http://hdl.handle.net/1974/803 2013-05-26T02:20:55Z http://hdl.handle.net/1974/8032 Title: A study of predicitive capacity and working memory in mild Alzheimer's disease and normal controls using saccadic eye movements Authors: Ruthirakuhan, MYURI Abstract: Alzheimer’s disease (AD) is a neurodegenerative disorder with no existing cure. Since cognitive control influences saccade behaviour, saccades provide a valuable tool when studying cognitive changes in healthy and pathological aging. This thesis aims to evaluate differences in predictive capacity and working memory between cognitively normal older adults (NC) and mild AD patients using customized saccade paradigms and a battery of neuropsychological tests. In the predictive paradigm, we hypothesize that AD participants would display a decreased level of prediction, predictive capacity and learning capacity. In the memory-guided paradigm, we hypothesize that AD participants would have a decreased ability to maintain fixation and capacity to retain information and reproduce it correctly. Overall, we found that in the predictive paradigm, NC displayed a greater degree of prediction than AD participants. However, both groups had an optimal level of prediction at intermediate inter-stimulus intervals (ISI) (750 and 1000 ms). As ISI increased, both groups, although more so in AD, elicited a greater proportion of SRTs below -200 ms and -400 ms. This may suggest that as ISI increased, participants switched from a predictive to an anticipatory/guessing strategy. At an ISI of 500 ms, NC’s learning capacity was greater than AD participants. Cognitive scores of neuropsychological tests did not correlate with learning capacity in NC. However, learning capacity in AD participants was positively correlated with working memory capacity and attentional control. The memory-guided paradigm revealed AD participants completed less viable trials, less correct trials, and had more combined directional and timing errors than NC. Cognitive correlations showed that NC’s working memory capacity positively correlated with the frequency of correct trials, whilst negatively correlating with saccade errors. Since AD participants completed 10% of viable trials correctly, the task may have been too difficult for AD participants to comprehend, rendering correlations invalid. These findings suggest that although the predictive paradigm does not solely assess for prediction, it may provide a measure to cognitively differentiate NC from AD patients, and detect AD severity. Since the memory-guided paradigm may be too difficult for AD participants, it may provide a better indicator of cognitive changes associated with healthy aging. Description: Thesis (Master, Neuroscience Studies) -- Queen's University, 2013-05-21 18:54:19.492 2013-05-22T04:00:00Z http://hdl.handle.net/1974/7802 Title: RAPID ADAPTATION OF REACTIVE FORCE CONTROL WHEN LIFTING OBJECTS Authors: Markovik, SIMONA Abstract: The control of object manipulation tasks involves the close interplay of predictive and reactive control mechanisms. For example, when lifting an object, people typically predict the weight based on object size and material as well as sensorimotor memory obtained from previous lifts of the object. When lifting objects with a precision grip, people increase vertical load force to a target level that slightly exceeds the predicted weight. When the object is heavier than expected, the mismatch between expected and actual tactile signals associated with lift-off triggers a corrective action within ~100 ms, that involves probing increases in load force that continue until the object is lifted. Here we investigated whether this correction action can be adaptively influenced by experience. Participants repeatedly lifted an object that was instrumented with force sensors to measure the forces applied by the fingertips, with weight that could be varied without the knowledge of the participant. In 80% of trials, the weight was set to 2 N and, in different blocks of 110 trials, the remaining 20 % of trials (2 trials randomly selected from each successive 10 trials) was set to either 4 or 6 N. We found that the rate of change of the reflexively triggered increase in load force that occurred in the 4 or 6 N trials, scaled with the additional weight. That is, following the initial increase in load force to ~2 N, the subsequent increase in load force was more rapid for the 6 N object than the 4 N object. In contrast, the onset time of the reactive increase in load force was independent of the additional weight. Finally, this adaptation of reactive load force control took place quickly and was evident after only a few lifts of the heavier weight. These results indicate that the reactive increases in load force that occur when a lifted object is heavier than expected can be adapted and tuned, to refine behavior. This further suggests that multiple predictions can be generated about object weight when lifting. Description: Thesis (Master, Neuroscience Studies) -- Queen's University, 2013-02-02 13:34:20.533 2013-02-04T05:00:00Z http://hdl.handle.net/1974/7626 Title: RODENT MODELS OF SCHIZOPHRENIA-LIKE SYMPTOMS INCREASE POLYDIPSIA Authors: Hawken, EMILY Abstract: Primary polydipsia, excessive drinking without known medical cause, continues to occur with a significant prevalence in psychiatric populations. While the etiology of polydipsia remains unknown, the fact that it is significantly associated with a diagnosis of schizophrenia has led some to postulate that the two may share common neurological pathophysiologies. Animal models of schizophrenia-like symptoms have focused on modeling the core behavioral and neurochemical features of the illness, like cognitive deficits and enhanced dopamine transmission. Here, we used three well-established models, including repeated amphetamine treatment, subchronic MK-801 (an N-methyl-D-aspartate [NMDA]-receptor antagonist), and post-weaning social isolation. We also examined a “double-hit” model, combining NMDA-receptor antagonism and social isolation. We paired these models to test the hypothesis that drinking will be enhanced in a paradigm of excessive drinking in the rat. In rodents, non-physiologic drinking can be induced by intermittent presentation of food (e.g., one sugar-pellet a minute) in the presence of a drinking spout to a hungry animal, termed schedule-induced polydipsia (SIP). Animals pretreated with pharmacological or non-pharmacological models of schizophrenia-like symptoms showed significantly increased SIP, The “double hit” model did not further increase drinking above that of either social isolation or MK-801 treatment alone. A moderate amount of spontaneous polydipsia in the homecage of MK-801-treated rats was also observed and resulted in one death secondary to excessive drinking, a phenomenon also found in inpatients with schizophrenia. Following repeated treatment with AMPH, there was some evidence that over time, animals learned to drink increased amounts independently of the scheduled food presentation. This evidence suggests that the excessive drinking behavior observed in polydipsia associated with schizophrenia may have a learned component. In summary, animal models of schizophrenia-like symptoms augmented SIP behavior, showing that polydipsia associated with schizophrenia may be modeled in rodents. As each model has been shown to modify dopamine transmission to some degree, the evidence suggests augmented SIP may reflect changes in dopamine transmission and dopamine may be the common link between polydipsia and schizophrenia. Further research is necessary to fully elucidate the mechanisms underlying SIP, polydipsia and schizophrenia. Description: Thesis (Ph.D, Neuroscience Studies) -- Queen's University, 2012-10-31 17:43:18.34 2012-10-31T04:00:00Z http://hdl.handle.net/1974/7621 Title: Modulation of short- and long-term plasticity in the rat auditory cortex Authors: Rosen, Laura Gillian Abstract: Plasticity of synapses is not static across the lifespan. As the brain matures and ages, the ability of neurons to undergo structural and functional change becomes more limited. Further, there are a number of modulatory factors that influence the expression of synaptic plasticity. Here, three approaches were taken to examine and manipulate plasticity in the auditory thalamocortical system of rats. Using an in vivo preparation, long-term potentiation (LTP) and paired pulse (PP) responses were used as measures of long- and short-term plasticity, respectively. First, the effect of intracortical zinc application in the primary auditory cortex (A1) on LTP was examined. Following theta burst stimulation (TBS) of the medial geniculate nucleus (MGN), juvenile and middle-age rats, but not young adults, showed greater levels of LTP with zinc application relative to age-matched control animals. Next, PP responses were examined between rats reared in unaltered acoustic conditions and those reared in continuous white noise (WN) from postnatal day (PD) 5 to PD 50-60 (i.e., subjected to patterned sound deprivation). Rats reared in WN demonstrated less PP depression relative to controls, indicating that WN rearing alters short-term thalamocortical synaptic responses. Furthermore, control males showed no change in PP response following LTP induction, indicating a postsynaptic locus of LTP, whereas increased PP depression following LTP induction was seen in WN animals, suggestive of a presynaptic involvement in LTP. Finally, differences in plasticity between male and female rats were investigated, and the result of early WN exposure on both sexes was examined. Males and females did not show consistent differences in LTP expression; however WN exposure appeared to affect LTP of females less than their male counterparts. PP responses were then compared between WN-reared males and females, and no difference was found. This indicates that short-term plastic properties of auditory thalamocortical synapses between the sexes do not differ, even though plasticity on a longer time scale following sensory deprivation does indicate some difference. Together, the experiments summarized here identify some of the important factors that contribute to the regulation of short- and long-term synaptic plasticity in the central auditory system of the mammalian brain. Description: Thesis (Master, Neuroscience Studies) -- Queen's University, 2012-10-30 16:01:28.796 2012-10-30T04:00:00Z