Lehmann, Hugo

Memories which typically require the hippocampus (HPC) can become represented in structures outside of the HPC, and therefore resistant to HPC damage, but, the properties of these memories are poorly understood. Some research has suggested that the HPC continually contributes to memories that are resistant to hippocampal damage, and without this support, they are weaker and more susceptible to loss. However, this hypothesis has yet to be tested experimentally. We examined this possibility in rats by assessing decay and extinction of a context fear memory that had become independent of the HPC via repeated learning episodes. We found that HPC-independent context fear memories decay and extinguish faster without continued HPC support, suggesting that the HPC plays a continued role in long-term memory. We also provide new evidence of a persistent interaction between the HPC and other memory systems, which strengthens non-HPC representations so that they withstand HPC damage at longer intervals.

Author Keywords: consolidation, context fear, hippocampus, memory, retrograde amnesia

Current literature on concussion management focuses primarily on the return to physical activity, while the return to learn process is less clearly understood. This knowledge gap is particularly problematic for adolescents, whose primary responsibility is academics. The present study sought to develop a more in-depth understanding of the return to learn process through the perspectives of adolescents who had sustained a concussion and their parents in in-person, semi-structured interviews. A substantive grounded theory of the return to learn process for adolescents that emerged from the data is provided. The basic model is consistent with many speculative, non-empirically based concussion management protocols, but extends these models by emphasizing the central role of parents in managing their child's recovery process, highlighting the importance of role fulfillment within the concussion management network, and identifying the impact of the adolescent's capacity and readiness for help-seeking. The results also highlight the vulnerability of concussed adolescents to losing their support structure as they move through key school transitions. Implications for educators, medical professionals, parents, and adolescents in the return to learn process are also discussed.

Author Keywords: Adolescent, Concussion, Concussion Management, Multidisciplinary Management, Return to Learn, Return to School

Temporal lobe epilepsy increases risk for developing major depression, and conversely, depression increases risk for development of epilepsy. The mechanisms responsible for the widely observed bi-directional relationship between epilepsy and depression are currently poorly understood. One reason why our understanding of shared etiology has had little improvement is due to the lack of availability of a reliable animal model for inducing depression in epileptic animals. The development of a reliable model of epilepsy-depression comorbidity would greatly improve the ability to mechanistically evaluate shared pathophysiology between the conditions. Recently there has been evidence that rapid kindling of the basolateral amygdala can evoke a behavioural phenotype that is comparable to the symptoms of anxiety and depression observed in depressed epileptic patients. However, this work has yet to be replicated, leaving question as to whether or not the behavioural phenotype can be reliably evoked. In the following series of experiments we assessed rapid amygdala kindling as a potential model of epilepsy-depression comorbidity and sought to improve the model with inclusion of the glucocorticoid corticosterone. Our findings may improve our understanding of the unique relationships between epilepsy and depression.

Author Keywords: animal models, depression, hippocampus, kindling, stress, temporal lobe epilepsy

Cognitive impairments, such as memory loss, are a frequent and devastating co-morbidity associated with epilepsy. The neurobiological mechanisms through which recurrent seizures induce cognitive impairments are not well understood. New neurons born after seizures develop abnormal morphological and functional characteristics that promote network hyperexcitability and hippocampal dysfunction. Previously, we found that kindling dramatically increases the rate of neurogenesis at early stages of seizure development, followed by a long-term suppression at later stages. These changes in the rate of cell proliferation coincides with aberrant modifications in the migration, excitability, and functional integration of these new neurons. It has been suggested that the long-term consequences of seizure-induced neurogenesis contributes to the development of cognitive impairment seen in chronic epilepsy. However, direct experimental evidence has been limited. The present series of experiments sough to determine if blocking aberrant seizure-induced neurogenesis can reduce cognitive deficits associated with chronic epilepsy. Our findings suggest that chronic seizures impair the ability of rats to differentiate between similar contexts. In addition, blocking aberrant seizure-induced neurogenesis through treatment with the cytotoxic agent temozolomide was capable of preventing some of the deficits in context discrimination learning when neurogenesis levels were reduced to non-epileptic control levels. This research provides further support of targeting aberrant neurogenesis as a novel treatment to restore cognitive functioning in individuals living with epilepsy.

Author Keywords: Amygdala kindling, Dentate gyrus, Hippocampus, Neurogenesis, Pattern separation, Seizures

Distributing contextual fear episodes makes the memory become HPC-independent, meaning increasingly reliant on non-HPC memory structures. It is unclear, however, whether distribution of the conditioning episodes alone is sufficient or whether a combination of distribution and high conditioning saliency is necessary to make the memory become HPC-independent. To resolve this issue, rats were trained using a distributed contextual fear conditioning protocol in which foot-shocks were manipulated to create a low (0.4mA), intermediate (0.7 mA) and high (1.0 mA) saliency condition. This thesis also aimed to determine brain structures supporting the HPC-independent memory by assessing retention-induced c-fos expression in the basolateral- amygdala, perirhinal and anterior cingulate cortices. The results suggest that HPC lesion rats in the high saliency condition displayed similar level of freezing as control rats, indicating "strongly salient" and distributed episodes creates a HPC independent memory. c-fos expression suggests together, an increased context representation in the perirhinal and anterior cingulate cortices and a strengthened fear representation in the basolateral-amygdala supports the HPC-independent memory.

Author Keywords: context fear memory, distributed reinstatements, hippocampus, IEG, rat, saliency

Seizures induce long-term changes in gene expression in the hippocampus. Experimental evidence has demonstrated a significant effect of epileptic activity on the activity of neurons that participate in complex cognitive and behavioural processes. The present series of experiments involving kindling with subconvulsive doses of PTZ demonstrates a link between seizures and altered immediate early gene expression within the hippocampus and dentate gyrus. In addition, newborn hippocampal neurons were shown to have decreased induction of plasticity-related genes, suggesting deficits in activity-dependent recruitment. These findings may shed light on the mechanisms underlying epileptogenesis and epilepsy-related hippocampal dysfunction in human patients.

Author Keywords: hippocampus, IEGs, kindling, neurogenesis, seizures

Evidence suggests that visuomotor system behaviour may be more sensitive to the prolonged effects of mild brain injuries than neuropsychological tests. We evaluated whether participants with a mild closed head injury (CHI) would show lingering visuomotor deficits, but not cognitive deficits, up to three years post-injury compared to participants with an orthopaedic injury and healthy controls. All three groups completed a tablet-based visuomotor assessment tool and a brief neuropsychological test battery. The CHI participants scored comparable to the control groups on the neuropsychological tests, but when assessed for visuomotor function requiring adjustment to a changing stimulus, CHI participants showed poorer performance than the control groups. Combined, these findings add to the evidence that CHI can lead to persistent visuomotor deficits that extend beyond those of neuropsychological tests. Therefore, visuomotor assessment should be included in brain injury and recovery evaluation, and this can be accomplished easily using tablet-based tasks.

Author Keywords: closed head injury, neuropsychological assessment, recovery, tablet, traumatic brain injury, visuomotor

Athletes' concussion risk is part of a complex system of personal and contextual factors. This study differentiated athletes based on attitudes and intentions towards protective behaviours. A cross-sectional survey design was used to sample varsity athletes. Three intention response subgroups (indifferent, reactive, and proactive) were identified. The indifferent group (28%) reported little-to-no intent to engage in risk reduction behaviours. These athletes reported lower belief in the efficacy of concussion management behaviours and greater risk acceptance attitudes. The proactive group (32%) reported intent to actively reduce personal concussion risk through engaging in behaviours such as confronting aggressive opponents about the risk they pose to others. The reactive group (40%) only reported intent to engage in concussion management behaviours. Indifferent athletes had the highest likelihood of concussion exposure followed by reactive athletes. The proactive athletes had the lowest likelihood. Concussion programs must address beliefs and intentions towards protective behaviours to improve effectiveness.

Author Keywords: Athlete, Attitudes, Concussion, Injury Prevention, Intentions, Risk

It is universally accepted that human motor performance is variable in both its timing and spatial qualities. However, it is unclear to what extent motor variability impedes performance when learning a new skill and to what extent it enables our ability to learn. The first experiment examined whether performance during a test task depended on whether participants practiced to constrain or vary the task-relevant parameter. Participants used their right hand to make simple point-to-point movements. Results demonstrated the importance of paying attention to test task demands to evaluate which form of practice is most beneficial. The second experiment examined whether levels of variability could be manipulated using a reward-based paradigm to enhance learning when adapting to a perturbation of a simple visually-guided reaching movement. A reward-based feedback task was designed to encourage exploration along the task-relevant dimension, specifically movement direction variability. Overall, I did not find any significant results.

Author Keywords: Adaptation, Motor Control, Motor Learning, Reaching

We investigated whether hand-proximity effects arise from the recruitment of visual-tactile bimodal cells. In Experiment 1, we executed right-hand open-loop reaching movements to targets, presented either near or far from the resting left-hand, and after applying repetitive transcranial magnetic stimulation (rTMS) to suppress neuronal activity in the PMd and AIP, in Experiment 2. Results from Experiment 1, indicated that near-hand targets improved accuracy and reduced variability. In Experiment 2, suppressing PMd showed similar near-hand effects as above. In contrast, applying rTMS to AIP disrupted the representation of target location, indicating less accuracy and greater error. Near-hand proximity effects possibly arise from the recruitment of visual-tactile bimodal cells within the human AIP.

Author Keywords: anterior intraparietal sulcus, peripersonal space, repetitive transcranial magnetic stimulation (rTMS), , rTMS, anterior intraparietal sulcus, AIP., visual-tactile bimodal neurons