Parallel and serial task processing in the PRP paradigm: a drift–diffusion model approach

Even after a long time of research on dual-tasking, the question whether the two tasks are always processed serially (response selection bottleneck models, RSB) or also in parallel (capacity-sharing models) is still going on. The first models postulate that the central processing stages of two tasks cannot overlap, producing a central processing bottleneck in Task 2. The second class of models posits that cognitive resources are shared between the central processing stages of two tasks, allowing for parallel processing. In a series of three experiments, we aimed at inducing parallel vs. serial processing by manipulating the relative frequency of short vs. long SOAs (Experiments 1 and 2) and including no-go trials in Task 2 (Experiment 3). Beyond the conventional response time (RT) analyses, we employed drift–diffusion model analyses to differentiate between parallel and serial processing. Even though our findings were rather consistent across the three experiments, they neither support unambiguously the assumptions derived from the RSB model nor those derived from capacity-sharing models. SOA frequency might lead to an adaptation to frequent time patterns. Overall, our diffusion model results and mean RTs seem to be better explained by participant’s time expectancies

Differential effects of speech and Language therapy and rTMS in chronic versus subacute post-stroke aphasia: Results of the NORTHSTAR-CA trial

Background & objective: Contralesional 1-Hz repetitive transcranial magnetic stimulation (rTMS) over the right pars triangularis combined with speech-language therapy (SLT) has shown positive results on the recovery of naming in subacute (5–45 days) post-stroke aphasia. NORTHSTAR-CA is an extension of the previously reported NORTHSTAR trial to chronic aphasia (\u3e6 months post-stroke) designed to compare the effectiveness of the same rTMS protocol in both phases. Methods: Sixty-seven patients with left middle cerebral artery infarcts (28 chronic, 39 subacute) were recruited (01-2014 to 07-2019) and randomized to receive rTMS (N = 34) or sham stimulation (N = 33) with SLT for 10 days. Primary outcome variables were Z-score changes in naming, semantic fluency and comprehension tests and adverse event frequency. Intention-to-treat analyses tested between-group effects at days 1 and 30 post-treatment. Chronic and subacute results were compared. Results: Adverse events were rare, mild, and did not differ between groups. Language outcomes improved significantly in all groups irrespective of treatment and recovery phase. At 30-day follow-up, there was a significant interaction of stimulation and recovery phase on naming recovery (P \u3c.001). Naming recovery with rTMS was larger in subacute (Mdn = 1.91/IQR =.77) than chronic patients (Mdn =.15/IQR = 1.68/P =.015). There was no significant rTMS effect in the chronic aphasia group. Conclusions: The addition of rTMS to SLT led to significant supplemental gains in naming recovery in the subacute phase only. While this needs confirmation in larger studies, our results clarify neuromodulatory vs training-induced effects and indicate a possible window of opportunity for contralesional inhibitory stimulation interventions in post-stroke aphasia. NORTHSTAR trial registration: https://clinicaltrials.gov/ct2/show/NCT02020421

Effects and mechanisms of working memory training in patients with Parkinson's disease

Objective: Cognitive decline is a common, debilitating non-motor symptom of patients with Parkinson’s Disease (PD), the second most frequent neurodegenerative disorder of older age. Non-pharmacological interventions including cognitive training are increasingly recognized to possibly prevent or delay the onset and/or slow down the progression of cognitive decline in patients with PD. In this context, targeted working memory training (WMT) is especially promising, considering (i) the vulnerability of working memory and executive functions in patients with PD, (ii) reliable short- and long-term near-transfer training effects following WMT in the working memory domain and potential far-transfer effects to other cognitive domains in healthy older adults, and (iii) overlapping neural correlates of working memory, WMT induced neural changes, and the pathophysiology of PD. The present thesis project aims to investigate the effects of targeted WMT in patients with PD. Furthermore, the understanding of mechanisms underlying WMT responsiveness should be promoted. Answering the question “who benefits most?” in terms of individual (e.g., sociodemographic, neuropsychological, biological) characteristics would perspectively help to match an individual participant to a specific form of cognitive intervention and, thereby, to maximize treatment outcomes against the debilitating cognitive decline associated with PD. Methods: The present thesis project comprises three studies. Study I evaluates a randomized controlled trial investigating the effects of a 5-week home-based computerized WMT in n = 76 patients with PD without cognitive impairment at posttest and 3-months follow-up. Study II constitutes a systematic review of n = 16 studies on predictors of WMT responsiveness in healthy older adults. Study III analyzes data of the randomized controlled trial reported in Study I with a structural equation modelling approach to investigate predictors of WMT responsiveness in patients with PD. Results: In Study I, WMT was feasible in patients with PD without cognitive impairment and evidence for positive near-transfer training effects in the working memory domain was found. No cognitive and clinical far-transfer effects were observed. Variability of training effects was large across participants. Study II revealed several methodological shortcomings of prognostic research in the field. Nevertheless, a pattern emerged according to which lower baseline performance and better hardware (e.g., younger age, higher intelligence) predict positive WMT responsiveness in healthy older adults. Study III revealed a similar pattern for patients with PD without clinically relevant cognitive decline. Lower baseline performance, younger age, higher fluid intelligence, higher education, and higher self-efficacy expectancy predicted larger positive WMT responsiveness in this patient group. Conclusion: Summarizing, the findings of the present thesis substantially contribute to the research area of evidence-based cognitive interventions against the debilitating cognitive decline associated with PD. Furthermore, the findings promote the implementation of precision medicine approaches in the context of cognitive interventions in general. The potential of non-pharmacological interventions against the debilitating age- and PD-associated cognitive decline is enormous and prognostic research may unlock the possibilities for modern healthcare on the road to precision medicine. High-quality research adhering to high methodological standards on the original-study-level as well as the synthesizing meta-level will be able to close the research gaps within the next years

Neuropsychological Gender Aspects in Patients with Morbus Parkinson

This review aims to summarize (neuro-)psychological gender effects in Parkinson's Disease (IPS). Women with IPS experience depressive symptoms more frequently than men; however, the gender distribution is more balanced than in the general population. Regarding cognition, recent research indicates that women with IPS show more verbal memory decline than men. HrQoL gender differences become more prevalent, when specific HrQoL domains are assessed separately. Summarizing, gender differences in IPS exist in several (neuro-)psychological areas and seem to be of clinical relevance. However, the current state of knowledge and underlying mechanisms are far from being clear. Thus, more research in this context is needed

A Systematic Review on Predictors of Working Memory Training Responsiveness in Healthy Older Adults: Methodological Challenges and Future Directions

Background: Research on predictors of working memory training responsiveness, which could help tailor cognitive interventions individually, is a timely topic in healthy aging. However, the findings are highly heterogeneous, reporting partly conflicting results following a broad spectrum of methodological approaches to answer the question who benefits most from working memory training. Objective: The present systematic review aimed to systematically investigate prognostic factors and models for working memory training responsiveness in healthy older adults. Method: Four online databases were searched up to October 2019 (MEDLINE Ovid, Web of Science, CENTRAL, and PsycINFO). The inclusion criteria for full texts were publication in a peer-reviewed journal in English/German, inclusion of healthy older individuals aged >= 55 years without any neurological and/or psychiatric diseases including cognitive impairment, and the investigation of prognostic factors and/or models for training responsiveness after targeted working memory training in terms of direct training effects, near-transfer effects to verbal and visuospatial working memory as well as far-transfer effects to other cognitive domains and behavioral variables. The study design was not limited to randomized controlled trials. Results: A total of 16 studies including n = 675 healthy older individuals with a mean age of 63.0-86.8 years were included in this review. Within these studies, five prognostic model approaches and 18 factor finding approaches were reported. Risk of bias was assessed using the Quality in Prognosis Studies checklist, indicating that important information, especially regarding the domains study attrition, study confounding, and statistical analysis and reporting, was lacking throughout many of the investigated studies. Age, education, intelligence, and baseline performance in working memory or other cognitive domains were frequently investigated predictors across studies. Conclusions: Given the methodological shortcomings of the included studies, no clear conclusions can be drawn, and emerging patterns of prognostic effects will have to survive sound methodological replication in future attempts to promote precision medicine approaches in the context of working memory training. Methodological considerations are discussed, and our findings are embedded to the cognitive aging literature, considering, for example, the cognitive reserve framework and the compensation vs. magnification account. The need for personalized cognitive prevention and intervention methods to counteract cognitive decline in the aging population is high and the potential enormous. Registration: PROSPERO, ID CRD42019142750

Health-Related Quality of Life Subdomains in Patients with Parkinson's Disease: The Role of Gender

The most frequently used instrument to assess health-related quality of life (HrQoL) in Parkinson's disease (PD) is the Parkinson's Disease Questionnaire 39 (PDQ-39). However, both the dimensionality of the eight PDQ-39 subscales and their summary score recently faced criticism. Furthermore, data on disease-related and neuropsychological determinants and the role of gender on HrQoL in PD are inconclusive yet. Therefore, our aim was to reevaluate the PDQ-39 structure and to further explore determinants of HrQoL, in PD. 245 PD patients (age: M = 69.64, SD = 8.43; 62.9% male; H&Y: Md = 3.00; cognitive assessment with PANDA: M. 24.82, SD = 3.57) from the baseline database of the Cologne Parkinson Network were used to reevaluate the dimensionality of the PDQ-39 with a principal component analysis (PCA). Multiple regression analyses were conducted to clarify general and domain-specific relationships between clinical, (neuro)psychological, and sociodemographic variables, gender in particular, and HrQoL. The PCA identified three HrQoL domains: physical-functioning, cognition, and socioemotional HrQoL. Depressive symptoms were identified as the most important determinant of HrQoL across all models. Disease-related HrQoL determinants (UPDRS-III, H&Y stage, and LEDD) were less strong and consistent HrQoL determinants than nonmotor symptoms. Analyses did not reveal a global gender effect; however, female gender was a negative predictor for physical-functioning and socioemotional HrQoL, whereas male gender was a negative predictor for cognition HrQoL. Our analyses suggest the consideration of a reevaluation of the PDQ-39. Only the full understanding of HrQoL, its determinants, and their interrelationships will allow the development of PD intervention strategies focusing on what matters the most for patients' I IrQoL. Gender is one relevant variable that should be considered in this context

Effects of working memory training in patients with Parkinson's disease without cognitive impairment: A randomized controlled trial

Objective: To determine the feasibility and evaluate effects of a computerized working memory (WM) training (WMT) in patients with Parkinson's Disease (PD) on cognitive and clinical outcomes. Methods: 76 patients with PD without cognitive impairment were randomized to either the WMT group (n = 37), who participated in a 5-week adaptive WMT, or a passive waiting-list control group (CG, n = 39). Patients underwent clinical and neuropsychological examination at baseline, after training, and at 3-months follow-up, with verbal WM and non-verbal WM as primary outcomes. Outcome assessors were blinded for group allocation. Results: All WMT participants completed the training successfully and reported high levels of motivation for and satisfaction with the training. Repeated-measures, linear mixed-effects models revealed positive training effects for the WMT group compared to the CG in verbal working memory with a small relative effect size 0.39 [95%CI 0.05; 0.76] for the 3-months follow-up only. No other reliable training effects in cognitive and clinical variables were found for either point of time. Conclusions: In this randomized controlled trial, WMT was feasible and yielded some evidence for 3-months follow-up training gains in patients with PD. WMT might be an effective intervention to prevent cognitive decline in this patient group, however, more longitudinal studies with longer follow-up periods and more sensitive assessment tools will have to proof this concept

Predicting Working Memory Training Responsiveness in Parkinson's Disease: Both System Hardware and Room for Improvement Are Needed

Background. Patients with Parkinson's disease (PD) are highly vulnerable to develop cognitive dysfunctions, and the mitigating potential of early cognitive training (CT) is increasingly recognized. Predictors of CT responsiveness, which could help to tailor interventions individually, have rarely been studied in PD. This study aimed to examine individual characteristics of patients with PD associated with responsiveness to targeted working memory training (WMT). Methods. Data of 75 patients with PD (age: 63.99 +/- 9.74 years, 93% Hoehn & Yahr stage 2) without cognitive dysfunctions from a randomized controlled trial were analyzed using structural equation modeling. Latent change score models with and without covariates were estimated and compared between the WMT group (n = 37), who participated in a 5-week adaptive WMT, and a waiting list control group (n = 38). Results. Latent change score models yielded adequate model fit (chi(2)-test p > .05, SRMR = .95). For the near-transfer working memory composite, lower baseline performance, younger age, higher education, and higher fluid intelligence were found to significantly predict higher latent change scores in the WMT group, but not in the control group. For the far-transfer executive function composite, higher self-efficacy expectancy tended to significantly predict larger latent change scores. Conclusions. The identified associations between individual characteristics and WMT responsiveness indicate that there has to be room for improvement (e.g., lower baseline performance) and also sufficient hardware (e.g., younger age, higher intelligence) to benefit in training-related cognitive plasticity. Our findings are discussed within the compensation versus magnification account. They need to be replicated by methodological high-quality research applying advanced statistical methods with larger samples

Working memory training increases neural efficiency in Parkinson’s disease: a randomized controlled trial

Impairment of working memory and executive functions is already frequently observed in early stages of Parkinson’s disease. Improvements in working memory performance in this cohort could potentially be achieved via working memory training. However, the specific neural mechanisms underlying different working memory processes such as maintenance as opposed to manipulation are largely under-investigated in Parkinson’s disease. Moreover, the plasticity of these correlates as a function of working memory training is currently unknown in this population. Thus, the working memory subprocesses of maintenance and manipulation were assessed in 41 cognitively healthy patients with Parkinson’s disease using a newly developed working memory paradigm and functional MRI. Nineteen patients were randomized to a 5-week home-based digital working memory training intervention while the remaining patients entered a control, wait list condition. Working memory task-related activation patterns and context-dependent functional connectivity, as well as the change of these neural correlates as a function of training, were assessed. While both working memory processes activated an extended frontoparietal–cerebellar network, only the manipulation of items within working memory also recruited the anterior striatum. The intervention effect on the neural correlates was small, but decreased activation in areas relevant for working memory could be observed, with activation changes correlating with behavioural change. Moreover, training seemed to result in decreased functional connectivity when pure maintenance was required, and in a reorganization of functional connectivity when items had to be manipulated. In accordance with the neural efficacy hypothesis, training resulted in overall reduced activation and reorganized functional connectivity, with a differential effect on the different working memory processes under investigation. Now, larger trials including follow-up examinations are needed to further explore the long-term effects of such interventions on a neural level and to estimate the clinical relevance to potentially delay cognitive decline in cognitively healthy patients with Parkinson’s disease.Keywords: idiopathic Parkinson’s disease, home-based working memory training, functional magnetic resonance imaging, blood oxygen level dependent signal, functional connectivit