novoinduction is more complex than previously thought. Using 4D live cell imaging, we observed that fluorescent structures are formed by four different pathways to yield [PSI +] cells. Biochemical analysis of de novo induced cultures indicates that newly formed SDS resistant oligomers change in size over time and lysates made from de novo induced cultures are able to convert [psi −] cells to [PSI +] cells. Taken together, our findings suggest that newly formed prion oligomers are infectious

Overwinter Changes in Dry Aggregate Size Distribution Influencing Wind Erodibility in a Spring Wheat-Summerfallow Cropping System

A long-term study of the wind erodibility properties of a two-year spring wheat-summerfallow cropping systems was started in 1988 in south-central North Dakota as part of an USDA-ARS led effort to construct a process-oriented soil erosion predictive model. Observations were conducted on a conservation tillage experiment established in 1984 on soil classified in the U.S. as Typic-Pachic Haploborolls and in Canada as Brown to Dark Brown Chenozemic. The experiment included four residue-management treatments defined by targeted residue coverages: no-till, \u3e 60% cover; minimal-till, 30% to 60% cover and undercutter dominated; conventional-till, \u3c 30% cover and disk dominated; low-residue, \u3c 5 % cover. Fall and spring measurements of dry aggregate size distribution (ASD) of surface soil (0 to 4 cm depth), and overwinter changes in ASD are reported here. A rotary sieve produced six size fractions ranging from \u3c 0.42 mm to \u3e 19.2 mm diameter. Measurements of ASD are expressed as geometric mean diameter (GMD) or erodible fraction (EF: fraction \u3c 0.84 mm). Two major influences on overwinter changes in ASD were observed: (i) During the drier part of a multiyear weather cycle (1988 to 1990), disaggregative changes were observed, with a lowering of GMDs and an increase in EFs. Wetter years (1991 to 1993) brought mixed to aggregative ASD changes. (ii) The phase of the 21-month fallow period strongly affected overwinter ASD change, with large, aggregative changes (GMD up, EF down) observed over the first winter of the fallow period (stubble phase) and mixed aggregative to disaggregative changes observed in the second winter of fallow (residue phase). Tillage treatments had little apparent effect on overwinter ASD changes. Single and multiple regressions indicate that various factors would associate with significant fractions of variance in overwinter GMD change: (i) weather factors - (a) number of days with snowcover, (b) number of freeze-thaw cycles, and (c) precipitation in the fall; (ii) crop growth in years before the year of fallow; (iii) phase of the fallow period; and (iv) GMD level in the fall

Deriving a Provisional Tolerable Intake for Intravenous Exposure to Silver Nanoparticles Released from Medical Devices

Silver nanoparticles (AgNP) are incorporated into medical devices for their anti-microbial characteristics. The potential exposure and toxicity of AgNPs is unknown due to varying physicochemical particle properties and lack of toxicological data. The aim of this safety assessment is to derive a provisional tolerable intake (pTI) value for AgNPs released from blood-contacting medical devices. A literature review of in vivo studies investigating critical health effects induced from intravenous (i. v.) exposure to AgNPs was evaluated by the Annapolis Accords principles and Toxicological Data Reliability Assessment Tool (ToxRTool). The point of departure (POD) was based on an i. v. 28-day repeated AgNP (20 nm) dose toxicity study reporting an increase in relative spleen weight in rats with a 5% lower confidence bound of the benchmark dose (BMDL05) of 0.14 mg/kg bw/day. The POD was extrapolated to humans by a modifying factor of 1,000 to account for intraspecies variability, interspecies differences and lack of long-term toxicity data. The pTI for long-term i. v. exposure to 20 nm AgNPs released from blood-contacting medical devices was 0.14 μg/kg bw/day. This pTI may not be appropriate for nanoparticles of other physicochemical properties or routes of administration. The methodology is appropriate for deriving pTIs for nanoparticles in general

Understanding Schools and Schooling. (Book Review)

A review of a book written by Clive Chitty (2002 with a useful focus on issues of equity and social justice, including prejudice, discrimination and bullying in secondary schools. Education policy makers need to explore the extent to which it is important to produce interested, motivated and socially balanced young adults. It is well researched and documented

Hereditary transthyretin amyloidosis: baseline characteristics of patients in the NEURO-TTR trial

Background: Hereditary transthyretin (ATTRm) amyloidosis is a rare, progressive and fatal disease with a range of clinical manifestations.Objective: This study comprehensively evaluates disease characteristics in a large, diverse cohort of patients with ATTRm amyloidosis.Methods: Adult patients (N = 172) with Stage 1 or Stage 2 ATTRm amyloidosis who had polyneuropathy were screened and enrolled across 24 investigative sites and 10 countries in the NEURO-TTR trial (www.clinicaltrials.gov, NCT01737398). Medical and disease history, quality of life, laboratory data, and clinical assessments were analyzed.Results: The NEURO-TTR patient population was diverse in age, disease severity, TTR mutation, and organ involvement. Twenty-seven different TTR mutations were present, with Val30Met being the most common (52%). One third of patients reported early onset disease (before age 50) and the average duration of neuropathy symptoms was 5.3 years. Symptoms affected multiple organs and systems, with nearly 70% of patients exhibiting broad involvement of weakness, sensory loss, and autonomic disturbance. Over 60% of patients had cardiomyopathy, with highest prevalence in the United States (72%) and lowest in South America/Australasia (33%). Cardiac biomarker NT-proBNP correlated with left ventricular wall thickness (p<.001). Quality of life, measured by Norfolk QoL-DN and SF-36 patient-reported questionnaires, was significantly impaired and correlated with disease severity.Conclusions: Baseline data from the NEURO-TTR trial demonstrates ATTRm amyloidosis as a systemic disease with deficits in multiple organs and body systems, leading to decreased quality of life. We report concomitant presentation of polyneuropathy and cardiomyopathy in most patients, and early involvement of multiple body systems

Chedoke Arm and Hand Activity Inventory-9 (CAHAI-9): Perceived clinical utility within 14 days of stroke

Purpose: The Chedoke Arm and Hand Activity Inventory-9 (CAHAI-9) is an activity-based assessment developed to include relevant functional tasks and to be sensitive to clinically important changes in upper limb function. The aim of this study was to explore both therapists' and clients' views on the clinical utility of CAHAI-9 within 14 days of stroke. Method: Twenty-one occupational therapists actively working in stroke settings were recruited by convenience sampling from 8 hospitals and participated in semistructured focus groups. Five clients within 14 days of stroke were recruited by consecutive sampling from 1 metropolitan hospital and participated in structured individual interviews. The transcripts were analyzed thematically. Results: Six themes emerged from the focus groups and interviews: collecting information, decisions regarding client suitability, administration and scoring, organizational demands, raising awareness, and clients' perceptions of CAHAI-9 utility. All therapists agreed CAHAI-9 was suited for the stroke population and assisted identification of client abilities or difficulties within functional contexts. Opinions varied as to whether CAHAI-9 should be routinely administered with clients who had mild and severe upper limb deficits, but therapists agreed it was appropriate for clients with moderate deficits. Therapists made suggestions regarding refinement of the scoring and training to increase utility. All clients with stroke felt that the assessment provided reassurance regarding their recovery. Conclusion: The findings indicate that CAHAI-9 shows promise as an upper limb ability assessment for clients within 14 days of stroke