Understanding how the brain represents and processes information is crucial for advancing neuroscience and artificial intelligence. Representational similarity analysis (RSA) has been instrumental in characterizing neural representations by comparing multivariate response patterns elicited by sensory stimuli. However, traditional RSA relies solely on geometric properties, overlooking crucial topological information. This thesis introduces topological RSA (tRSA), a novel framework that combines geometric and topological properties of neural representations. tRSA applies nonlinear monotonic transforms to representational dissimilarities, emphasizing local topology while retaining intermediate-scale geometry. The resulting geo-topological matrices enable model comparisons that are robust to noise and individual idiosyncrasies. This thesis introduces several key methodological advances: (1) Topological RSA (tRSA) identifies computational signatures as accurately as RSA while compressing unnecessary variation with capabilities to test topological hypotheses; (2) Adaptive Geo-Topological Dependence Measure (AGTDM) provides a robust statistical test for detecting complex multivariate relationships; (3) Procrustes-aligned Multidimensional Scaling (pMDS) aligns time-resolved representational geometries to illuminate processing stages in neural computation; (4) Temporal Topological Data Analysis (tTDA) applies spatio-temporal filtration techniques to reveal developmental trajectories in biological systems; and (5) Single-cell Topological Simplicial Analysis (scTSA) characterizes higher-order cell population complexity across different stages of development. Through analyses of neural recordings, biological data, and simulations of neural network models, this thesis demonstrates the power and versatility of these new methods. By advancing RSA with topological techniques, this work provides a powerful new lens for understanding brains, computational models, and complex biological systems. These methods not only offer robust approaches for adjudicating among competing models but also reveal novel theoretical insights into the nature of neural computation. This thesis lays the foundation for future investigations at the intersection of topology, neuroscience, and time series data analysis, promising to deepen our understanding of how information is represented and processed in biological and artificial neural networks. The methods developed here have potential applications in fields ranging from cognitive neuroscience to clinical diagnosis and AI development, paving the way for more nuanced understanding of brain function and dysfunction.

Purpose/Statement of Problem: Disorders of Consciousness (DoC) are a group of disorders encompassing Coma, Unresponsive Wakefulness Syndrome (UWS), and Minimally Conscious State. These disorders are characterized by altered or absent alertness and consciousness and inability to follow commands or participate in daily activities or function. DoC can be caused by a multitude of etiologies including trauma, stroke, tumors, metabolic disarray, and many others. Individuals with severe DoC are profoundly functionally and cognitively impaired, and frequently require extensive rehabilitation in order to return to their prior level of function. Additionally, a category has recently been discovered within the umbrella of DoC called Cognitive Motor Dissociation (CMD), in which individuals may show no outward signs of the ability to follow commands but can be seen to respond appropriately to commands when monitored by Electroencephalography (EEG). The current standard of rehabilitative care for individuals with severe DoC is minimal. There are no clear guidelines for rehabilitation of these individuals, particularly in the acute stage. Rehabilitation is often initiated once individuals are awake and able to follow commands, despite evidence that earlier intervention (particularly in the form of stimulation) may accelerate recovery. In this retrospective study, we had three primary aims and one case study. The first aim was to characterize the time frame in which a cohort of individuals with severe DoC received therapy and whether the timeframe in which they received therapy was appropriate. The second aim was to retrospectively determine which therapy and demographics factors could predict better short- and long-term outcomes. The third aim was to determine whether the presence of CMD had a mediating effect on therapy. Finally, the case study was intended to determine safety of a prospective study recruiting individuals extremely early after admission for a standardized stimulation intervention. Procedures and Methods: This study was a retrospective analysis of data from a cohort of individuals who were recruited to participate in multiple studies of consciousness in the neurological intensive care unit (NICU) in an academic medical center in New York City between 2014 and 2021, heretofore referred to as the parent study. All individuals had a severe DoC, were connected to EEG, had no previous history of brain injury, and were tested for presence of CMD. Charts were examined to determine whether individuals could have received therapy earlier. Regression modeling was used to determine the effect of various therapy factors (such as timing, volume, frequency, and therapy content) as well as demographics data on a variety of short term and long-term outcome measures. These outcome measures included scores on the Coma Recovery Scale-Revised, scores on the AM-PAC “6 Clicks” Basic Mobility and Daily Activity short forms, recovery of active participation in therapy, discharge destination, and Glasgow Outcomes Scale-Extended scores. Analyses were also performed on the individual effect of each therapy variable on the effect of CMD status, and on the overall effect of CMD status on outcomes. Results: Thirty-eight of the fifty eight (65.52%) individuals in this cohort who received therapy after the median day received for the cohort could have safely received therapy earlier in the form of a standardized stimulation protocol. Multiple therapy variables were implicated in both short- and long-term outcomes. More specifically, therapy frequency, therapy volume, CMD status, sitting at edge of bed, and age were all implicated in both short- and long-term outcomes. Therapy timing was not an independent predictor for any outcomes but was significantly associated with therapy frequency. Therapy frequency was an independent predictor of multiple outcomes including discharge destination, Basic Mobility scores, and GOS-E scores. Sitting at the edge of the bed was an independent predictor of Daily Activity Score, and all therapy variables except timing were independent predictors of change in Basic Mobility Score. CMD status had a modulatory effect on multiple therapy variables (variable based on outcome) and was an independent predictor of long-term outcomes. Conclusions: Individuals with severe DoC were an underserved population from a therapy perspective. With the current standard of care, individuals with severe DoC frequently overlooked in favor of those who are more able to participate in active therapy. Analyses performed in this study indicated that individuals with severe DoC could a.) safely receive therapy sooner, b.) benefit from increased therapy frequency and specific modes of therapy, c.) could make excellent functional progress and d.) might have performed better with therapy if they had CMD. These results indicate that individuals with severe DoC might benefit earlier and more consistent therapy to maximize their chances of functional recovery.

Monitoring actions is essential for goal-directed behavior. However, as opposed to short-lasting, and regularly reinstating monitoring functions, the neural processes underlying continuous actionmonitoring are poorly understood. We investigate this using a pursuit-tracking paradigm. We show that beta band activity likelymaintains the sensorimotor program, while theta and alpha bands probably support attentional sampling and information gating, respectively. Alpha and beta band activity are most relevant during the initial tracking period, when sensorimotor calibrations are most intense. Theta band shifts from parietal to frontal cortices throughout tracking, likely reflecting a shift in the functional relevance from attentional sampling to action monitoring. This study shows that resource allocation mechanisms in prefrontal areas and stimulus-response mapping processes in the parietal cortex are crucial for adapting sensorimotor processes. It fills a knowledge gap in understanding the neural processes underlying action monitoring and suggests new directions for examining sensorimotor integration in more naturalistic experiments.

Two conflicting findings characterize cognitive processing accompanying bilingualism. The “bilingual advantage” refers to improved cognitive performance for bilingual compared to monolingual participants. Most bilingual advantages fall under the umbrella of cognitive control mechanisms, most frequently demonstrated using the Stroop task and the Simon task (e.g., Bialystok, 2008; Coderre, Van Heuven, & Conklin, 2013). The “bilingual disadvantage,” on the other hand, refers to bilinguals’ diminished performance on tasks that require word retrieval or switching between languages. This study examined the intersection of the bilingual advantage and the bilingual disadvantage to investigate whether they stem from a single cognitive control process. The bilingual advantage was measured as speech onset time differences between monolingual and bilingual participants in the Stroop task after being primed in the same language (i.e., English prime and English Stroop for monolinguals, and either English prime and English Stroop or Spanish prime and Spanish Stroop for bilinguals). The bilingual disadvantage was measured as differences in bilingual participants’ speech onset times between the same-language conditions described above and cross-language conditions (i.e., either English prime and Spanish Stroop or Spanish prime and English Stroop). Monolinguals performed better than bilinguals did on the same-language Stroop [F(3,1) = 83.5, p < 0.001, MSE = 15415], so a bilingual advantage was not demonstrated. However, bilinguals did perform better in same-language blocks than cross-language blocks [F(7,3) = 24.6, p < 0.001, MSE = 22648]. This suggests that the current protocol successfully elicits the bilingual disadvantage. Further research is needed to evaluate whether the same cognitive control processes are responsible for the two effects. Possible extensions of this work include observing a larger number of participants to rule out between-subjects effects and using a button press rather than spoken response during the Stroop task.

Attention uses sensory inputs and goals to select information from our environment. Monkey electrophysiological literature demonstrates that visuo-tactile bimodal neurons (respond to visual and tactile stimuli presented on/near the hand) facilitate multisensory integration. Human behavioral studies show that hand position/function bias visual attention. Event-related potentials (ERPs) reveal the cortical dynamics coordinating visual inputs, body position, and action goals. Early, sensory ERPs (N1) indicate multisensory integration. Later, cognitive ERPs (P3) reflect task-related processing. Study 1 investigates a discrepancy between monkey and human literatures. Monkey studies demonstrate bimodal neuron responses equidistantly around the whole hand, but human studies demonstrate attentional bias for grasping space. In a visual detection paradigm, participants positioned their hand so target and non-target stimuli appeared near the palm or back of the hand; ERPs were measured. N1 components indicated no amplitude differences between Palm vs. Back conditions, but P3 components revealed greater target vs. non-target differentiation for Palm conditions. Results suggest cortical timing underlies grasping vs. whole hand bias differences: early processing does not differentiate using hand function, but cognitive processing does when stimuli are discriminated for action. Study 2 investigates whether proprioceptive inputs facilitate visual processing. In a visual detection paradigm, participants viewed stimuli presented between occluders blocking view of a hand positioned either near or far from the stimuli. N1 amplitudes were similar for near and far conditions, but P3 amplitudes for target/non-target differences were accentuated for near conditions. Proprioceptive effects emerge later in processing. ERP reveals the cortical dynamics underlying hand position effects on vision.

Humans effortlessly and accurately judge their subjective probability of being correct in a given decision, leading to the view that metacognition is integral to decision making. This thesis reports a series of experiments assessing people’s confidence and error-detection judgements. These different types of metacognitive judgements are highly similar with regard to their methodology, but have been studied largely separately. I provide data indicating that these judgements are fundamentally linked and that they rely on shared cognitive and neural mechanisms. As a first step towards such a joint account of confidence and error detection, I present simulations from a computational model that is based on the notion these judgements are based on the same underlying processes. I next focus on how metacognitive signals are utilised to enhance cognitive control by means of a modulation of information seeking. I report data from a study in which participants received performance feedback, testing the hypothesis that participants will focus more on feedback when they are uncertain whether they were correct in the current trial, whilst ignoring feedback when they are certain regarding their accuracy. A final question addressed in this thesis asks which information contributes internally to the formation of metacognitive judgements, given that it remains a challenge for most models of confidence to explain the precise mechanisms by which confidence reflects accuracy, under which circumstances this correlation is reduced, and the role other influences might have, such as the inherent reliability of a source of evidence. The results reported here suggest that multiple variables – such as response time and reliability of evidence – play a role in the generation of metacognitive judgements. Inter-individual differences with regard to the utilisation of these cues to confidence are tested. Taken together, my results suggest that metacognition is crucially involved in decision making and cognitive control.

Reward expectation and spatial attention both exert powerful control over behaviour and modulate neural activity. The experiments in this thesis aimed to chart the dynamics of reward expectation effects across the time course of information processing and examine the relationship between reward and attention. Experiments 3.1 and 3.2 parametrically manipulated reward magnitude in the presence or absence of attention and demonstrated reward could influence reaction time (RT) under conditions of time pressure. Experiments 4.1 and 4.2 independently varied reward and spatial probabilities and illustrated independent and interactive effects of reward and attention at late stages of cognitive processing (the P300 potential), as well as modulation of detection sensitivity (d') by reward under conditions of uncertainty when reward was able to work through feature-based attention. The experiment of Chapter 5 cued reward and attention trial by trial and showed under these conditions, not only could reward influence late stages of information processing, but expectation of reward reduced peak latency of the visual N1 potential. Reward and attention also modulated motor preparation with both independent and interactive effects. The experiment of Chapter 6 examined the dynamics of reward association with task-relevant targets and irrelevant distracters during visual search and demonstrated that task-irrelevant but motivationally-salient distracter items could capture attentional resources away from the target, guided by endogenous reward association alone. The experiments of this thesis demonstrated the ability of reward expectation to modulate both behaviour and multiple stages of information processing, with effects predominantly independent from those of attention. Reward could influence processing from early visual analysis and target detection stages. Interaction between the two systems occurred at late processing stages, whereby reward and attentional information may have been integrated to provide a cohesive representation of the stimulus given the current environmental conditions.

Regular aerobic exercise has a wide range of positive effects on health and cognition. Exercise has been demonstrated to provide a particularly powerful and replicable method of triggering a wide range of structural changes within both human and animal brains. However, the details and mechanisms of these changes remain poorly understood. This thesis undertakes a comprehensive examination of the relationship between brain plasticity and aerobic exercise. A large, longitudinal experiment was conducted in which healthy but sedentary participants were scanned before and after six-weeks of monitored aerobic exercise. Increases in the volume of the anterior hippocampus were observed, as previously reported in an older cohort after a longer exercise intervention. Multimodal imaging methods allowed an in-depth exploration of the mechanisms underlying this volume change, which proved to be dominated by white matter changes rather than the vascular changes that have been previously reported. A surprising global change in the balance of CSF, blood, and brain tissue within the cranial cavity was also observed. Cross-sectional differences in memory and brain structure associated with fitness were also observed. The volume of the anterior hippocampus was shown to correlate with a measure of working memory. Higher cerebral blood volume throughout the brain was found to correlate with greater fitness and better working memory. Focal associations between fitness and magnetic susceptibility, a measure of iron content, were also observed in the basal ganglia. These findings demonstrate that aerobic fitness is associated with improved cognition and brain structure throughout the lifespan rather than simply acting to mitigate age related brain atrophy or accelerate brain development. Finally, a new pipeline was developed for analysing hippocampal morphometry using high-resolution, 7 Tesla scans. Striking variability in the convolution of the hippocampal surface is reported. This technique shows promise for imaging the precise nature of the change in hippocampal volume associated with aerobic exercise. This thesis adds to the evidence that aerobic exercise is a potent catalyst for behavioural and brain plasticity while also demonstrating that the mechanisms for those plastic changes are likely different than previously supposed. Future work will refine these measurement techniques, perhaps to a point where brain changes can be monitored on a single subject level. This work will provide an important tool to understand how best to utilize aerobic exercise to facilitate adaptive behavioural changes, mitigate the negative effects of ageing and disease on the brain, and maximize the benefits of active lifestyles.

It is increasingly recognised that, in adulthood, attentional control plays an important role in optimising the ability to encode and maintain items in visual short-term memory (VSTM). Memory capacity limits increase dramatically over childhood, but the mechanisms through which children guide attention to maximise VSTM remain poorly understood. Through a number of experiments manipulating different parameters, the current thesis aimed to explore the developmental trajectories of the neurocognitive mechanisms underlying selective attention within VSTM and to examine whether variations in attentional control are accompanied by individual differences in VSTM capacity. Chapters 2 and 3 investigated the development of attentional orienting in preparation for encoding and during maintenance. Younger children emerged as less able than older children and adults to orient attention to internally held representations. Therefore, Chapter 4 tested whether younger children’s attentional orienting is differentially affected by memory load. While attentional orienting prior to encoding was more beneficial when required to remember a greater number of items, cueing benefits during maintenance were similar across load conditions. Chapter 5 investigated whether temporal parameters influence younger children’s variable ability to orient attention during maintenance. Attentional orienting operated more efficiently on transient iconic traces rather than on VSTM representations due to passive decay of the memory traces as a function of time. Chapter 6 assessed whether the characteristics of the memoranda constrain the efficiency of attentional orienting within VSTM. Attentional orienting supported differentially the maintenance of familiar and meaningless items and pinpointed the quantitative improvement of mnemonic strategies over development. Finally, Chapter 7 examined the temporal dynamics of prospective and retrospective orienting of attention in VSTM. Children deployed neural pathways underpinning attentional orienting less efficiently than adults and differentially across the two orienting conditions suggesting their neural dissociation. Overall, findings from the current thesis define how children develop the ability to deploy attentional control in service of VSTM.

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.