The role of inhibitory functioning in age-related working memory decline and the moderating effect of time course changes in inhibitory functioning with age

The current thesis investigated whether and how inhibitory and working memory functioning change with age in the context of a sequential action paradigm. The approach taken was guided by (1) propositions that inhibitory functions decline with age and negatively impact higher order abilities, and (2) the utility of better understanding cognitive mechanisms underlying sequential activities. In Study 1, I examined the extent to which age-related decline in deletion-type inhibition (suppression of no-longer-relevant information) accounted for age differences in working memory performance. Unlike much of the prior research, I examined inhibitory changes with respect to working memory components (processing and storage). I observed that reduced deletion-type inhibition with age accounted for sizable proportions of age differences in working memory components, with significant findings in storage and marginal findings in processing components. This finding indicates that changes in executive function with age, such as inhibitory control, have direct implications for working memory functioning at the componential level. Moreover, given the observation of age-related decline in deletion-type inhibition in Study 1, a finding that has been inconsistent in the literature, in two subsequent studies I examined the nature of inhibitory changes with age. In particular, I examined whether compared to younger adults, older adults’ have reduced ability to engage deletion-type inhibition in a timely manner, beyond the effects of age-related general slowing. In Study 2, I did not observe age differences in the time course of deletion-type inhibition when I examined erroneous responses to the prior, no-longer-relevant, item (n - 1 repeat). However, this finding may have been limited by low error rates obtained. Thus, in Study 3, response latencies on n - 1 repeats were examined for changes in low-level (unintentional) deletion-type inhibition across variable numbers of distractors, corresponding to variable time delays. Compared to younger adults, older adults had difficulty engaging deletion-type inhibition. This finding suggests that more detailed specification of inhibitory changes with age might depend on examining the temporal dynamics of inhibitory functioning in young and older adults. Taken together, this work highlights the important role of inhibitory functioning with age in higher order cognition (working memory) and emphasizes the utility of examining age effects in the time course of cognitive functions in sequential tasks

Bilateral sequential theta burst stimulation in depressed veterans with service related posttraumatic stress disorder: a feasibility study

Background: Depression comorbid with posttraumatic stress disorder (PTSD) can be disabling and treatment resistant. Preliminary evidence suggests that repetitive transcranial magnetic stimulation (rTMS), may have a role in helping these patients. There are only few published studies using different rTMS paradigms including bilateral intermittent theta burst (iTBS) and low frequency rTMS. Methods: In this small cohort observation study, we examined the efficacy of bilateral sequential theta-burst stimulation (bsTBS) in 8 treatment resistant depression (TRD) military veterans with PTSD comorbidity stemming from military service experience. Results: bsTBS was generally well tolerated and resulted in 25% and 38% remission and response rates on Depression scores respectively; 25% remission and response rate on PTSD scores. Discussion: This study demonstrates preliminary feasibility and safety of bsTBS in TRD with comorbid military service related PTSD. We concluded that this paradigm might hold promise as a therapeutic tool to help patients with TRD co-morbid with military service related PTSD. Further adequately powered studies to compare rTMS treatment paradigms in this patient group are warranted

An investigation of chunking and inhibitory processes in young and older adults using a sequential action paradigm

The completion of a sequence of actions in a fixed order is necessary to perform everyday activities. One line of research posits that all actions in a sequence are activated simultaneously and inhibited upon completion whereas another viewpoint suggests the successive activation of chunks of to-be-performed actions. Previous work using a sequential monitoring task indicated that chunks of items were retrieved successively from long-term memory and inhibited upon completion, suggesting a hybrid model of serial behaviour. The objective of this thesis was to examine inhibitory and chunking processes in sequential behaviour and how they change with aging. Participants learned an 8-item sequence and subsequently responded to these items in the order learnt while ignoring distractors (items out of sequence). Chunking and inhibitory processes were simulated by training participants to use overt articulation of chunked items, either with or without suppression of completed items: One group of participants continuously recited both items in each chunk in an 8-item sequence (chunking only) whereas another grouped recited both chunk items initially but subsequently updated their recital to the last item of the chunk (chunking plus inhibition). The role of chunking in sequential behaviour was supported as the chunking strategies employed resulted in similar findings as previous research. Further, suppression of previous items from conscious awareness was evident in YA compared to OA, consistent with the inhibition deficit hypothesis, which states that the ability to suppress previous task-relevant information declines with aging. Together, these results support the proposed hybrid model of sequential performance

Longitudinal associations of need for cognition, cognitive activity, and depressive symptomatology with cognitive function in recent retirees

Objectives.This study investigated how interindividual differences in cognitive function are related to interindividual differences in the motivational trait of need for cognition, cognitive activity levels, and depressive symptomatology in a sample of young-old adults.Method.The sample comprised 333 recent retirees from the Concordia Longitudinal Retirement Project (mean age = 59.06 years at entry into study), assessed at 4 annual time points. Cognitive function was measured at 2 time points with the Montreal Cognitive Assessment. We used structural equation modeling to examine a longitudinal mediation model controlling for age, education, years since retirement, and prior occupation.Results.Need for cognition was positively associated with change in cognitive status 2 years later. Variety of cognitive activities was positively associated with level of cognitive status 1 year later. Depressive symptomatology was negatively associated with level of cognitive status 1 year later.Discussion.Our findings indicate that motivational disposition plays a significant role in enhancing cognitive status in retirees, as do variety of cognitive activities. Additionally, subclinical depressive symptomatology can negatively influence cognitive status in young-old retirees. These results have implications for the design of interventions aimed at maintaining the cognitive health of retirees

Oxytocin for frontotemporal dementia

ObjectiveTo determine the safety and tolerability of 3 doses of intranasal oxytocin (Syntocinon; Novartis, Bern, Switzerland) administered to patients with frontotemporal dementia (FTD).MethodsWe conducted a randomized, parallel-group, double-blind, placebo-controlled study using a dose-escalation design to test 3 clinically feasible doses of intranasal oxytocin (24, 48, or 72 IU) administered twice daily for 1 week to 23 patients with behavioral variant FTD or semantic dementia (clinicaltrials.gov registration number NCT01386333). Primary outcome measures were safety and tolerability at each dose. Secondary measures explored efficacy across the combined oxytocin vs placebo groups and examined potential dose-related effects.ResultsAll 3 doses of intranasal oxytocin were safe and well tolerated.ConclusionsA multicenter trial is warranted to determine the therapeutic efficacy of long-term intranasal oxytocin for behavioral symptoms in FTD.Classification of evidenceThis study provides Class I evidence that for patients with FTD, intranasal oxytocin is not significantly associated with adverse events or significant changes in the overall neuropsychiatric inventory