Effects of deep brain stimulation of the subthalamic nucleus and the pedunculopontine nucleus on cognitive function in Parkinson's disease

The general aim of this thesis was to investigate the cognitive effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) or the pedunclopontine nucleus (PPN) in Parkinson’s disease (PD). In Study 1, acute STN stimulation did not induce impulsivity on a probabilistic decisionmaking task, suggesting STN-DBS induced impulsivity may occur in tasks involving conflict, reward or time pressure. This study has clarified that the inhibitory deficits associated with STN-DBS are situation and task specific, which makes it clear why new cases of post-operative impulse control disorders are only reported in some patients. In Study 2, the STN-DBS induced decline in verbal fluency (VF), greater for semantic than phonemic fluency, was found to be a surgical rather than an acute stimulation effect, mainly due to reduced switching but no change in cluster size. Therefore, future work in identifying the mechanisms of the STN-DBS induced VF decline should focus on surgical rather than stimulation effects. In Study 3, patients failed to benefit from corrective feedback to enhance their learning relative to a trial-and-error version when performing visual conditional associative learning tasks (VCLT) with STN-DBS on versus off. STN-DBS seemed to influence proactive interference resolution on the VCLTs. These results have implications for the use of adjunct interventions such as speech therapy or physiotherapy following STN-DBS surgery. In Study 4, PPN-DBS surgery did not have an impact on most aspects of cognition assessed and the only consistent decline was in switching category VF. For the two patients who developed dementia after PPN-DBS surgery, resuming low frequency stimulation improved working memory and attention. The findings from these studies provide further evidence and clarity regarding the cognitive sequel of STN-DBS and PPN-DBS for PD and confirm that the former can be a good treatment of choice for mid to late-stage Parkinson’s disease without the risk of major cognitive adverse effects

Diversity within species: interpreting strains in microbiomes

Studying within-species variation has traditionally been limited to culturable bacterial isolates and low-resolution microbial community fingerprinting. Metagenomic sequencing and technical advances have enabled culture-free, high-resolution strain and subspecies analyses at high throughput and in complex environments. This holds great scientific promise but has also led to an overwhelming number of methods and terms to describe infraspecific variation. This Review aims to clarify these advances by focusing on the diversity within bacterial and archaeal species in the context of microbiomics. We cover foundational microevolutionary concepts relevant to population genetics and summarize how within-species variation can be studied and stratified directly within microbial communities with a focus on metagenomics. Finally, we describe how common applications of within-species variation can be achieved using metagenomic data. We aim to guide the selection of appropriate terms and analytical approaches to facilitate researchers in benefiting from the increasing availability of large, high-resolution microbiome genetic sequencing data