Although our understanding of the mechanisms underlying motor adaptation has greatly benefited from previous computational models, the architecture of motor memory is still uncertain. On one hand, two-state models that contain both a fast-learning-fast-forgetting process and a slow-learning-slow-forgetting process explain a wide range of data on motor adaptation, but cannot differentiate whether the fast and slow processes are arranged serially or in parallel and cannot account for learning multiple tasks simultaneously. On the other hand, multiple parallel-state models learn multiple tasks simultaneously but cannot account for a number of motor adaptation data. Here, we investigated the architecture of human motor memory by systematically testing possible architectures via a combination of simulations and a dual visuomotor adaptation experimental paradigm. We found that only one parsimonious model can account for both previous motor adaptation data and our dual-task adaptation data: a fast process that contains a single state is arranged in parallel with a slow process that contains multiple states switched via contextual cues. Our result suggests that during motor adaptation, fast and slow processes are updated simultaneously from the same motor learning errors.

Although intermixing different motor learning tasks via random schedules enhances long-term retention compared with "blocked" schedules, the mechanism underlying this contextual interference effect has been unclear. Furthermore, previous studies have reported inconclusive results in individuals poststroke. We instructed participants to learn to produce three grip force patterns in either random or blocked schedules and measured the contextual interference effect by long-term forgetting: the change in performance between immediate and 24-h posttests. Nondisabled participants exhibited the contextual interference effect: no forgetting in the random condition but forgetting in the blocked condition. Participants at least 3 mo poststroke exhibited no forgetting in the random condition but marginal forgetting in the blocked condition. However, in participants poststroke, the integrity of visuospatial working memory modulated long-term retention after blocked schedule training: participants with poor visuospatial working memory exhibited little forgetting at 24 h. These counterintuitive results were predicted by a computational model of motor memory that contains a common fast process and multiple slow processes, which are competitively updated by motor errors. In blocked schedules, the fast process quickly improved performance, therefore reducing error-driven update of the slow processes and thus poor long-term retention. In random schedules, interferences in the fast process led to slower change in performance, therefore increasing error-driven update of slow processes and thus good long-term retention. Increased forgetting rates in the fast process, as would be expected in individuals with visuospatial working memory deficits, led to small updates of the fast process during blocked schedules and thus better long-term retention. stroke; neurorehabilitation; motor learning; computational neuroscience DURING NEUROREHABILITATION after brain injury, but also in activities such as sports, technical training, and music, one must often learn, or relearn, multiple motor tasks within a given period. Intermixing the learning of different tasks via random schedules reduces performance during training but enhances long-term retention compared with blocked schedules, (e.g., Schmidt and Lee 1999;Shea and Morgan 1979;Tsuitsui et al. 1998). This phenomenon is known as the contextual interference (CI) effect.Despite close to a century of research (Pyle 1919), however, the mechanism underlying the CI effect are unclear. According to the "forgetting-reconstruction" hypothesis of the CI effect, short-term forgetting between successive presentations of the same task during random training requires the learner to "reconstruct the action plan at each presentation," resulting in stronger memory representations (Lee and Magill 1983;Lee et al. 1985). Recent computational models similarly suggest a crucial role of working memory in the CI effect. It has notably been proposed that motor adaptation occurs via simultaneous update of a fast proce...

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Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection in infants, young children, and the elderly. Two subtypes of RSV, A and B, circulate alternately at 1-2-year intervals during epidemics. The attachment glycoprotein (G protein) of RSV is one of the major targets for immune responses. In this study, we generated a recombinant fusion protein, GcfAB, which consists of the central regions (a.a. residues 131–230) of the G proteins of both RSV A (A2 strain) and B (B1 strain) subtypes, and investigated immunogenicity, protective efficacy, and immunopathology. We immunized mice with GcfAB plus cholera toxin as a mucosal adjuvant via intranasal (IN) or sublingual (SL) routes. The IN group showed higher levels of RSV G-specific antibody responses, including serum IgG and mucosal IgA, compared with the SL group. On the contrary, more vigorous RSV G-specific CD4+ T-cell responses were elicited in the SL group than in the IN group after RSV-A but not RSV-B viral challenge. Furthermore, the SL group showed more pulmonary eosinophil recruitment and body weight loss than did the IN group after RSV-A challenge. Both IN and SL immunization with GcfAB provided potential protection against both subtypes of infections. Together, these results suggest that vaccination with GcfAB via an IN route could be a universal vaccine regimen preventing both RSV A and B infections.

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