Although several studies have investigated the effects of aging on aspects of motor planning and control, there remains a lack of consensus about the underlying mechanisms responsible for the motor slowing associated with aging. This may, at least partially, be due to the fact that few studies have kinematically examined both the transport and grasp components in both younger and older adults, and furthermore, even fewer have examined these movements when the context of the task is changed, such as when the movement is performed in isolation compared to when it is embedded in a sequence. Therefore, the purpose of this thesis was threefold: 1) to investigate how aging affects performance on a single reach-to-grasp movement, 2) to examine how movement context affects performance on the reach-to-grasp movement when it is performed alone or as the first movement in a two-movement sequence- in other words, are older adults able to plan the first motor task movement in anticipation of performing a subsequent task, and 3) whether younger and older adults are able to plan, execute, and modify that movement in accordance with the extrinsic properties of the subsequent movement task (near versus far target for second movement). To address this, the movement profiles of both younger (N=14; mean age= 20.7 years; 4 males, 10 females) and older (N=11; mean age= 75.1 years; 3 males, 8 females) healthy right-handed adults were compared on performing a reach-to-grasp movement under 3 different movement conditions: single-movement task, two-movement sequence to near target, and two-movement sequence to far target. For the two-movement sequence conditions, participants were instructed to reach and grasp the object (like the single-movement task), but then to move and place it on either a closer (near condition) or farther (far condition) target location. Overall, the results from this study are in agreement with the literature showing older adults to have slower movements in general and consistently taking longer to both initiate and execute the reach-to-grasp movement than the younger adults for all conditions. There were no other differences between groups on the single-movement condition. For all participants, the reach-to-grasp movement took longer when it was performed in isolation than when it was embedded as the first part of a two-movement sequence. This finding can be explained by the movement termination effect and is consistent with findings from studies on aiming movements showing that when the movement plan involves stabilizing the arm at the first target (single-movement) as opposed to merely slowing it down (two-movement sequence tasks), the constraint of achieving a stabile position imposes a greater demand, thus requiring the movement iv to be made more slowly. The results obtained from the study indicate that the movement termination effect is also seen in the context of prehensile movements and furthermore, this effect on performance persists with age. Not only do the findings from this study show that this effect persists with age, but also that this effect increases with age, as revealed by a Group by Condition effect for reaction time, movement time, and relative timing of the velocity profile, indicating greater changes in reaching performance between single- and two-movement conditions for the older adults than for the younger adults. Upon further examination of the details of the movement, it is apparent this movement termination effect is reflected in the ballistic phase of the movement. This last notion is inconsistent with previous studies, which showed the increased movement time associated with the movement termination effect was the result of changes in the amount of time spent in the deceleration phase toward the end of the movement rather than the beginning of the movement. Lastly, when reach-to-grasp performance was compared between moving to a near- compared to a far-target in the two-movement conditions, no differences were found between any of the movement features for either group. This suggests that the increased proportion of time spent in deceleration for the dual-movement conditions compared to the single-movement condition in older adults is due to online feedback control for terminating the first movement rather than online planning of the second movement. Despite the changes seen in the transport component, the findings for the manipulation component indicate that the formation of the grasp and its relative coupling with the transport component remains intact with age.

Memory and concentration problems are frequently reported long after experiencing a mild traumatic brain injury (mild TBI), though conflict with null findings of deficits on standard neuropsychological tests. Experimental research shows that these inconsistencies are, in part, due to the simplicity of neuropsychological tests. As well, past research suggests that when neuropsychological deficits are occasionally detected within this population, they could be influenced by diagnosis threat: an expectation bias for impaired performance when individuals are merely informed that cognitive problems may be experienced following a mild TBI. The main goal of this thesis was to specify the long-term cognitive effects of mild TBI, with the prediction that, while cognitive complaints may be over-reported due to diagnosis threat, significant deficits can be detected using sensitive measures in experimental paradigms. Experiment 1 sought to document whether diagnosis threat influenced self-report of everyday attention and memory problems and neuropsychological task performance in individuals with a remote history of mild TBI. We found that undergraduate students with a mild TBI were significantly more likely to report having attention and memory failures in their daily lives when exposed to diagnosis threat, compared to undergraduate students not exposed to diagnosis threat. These findings call into question the efficacy of using of self-report measures to identify long-term cognitive deficits following a mild TBI. In an attempt to further specify persistent significant cognitive deficits, we designed two different experimental paradigms that uniquely manipulated the demand place on executive processes, as past research suggested deficits emerge only when tasks require considerable cognitive resources. In Experiment 2a, we manipulated processing load on a visual working memory task, across two conditions, while also limiting the potential effect of diagnosis threat. While self-report and neuropsychological measures of attention and memory did not differentiate the groups, the mild TBI group took significantly longer to accurately detect repeated targets on our working memory task. Accuracy was comparable in the low-load condition and, unexpectedly, mild TBI performance surpassed that of controls in the high-load condition. Temporal analysis of target identification suggested a strategy difference between groups: mild TBI participants made a significantly greater number of accurate responses following the target’s offset, and significantly fewer erroneous distracter responses prior to target onset, compared to controls. In Experiment 2b we also examined whether manipulating executive processing demands would differentiate mild TBI from controls, this time on a routine action task that required participants to learn a sequence of hand movements to targets. While not significant, we found a trend such that mild TBI participants were slower to respond on trials with a large executive demand compared controls, while no differences were found on trials with relatively low executive requirements. Results from Experiments 2a and 2b provide stronger evidence for mild TBI-related slowing during a working memory task with an executive component compared to a skilled action task that also had an executive component, but placed minimal demand on memory. To more precisely identify the brain basis of this cognitive slowing, in Experiment 3 we administered a visual n-back task in which we systematically increased working memory demands from 0- to 3-item loads. We found that, compared to controls, mild TBI participants showed a reduction in P300 amplitude, conceptualized as an index of available cognitive resources for stimulus classification. While no late stage response differences were found between groups, P300 amplitude was negatively correlated with response times at higher loads in both control and mild TBI participants. Findings suggest that high functioning young adults who sustained a mild TBI in their remote past, have a reduced amount, or inefficient recruitment of, cognitive resources for target detection; a potential mechanism underlying mild TBI-related response slowing on tasks that place a heavy demand on processing resources. Similar to the effects of mild TBI, aging is also known to negatively impact cognition. In Experiment 4, we examined whether TBI-related deficits persist into older adulthood, and compound the negative effect of aging on cognition. We administered the same working memory task as in Experiment 2a, along with a variety of neuropsychological tests in order to investigate the effect of a TBI sustained an average of 50 years in the past. While no group differences emerged on our experimental working memory task, older adults with a history of 1 or 2 TBIs performed significantly worse than non head-injured older adults only on neuropsychological measures of attention that had an executive component. Such results suggest that a remote TBI sustained early in life further compounds normal age-related cognitive decline. Together, these experiments help specify the measures that best detect long lasting cognitive changes following TBI. Particularly, our findings provide a potential explanation for why long-term cognitive deficits are difficult to identify in the young mild TBI population: the majority of neuropsychological tests are insensitive to minor changes in information processing speed and, as a result, the execution of slowing strategies to maintain accuracy may go undetected. Our findings also demonstrate the importance of investigating longer-term effects of TBI, as they may be chronic and impact cognitive task performance in old age, amplifying normal age-related cognitive deficits.

In our pilot study investigating Texas Hold ‘em poker, we found that players bluffing (with a losing hand) elicits a similar physiological arousal response (as measured by skin conductance levels) to those in a position of strength and poised to win. Since arousal has been suggested to be a reinforcing factor in problematic gambling behaviour, we sought to replicate the findings of our pilot study in the current investigation. We aimed to extend our previous findings further by: isolating truthful betting (strong betting) to disambiguate deception when players are in positions of strength (i.e. trapping), measuring subjective excitement levels and risk assessments, investigating the physiological arousal responses following wins versus losses, and finally, exploring group differences (i.e. problem gambling status, experience levels). 71 participants played 20 naturalistic rounds of Texas Hold ‘em poker for monetary rewards. We were able to replicate our previous findings that bluffing triggers a physiological arousal (as measured by skin conductance responses) similar to truthful strong betting. Trapping was also found to elicit a skin conductance response similar to both bluffing and strong betting. Measures of subjective excitement revealed a pattern that converged with physiological data. Furthermore, wins were found to be more arousing than losses. Finally, our exploratory analysis of group differences (i.e. problem gambling status, experience) proved to be an insignificant factor with all measures. We conclude that the effect of bluffing on physiological arousal is so powerful that it pervades all participants; which is problematic due to its risky nature and potential to be self-triggered. With its ever increasing popularity and availability, more research on Texas Hold ‘em poker is warranted for treatment implications.

The following two studies examined the influence of spatial regularities on our ability to learn and predict frequencies and sequences of events. Research into statistical and sequence learning has demonstrated that we can learn the statistical properties of events and use this knowledge to make predictions about future events. Research has also demonstrated that redundant spatial features associated with events can influence our ability to respond to and discriminate between different stimuli. The goal of this thesis was to test whether redundant spatial features could influence our ability to notice non-spatial regularities in an environment. Using a computerized version of the children’s game ‘rock-paper-scissors’ (RPS), undergraduates were instructed to win as often as possible against a computer that played varying strategies. For each strategy, the computer’s plays were either presented with spatial regularity (i.e., ‘rock’ would always appear on the left of the screen, ‘paper’ in the middle, and ‘scissors’ on the right) or without spatial regularity (i.e., the items were equally likely to appear in any of the three screen locations). The results showed that, although irrelevant to the task itself, spatial regularities had a moderate influence when participants learned to exploit easy strategies, and a more pronounced influence when learning to exploit harder strategies. This research suggests that redundant spatial features can influence our ability to learn and represent distributions of events.

<p>Problematic alcohol consumption develops concurrently with deficits in decision-making.  These deficits may be due to alterations in dorsal medial prefrontal cortex (dmPFC) neural activity, as it is essential for the evaluation and implementation of behavioral strategies. In this study, we hypothesized that differences in cognitive control would be evident between Wistars and alcohol-preferring P rats. Cognitive control can be split into proactive and reactive components. Proactive control maintains goal-directed behavior independent of a stimulus whereas reactive control elicits goal-directed behavior at the time of a stimulus. Specifically, it was hypothesized that Wistars would show proactive control over alcohol-seeking whereas P rats </p> <p>would show reactive control over alcohol-seeking. Proactive control in our rodent model is defined as responding to distal task cues whereas reactive control is responding to proximal cues. This was tested in rodents performing a 2-way Cued Access Protocol (2CAP) that facilitates measurements of alcohol seeking and drinking. Congruent sessions were the typical, default 2CAP sessions that consisted of the CS+ being on the same side as alcohol access. These were compared with incongruent sessions where alcohol access was opposite of the CS+. Wistars exhibited an increase in incorrect approaches during the incongruent sessions, which was not detectable in P rats. A trial-by-trial analysis indicated that the increases in incorrect responses </p> <p>was explained by Wistars utilizing the previously learned task-rule, whereas the P rats did not. </p> <p>This motivated the subsequent hypothesis that neural activity patterns corresponding to proactive control would be observable in Wistars but not P rats. Principal Component Analysis indicated that neural ensembles in the dmPFC of Wistars exhibited decreased activity to the cue light in incongruent sessions whereas P rat ensembles displayed increased activity at timepoints associated with the onset and end of alcohol access. Overall, it was observed that P rats showed the most differences in neural activity at times relevant for alcohol delivery; specifically, when the sipper came into the apparatus and left. Conversely, Wistars showed differences prior to approach as evidenced by both differences in cue-related activity as well as differences in </p> <p>spatial-strategies. Together, these results support our hypothesis that Wistars are more likely to engage proactive cognitive control strategies whereas P rats are more likely to engage reactive cognitive control strategies. Although P rats were bred to prefer alcohol, differences in cognitive control phenotypes may have concomitantly occurred that are of clinical relevance.</p>

<p>Environmental exposure to lead (Pb) and cannabis use are two of the largest public health issues facing modern society in the United States and around the world. Exposure to Pb in early life has been unequivocally shown to have negative impacts on development, and recent research is mounting showing that it may also predispose individuals for risk of developing substance use disorders (SUD). At the same time, societal and legal attitudes towards cannabis (main psychoactive component delta-9-tetrahydrocannabinol) have been shifting, and many American states have legalized the recreational use of cannabis. It is also the 3^rdmost widely used drug of abuse in the US, and rates of cannabis use disorder are on the rise. This thesis sets out to establish whether there is a link between early life Pbexposure and later THC-related behavior in C57BL6/J mice, as has been demonstrated for other drugs of abuse. The first aim seeks to answer whether Pbexposure affects physiological THC sensitivity (as measured by the cannabinoid-induced tetrad). The secondaimseeks to answer whether Pbexposure affects edible THC self-administration and the development of THC tolerance (also measured by the tetrad).It was hypothesized that Pbexposure would decrease THC sensitivity (Aim 1), would enhance THC self-administration (Aim 2), enhance the development of THC tolerance (Aim 2), and finally that sex-dependent effects of Pb-exposure and THC would be observed (Aims 1 & 2). These hypotheses ended up not being supported, but Aim 1 produced findings indicating that THC sensitivity was increased by Pbexposure, but only in female mice. Future researchwill hopefully be able to fully explore the implications of these findings.</p>

<p dir="ltr">Compulsive alcohol drinking is a defining feature of alcohol use disorder and is characterized as drinking alcohol despite knowledge of negative consequences. This behavior is hypothesized to be due to a disruption in the decision-making process. Decision making relies on a balance between goal-directedness and habit systems to efficiently execute behavior. An important distinction between compulsive and non-compulsive individuals is the ability to withhold drinking in the face of a negative consequence. The dorsomedial striatum (DMS) and dorsomedial prefrontal cortex (dmPFC) are brain regions necessary for goal directed behavior where the dmPFC is important for cognitive control and behavioral inhibition while the DMS is important for action selection. Importantly, the dmPFC sends a glutamatergic input to the DMS. We hypothesize this input is a behavioral control which is necessary to withhold action selection. Thus, in order to maintain non-compulsive alcohol use, the dmPFC and DMS need to work together to orchestrate inhibition of action selection in the face of negative consequences. Previous research shows a causal role for both the dmPFC and DMS in preventing compulsive alcohol drinking and a role for the projections from the dmPFC to DMS in behavioral inhibition. However, no research has demonstrated a role for this circuit’s activity in prevention of compulsive alcohol use. The current experiment tested the hypothesis that inhibiting the glutamatergic projection from the dmPFC to the DMS will cause non-compulsive Wistar rats to drink alcohol compulsively.</p>

The current thesis explores the complex relationship between cognitive control and memory. A series of experiments combined task-switching paradigms with recognition memory tests to measure how switching between tasks influences effective control over long-term memory. In these experiments, participants were presented with compound stimuli consisting of a picture and an overlaid word, and were cued in each trial whether the word or the picture was relevant (attended) or irrelevant (unattended). Participants were then tested for their memory of items presented during task switching. Experiments 1-2 indicated that switching between tasks reduces the selectivity of processing: Switching was associated with impaired task performance as well as more similar memory ratings for attended and unattended items. Experiments 3-5 extended these findings by showing that enhanced top-down control positively affected task-performance as well as memory, in both cases by increasing the selectivity of processing toward task-relevant information. Experiments 6-7 replicated key effects with simple switches of visual attention, and explored the neural correlates of successful task performance and encoding using EEG. The key finding here was that previously observed ―subsequent memory‖ effects reflect, at least in part, selective encoding processes. The last chapter extended the focus of the investigation to explore the role of control in long-term memory retrieval. FMRI meta- analyses indicated considerable overlap in neural activation found during task switching and during the adoption of different retrieval sets. The results of Experiment 8 indicated that switching during task performance and later memory retrieval were both associated with decreased selectivity of processing. Collectively, the results of this thesis suggest that selectivity of processing is a critical factor in effective task performance and successful memory, with potentially very similar mechanisms underlying the two. This work demonstrates the fruitfulness of combining research on cognitive control and memory to study questions relevant for both fields.

The physical properties of the distal stimuli activating our senses are often correlated in nature; it would therefore be advantageous to exploit such correlations to better process sensory information. Stimulus correlations can be contingent and readily available to the senses (like the temporal correlation between mouth movements and vocal sounds in speech), or can be the results of the statistical co-occurrence of certain stimulus properties that can be learnt over time (like the relation between the frequency of acoustic resonance and the size of the resonator). Over the last century, a large body of research on multisensory processing has demonstrated the existence of compatibility effects between individual features of stimuli from different sensory modalities. Such compatibility effects, termed crossmodal correspondences, possibly reflect the internalization of the natural correlation between stimulus properties. The present dissertation assesses the effects of crossmodal correspondences on multisensory processing and reports a series of experiments demonstrating that crossmodal correspondences influence the processing rate of sensory information, distort perceptual experiences and lead to stronger multisensory integration. Moreover, a final experiment investigating the effects of contingent signals’ correlation on multisensory processing demonstrates the key role of temporal correlation in inferring whether two signals have a common physical cause or not (i.e., the correspondence problem). A Bayesian framework is proposed to interpret the present results whereby stimulus correlations, represented on the prior distribution of expected crossmodal co-occurrence, operate as cues to solve the correspondence problem.

Associative plasticity, which involves modification of synaptic strength by coactivation of two synaptic inputs, has been demonstrated in many species. Here I explore whether it is possible to induce associative plasticity within a corticocortical pathway in the human brain using a novel protocol that activates two brain areas repeatedly with double-site transcranial magnetic stimulation (TMS). The pathway between ventral premotor cortex (PMv) and primary motor cortex (M1) which computes hand movements for precision grasp was manipulated. First, I selectively potentiated physiological connectivity between the stimulated brain areas. The effects as assessed with paired-pulse TMS were in accordance with principles of spike timing-dependent plasticity (STDP), pathwayspecific and showed a different pattern of expression during rest and during performance of a naturalistic prehension task. Furthermore, I demonstrated that effects evolved rapidly, lasted for up to three hours and were reversible. In a follow-up study, the protocol‘s effects on network interactions were investigated using functional magnetic resonance imaging (fMRI), specifically focussing on functional connectivity of network nodes within the wider parietofrontal circuit controlling reaching-and-grasping. The study demonstrated that functional connectivity was causally modified between stimulated nodes and that those changes in coupling also affected parallel, functionally-related pathways. Comparison of neurophysiological (paired-pulse TMS) and functional (fMRI) connectivity between individuals revealed a linear relationship of these connectivity indices; the first can assess the physiological nature of the interaction, whereas the latter can elucidate global network effects, making the techniques complementary. Neurophysiological interactions of ipsilesional and contralesional PMv-M1 were tested in chronic subcortical stroke patients during grasping. Patients showed a diminished facilitatory influence of ipsilesional PMv on M1 compared to healthy controls which might contribute to their motor disability. Application of paired-associative TMS “normalised“ the reduced effective influence of ipsilesional PMv on M1 and this effect correlated with the patient‘s potential to improve their dexterity.