Transfer of Learning After Updating Training Mediated by the Striatum

Abstract

MRE11 by either MRN component or by MDC1 (Fig. 3C). However, upon immobilization of NBS1 or MRE11, the accumulation of the downstream factors MDC1 and 53BP1 was strongly impaired in the absence of H2AX (Fig. 3C). Recruitment of MDC1 by ATM 1300-3060 was similarly decreased, suggesting that phosphorylation of H2AX is an important step in recruiting and maintaining these factors at sites of damage (17, 19).To finally test whether individual repair factors are sufficient to induce a physiological DDR, we assessed the effect of immobilization on cell cycle progression (Fig. 4). Upon targeting of NBS1, MRE11, MDC1, or ATM, but not Chk1 or Chk2, to chromatin, cells accumulated in G 2 phase as determined by staining of pericentromeric heterochromatin with an antibody to phosphoS10H3 (Fig. 4A) (20). Cell cycle delay was confirmed by increased phosphorylation of retinoblastoma protein at Ser 807 /Ser 811 ( fig. S6). Furthermore, the cell cycle delay was sensitive to the presence of Chk2 and required ATM activity, suggesting involvement of the checkpoint kinase Chk2 (Fig. 4A). H2AX −/− cells were resistant to G 2 /M delays upon immobilization of repair factors (Fig. 4B). This observation is in line with the finding that cells lacking H2AX manifest a G 2 /M checkpoint defect after exposure to low doses of irradiation (21).We report here that activation of cellular DNA damage response pathways does not require DNA damage but can be triggered by stable association of single repair factors with chroma-tin. Our observations suggest that the physical interaction of DNA repair factors with chromatin is a key step in activation of the DDR signaling cascade, and that the observed buildup at DNA damage foci probably contributes appreciably to establishing the cellular response to damaged DNA (4). Our observation that immobilized downstream factors can recruit upstream components indicates that activation of a full DDR involves amplification via formation of multiple repair complexes and perpetuation of gH2AX phosphorylation. A critical role for signal amplification on DNA is also suggested by the findings that in the absence of gH2AX or MDC1, several repair factors, including NBS1 and 53BP1, are recruited to sites of double-strand breaks, but do not accumulate and are not efficiently retained (16, 19). Our observation of phosphorylation of several key components of the DDR, including H2AX, NBS1, and ATM, and the appearance of cell cycle delays upon tethering indicate that the observed cellular response mimics to a large extent the physiological DDR. Given the apparent importance of the physical interaction of DNA repair factors with chromatin, it will be essential to uncover the precise role of higher-order chromatin structure and chromatin-remodeling complexes in triggering the DDR.Process-specific training can improve performance on untrained tasks, but the magnitude of gain is variable and often there is no transfer at all. We demonstrate transfer to a 3-back test of working memory after 5 weeks of training in updating. The trans...

On the validity and generality of transfer effects in cognitive training research

“…Another possible transfer model can be derived from the neuronal overlap hypothesis, which posits that transfer can only be expected if trained task and transfer task share some overlap in neuronal activation (e.g., Dahlin et al 2008;Jonides et al, 2004;Kuwajima & Sawaguchi, 2010;Lustig, et al, 2009;Thorell et al, 2009). As a test of the model, this overlap has to be shown to be sensitive and specific to the process or ability of interest.…”

Working memory for meaningless manual gestures.

“…One example is the reading span task (Daneman & Carpenter, 1980;Rönnberg, Arlinger, Lyxell & Kinnefors, 1989) which taps parallel storage and processing capacity by requiring participants to read and semantically process sentences while at the same time retaining their content in memory. However, when to-be-remembered items have no existing representations in long-term memory, another approach is needed; one candidate is the nback task (Cohen, Forman, Braver, Casey, Servan-Schreiber, Noll, 1994;Dahlin, Stigsdotter Neely, Larsson, Bäckman & Nyberg, 2008).…”

Comparing the Transfer Effects of Simultaneously and Sequentially Combined Aerobic Exercise and Cognitive Training in Older Adults

“…Therefore, the selective effect of training format may reflect the relative functional overlap between the trained divided attention task and the outcome measures, with working memory showing the greatest sensitivity and overlap, memory and processing speed showing non-specific improvement after training (some functional overlap), and inhibition showing no improvement (little functional overlap). Similarly, one can consider the principle of neural overlap (Dahlin et al 2008;Lustig et al 2009), in that the brain regions showing increased neural efficiency in prefrontal cortex after the same DT training (Erickson et al 2007a, b) are also associated with a variety of working memory tasks (e.g., Braver et al 1997;D'Esposito et al 2000;Kane and Engle 2002). The advantage observed in the sequential training group for the working memory outcomes may reflect the benefits of training under full attention (i.e., without concurrent exercise).…”

“…From the array of cognitive outcome measures chosen (measuring response inhibition, switching, working memory, immediate and delayed recall), we anticipated that the training-related benefits would be more pronounced for outcome measures with the greatest functional and neural overlap with the trained dual task (Dahlin et al 2008), namely measures of divided attention or working memory. Based upon the literature on age-related increases in cognitive-motor DT costs (Li et al 2001), we hypothesized that sequential training would confer greater cognitive benefits than simultaneous training, due to the cognitive advantage of training under full attention.…”

“…Such DT training is thought to improve processes such as task coordination and working memory (Bherer et al 2005). Dahlin et al (2008) demonstrated that the degree of transfer follows the principle of neural overlap, such that gains are greater when the trained task and outcome measures share neural substrates. This implies that not all cognitive outcome variables should show equivalent transfer effects but that the magnitude of improvement should depend on the relationship to the trained task.…”