Modulation of resting-state networks following repetitive transcranial alternating current stimulation of the dorsolateral prefrontal cortex.

Transcranial alternating current stimulation (tACS) offers a unique method to temporarily manipulate the activity of the stimulated brain region in a frequency-dependent manner. However, it is not clear if repetitive modulation of ongoing oscillatory activity with tACS over multiple days can induce changes in grey matter resting-state functional connectivity and white matter structural integrity. The current study addresses this question by applying multiple-session theta band stimulation on the left dorsolateral prefrontal cortex (L-DLPFC) during arithmetic training. Fifty healthy participants (25 males and 25 females) were randomly assigned to the experimental and sham groups, half of the participants received individually adjusted theta band tACS, and half received sham stimulation. Resting-state functional magnetic resonance (rs-fMRI) and diffusion-weighted imaging (DWI) data were collected before and after 3 days of tACS-supported procedural learning training. Resting-state network analysis showed a significant increase in connectivity for the frontoparietal network (FPN) with the precuneus cortex. Seed-based analysis with a seed defined at the primary stimulation site showed an increase in connectivity with the precuneus cortex, posterior cingulate cortex (PCC), and lateral occipital cortex. There were no effects on the structural integrity of white matter tracts as measured by fractional anisotropy, and on behavioral measures. In conclusion, the study suggests that multi-session task-associated tACS can produce significant changes in resting-state functional connectivity; however, changes in functional connectivity do not necessarily translate to changes in white matter structure or behavioral performance.

Functional (un-)Coupling: Impairment, Compensation, and Future Progression in Alzheimer's Disease.

Background: Functional (un-)coupling (task-related change of functional connectivity) between different sites of the brain is a mechanism of general importance for cognitive processes. In Alzheimer's disease (AD), prior research identified diminished cortical connectivity as a hallmark of the disease. However, little is known about the relation between the amount of functional (un-)coupling and cognitive performance and decline in AD. Method: Cognitive performance (based on CERAD-Plus scores) and electroencephalogram (EEG)-based functional (un-)coupling measures (connectivity changes from rest to a Face-Name-Encoding task) were assessed in 135 AD patients (age: M = 73.8 years; SD = 9.0). Of these, 68 patients (M = 73.9 years; SD = 8.9) participated in a follow-up assessment of their cognitive performance 1.5 years later. Results: The amounts of functional (un-)coupling in left anterior-posterior and homotopic interhemispheric connections in beta1-band were related to cognitive performance at baseline (ß = .340; p < .001; ß = .274; P = .001, respectively). For both markers, a higher amount of functional coupling was associated with better cognitive performance. Both markers also were significant predictors for cognitive decline. However, while patients with greater functional coupling in left anterior-posterior connections declined less in cognitive performance (ß = .329; P = .035) those with greater functional coupling in interhemispheric connections declined more (ß = -.402; P = .010). Conclusion: These findings suggest an important role of functional coupling mechanisms in left anterior-posterior and interhemispheric connections in AD. Especially the complex relationship with cognitive decline in AD patients might be an interesting aspect for future studies.

Revisiting the Role of Worries in Explaining the Link Between Test Anxiety and Test Performance.

The inverse relationship between test anxiety and test performance is commonly explained by test-anxious students' tendency to worry about a test and the consequences of failing. However, other cognitive facets of test anxiety have been identified that could account for this link, including interference by test-irrelevant thoughts and lack of confidence. In this study, we compare different facets of test anxiety in predicting test performance. Seven hundred thirty university students filled out the German Test Anxiety Inventory after completing a battery of standardized tests assessing general intelligence and mathematical competencies. Multiple regressions revealed that interference and lack of confidence but not worry or arousal explained unique variance in students' test performance. No evidence was found for a curvilinear relationship between arousal and performance. The present results call for revisiting the role of worries in explaining the test anxiety-performance link and can help educators to identify students who are especially at risk of underperforming on tests.

Oscillatory electroencephalographic patterns of arithmetic problem solving in fourth graders.

Numerous studies have identified neurophysiological correlates of performing arithmetic in adults. For example, oscillatory electroencephalographic (EEG) patterns associated with retrieval and procedural strategies are well established. Whereas fact retrieval has been linked to enhanced left-hemispheric theta ERS (event-related synchronization), procedural strategies are accompanied by increased bilateral alpha ERD (event-related desynchronization). It is currently not clear if these findings generalize to children. Our study is the first to investigate oscillatory EEG activity related to strategy use and arithmetic operations in children. We assessed ERD/ERS correlates of 31 children in fourth grade (aged between nine and ten years) during arithmetic problem solving. We presented multiplication and subtraction problems, which children solved with fact retrieval or a procedure. We analyzed these four problem categories (retrieved multiplications, retrieved subtractions, procedural multiplications, and procedural subtractions) in our study. In summary, we found similar strategy-related patterns to those reported in previous studies with adults. That is, retrieval problems elicited stronger left-hemispheric theta ERS and weaker alpha ERD as compared to procedural problems. Interestingly, we observed neurophysiological differences between multiplications and subtractions within retrieval problems. Although there were no response time or accuracy differences, retrieved multiplications were accompanied by larger theta ERS than retrieved subtractions. This finding could indicate that retrieval of multiplication and subtraction facts are distinct processes, and/or that multiplications are more frequently retrieved than subtractions in this age group.

Theta Band Transcranial Alternating Current Stimulation Enhances Arithmetic Learning: A Systematic Comparison of Different Direct and Alternating Current Stimulations.

Over the last decades, interest in transcranial electrical stimulation (tES) has grown, as it might allow for causal investigations of the associations between cortical activity and cognition as well as to directly influence cognitive performance. The main objectives of the present work were to assess whether tES can enhance the acquisition and application of arithmetic abilities, and whether it enables a better assessment of underlying neurophysiological processes. To this end, the present, double-blind, sham-controlled study assessed the effects of six active stimulations (three tES protocols: anodal transcranial direct current stimulation (tDCS), alpha band transcranial alternating current stimulation (tACS), and theta band tACS; targeting the left dorsolateral prefrontal cortex or the left posterior parietal cortex) on the acquisition of an arithmetic procedure, arithmetic facts, and event-related synchronization/desynchronization (ERS/ERD) patterns. 137 healthy adults were randomly assigned to one of seven groups, each receiving one of the tES-protocols during learning. Results showed that frontal theta band tACS reduced the repetitions needed to learn novel facts and both, frontal and parietal theta band tACS accelerated the decrease in calculation times in fact learning problems. The beneficial effect of frontal theta band tACS may reflect enhanced executive functions, allowing for better control and inhibition processes and hence, a faster acquisition and integration of novel fact knowledge. However, there were no significant effects of the stimulations on procedural learning or ERS/ERD patterns. Overall, theta band tACS appears promising as a support for arithmetic fact training, but effects on procedural calculations and neurophysiological processes remain ambiguous.

Effects of transcranial stimulation in developmental neurocognitive disorders: A critical appraisal.

Non-invasive brain stimulation (NIBS) has been highlighted as a powerful tool to promote neuroplasticity, and an attractive approach to support cognitive remediation. Here we provide a systematic review of 26 papers using NIBS to ameliorate cognitive dysfunctions in three prevalent neurodevelopmental disorders: Attention-Deficit/Hyperactivity Disorder (ADHD), Developmental Dyslexia and Developmental Dyscalculia. An overview of the state of research shows a predominance of studies using repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) techniques, and an unequal distribution among clinical conditions. Regarding the utility of NIBS, the results are promising but also ambiguous. Twenty-three papers reported beneficial effects, but many of these effects were found only once or were only partially replicated and some studies even reported detrimental effects. Furthermore, most studies differed in at least one core aspect, the NIBS applied, the questionnaires and cognitive tests conducted, or the age group investigated, and sample sizes were mostly small. Hence, further studies are needed to rigorously examine the potential of NIBS in the remediation of cognitive functions. Finally, we discuss potential caveats and future directions. We reason that if adequately addressing these challenges NIBS can be feasible, with potential benefits in treating neurodevelopmental disorders.

Effects of Anodal tDCS on Arithmetic Performance and Electrophysiological Activity.

Arithmetic abilities are among the most important school-taught skills and form the basis for higher mathematical competencies. At the same time, their acquisition and application can be challenging. Hence, there is broad interest in methods to improve arithmetic abilities. One promising method is transcranial direct current stimulation (tDCS). In the present study, we compared two anodal tDCS protocols in their efficacy to improve arithmetic performance and working memory. In addition, we investigated stimulation-related electrophysiological changes. Three groups of participants solved arithmetic problems (additions and subtractions) and an n-back task before, during, and after receiving either frontal or parietal anodal tDCS (25 min; 1 mA) or sham stimulation. EEG was simultaneously recorded to assess stimulation effects on event-related (de-) synchronisation (ERS/ERD) in theta and alpha bands. Persons receiving frontal stimulation showed an acceleration of calculation speed in large subtractions from before to during and after stimulation. However, a comparable, but delayed (apparent only after stimulation) increase was also found in the sham stimulation group, while it was absent in the group receiving parietal stimulation. In additions and small subtractions as well as the working memory task, analyses showed no effects of stimulation. Results of ERS/ERD during large subtractions indicate changes in ERS/ERD patterns over time. In the left hemisphere there was a change from theta band ERD to ERS in all three groups, whereas a similar change in the right hemisphere was restricted to the sham group. Taken together, tDCS did not lead to a general improvement of arithmetic performance. However, results indicate that frontal stimulation accelerated training gains, while parietal stimulation halted them. The absence of general performance improvements, but acceleration of training effects might be a further indicator of the advantages of using tDCS as training or learning support over tDCS as a sole performance enhancer.

Specific Neuropsychiatric Symptoms Are Associated with Faster Progression in Alzheimer's Disease: Results of the Prospective Dementia Registry (PRODEM-Austria).

BACKGROUND: Neuropsychiatric symptoms (NPS) occur frequently in the course of Alzheimer's disease (AD) and are suspected to be associated with a faster dementia progression. Numerous reports have defined specific subsyndromes, summarized in clusters of items of the Neuropsychiatric Inventory (NPI). OBJECTIVE: This study investigated the influence of specific NPI subsyndromes and clinical patient characteristics on dementia progression. METHODS: Data of the prospective registry on dementia in Austria (PRODEM) were retrospectively analyzed. Cognitive functioning was determined at baseline and 2 yearly follow-up visits using the Mini-Mental State Examination (MMSE) and the Consortium to Establish a Registry for Alzheimer's dementia neuropsychological test battery (CERAD). To assess NPS, the NPI was used: NPI items were classified in three subsyndromes (psychotic cluster, behavioral cluster, emotional cluster). RESULTS: Out of the 662 included patients (mean age 76.4±8.4 years), 43% completed follow-up visits for two years. Significant correlation between higher scores in all three subsyndromes and worse cognitive performance were found for MMSE score, naming, and verbal fluency. Results of linear mixed model analysis revealed lower age and higher scores in the psychotic cluster as significant predictors of changes in MMSE with time. CONCLUSION: In this study, we report the influence of psychotic subsyndromes and lower age on faster MMSE decline in early AD. These results emphasize the importance of not only assessing but also differentiating neuropsychiatric symptoms in subsyndromes in the early stages of AD as a possible predictor of disease progression.

Neuroimaging markers of global cognition in early Alzheimer's disease: A magnetic resonance imaging-electroencephalography study.

INTRODUCTION: Magnetic resonance imaging (MRI) and electroencephalography (EEG) are a promising means to an objectified assessment of cognitive impairment in Alzheimer's disease (AD). Individually, however, these modalities tend to lack precision in both AD diagnosis and AD staging. A joint MRI-EEG approach that combines structural with functional information has the potential to overcome these limitations. MATERIALS AND METHODS: This cross-sectional study systematically investigated the link between MRI and EEG markers and the global cognitive status in early AD. We hypothesized that the joint modalities would identify cognitive deficits with higher accuracy than the individual modalities. In a cohort of 111 AD patients, we combined MRI measures of cortical thickness and regional brain volume with EEG measures of rhythmic activity, information processing and functional coupling in a generalized multiple regression model. Machine learning classification was used to evaluate the markers' utility in accurately separating the subjects according to their cognitive score. RESULTS: We found that joint measures of temporal volume, cortical thickness, and EEG slowing were well associated with the cognitive status and explained 38.2% of ifs variation. The inclusion of the covariates age, sex, and education considerably improved the model. The joint markers separated the subjects with an accuracy of 84.7%, which was considerably higher than by using individual modalities. CONCLUSIONS: These results suggest that including joint MRI-EEG markers may be beneficial in the diagnostic workup, thus allowing for adequate treatment. Further studies in larger populations, with a longitudinal design and validated against functional-metabolic imaging are warranted to confirm the results.

Gender-Specific Differences in Cognitive Profiles of Patients with Alzheimer's Disease: Results of the Prospective Dementia Registry Austria (PRODEM-Austria).

BACKGROUND: Alzheimer's disease (AD) is one of the most common age-related diseases in the western world. Gender differences in neuropsychological functions are seldom evaluated in AD. OBJECTIVE: Recent investigations suggested that gender may be an important modifying factor in the development and progression of AD. We examined gender-specific differences in the pattern of cognitive dysfunction of patients with mild to moderate AD. METHODS: We examined 113 males (mean age 78) and 173 females (mean age 80) of the prospective registry on dementia in Austria (PRODEM). We analyzed differences in the cognitive profile between male and female AD patients on the CERAD-Plus test battery. RESULTS: We found gender-related differences in the neuropsychological domains of verbal learning; the women tended to perform worse than men. Controlling for depression, stage and duration of dementia, and the level of education, there was still a significant effect of gender on verbal episodic memory. CONCLUSION: There is an interaction between gender and cognitive function, most notable in verbal episodic memory; female patients in the early stage of AD performed worse on verbal episodic memory than men. This indicates that the gender-specificities of neuropsychological functions should be given careful consideration in clinical diagnosis of dementia.

Affective processing in positive schizotypy: Loose control of social-emotional information.

Behavioral studies suggested heightened impact of emotionally laden perceptual input in schizophrenia spectrum disorders, in particular in patients with prominent positive symptoms. De-coupling of prefrontal and posterior cortices during stimulus processing, which is related to loosening of control of the prefrontal cortex over incoming affectively laden information, may underlie this abnormality. Pre-selected groups of individuals with low versus high positive schizotypy (lower and upper quartile of a large screening sample) were tested. During exposure to auditory displays of strong emotions (anger, sadness, cheerfulness), individuals with elevated levels of positive schizotypal symptoms showed lesser prefrontal-posterior coupling (EEG coherence) than their symptom-free counterparts (right hemisphere). This applied to negative emotions in particular and was most pronounced during confrontation with anger. The findings indicate a link between positive symptoms and a heightened impact particularly of threatening emotionally laden stimuli which might lead to exacerbation of positive symptoms and inappropriate behavior in interpersonal situations.