Search

Introduction: Rhythmic transcranial magnetic stimulation (rhTMS) has been shown to enhance auditory working memory manipulation, specifically by boosting theta oscillatory power in the dorsal auditory pathway during task performance. It remains unclear whether these enhancements (i) persist beyond the period of stimulation, (ii) if they can accelerate learning and (iii) if they would accumulate over several days of stimulation. In the present study, we investigated the lasting behavioral and electrophysiological effects of applying rhTMS over the left intraparietal sulcus (IPS) throughout the course of seven sessions of cognitive training on an auditory working memory task. Methods: A limited sample of 14 neurologically healthy participants took part in the training protocol with an auditory working memory task while being stimulated with either theta (5 Hz) rhTMS or sham TMS. Electroencephalography (EEG) was recorded before, throughout five training sessions and after the end of training to assess to effects of rhTMS on behavioral performance and on oscillatory entrainment of the dorsal auditory network. Results: We show that this combined approach enhances theta oscillatory activity within the fronto-parietal network and causes improvements in auditoryworking memory performance. We show that compared to individuals who received sham stimulation, cognitive training can be accelerated when combined with optimized rhTMS, and that task performance benefits can outlast the training period by ~ 3 days. Furthermore, we show that there is increased theta oscillatory power within the recruited dorsal auditory network during training, and that sustained EEG changes can be observed ~ 3 days following stimulation. Discussion: The present study, while underpowered for definitive statistical analyses, serves to improve our understanding of the causal dynamic interactions supporting auditory working memory. Our results constitute an important proof of concept for the potential translational impact of non-invasive brain stimulation protocols and provide preliminary data for developing optimized rhTMS and training protocols that could be implemented in clinical populations. [ABSTRACT FROM AUTHOR]

Individuals who have Down syndrome (caused by trisomy of chromosome 21), have a greatly elevated risk of early-onset Alzheimer's disease, in which amyloid-β accumulates in the brain. Amyloid-β is a product of the chromosome 21 gene APP (amyloid precursor protein) and the extra copy or 'dose' of APP is thought to be the cause of this early-onset Alzheimer's disease. However, other chromosome 21 genes likely modulate disease when in three-copies in people with Down syndrome. Here we show that an extra copy of chromosome 21 genes, other than APP, influences APP/Aβ biology. We crossed Down syndrome mouse models with partial trisomies, to an APP transgenic model and found that extra copies of subgroups of chromosome 21 gene(s) modulate amyloid-β aggregation and APP transgene-associated mortality, independently of changing amyloid precursor protein abundance. Thus, genes on chromosome 21, other than APP, likely modulate Alzheimer's disease in people who have Down syndrome. [ABSTRACT FROM AUTHOR]

The 2021 Annual Joint Meeting (AJM) and Young Investigators' Forum of the Canadian Society for Clinical Investigation / Société Canadienne de Recherches Clinique (CSCI/SCRC) and Clinician Investigator Trainee Association of Canada/Association des Cliniciens-Chercheurs en Formation du Canada (CITAC/ACCFC) was hosted virtually on November 14-16th, 2021. The theme of the AJM was "Communication, Collaboration, and Tools for the Next Generation of Clinician Scientists", and emphasized lectures, panels and interactive workshops designed to provide knowledge and skills for professional development of clinician investigator trainees. The opening remarks were given by Nicola Jones (President of CSCI/SCRC) and Adam Pietrobon (Past President of CITAC/ACCFC). The keynote speaker was Dr. Timothy Caulfield, who delivered the presentation titled "Communication in the Era of Misinformation". Dr. Michael Hill (University of Calgary) received the CSCI Distinguished Scientist Award and Dr. Philippe Campeau (Université de Montréal) received the CSCI Joe Doupe Young Investigator Award. Each of the scientists delivered award winning talks during the symposium titled "All the King's Horses and All the King's Men" and "Understanding Growth Plate Disorders to Better Treat Them", respectively. The three interactive workshops included "Data Visualization", "Science Communication on Social Media" and "Mentorship in Action". The two panels were "CIHR Engagement: Challenges and Opportunities in the Clinician Investigator Career Path" and "Early Career Investigator Panel". The AJM also included presentations from clinician investigator trainees from across the country. Over 60 abstracts were showcased at this year's meeting, most of which are summarized in this review. Six outstanding abstracts were selected for oral presentations during the President's Forum. [ABSTRACT FROM AUTHOR]

The Clinician Investigator Trainee Association of Canada (CI) trainees across the country around the common goal of improving training conditions for those pursuing a career at the junction of research and medicine. Since then, the CI training landscape has shifted dramatically. The number of Canadian CI trainees enrolled totaling 289 MD-PhD trainees and 389 Clinical Investigator Program (CIP) trainees as of 2019 [1]. Alumni outcome data have presented conclusive evidence that MD-PhD training programs are effective in producing CI careers [2-4]. [ABSTRACT FROM AUTHOR]

On behalf of the Clinical Investigator Trainee Association of Canada (CITAC) Board of Directors, I would like to extend an enthusiastic welcome to our new MD+ trainee members! I hope you soaked up all that summer had to offer and are in good back-to-school spirits. A new academic year is upon us, and opportunities abound for the Canadian physician scientist trainee community. [ABSTRACT FROM AUTHOR]

I hope you’re taking care and found some time to relax this summer. A new semester may mean a big transition—some folks are starting their graduate studies, re-entering clerkship, starting residency or entering a fellowship. For some, there will be little or no change at all; but just a continuation of one of the many phases of the physician-scientist training pathway. Whatever stage you’re at, the Clinical Investigator Trainee Association of Canada (CITAC) community is here to support and advocate for you! [ABSTRACT FROM AUTHOR]

Down syndrome, caused by trisomy of chromosome 21, is the single most common risk factor for early-onset Alzheimer's disease. Worldwide approximately 6 million people have Down syndrome, and all these individuals will develop the hallmark amyloid plaques and neurofibrillary tangles of Alzheimer's disease by the age of 40 and the vast majority will go on to develop dementia. Triplication of APP, a gene on chromosome 21, is sufficient to cause early-onset Alzheimer's disease in the absence of Down syndrome. However, whether triplication of other chromosome 21 genes influences disease pathogenesis in the context of Down syndrome is unclear. Here we show, in a mouse model, that triplication of chromosome 21 genes other than APP increases amyloid-β aggregation, deposition of amyloid-β plaques and worsens associated cognitive deficits. This indicates that triplication of chromosome 21 genes other than APP is likely to have an important role to play in Alzheimer's disease pathogenesis in individuals who have Down syndrome. We go on to show that the effect of trisomy of chromosome 21 on amyloid-β aggregation correlates with an unexpected shift in soluble amyloid-β 40/42 ratio. This alteration in amyloid-β isoform ratio occurs independently of a change in the carboxypeptidase activity of the γ-secretase complex, which cleaves the peptide from APP, or the rate of extracellular clearance of amyloid-β. These new mechanistic insights into the role of triplication of genes on chromosome 21, other than APP, in the development of Alzheimer's disease in individuals who have Down syndrome may have implications for the treatment of this common cause of neurodegeneration.