Research Doctorate - Doctor of Philosophy / It is well established that there are changes in cognition and in peripheral sensory mechanisms that occur with age. However, there is much less known about the cause of either change or indeed the relationship between age-related change in sensory processing and age-associated cognitive decline. Understanding these mechanisms could improve our capacity to devise strategies which could assist older adults in aging successfully. In this thesis, I aim to bridge a gap in our knowledge concerning the relationship between age-related change in sensory processing and age-associated cognitive decline by studying the effect of age on what can be considered an intermediary process, sensory memory (in the auditory modality). I continue this line of research by examining the relationship between auditory sensory memory and other types of memory for auditory information in young and older adults. To address these goals, I adopted a cognitive neuroscience approach, relating electrophysiological data to data derived from behavioural memory assessments. In the following thesis, I present a literature review, four studies, and a general discussion of results. Several waveforms of the auditory event-related potential (ERP), including N1, P2, repetition positivity (RP), and mismatch negativity (MMN) were studied. More specifically, in study 1, we looked at the effect of age on N1 and P2 amplitude. In study 2, we examined the conditions eliciting two repetition effects, RP and the MMN memory trace effect, in the auditory ERP of young adults. Studies 3 and 4 concerned the effect of age on RP and the relationship between RP and implicit memory for contextual information as well as explicit memory for auditory information. We concluded that i) age affects auditory sensory memory, ii) the potential relationship between auditory sensory memory and implicit memory for auditory information requires re-investigation, and iii) there is a relationship between auditory sensory memory and explicit memory for auditory information that is altered with age. That is, we concluded that RP occurring in the N1/P2 and MMN latency period indicates memory trace formation and that age affects RP amplitude (restricted to an anterior RP generator). In addition, we showed that RP may be related to implicit memory (priming) in both young and older adults. Across two studies, we found a positive correlation between the response to repetition in the ERP (due to RP activity) and explicit auditory verbal memory in young adults but a negative correlation in older adults. Therefore, although age-related change in RP could reflect the capacity of older adults to encode the context of auditory stimulation, this is potentially due to compensatory activity. We argue it is possible that implicit memory changes with age as a result of age-related change in explicit episodic memory. As a result of well established changes that occur in episodic memory with age, older adults may begin to rely on implicit memory as a source of memory more so than young adults. Our data shows that the implicit memory system may, as a result, favour content over contextual information. An important theme outlined in the discussion of results involves the idea that age-related changes in cognition that are commonly interpreted as cognitive deficits may in fact be beneficial in certain circumstances. We review our results in relation to cognitive theories of aging and find that several theories are applicable to the data, including the frontal hypothesis (incorporating the inhibitory deficit hypothesis), the information degradation hypothesis, and the speed of processing hypothesis. Future research in this area could focus on exploring whether top-down or bottom-up or influences primarily contribute to the age effect on auditory sensory memory and RP, as well as evaluating our hypothesis that the age-related change in RP may be beneficial for explicit item memory but detrimental for implicit contextual memory in older adults (i.e. compensatory mechanisms). While the studies presented in this thesis have provided the foundations guiding our understanding of these issues, researchers in the field of cognitive neuroscience are well equipped to resolve such questions in the future.

Transcranial direct current stimulation (tDCS) is a non-invasive form of brain stimulation which uses a very weak constant current to temporarily excite or inhibit activity in the brain area of interest via electrodes placed on the scalp, depending on the polarity and strength of the current. Presently, tDCS is being used as a tool to investigate frontal cognition in healthy controls and to improve symptoms in neurological and psychiatric patients. Relatively little research has been conducted with respect to tDCS and the auditory cortex (AC). The primary aim of this thesis was to elucidate the effects of tDCS on auditory sensory discrimination, assessed with the mismatch negativity (MMN) event-related potential (ERP). In the first pilot study, healthy participants were assessed in a randomized, double-blind, sham-controlled design, in which participants received anodal tDCS over the primary AC (2 mA for 20 minutes) in one session and ‘sham’ stimulation (i.e. no stimulation) in the other. Pitch MMN was found to be enhanced after receiving anodal tDCS, with the effects being evidenced in individuals with relatively low (vs. high) baseline amplitudes. No significant effects were seen with sham stimulation. A second study examined the separate and interacting effects of anodal and cathodal tDCS on MMN measures. MMN was assessed pre- and post-tDCS (2 mA, 20 minutes) in 2 separate sessions, one involving sham stimulation, followed by anodal stimulation, and one involving cathodal stimulation, followed by anodal stimulation. Only anodal tDCS over the AC increased pitch MMN in baseline-stratified groups, and while cathodal tDCS decreased MMN, subsequent anodal stimulation did not significantly alter MMNs. As evidence has shown that tDCS lasting effects may be dependent on N-methyl-D-aspartate (NMDA) receptor activity, a pharmacological study investigated the use of dextromethorphan (DMO), an NMDA antagonist, to assess possible modulation of tDCS’ effects on both MMN and working memory (WM) performance. The study involved four test sessions that compared pre- and post-anodal tDCS over the AC and sham stimulation with both DMO (50 mL) and placebo administration. MMN amplitude increases were only seen with anodal tDCS with placebo administration, not with sham stimulation, nor with DMO administration. In the sham condition, DMO decreased MMN amplitudes. Anodal tDCS improved WM performance in the active drug condition. Findings from this study contribute to the understanding of underlying neurobiological mechanisms mediating tDCS-sensory and memory improvements. As cognitive impairment has been proposed to be the core feature of schizophrenia disorder (Sz) and MMN is a putative biomarker of Sz, a pilot study was conducted to assess the effects of pre- and post-tDCS on MMN measures in 12 Sz patients, as well as WM performance. Temporal, frontal and sham tDCS were applied in separate sessions. Results demonstrated a trend for pitch MMNs to increase with anodal temporal tDCS, which was significant in a subgroup of Sz individuals with auditory hallucinations, who had low MMNs at baseline. Anodal frontal tDCS significantly increased WM performance, which was found to positively correlate with MMN-tDCS effects. The findings contribute to our understanding of tDCS effects for MMN-indexed sensory discrimination and WM performance in healthy participants and individuals with Sz disorder and may have implications for treatment of sensory processing deficits in neuropsychiatric illness.