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The brain has the capacity to modify itself structurally and functionally, to adapt to novel circumstances. Adaptive changes in neural circuitry that become intransigent, such as continued hypervigilance after resolution of a threat situation, become maladaptive and may facilitate development of psychiatric disorders such as Major Depressive Disorder (MDD). Although MDD pathogenesis is unclear, hypothalamic-pituitary-adrenal axis dysregulation may facilitate the neuroplastic changes observed in MDD. Whether these neuroplastic changes facilitate the development of MDD or develop due to MDD remains unclear. The characterization of neuroplastic changes in MDD has resulted in sometimes contradictory findings. There are gaps in understanding the timing of neuroplastic changes in MDD, and how and when they are affected by antidepressant treatment. Characterization of neuroplasticity in MDD may uncover different phenotypes and aid in the discovery of a predictive biomarker of antidepressant treatment response. This dissertation presents the results of a series of neuroimaging studies. Chapter 1 provides an introduction to neuroplasticity and MDD. In Chapter 2 results of a study examining hippocampal memory function in treatment naïve patients with MDD are presented. Chapter 3 exhibits findings from a study examining effects of an acute tryptophan depletion paradigm in midlife women receiving estrogen-based treatment on an emotional conflict task. Chapter 4 discusses results from an examination of unmedicated patients with MDD and healthy control participants on an emotional conflict task. Chapter 5 presents longitudinal data of the sample from Chapter 4, and the effect of 8 weeks of treatment with antidepressant escitalopram on performance on an emotional conflict task. In Chapter 6 a case study is presented of a patient with long-standing overt ventriculomegaly, whose chief complaint was of mood and cognitive impairments. Chapter 7 summarizes the findings and contributions of this body of research and discusses clinical implications and future directions. / Dissertation / Doctor of Philosophy (PhD) / The characterization of brain changes in Major Depressive Disorder (MDD) has resulted in contradictory findings, and gaps in understanding how the brain changes in response to antidepressant treatment. This dissertation aims to characterize brain changes in MDD through a series of neuroimaging studies. Chapter 1 provides an introduction to MDD and brain changes in MDD. Chapter 2 presents an examination of memory in treatment naïve patients with MDD. Chapter 3 presents a study of acute tryptophan depletion in midlife women receiving estrogen-based treatment on an emotional conflict task. Chapter 4 examines unmedicated patients with MDD and healthy control participants on an emotional conflict task. Chapter 5 examines the effects of antidepressant treatment on performance on an emotional conflict task. Chapter 6 presents a case study of a patient with ventriculomegaly with mood and cognitive impairments. Chapter 7 summarizes the contributions of this research and discusses implications and future directions.

INTRODUCTION: Altered walking patterns in individuals with knee osteoarthritis (OA) are a key driver of disease; however, mechanisms underlying this relationship are not clear. Central sensitization is now recognized as an important contributor to pain experience in people with knee OA. In the presence of chronic pain and central sensitization, there are alterations in activity and connectivity across multiple brain regions (e.g., prefrontal cortex, primary motor cortex) that could influence dynamic control of gait. However, the association of central sensitization with gait patterns in knee OA has not been studied. Our objective was to investigate whether central sensitization in individuals with knee OA is associated with dynamic control of gait as assessed using wearable sensor-derived measures of gait complexity and dynamic stability. We hypothesized that a greater degree of sensitization would be associated with lower gait complexity and stability. METHODS: We used data from the 12th-year visit of the Multicenter Osteoarthritis Study, a longitudinal cohort study of individuals with and without knee OA. This was the first visit at which the relevant gait parameters were collected using wearable sensors. Individuals from this visit with valid data available for all measures contained in this analysis were included. Mechanical temporal summation (TS), an augmented response to repetitive mechanical stimulation, is a reliable and valid measure of central sensitization. To assess TS, participants’ pain ratings were assessed after a single wrist stimulus was applied with successively weighted probes until a pain rating of at least 4/10 was achieved (the highest weighted probe was used if that pain rating was not obtained), then was assessed again after 10 repeated stimuli at a rate of 1 Hz was applied with the same probe. A post-stimulation pain rating larger than the initial pain rating reflected facilitated TS. For gait analyses, participants completed 2 trials of a 20m walking test at their usual walking pace while wearing inertial sensors on their lower back and both feet. The lower back sensor was used to calculate sample entropy and Lyapunov exponent, both of which may provide a window into how dynamic control of gait is altered in disease. Sample entropy measures the inter-stride predictability or regularity of gait kinematics. Lower sample entropy represents a more regular or predictable (i.e., less complex) gait pattern and may reflect a reduced ability of the neuromotor system to adapt to ongoing changes experienced in daily walking. LE measures the inter-stride stability of gait kinematics. Large LE values represent more gait instability and may reflect a reduced ability of the motor system to recover from small perturbations. We averaged the gait outcomes across the two trials. Exposure variables were standardized. We determined the association between TS and gait parameters using linear regression while adjusting for age, sex, race, body mass index (BMI), depressive symptoms, education, and presence of radiographic knee OA. Analyses were not adjusted for pain or gait speed because we hypothesized that these impairments were on the causal pathway between our exposure and outcomes. RESULTS: Data from 2,179 participants (age = 62.4 ± 10.0 years, BMI = 29.1 ± 5.5 kg/m2, 56.3% female) were included in the analysis. One standard deviation (SD) increase in TS was associated with a -0.024 [95% Confidence intervals -0.038, -0.010] change in sample entropy (i.e., more regular gait) but not with a change in LE (-0.002 [95% Confidence intervals -0.008, 0.004]). CONCLUSION: Individuals with knee OA and central sensitization display a less complex or more predictable gait pattern, evidenced by lower sample entropy, likely reflecting a deterioration in dynamic control of gait. However, central sensitization was not associated with an individual’s ability to respond to natural fluctuations that occur in walking, as evidenced by a lack of association with LE. We propose a plausible mechanism in which central sensitization may cause a reduction in gait complexity via continuous nociceptor release of glutamate, NMDAR activation, and changes in motoneuron excitability and inhibition at multiple sites along the motor pathway. Although causality cannot be determined from this cross-sectional study, these findings provide support for an association between central sensitization and specific aspects of the walking pattern in people with knee OA. Interventions to mitigate central sensitization may be useful to improve gait quality in people with knee OA.

In order to assess flexibility in acquiring and using conflicting response rules, rats with selective lesions of the NBM or sham-lesion controls were subjected to serial reversal training in a simple operant discrimination paradigm. The NBM lesion group did not differ from the control group in acquisition of the original rules; the NBM lesion group required more time to master the changes in rules in the first reversal, but not in subsequent reversals.

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This Master thesis is focused on ecological validity of a cognitive training in university students. Forty-five students participated in three months research during which 30 of them took regular personalized cognitive training using CogniFit programme on their computers. The study examines the impact of the cogntitive training on everyday cognitive functioning of students. The scientific methods used for the ecological validity research were the following self-reporting questionnaires: Cognititive Failure Questionnaire, Everyday Memory Questionnaire and Dysexecutive Questinnaire. Students also filled in Schwartz Outcome Scale - 10 and Self-image questionnaire for detailed exploration of more variables. For the research, we applied test-retest design and used control group of fifteen students for results comparison. Analysis of the gathered data proved little evidence of ecological validity of cognitive training, which can be attributed to considerable cognitive stress at students. An unexpected outcome of the study which proved to be very significant is relation between executive functions and well-being of a student. This relation was confirmed repeatedly. Possible improvements of methodology and also problem with randomization of students is discussed. Proposal for the further development of...

The purpose of this Master thesis was to evaluate the effects of the Mirror program on upper- limb motor recovery, self-sufficiency and active range of wrist movement in patients after brain injury. It was included sixteen participants within maximal four months after stroke. Patients were separated into experimental and control group, both with eight members. Experimental group underwent Mirror therapy. Both group participated in a standard rehabilitation program included Physiotherapy, Occupational therapy, physical therapy and movement practice on device. Experimental group patients additionally participated in Mirror therapy program for 30 mins, four times a week, for three weeks. The Fugl-Meyer Assessment, Functional Independence Measure and goniometric measurement of active movement were used to assess recovery of upper-limb movement. Mirror therapy improve upper-limb motor recovery in patients after brain injury. This research demonstrates it with significant difference between both groups, where the experimental group have improved (0,02). I have also proved Mirror therapy, when included in occupational therapy, improves the self-sufficiency of people with neurological deficit. Comparing the data from Functional Independence Measurement, I found the difference between groups statistically...