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Identifier 000440878
Title Η επίδραση της εξάσκησης της μνήμης εργασίας σε γνωσιακές λειτουργίες και το νευροβιολογικό υπόβαθρο της σε ποντίκια και ανθρώπους
Alternative Title The effect of working memory training on cognitive function and the neural substrate of humans and mice
Author Σταυρουλάκη, Βασιλική
Thesis advisor Μπίτσιος, Παναγιώτης
Reviewer Σιδηροπουλου, Κυριακή
Γιακουμάκη, Γ. Στυλιανή
Καραγωγέως, Δόμνα
Σπανάκη, Κλεάνθη
Σταματάκης, Αντώνιος
Παναγής, Γεώργιος
Abstract Neuroplasticity is the ability of the adult brain to learn new behaviours, to form new memories and also to change the underlying neural circuit that is responsible for this learning. This feature may be helpful against cognitive disorders that coincide with systemic nervous changes, such as aging or the onset of schizophrenia. Thus, the question that arises is whether innovative activities can lead to changes in basic cognitive function. One such activity is the training of working memory, which is a very popular theme of study. Working memory, as the ability to store and process information, is a fundamental cognitive function. It is systematically considered essential for aspects of daily functioning, such as the ability to retain attention. One way to improve working memory capacity is through training. A large amount of research studies and several meta-analyses have tested the benefits of this training and several of them arguing, whether training can lead to improvements of other cognitive functions that are related to it. This ability, which constitutes cognitive transfer, is the aim of this study. In particular, the present study seeks to investigate whether training of working memory can improve cognitive flexibility in both human and mice. Cognitive flexibility is a superior executive function, which can be defined as the ability to adapt behaviours in a changing environment. One prerequisite for improving cognitive flexibility is that the two tasks (training and transfer) must use a common neuroanatomical and neurophysiological background. In the present study this is accomplished, since the neuroanatomical background of working memory focuses on the prefrontal cortex, an upper area of the brain that supports executive functions. The prefrontal cortex, however, is associated with both the hippocampus, the area that supports spatial memory, and the orbitofrontal cortex, which supports adaptability to changing rules. In particular, the human study examined the effects of working memory training on cognitive flexibility in a sample of 144 healthy participants, 18-43 years old (74: men & 65: women), who were divided into three groups. In a)control group: participants had no involvement in the study for six days following the baseline assessment session, b)partially adapted group: for six consecutive days following the baseline assessment session, participants were administered the LNS up to the strings with three digits and c)fully adapted group: for six consecutive days following the baseline assessment session, participants were administered the LNS up to the last string. One week after the baseline assessment session, all participants were administered the Intra / Extra Dimensional Shift test (ID/EDS). During the baseline assessment session, mouthwash samples of participants were additionally taken. The aim of this step was the correlation of the performance of the three group of participants with specific genetic polymorphisms, the COMT (rs4680) and BDNF (rs6265). The results showed a statistically significant effect of working memory training on cognitive flexibility. More specifically, it turned out that the fully adapted group made less mistakes, presented with fewer latency and made less efforts to complete the stages of the task compared to the control group. Regarding gender, it was found that men compared to women participants took longer to complete the nine stages of the ID / EDS test. However, no other sex differences were observed in the cognitive flexibility task. Regarding the correlation between the genetic background and the group, it was found that only in the control group, the participants carrying the Met / Val allele (heterozygotes) needed a larger number of trials to complete the stages of the task compared to the homozygous participants ( Val / Val and Met / Met) of control group and also the heterozygotes participants of partially and fully adapted groups. Using a similar experimental design, based on the second objective, the animal study examines the effect of working memory training, using the Delayed Alternation Task (DAT) in the T-maze, on cognitive flexibility. Specifically, 79 C57BL/6 mice, 2-9 month of age were used (67: males & 32: females). The animals were divided into three groups, in: a)naive group: mice remained in their home cage and had no involvement in the task, b)partially adaptive group: mice learned to alternate arms but, without any delays in the delayed alternation task and c)fully adaptive group: mice performed the alternation procedure with increasing delays of 10, 20, 30, 40 and 50 seconds, in the same task. The working memory training lasted nine days and two days later, all the mice underwent a cognitive flexibility assessment task, the Attentional Set - Shifting Task (AST). Also, in 15 animals of all three groups, the tasks of memory recognition of objects and the contextual fear learning were performed. At the end of the behavioural tasks, 26 mice were euthanised and their brains were removed and subject to Golgi-Cox staining technique and Nissl staining. The results show that the fully adapted group performed better, as it made fewer errors and fewer trials to complete the stages of AST compared to the partially adapted group. This improved image of the fully adapted group was observed in key stages of the task, one of which require the shifting within dimension (Compound discrimination reversal -CDR). Also, in the case of female mice, it was found significant differences in the latency in the same task, as it was found that the fully and partially adapted groups presented with fewer latency in the cases of right and total trials, in choosing one of the two bowls and the time finding the food reward, compared to the naive group. Regarding age differences, it was found in Simple Discrimination and Intradimensional Shift I stage, that the animals aged 6-9 months in the naive group presented with decreased number of errors compared to the younger ones (2-5 months). Also, the older animals in the partially adapted group needed a more trials to complete the Extradimentional Shift stage compared to the younger ones, effect that was not observed in the other two groups. These differences observed in the three groups in cognitive flexibility were not observed in the tasks of memory recognition and contextual fear learning. Finally, with the use of Golgi Cox staining, it was found that younger male mice showed a higher density of total and mature spines compared to the 6-8 months of age mice, in the areas of the prefrontal cortex and hippocampus. Also, the fully adapted group showed an increased density of mature spines of the prefrontal cortex (for both sexes) and hippocampus (CA1 region) (only for male mice) in comparison with naive group. However, no differences were observed in the thickness of the prefrontal cortex and hippocampus in the three groups, with Nissl staining. In summary, the findings of this thesis support the importance of translation for investigating the effects of working memory training on other cognitive functions. This multifaceted approach contributes to better understanding of the effects of cognitive training and to the attempt to explore the neural circuit that working memory training acts. The findings have potential implications in the development of customised early intervention programmes in populations at-risk, with mild forms of problem.
Language Greek
Subject Cognitive flexibility
Transfer plasticity
Issue date 2021-07-30
Collection   School/Department--School of Medicine--Department of Medicine--Doctoral theses
  Type of Work--Doctoral theses
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