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Background: Deficits in cognition like working memory (WM) are highly prevalent symptoms related to major depressive disorder (MDD). Neuroimaging studies have described frontoparietal abnormalities in patients with MDD as a basis for these deficits. Based on research in healthy adults, it is hypothesized that increased physical fitness might be a protective factor for these deficits in MDD. However, the relationship between physical fitness and WM-related neural activity and performance has not been tested in MDD, to date. Understanding these associations could inform the development of physical exercise interventions in MDD., Methods: Within a larger project, 111 (53female) MDD outpatients and 56 (34female) healthy controls performed an n-back task (0-, 1-, 2-, 3-back) during functional Magnetic Resonance Imaging. Physical fitness from a graded exercise test on a cycle ergometer was performed by 106 MDD patients., Results: Patients showed reduced performance particularly at high loads of the n-back WM task and prolonged reaction times at all n-back loads. A whole-brain interaction analysis of group by WM load revealed reduced neural activity in six frontoparietal clusters at medium and high WM loads in MDD patients compared to healthy controls. Analysis of covariance within the MDD sample showed that physical fitness was associated with neural activity in right and left superior parietal lobules. Externally defined Regions of Interest confirmed this analysis., Conclusions: Results indicate frontoparietal hypoactivity in MDD at high demands, arguing for decreased WM capacity. We demonstrate a parietal fitness correlate which could be used to guide future research on effects of exercise on cognitive functioning in MDD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Alterations in frontal and parietal neural activations during working memory task performance have been suggested as a candidate endophenotype of obsessive-compulsive disorder (OCD) in studies involving first-degree relatives. However, the direct link between genetic risk for OCD and neuro-functional alterations during working memory performance has not been investigated to date. Thus, the aim of the current functional magnetic resonance imaging (fMRI) study was to test the direct association between polygenic risk for OCD and neural activity during the performance of a numeric n-back task with four working memory load conditions in 128 participants, including patients with OCD, unaffected first-degree relatives of OCD patients, and healthy controls. Behavioral results show a significant performance deficit at high working memory load in both patients with OCD and first-degree relatives (p < 0.05). A whole-brain analysis of the fMRI data indicated decreased neural activity in bilateral inferior parietal lobule and dorsolateral prefrontal cortex in both patients and relatives. Most importantly, OCD polygenic risk scores predicted neural activity in orbitofrontal cortex. Results indicate that genetic risk for OCD can partly explain alterations in brain response during working memory performance, supporting the notion of a neuro-functional endophenotype for OCD., (© 2021. The Author(s).)

Breaks filled with different break activities often interrupt cognitive performance in everyday life. Previous studies have reported that both enhancing and deteriorating effects on challenging ongoing tasks such as working memory updating, depend on the type of break activity. However, neural mechanisms of these break-related alterations in working memory performance have not been studied, to date. Therefore, we conducted a brain imaging study to identify the neurobiological correlates of effects on the n-back working memory task related to different break activities. Before performing the n-back task in the magnetic resonance imaging (MRI) scanner, young adults were exposed to break activities in the MRI scanner involving (i) eyes-open resting, (ii) listening to music, and (iii) playing the video game "Angry Birds". Heart rate was measured by a pulse oximeter during the experiment. We found that increased heart rate during gaming as well as decreased relaxation levels after a video gaming break was related to poorer n-back task performance, as compared to listening to music. On the neural level, video gaming reduced supplementary motor area activation during working memory performance. These results may indicate that video gaming during a break may affect working memory performance by interfering with arousal state and frontal cognitive control functions., Competing Interests: The authors have declared that no competing interests exist.

Previous research in patients with obsessive-compulsive disorder (OCD) has indicated performance decrements in working memory (WM) and response inhibition. However, underlying neural mechanisms of WM deficits are not well understood to date, and empirical evidence for a proposed conceptual link to inhibition deficits is missing. We investigated WM performance in a numeric n-back task with four WM load conditions during functional Magnetic Resonance Imaging (fMRI) in 51 patients with OCD and 49 healthy control participants who were matched for age, sex, and education. Additionally, a stop signal task was performed outside the MRI scanner in a subsample. On the behavioral level, a significant WM load by group interaction was found for both accuracy (p < 0.02) and reaction time measures (p < 0.03), indicating increased reaction times as well as reduced accuracy specifically at high WM load (3-back) in patients with OCD. Whole-brain analyses of fMRI-data identified neural correlates of a load-dependent WM decrement in OCD in the supplementary motor area (SMA) and the inferior parietal lobule (IPL). Within the OCD sample, SMA-activity as well as n-back performance were correlated with stop signal task performance. Results from behavioral and fMRI-analyses indicate a reduced WM load-dependent modulation of neural activity in OCD and suggest a common neural mechanism for inhibitory dysfunction and WM decrements in OCD.

Theoretical models and preceding studies have described age-related alterations in neuronal activation of frontoparietal regions in a working memory (WM) load-dependent manner. However, to date, underlying neuronal mechanisms of these WM load-dependent activation changes in aging remain poorly understood. The aim of this study was to investigate these mechanisms in terms of effective connectivity by application of dynamic causal modeling with Bayesian Model Selection. Eighteen healthy younger (age: 20-32 years) and 32 older (60-75 years) participants performed an n-back task with 3 WM load levels during functional magnetic resonance imaging (fMRI). Behavioral and conventional fMRI results replicated age group by WM load interactions. Importantly, the analysis of effective connectivity derived from dynamic causal modeling, indicated an age- and performance-related reduction in WM load-dependent modulation of connectivity from dorsolateral prefrontal cortex to inferior parietal lobule. This finding provides evidence for the proposal that age-related WM decline manifests as deficient WM load-dependent modulation of neuronal top-down control and can integrate implications from theoretical models and previous studies of functional changes in the aging brain., (Copyright © 2017 Elsevier Inc. All rights reserved.)

As indicated by previous research, aging is associated with a decline in working memory (WM) functioning, related to alterations in fronto-parietal neural activations. At the same time, previous studies showed that WM training in older adults may improve the performance in the trained task (training effect), and more importantly, also in untrained WM tasks (transfer effects). However, neural correlates of these transfer effects that would improve understanding of its underlying mechanisms, have not been shown in older participants as yet. In this study, we investigated blood-oxygen-level-dependent (BOLD) signal changes during n-back performance and an untrained delayed recognition (Sternberg) task following 12sessions (45min each) of adaptive n-back training in older adults. The Sternberg task used in this study allowed to test for neural training effects independent of specific task affordances of the trained task and to separate maintenance from updating processes. Thirty-two healthy older participants (60-75years) were assigned either to an n-back training or a no-contact control group. Before (t1) and after (t2) training/waiting period, both the n-back task and the Sternberg task were conducted while BOLD signal was measured using functional Magnetic Resonance Imaging (fMRI) in all participants. In addition, neuropsychological tests were performed outside the scanner. WM performance improved with training and behavioral transfer to tests measuring executive functions, processing speed, and fluid intelligence was found. In the training group, BOLD signal in the right lateral middle frontal gyrus/caudal superior frontal sulcus (Brodmann area, BA 6/8) decreased in both the trained n-back and the updating condition of the untrained Sternberg task at t2, compared to the control group. fMRI findings indicate a training-related increase in processing efficiency of WM networks, potentially related to the process of WM updating. Performance gains in untrained tasks suggest that transfer to other cognitive tasks remains possible in aging., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In the domain of working memory (WM), a sigmoid-shaped relationship between WM load and brain activation patterns has been demonstrated in younger adults. It has been suggested that age-related alterations of this pattern are associated with changes in neural efficiency and capacity. At the same time, WM training studies have shown that some older adults are able to increase their WM performance through training. In this study, functional magnetic resonance imaging during an n-back WM task at different WM load levels was applied to compare blood oxygen level-dependent (BOLD) responses between younger and older participants and to predict gains in WM performance after a subsequent 12-session WM training procedure in older adults. We show that increased neural efficiency and capacity, as reflected by more "youth-like" brain response patterns in regions of interest of the frontoparietal WM network, were associated with better behavioral training outcome beyond the effects of age, sex, education, gray matter volume, and baseline WM performance. Furthermore, at low difficulty levels, decreases in BOLD response were found after WM training. Results indicate that both neural efficiency (i.e., decreased activation at comparable performance levels) and capacity (i.e., increasing activation with increasing WM load) of a WM-related network predict plasticity of the WM system, whereas WM training may specifically increase neural efficiency in older adults.

Objectives: Recent work suggests that a genetic variation associated with increased dopamine metabolism in the prefrontal cortex (catechol-O-methyltransferase Val158Met; COMT) amplifies age-related changes in working memory performance. Research on younger adults indicates that the influence of dopamine-related genetic polymorphisms on working memory performance increases when testing the cognitive limits through training. To date, this has not been studied in older adults., Method: Here we investigate the effect of COMT genotype on plasticity in working memory in a sample of 14 younger (aged 24-30 years) and 25 older (aged 60-75 years) healthy adults. Participants underwent adaptive training in the n-back working memory task over 12 sessions under increasing difficulty conditions., Results: Both younger and older adults exhibited sizeable behavioral plasticity through training (P < .001), which was larger in younger as compared to older adults (P < .001). Age-related differences were qualified by an interaction with COMT genotype (P < .001), and this interaction was due to decreased behavioral plasticity in older adults carrying the Val/Val genotype, while there was no effect of genotype in younger adults., Discussion: Our findings indicate that age-related changes in plasticity in working memory are critically affected by genetic variation in prefrontal dopamine metabolism.

Previous studies on working memory training have indicated that transfer to non-trained tasks of other cognitive domains may be possible. The aim of this study is to compare working memory training and transfer effects between younger and older adults (n = 60). A novel approach to adaptive n-back training (12 sessions) was implemented by varying the working memory load and the presentation speed. All participants completed a neuropsychological battery of tests before and after the training. On average, younger training participants achieved difficulty level 12 after training, while older training participants only reached difficulty level 5. In younger participants, transfer to Verbal Fluency and Digit Symbol Substitution test was found. In older participants, we observed a transfer to Digit Span Forward, CERAD Delayed Recall, and Digit Symbol Substitution test. Results suggest that working memory training may be a beneficial intervention for maintaining and improving cognitive functioning in old age.