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Working memory is the cognitive capacity for temporarily holding information in mind for processing or use, and supports most of our actions and behaviors. Although activity in the rodent prefrontal cortex (PFC) is necessary for successful rodent spatial working memory utilization, rodent spatial working memory tasks do not always evoke robust PFC delay encoding of retrospective spatial information. We hypothesized that, like in nonhuman primates (NHPs), increasing spatial optionality might facilitate the detection of retrospective spatial encoding in the PFC. We therefore used an automated 8-arm radial maze to implement a novel match-to-sample rodent spatial working memory task with seven options on each trial, and recorded calcium activity in PFC neurons during task performance. We found that, during the delay phase of the task, PFC neurons indeed encoded retrospective spatial representations of the arm visited in the preceding sample phase, at both single-cell and population levels, in a distributed manner. Also, in accordance with recent NHP work, these representations were evident in considering dynamic, heterogenous neural activity, and in considering a low-dimensional subspace, where time-invariant retrospective spatial information could be decoded. Thus, this work reveals that in rodents, freely-moving, spatially-demanding behavioral paradigms can evoke distributed spatial working memory representations in the prefrontal cortex, with reasonable similarity to the working memory representations observed in nonhuman primates.

Fluctuations in attention are ubiquitous. We all experience the waxing and waning of our attention, with periods of focus alternating with periods of distraction by irrelevant thoughts or external sensations. Given the pervasiveness of these fluctuations, it is important to understand how they influence both our behavior in the moment and the structure of our memory. In this dissertation, I use behavioral studies and eye tracking to measure spontaneous attentional fluctuations and examine how these fluctuations shape online behavior and subsequent memory. I test my primary hypothesis that optimal attentional states help us link experiences over time to allow our memories to be temporally organized, whereas suboptimal states disrupt the temporal structure of memory. In Chapter 1, I present four studies using a novel experimental design to connect research on sustained attention and memory. I replicate prior findings linking response-time-based measures of attention to online behavior. Surprisingly, I found that these response-time measures of attention do not predict the temporal structure of free recall. In Chapter 2, I indexed attentional fluctuations with both response times and pre-trial pupil size and demonstrated that these measures of attention predict complementary aspects of behavior. Attentional fluctuations, as indexed by pupil size, predicted the temporal organization of memory but not attentional lapses in online behavior. Conversely, response times predicted attentional lapses in the moment but did not predict the temporal organization of memory. Finally, in ongoing work in Chapter 3, I examine whether providing cues at retrieval enhances or diminishes the effects of attentional fluctuations on the temporal organization of memory. Together, my results shed light on the complex interactions between fluctuations in attention and episodic memory. Critically, I show that different measures of attention – behavioral vs. physiological approaches – capture distinct aspects of cognitive function, and suggest that the attentional states that shape online behavior and later memory are at least partly distinct.

Memories are not static records of our experiences. They are dynamic and undergo continuous change. Yet how memories transform awaits further characterization. This dissertation examines different forms of memory transformation through the lens of reactivation. Across three studies, I leverage the close link between memory transformation and reactivation to explore the transformation of repeated and once-encoded memories. In chapter one, I focus on the process of ongoing memory consolidation, examining the offline reactivation dynamics of thrice- and once-encoded memories. I show that repeated learning leads to enhanced cortical reactivation and hippocampal-cortical coordinated reactivation during post-encoding rest periods, potentially accelerating systems-level consolidation. Chapter two examines how successful retrieval of repeated memories is supported by reactivation in functionally distinct brain regions. This study demonstrates that the ventral temporal cortex preferentially reactivates the first occurrence of repeated events during active retrieval, but reactivation of the last occurrence in the left ventrolateral prefrontal cortex predicts memory accessibility. Lastly, chapter three addresses the mechanistic role of memory reactivation in modulating the updating of repeated (strong) and once-encoded (weak) memories. I show that strongly encoded memories are more resistant to updating with new, conflicting information than weak memories. However, updating of a strong memory can be predicted by the degree of its reactivation at the time of new encoding. Further, weak memories, which are more flexible in incorporating new information compared to strong memories, exhibit overall heightened reactivation upon memory violation. Together, these findings highlight that reactivation both reflects and modulates memory transformation, and that memory transformation and reactivation are adaptive to the repetitive yet ever-changing nature of our everyday experiences.

There are numerous clinical and experimental accounts of retrograde and anterograde amnesia resulting from damage to the hippocampus (HPC). Several theories on the HPC hold that only certain types of recent memories should be affected by HPC damage. These theories do not accurately predict the circumstances within which memories are vulnerable to HPC damage. Here I show the HPC plays a role in the formation and storage of a wider range of memories than is posited in contemporary theories. I will demonstrate that an important factor in elciting retrograde amnesia is the number of similar learning episodes. Exposure to multiple problems in the same task context leads to retorgrade amnesia that is not observed when only one problem is learned under otherwise identical parameters. When multiple discriminations are learned, the output of the HPC blocks recall from and future use of the extra-HPC memory system. / x, 78 leaves : ill. ; 29 cm.

Distinct brain regions process innocuous vibration and cutaneous heat pain. The role of these areas in the perception of pain is still a matter of debate; and the role of these areas in the mediation of memory of somatosensory stimuli is uncertain and has not been studied with brain imaging in healthy human volunteers. All experiments described here, involved an experimental design, which included a delayed-discrimination paradigm and functional magnetic resonance imaging (fMRI). In manuscript #1, we aimed at unraveling the cerebral correlates of attention and spatial localization of innocuous vibrotactile stimuli applied to the right volar surface of the forearm. In this study, we report that increased degrees of attention to the vibrotactile stimuli were associated with heightened levels of activation in several brain areas. In manuscript #2, we investigated the short-term memory for sensory aspects (intensity and location) of cutaneous heat pain delivered to two areas (thenar and hypothenar eminences) of the palm of the right hand. In this experiment, the memory and control trials were presented in blocks, whereby the subjects could predict what trials were going to follow. This study revealed that the presentation of painful stimuli evoked activation in different brain regions than those activated during the online maintenance (interstimulus interval or ISI) of the intensity and spatial features of those stimuli; a process, which I will refer to short-term memory. In manuscript #3, we investigated again short-term memory for sensory aspects of heat pain (as in manuscript #2), but in this case, the memory and control trials were presented in a randomized order. In this study, we found that the perception and short-term memory of pain were processed by a comparable network of areas. The predictability of the memory and control trials may have contributed to these findings. / La vibration inoffensive ainsi que la chaleur douloureuse cutanée sont traitées pardifférentes régions du cerveau. Le rôle de ces régions dans la perception de la douleurest controversé; et le rôle de ces régions dans la mémoire des stimuli somatosensorielsest incertain et n'a jamais encore été étudié en imagerie cérébrale chez des sujetshumains sains. Le design expérimental de toutes les études décrites ici comprenait unparadigme de 'delayed-discrimination' et l'imagerie par résonance magnétiquefonctionnelle (IRMf). L'étude #1 visait à élucider les corrélats cérébraux de l'attention etde la localisation spatiale des stimuli vibrotactiles inoffensifs présentés à la faceantérieure de l'avant-bras droit. Dans cette étude, nous avons trouvé que des degrésélevés d'attention portée aux stimuli vibrotactiles étaient associés à des niveaux accrusd'activation dans plusieurs zones du cerveau. Dans l'étude #2, nous avons enquêté surla mémoire à court-terme des caractéristiques sensorielles (intensité et emplacement)de la chaleur douloureuse cutanée présentée à deux endroits (éminences thénar ethypothénar) de la paume de la main droite. Dans cette étude, les essais mémoire etcontrôle étaient présentés en bloc, ou de sorte que les participants pouvaient prévoir dequel type serait le prochain essai. Cette étude a révélé que la présentation des stimulidouloureux a évoqué une activation de différentes régions cérébrales que celles quiétaient activées lors de la rétention de l'intensité et de l'emplacement des stimulationsdurant l'intervalle inter-stimuli (liS); un processus que je qualifierai de mémoire à courtterme.Dans l'étude #3, nous avons également enquêté sur la 'mémoire à court-termedes aspects sensoriels de la chaleur douloureuse (tout comme dans l'étude #2), maisdans ce cas, les essais mémoire et contrôle étaient présentés de façon aléatoire. Danscette étude, nous avons trouvé que la perception de la douleur ainsi que la mémoire àcourt-terme de la douleur étaient traitées par un réseau de régions semblable. Laprévisibilité des essais mémoire et contrôle peut avoir contribué à ce résultat.

M.Tech. (Chiropractic) / Brain hibernation or cerebral dysfunction theory is the diminishing of brain function due to poor blood flow as a result of compression of the vertebral, basilar, internal carotid and subclavian arteries (Buchanan, 2004). Compression is usually due to skeletal malalignment, ligamentous or muscular in origin and correction of this by cervical spine manipulation suggests that the above difficulties may be improved with manipulative and manual techniques (Buchanan, 2005). Thomas and Wood (1992), suggest that there is a correlation between upper cervical adjustments and improved mental function. This has been shown by Shambaugh, Pearlman and Hauck (1991), who showed that after an adjustment, there was an improved brain stem evoked response which indicated that neural messages were travelling through the brain stem quicker or with less delay. Terrett (1993), has proposed that cervical manipulative therapy results in augmented cerebral blood flow, which culminates in hibernating areas of the brain becoming functional again. The higher cognitive skills tend to be affected by the decrease in blood flow. Cognitive skills are vital to the process of learning, spelling and reading. Edublox is a company that has special training programmes to develop these skills to maximise a childs potential. The aim of this study is to determine the effects of cervical manipulations combined with Edublox training versus Edublox training alone on visual spatial memory. The focus of the study would be to determine whether chiropractic cervical manipulation has a significant effect on mental function and visual memory when combined with Edublox training. The study will include a total of 34 participants split into two groups, one receiving Edublox training and the other receiving Edublox training combined with cervical spine manipulations. Participants approximately between the ages of ten and thirteen years of age will be included in this study. The manipulation group will receive spinal manipulative therapy followed by both groups receiving the same Edublox training session to limit variation. The participants shall receive an intense program of Edublox training, every day for the duration of five days and the combined group will receive adjustment every other day. The research will be conducted at the premises of Confidence College. Subjective and objective measurements will be taken at the beginning and at the end of the five days. The subjective measurement will include an Observer Memory Questionnaire – Parent Form that will be completed by the parent of the child based on their view of their child’s memory. The objective measurement will include two sub-tests from the Visual Perceptual Skills Test 3, namely the visual memory (VM) and visual sequential memory (VSM) components.

My experiment concerned the influence of chronobiological (circadian) rhythm on fatigue, effort, and cardiovascular (CV) response. It evaluated responses of morning people (Larks) presented an easy or difficult recognition memory task at a time congruent or incongruent with their rhythm. Based on an extension of a conceptual analysis of fatigue influence, my central prediction was that circadian rhythm would combine interactionally with task difficulty to determine effort and associated CV responses. Specifically, effort and associated CV responses were expected to be (1) positively correspondent to task difficulty in the morning (stronger where difficulty is high), but (2) negatively correspondent to difficulty in the evening (stronger where difficulty is low). Preliminary results showed concerning gender effects on difficulty appraisal of the task, thus we examined women and men's data separately. CV findings for women were broadly, but not completely, consistent with predictions. Analyses revealed no group differences in CV response for Lark men.

No description available.

Cognitive processes in the human brain are mediated by complex interactions among distributed brain regions. The interaction between the hippocampus and neocortical regions is crucial for physiologic and pathologic long-term episodic memory processing in the brain. However, the network mechanisms of this hippocampal-cortical communication remain unclear. To address this issue, we first designed organic materials and conformable electronics to create integrated neural interface devices that increase the spatiotemporal resolution of electrophysiologic monitoring. These devices enabled acquisition of local field potentials and action potentials of individual cortical neurons from the surface of the human brain, enhancing the ability to investigate neural network mechanisms without breaching the tissue interface. Next, we employed these devices in tandem with hippocampal probes to analyze hippocampal-cortical interactions in the context of memory tasks in freely moving rodents. We determined that in the physiologic state, the spatial properties of cortical spindle oscillations predict the likelihood of coupling with hippocampal ripples and are modulated by memory demand. In the pathologic state, we showed that interictal epileptiform discharges (IEDs), ubiquitous markers of epileptic networks, disrupt hippocampal-cortical coupling required for memory consolidation. These IEDs induce spindle oscillations in the synaptically connected cortex, producing prolonged, hypersynchronous neuronal spiking and expanding the brain territory capable of generating IEDs. Spatiotemporally targeted closed-loop electrical stimulation triggered on hippocampal IED occurrence eliminated the abnormal cortical activity patterns, preventing spread of the epileptic network and ameliorating long-term spatial memory deficits in rodents. Our findings provide new insights into mechanisms of physiologic and pathologic memory processing and offer novel approaches to therapies aimed at addressing distributed network dysfunction in neuropsychiatric disorders.