Thesis advisor: Scott D. Slotnick / Episodic memory is a constructive process in which a system of sensory and control processes works to transport one’s conscious mind through time–in essence, recreating a previous perceptual experience. For instance, sensory-specific activity that was associated with an original encoding experience is reinstated during retrieval–almost as if the sensory regions are processing the stimulus again, albeit this activation is smaller in spatial extent. This process of sensory-specific reinstatement occurs across all sensory modalities (e.g., Gottfried et al., 2004; Nyberg et al., 2001; Vaidya et al., 2002; Wheeler et al., 2000). That is, retrieval of a visually encoded stimulus (e.g., a picture of a dog) reinstates activity in the visual cortex, while retrieval of an aurally encoded stimulus (e.g., a barking dog) reinstates activity in the auditory cortex. In Chapter 1 and Chapter 2, I demonstrate the specificity of such sensory reinstatement during true memory for visual features and investigate the role of such sensory regions during the construction of false memory for visual features. In addition to sensory processes, our conscious experience of memory also relies on control regions. At the center of this memory control network sits a key memory structure, the hippocampus, as well as other important control regions such as the dorsolateral prefrontal cortex and the parietal cortex. Furthermore, the parahippocampal cortex appears to play a critical role in memory; however, the exact role of this region has been debated (Aminoff, Kverga, & Bar, 2013). In Chapter 3, I investigate the functional role of the parahippocampal cortex during true memory and false memory, and provide evidence that the parahippocampal cortex mediates general contextual processing.

It is now widely accepted that the experience of pain is subject to cognitive influences that may determine the severity of subjectively perceived pain. Many of these top-down factors rely on memory-based processes, which in turn are related to prior experience, learned beliefs and behaviours about pain. As such, memory for pain heavily contributes to the physical pain experience. We posit that pain memory is bidirectional in that following each painful event a trace is stored and that these traces in turn may modify future pain perception prospectively. The following body of work explores aspects of what we have termed a memory template for pain. The results of these chapters taken together, examine these bidirectional aspects of short-term memory for pain employing a recall pain task. Specifically, we explore how, after an acute pain event, a short-term mental representation of the initial event persists. We show that during this time, sensory re-experiencing of the painful event is possible. Furthermore, we investigate aspects of recalled pain, namely intensity and vividness. Data suggests that the intensity and the vividness of this mental representation are determined by the intensity of the initial stimulus, as well as the time-to-test delay. We identify regions that characterise short-term memory for pain. Following on from studies in motor and visual imagery, we explore how pain imagery in the form of recall may affect subsequent pain perception. Our results demonstrate that the inclusion of pain-related imagery preceding physical pain events reduces affective qualities of pain. Testing healthy, naïve subjects, we replicate the effect observed in studies using attention management and imagery strategies, which normally require extensive training. Finally, in a cohort of neuropathic pain patients we show significant reductions in white matter connectivity between areas responsible for working and prospective memory. Collectively, these studies emphasise and elucidate the role of short-term memory of pain in physical pain perception. Acting both retrospectively and prospectively, cognitive reinforcement can increase or decrease the subjective feeling of pain, and therefore manipulating how pain is recalled may have therapeutic potential.

Following a stroke, normal usage of the impaired limb guides spontaneous recovery across many months or even years; however, recovery is rarely complete. Pre-clinical tools are needed to investigate stroke-induced cortical reorganization over long periods. This thesis aims to characterize stroke impairment and spontaneous recovery in parallel with a battery of behaviour tasks in a mouse model of focal stroke. Young adult Thy1-ChR2 mice were implanted with a transcranial window over the intact skull permitting cortex visualization and enabling longitudinal assessments with light-based motor mapping and intrinsic signal optical imaging. Furthermore, mice were tested on sensorimotor behavioural tasks in parallel to the mapping experiments. These experiments allowed for the quantification of impairments in the sensorimotor cortex and forelimb function while identifying regions within the sensorimotor cortex that show re-mapping associated with behavioural recovery. Following primary motor cortex-stroke induction, both sensory and motor map impairments occurred. Sensory map transient impairments recovered within the same atlas-defined regions two weeks after a primary motor cortex stroke as identified by intrinsic signal optical imaging. In contrast, motor forelimb recovery was observed four weeks after the stroke in the peri-infarct region, the supplemental motor cortex, and the contralesional motor cortex. This recovery was identified through a combination of analyses, including changes in the mapped area and the amplitude of evoked forelimb movements using light-based motor mapping. Behavioural recovery occurred four to six weeks post-stroke, depending on the sensitivity of the task in forelimb impairment. Additionally, the contralesional hemisphere and forelimb did not show impairment acutely but evoked forelimb amplitude was significantly increased by post-stroke week four for both forelimbs. As the first study to conduct within-animal longitudinal spontaneous recovery sensory and motor map experiments using bilateral forelimb and hemispheric representations, we show that 1) photothrombotic stroke impacts both forelimb representations pertained within the ipsilesional hemisphere in LBMM experiments, 2) recovery of the impaired forelimb occurs ipsilesionally and contralesionally and, 3) impairments from stroke observed through motor mapping are functionally relevant and precede behavioural recovery ranging from zero to two or more weeks depending on the motor cortex's involvement in the behavioural task.