Structural MRI of the basal forebrain as predictor of cognitive response to galantamine in healthy older adults-A randomized controlled double-blinded crossover study.

INTRODUCTION: Cholinesterase inhibitors can enhance cognitive functions in healthy elderly and delay cognitive decline in patients with Alzheimer`s disease (AD). However, not everyone benefits from this treatment (non-responders). Current studies show clinical meaningful improvements only in one third of AD patients treated with cholinesterase inhibitors. METHODS: Here we investigate structural magnetic resonance imaging of the basal forebrain cholinergic system volume (BFvol) as a potential predictor of cognitive response to a single dose of galantamine in healthy adults (n = 18; 59 to 75 years). RESULTS: We observed that the cognitive response to galantamine, more specifically the attention-dependent filtering performance in a delayed match-to-sample working memory task, correlated with BFvol: Only participants with high BFvol showed a significant positive effect of galantamine on the ability to filter out distracting information during the working memory encoding process. DISCUSSION: Future studies need to assess whether BFvol may serve as a predictor of the galantamine response in AD patients, too.

High Working Memory Capacity at the Cost of Precision?

Working memory capacity (WMC) varies tremendously among individuals. Here, we investigate the possibility that subjects with high WMC use this limited resource more efficiently by reducing the precision with which they store information in demanding tasks. Task difficulty was increased by (a) presenting more objects to be memorized, (b) informing subjects only after the encoding phase about the relevant objects, and (c) delivering distracting features at retrieval. Precision was assessed by means of a continuous delayed-estimation task, in which object features had to be estimated from memory. High WMC subjects did not show a stronger drop in precision in difficult tasks. Instead, a positive correlation between precision and general WMC emerged. These findings suggest that high WMC subjects do not necessarily trade in quantity for quality when forming working memory (WM) representations under increasing demand. Instead, they seem to be able to devote more cognitive resources to support WM storage.

Filtering and storage working memory networks in younger and older age.

INTRODUCTION: Working memory (WM) is a multi-component model that among others involves the two processes of filtering and storage. The first reflects the necessity to inhibit irrelevant information from entering memory, whereas the latter refers to the active maintenance of object representations in memory. In this study, we aimed at a) redefining the neuronal networks sustaining filtering and storage within visual working memory by avoiding shortcomings of prior studies, and b) assessing age-related changes in these networks. METHODS: We designed a new paradigm that strictly controlled for perceptual load by presenting the same number of stimuli in each of three conditions. We calculated fMRI contrasts between a baseline condition (low filter and low storage load) and conditions that posed high demands on filtering and storage, respectively, in large samples of younger (n = 40) and elder (n = 38) participants. RESULTS: Our approach of comparing contrasts between groups revealed more extensive filter and storage WM networks than previous studies. In the younger group, filtering involved the bilateral insulae, the right occipital cortex, the right brainstem, and the right cerebellum. In the elder group, filtering was associated with the bilateral insulae, right precuneus, and bilateral ventromedial prefrontal cortex. An extensive neuronal network was also found during storage of information in the bilateral posterior parietal cortex, the left ventromedial prefrontal cortex, and the right precuneus in the younger participants. In addition to these brain regions, elder participants recruited the bilateral ventral prefrontal cortex, the superior, middle and inferior and temporal cortex, the left cingulum and the bilateral parahippocampal cortex. CONCLUSIONS: In general, elder participants recruited more brain regions in comparison to younger participants to reach similar accuracy levels. Furthermore, in elder participants one brain region emerged in both contrasts, namely the left ventromedial prefrontal cortex. Hence, elder participants seem to routinely recruit this brain region in demanding tasks, irrespective of whether filtering or storing is challenged.

Working Memory Network Changes in ALS: An fMRI Study.

We used amyotrophic lateral sclerosis (ALS) as a model of prefrontal dysfunction in order to re-assess the potential neuronal substrates of two sub processes of working memory, namely information storage and filtering. To date it is unclear which exact neuronal networks sustain these two processes and the prefrontal cortex was suggested to play a crucial role both for filtering out of irrelevant information and for the storage of relevant information in memory. Other research has attributed information storage to more posterior brain regions, including the parietal cortex and stressed the role of subcortical areas in information filtering. We studied 14 patients suffering from ALS and the same number of healthy controls in an fMRI-task that allowed calculating separate storage and filtering scores. A brain volume analysis confirmed prefrontal atrophy in the patient group. Regarding their performance in the working memory task, we observed a trend toward slightly impaired storage capabilities whereas filtering appeared completely intact. Despite the rather subtle behavioral deficits we observed marked changes in neuronal activity associated with ALS: Compared to healthy controls patients showed significantly reduced hemodynamic responses in the left occipital cortex and right prefrontal cortex in the storage contrast. The filter contrast on the other hand revealed a relative hyperactivation in the superior frontal gyrus of the ALS patients. This hyperactivation might reflect a possible compensational mechanism for the prefrontal degeneration found in ALS. The reduced hemodynamic responses in the storage contrast might reflect a disruption of prefrontal top-down control of posterior brain regions, a process which was especially relevant in the most difficult high load memory task. Taken together, the present study demonstrates marked neurophysiological changes in ALS patients compared to healthy controls during the filtering and storage of information in spite of largely intact behavior. With respect to the neuronal substrates of the two working memory processes under investigation here, the results suggest that it is rather the degree to which top-down control is required for task completion that determines prefrontal cortex involvement than the specific nature of the process, i.e., storage vs. filtering.

Training of Attentional Filtering, but Not of Memory Storage, Enhances Working Memory Efficiency by Strengthening the Neuronal Gatekeeper Network.

Memory training (MT) in older adults with memory deficits often leads to frustration and, therefore, is usually not recommended. Here, we pursued an alternative approach and looked for transfer effects of 1-week attentional filter training (FT) on working memory performance and its neuronal correlates in young healthy humans. The FT effects were compared with pure MT, which lacked the necessity to filter out irrelevant information. Before and after training, all participants performed an fMRI experiment that included a combined task in which stimuli had to be both filtered based on color and stored in memory. We found that training induced processing changes by biasing either filtering or storage. FT induced larger transfer effects on the untrained cognitive function than MT. FT increased neuronal activity in frontal parts of the neuronal gatekeeper network, which is proposed to hinder irrelevant information from being unnecessarily stored in memory. MT decreased neuronal activity in the BG part of the gatekeeper network but enhanced activity in the parietal storage node. We take these findings as evidence that FT renders working memory more efficient by strengthening the BG-prefrontal gatekeeper network. MT, on the other hand, simply stimulates storage of any kind of information. These findings illustrate a tight connection between working memory and attention, and they may open up new avenues for ameliorating memory deficits in patients with cognitive impairments.

Entrainment of Human Alpha Oscillations Selectively Enhances Visual Conjunction Search.

The functional role of the alpha-rhythm which dominates the human electroencephalogram (EEG) is unclear. It has been related to visual processing, attentional selection and object coherence, respectively. Here we tested the interaction of alpha oscillations of the human brain with visual search tasks that differed in their attentional demands (pre-attentive vs. attentive) and also in the necessity to establish object coherence (conjunction vs. single feature). Between pre- and post-assessment elderly subjects received 20 min/d of repetitive transcranial alternating current stimulation (tACS) over the occipital cortex adjusted to their individual alpha frequency over five consecutive days. Compared to sham the entrained alpha oscillations led to a selective, set size independent improvement in the conjunction search task performance but not in the easy or in the hard feature search task. These findings suggest that cortical alpha oscillations play a specific role in establishing object coherence through suppression of distracting objects.