Effects of Multisession Prefrontal Transcranial Direct Current Stimulation on Long-term Memory and Working Memory in Older Adults.

Transcranial direct current stimulation (tDCS) is a noninvasive form of electrical brain stimulation popularly used to augment the effects of working memory (WM) training. Although success has been mixed, some studies report enhancements in WM performance persisting days, weeks, or even months that are actually more reminiscent of consolidation effects typically observed in the long-term memory (LTM) domain, rather than WM improvements per se. Although tDCS has been often reported to enhance both WM and LTM, these effects have never been directly compared within the same study. However, given their considerable neural and behavioral overlap, this is a timely comparison to make. This study reports results from a multisession intervention in older adults comparing active and sham tDCS over the left dorsolateral pFC during training on both an n-back WM task and a word learning LTM task. We found strong and robust effects on LTM, but mixed effects on WM that only emerged for those with lower baseline ability. Importantly, mediation analyses showed an indirect effect of tDCS on WM that was mediated by improvements in consolidation. We conclude that tDCS over the left dorsolateral pFC can be used as an effective intervention to foster long-term learning and memory consolidation in aging, which can manifest in performance improvements across multiple memory domains.

Post-training stimulation of the right dorsolateral prefrontal cortex impairs working memory training performance.

Research investigating transcranial direct current stimulation (tDCS) to enhance cognitive training augments both our understanding of its long-term effects on cognitive plasticity as well as potential applications to strengthen cognitive interventions. Previous work has demonstrated enhancement of working memory training while applying concurrent tDCS to the dorsolateral prefrontal cortex (DLPFC). However, the optimal stimulation parameters are still unknown. For example, the timing of tDCS delivery has been shown to be an influential variable that can interact with task learning. In the present study, we used tDCS to target the right DLPFC while participants trained on a visuospatial working memory task. We sought to compare the relative efficacy of online stimulation delivered during training to offline stimulation delivered either immediately before or afterwards. We were unable to replicate previously demonstrated benefits of online stimulation; however, we did find evidence that offline stimulation delivered after training can actually be detrimental to training performance relative to sham. We interpret our results in light of evidence suggesting a role of the right DLPFC in promoting memory interference, and conclude that while tDCS may be a promising tool to influence the results of cognitive training, more research and an abundance of caution are needed before fully endorsing its use for cognitive enhancement. This work suggests that effects can vary substantially in magnitude and direction between studies, and may be heavily dependent on a variety of intervention protocol parameters such as the timing and location of stimulation delivery, about which our understanding is still nascent.

Interaction of prior category knowledge and novel statistical patterns during visual search for real-world objects.

Two aspects of real-world visual search are typically studied in parallel: category knowledge (e.g., searching for food) and visual patterns (e.g., predicting an upcoming street sign from prior street signs). Previous visual search studies have shown that prior category knowledge hinders search when targets and distractors are from the same category. Other studies have shown that task-irrelevant patterns of non-target objects can enhance search when targets appear in locations that previously contained these irrelevant patterns. Combining EEG (N2pc ERP component, a neural marker of target selection) and behavioral measures, the present study investigated how search efficiency is simultaneously affected by prior knowledge of real-world objects (food and toys) and irrelevant visual patterns (sequences of runic symbols) within the same paradigm. We did not observe behavioral differences between locating items in patterned versus random locations. However, the N2pc components emerged sooner when search items appeared in the patterned location, compared to the random location, with a stronger effect when search items were targets, as opposed to non-targets categorically related to the target. A multivariate pattern analysis revealed that neural responses during search trials in the same time window reflected where the visual patterns appeared. Our finding contributes to our understanding of how knowledge acquired prior to the search task (e.g., category knowledge) interacts with new content within the search task.

Rapid category selectivity for animals versus man-made objects: An N2pc study.

Visual recognition occurs rapidly at multiple categorization levels, including the superordinate level (e.g., animal), basic level (e.g., cat), or exemplar level (e.g., my cat). Visual search for animals is faster than for man-made objects, even when the images from those categories have comparable gist statistics (i.e., low- or mid-level visual information), which suggests that higher-level, conceptual influences may support this search advantage for animals. However, it remains unclear whether the search advantage can be explained in part by early visual search processes via the N2pc ERP component, which emerges earlier than behavioral responses, across different categorization levels. Participants searched for 1) an exact image (e.g., a specific squirrel image, Exemplar-level Search), 2) any images of an item (e.g., any squirrels, Basic-level Search), or 3) any items in a category (e.g., any animals, Superordinate-level Search). In addition to Target Present trials, Foil trials measured involuntary attentional selection of task-irrelevant images related to the targets (e.g., other squirrel images when searching for a specific squirrel image, or other animals when searching for squirrels). ERP results revealed 1) a larger N2pc amplitude during Foil trials in Exemplar-level Search for animals than man-made objects, and 2) faster onset latencies for animal search than man-made object search across all categorization levels. These results suggest that the search advantage for animals over man-made objects emerges early, and that attentional selection is more biased toward the basic-level (e.g., squirrel) for animals than for man-made objects during visual search.

Multisensory Facilitation of Working Memory Training.

Research suggests that memorization of multisensory stimuli benefits performance compared to memorization of unisensory stimuli; however, little is known about multisensory facilitation in the context of working memory (WM) training and transfer. To investigate this, 240 adults were randomly assigned to an N-back training task that consisted of visual-only stimuli, alternating visual and auditory blocks, or audio-visual (multisensory) stimuli, or to a passive control group. Participants in the active groups completed 13 sessions of N-back training (6.7 hours in total) and all groups completed a battery of WM tasks: untrained N-back tasks, Corsi Blocks, Sequencing, and Symmetry Span. The Multisensory group showed similar training N-level gain compared to the Visual Only group, and both of these groups outperformed the Alternating group on the training task. As expected, all three active groups significantly improved on untrained visual N-back tasks compared to the Control group. In contrast, the Multisensory group showed significantly greater gains on the Symmetry Span task and to a certain extent on the Sequencing task compared to other groups. These results tentatively suggest that incorporating multisensory objects in a WM training protocol can benefit performance on the training task and potentially facilitate transfer to complex WM span tasks.

Expanding the product profile of a microbial alkane biosynthetic pathway.

Microbially produced alkanes are a new class of biofuels that closely match the chemical composition of petroleum-based fuels. Alkanes can be generated from the fatty acid biosynthetic pathway by the reduction of acyl-ACPs followed by decarbonylation of the resulting aldehydes. A current limitation of this pathway is the restricted product profile, which consists of n-alkanes of 13, 15, and 17 carbons in length. To expand the product profile, we incorporated a new part, FabH2 from Bacillus subtilis , an enzyme known to have a broader specificity profile for fatty acid initiation than the native FabH of Escherichia coli . When provided with the appropriate substrate, the addition of FabH2 resulted in an altered alkane product profile in which significant levels of n-alkanes of 14 and 16 carbons in length are produced. The production of even chain length alkanes represents initial steps toward the expansion of this recently discovered microbial alkane production pathway to synthesize complex fuels. This work was conceived and performed as part of the 2011 University of Washington international Genetically Engineered Machines (iGEM) project.