Age-Specific Barriers and Facilitators to Research Participation Amongst African Americans in Observational Studies of Memory and Aging.

BACKGROUND: Black/African Americans experience a high burden of Alzheimer disease and related dementias yet are critically underrepresented in corresponding research. Understanding barriers and facilitators to research participation among younger and older African Americans is necessary to inform age-specific strategies to promote equity in studies of early- and late-onset neurodegenerative diseases. STUDY DESIGN: Survey respondents (n = 240) rated barriers and facilitators of research participation. Age-specific differences were evaluated using nonparametric Kruskal-Wallis tests across respondents aged 18-44 years (n = 76), 45-64 years (n = 83), and ≥ 65 years (n = 81). Strategies to mitigate barriers and promote facilitators were further explored via community-based focus groups. Pooled frequency of common themes discussed in focus groups were evaluated and compared across different ages including ≥ 45 years, ≥ 65 years, and mixed ages ≥ 45 years. RESULTS: Younger respondents (aged 18-44 and 45-64 years) expressed a greater need for flexibility in when, where, and how research testing takes place versus adults ≥ 65 years. Focus groups emphasized long-lasting consequences of systemic racism and the need to build and foster trust to resolve barriers and promote research engagement amongst African Americans. DISCUSSION: Age-specific strategies are needed to increase engagement, address recruitment disparities, and promote retention of African American participants in memory and aging studies across the lifespan.

Efficacy of Transcranial Alternating Current Stimulation in the Enhancement of Working Memory Performance in Healthy Adults: A Systematic Meta-Analysis.

BACKGROUND: Transcranial alternating current stimulation (tACS)-a noninvasive brain stimulation technique that modulates cortical oscillations in the brain-has shown the capacity to enhance working memory (WM) abilities in healthy individuals. The efficacy of tACS in the improvement of WM performance in healthy individuals is not yet fully understood. OBJECTIVE/HYPOTHESIS: This meta-analysis aimed to systematically evaluate the efficacy of tACS in the enhancement of WM in healthy individuals and to assess moderators of response to stimulation. We hypothesized that active tACS would significantly enhance WM compared with sham. We further hypothesized that it would do so in a task-dependent manner and that differing stimulation parameters would affect response to tACS. MATERIALS AND METHODS: Ten tACS studies met the inclusion criteria and provided 32 effects in the overall analysis. Random-effect models assessed mean change scores on WM tasks from baseline to poststimulation. The included studies involved varied in stimulation parameters, between-subject and within-subject study designs, and online vs offline tACS. RESULTS: We observed a significant, heterogeneous, and moderate effect size for active tACS in the enhancement of WM performance over sham (Cohen's d = 0.5). Cognitive load, task domain, session number, and stimulation region showed a significant relationship between active tACS and enhanced WM behavior over sham. CONCLUSIONS: Our findings indicate that active tACS enhances WM performance in healthy individuals compared with sham. Future randomized controlled trials are needed to further explore key parameters, including personalized stimulation vs standardized electroencephalography frequencies and maintenance of tACS effects, and whether tACS-induced effects translate to populations with WM impairments.

Through Thick and Thin: Baseline Cortical Volume and Thickness Predict Performance and Response to Transcranial Direct Current Stimulation in Primary Progressive Aphasia.

Objectives: We hypothesized that measures of cortical thickness and volume in language areas would correlate with response to treatment with high-definition transcranial direct current stimulation (HD-tDCS) in persons with primary progressive aphasia (PPA). Materials and Methods: In a blinded, within-group crossover study, PPA patients (N = 12) underwent a 2-week intervention HD-tDCS paired with constraint-induced language therapy (CILT). Multi-level linear regression (backward-fitted models) were performed to assess cortical measures as predictors of tDCS-induced naming improvements, measured by the Western Aphasia Battery-naming subtest, from baseline to immediately after and 6 weeks post-intervention. Results: Greater baseline thickness of the pars opercularis significantly predicted naming gains (p = 0.03) immediately following intervention, while greater thickness of the middle temporal gyrus (MTG) and lower thickness of the superior temporal gyrus (STG) significantly predicted 6-week naming gains (p's < 0.02). Thickness did not predict naming gains in sham. Volume did not predict immediate gains for active stimulation. Greater volume of the pars triangularis and MTG, but lower STG volume significantly predicted 6-week naming gains in active stimulation. Greater pars orbitalis and MTG volume, and lower STG volume predicted immediate naming gains in sham (p's < 0.05). Volume did not predict 6-week naming gains in sham. Conclusion: Cortical thickness and volume were predictive of tDCS-induced naming improvement in PPA patients. The finding that frontal thickness predicted immediate active tDCS-induced naming gains while temporal areas predicted naming changes at 6-week suggests that a broader network of regions may be important for long-term maintenance of treatment gains. The finding that volume predicted immediate naming performance in the sham condition may reflect the benefits of behavioral speech language therapy and neural correlates of its short-lived treatment gains. Collectively, thickness and volume were predictive of treatment gains in the active condition but not sham, suggesting that pairing HD-tDCS with CILT may be important for maintaining treatment effects.

Electric Field Strength From Prefrontal Transcranial Direct Current Stimulation Determines Degree of Working Memory Response: A Potential Application of Reverse-Calculation Modeling?

BACKGROUND: Transcranial direct current stimulation (tDCS) for working memory is an enticing treatment, but there is mixed evidence to date. OBJECTIVES: We tested the effects of electric field strength from uniform 2 mA dosing on working memory change from prestimulation to poststimulation. Second, we statistically evaluated a reverse-calculation method of individualizing tDCS dose and its effect on normalizing electric field at the cortex. MATERIALS AND METHODS: We performed electric field modeling on a data set of 28 healthy older adults (15 women, mean age = 73.7, SD = 7.3) who received ten sessions of active 2 mA tDCS (N = 14) or sham tDCS (N = 14) applied over bilateral dorsolateral prefrontal cortices (DLPFC) in a triple-blind design. We evaluated the relationship between electric field strength and working memory change on an N-back task in conditions of above-median, high electric field from active 2 mA (N = 7), below-median, low electric field from active 2 mA (N = 7), and sham (N = 14) at regions of interest (ROI) at the left and right DLPFC. We then determined the individualized reverse-calculation dose to produce the group average electric field and measured the electric field variance between uniform 2 mA doses vs individualized reverse-calculation doses at the same ROIs. RESULTS: Working memory improvements from pre- to post-tDCS were significant for the above-median electric field from active 2 mA condition at the left DLPFC (mixed ANOVA, p = 0.013). Furthermore, reverse-calculation modeling significantly reduced electric field variance at both ROIs (Levene's test; p < 0.001). CONCLUSIONS: Higher electric fields at the left DLPFC from uniform 2 mA doses appear to drive working memory improvements from tDCS. Individualized doses from reverse-calculation modeling significantly reduce electric field variance at the cortex. Taken together, using reverse-calculation modeling to produce the same, high electric fields at the cortex across participants may produce more effective future tDCS treatments for working memory.

Impact of Transcranial Direct Current Stimulation and Cognitive Training on Frontal Lobe Neurotransmitter Concentrations.

Objective: This study examines the impact of transcranial direct current stimulation (tDCS) combined with cognitive training on neurotransmitter concentrations in the prefrontal cortex. Materials and Methods: Twenty-three older adults were randomized to either active-tDCS or sham-tDCS in combination with cognitive training for 2 weeks. Active-tDCS was delivered over F3 (cathode) and F4 (anode) electrode placements for 20 min at 2 mA intensity. For each training session, 40-min of computerized cognitive training were applied with active or sham stimulation delivered during the first 20-min. Glutamine/glutamate (Glx) and gamma-aminobutyric acid (GABA) concentrations via proton magnetic resonance spectroscopy were evaluated at baseline and at the end of 2-week intervention. Results: Glx concentrations increased from pre- to post-intervention (p = 0.010) in the active versus sham group after controlling for age, number of intervention days, MoCA scores, and baseline Glx concentration. No difference in GABA concentration was detected between active and sham groups (p = 0.650) after 2-week intervention. Conclusion: Results provide preliminary evidence suggesting that combining cognitive training and tDCS over the prefrontal cortex elicits sustained increase in excitatory neurotransmitter concentrations. Findings support the combination of tDCS and cognitive training as a potential method for altering neurotransmitter concentrations in the frontal cortices, which may have implications for neuroplasticity in the aging brain.

Individualized tDCS modeling predicts functional connectivity changes within the working memory network in older adults.

BACKGROUND: Working memory decline has been associated with normal aging. The frontal brain structure responsible for this decline is primarily located in the prefrontal cortex (PFC). Our previous neuroimaging study demonstrated a significant change in functional connectivity between the left dorsolateral PFC (DLPFC) and left ventrolateral PFC (VLPFC) when applying 2 mA tDCS in MRI scanner during an N-Back task. These regions were part of the working memory network. The present study is the first study that utilizes individualized finite element models derived from older adults' MRI to predict significant changes of functional connectivity observed from an acute tDCS application. METHODS: Individualized head models from 15 healthy older adults (mean age = 71.3 years) were constructed to create current density maps. Each head model was segmented into 11 tissue types: white matter, gray matter, CSF, muscle, blood vessels, fat, eyes, air, skin, cancellous, and cortical bone. Electrodes were segmented from T1-weighted images and added to the models. Computed median and maximum current density values in the left DLPFC and left VLPFC regions of interest (ROIs) were correlated with beta values as functional connectivity metrics measured in different timepoint (baseline, during stimulation) and stimulation condition (active and sham). MAIN RESULTS: Positive significant correlations (R2 = 0.523 for max J, R2 = 0.367 for median J, p < 0.05) were found between the beta values and computed current densities in the left DLPFC ROIs for active stimulation, but no significant correlation was found during sham stimulation. We found no significant correlation between connectivity and current densities computed in the left VLPFC for both active and sham stimulation. CONCLUSIONS: The amount of current within the left DLPFC ROIs was found positively correlated with changes in functional connectivity between left DLPFC and left VLPFC during active 2 mA stimulation. Future work may include expansion of number of participants to further test the accuracy of tDCS models used to predict tDCS-induced functional connectivity changes within the working memory network.

Independent Contributions of Dorsolateral Prefrontal Structure and Function to Working Memory in Healthy Older Adults.

Age-related differences in dorsolateral prefrontal cortex (DLPFC) structure and function have each been linked to working memory. However, few studies have integrated multimodal imaging to simultaneously investigate relationships among structure, function, and cognition. We aimed to clarify how specifically DLPFC structure and function contribute to working memory in healthy older adults. In total, 138 participants aged 65-88 underwent 3 T neuroimaging and were divided into higher and lower groups based on a median split of in-scanner n-back task performance. Three a priori spherical DLPFC regions of interest (ROIs) were used to quantify blood-oxygen-level-dependent (BOLD) signal and FreeSurfer-derived surface area, cortical thickness, and white matter volume. Binary logistic regressions adjusting for age, sex, education, and scanner type revealed that greater left and right DLPFC BOLD signal predicted the probability of higher performing group membership (P values<.05). Binary logistic regressions also adjusting for total intracranial volume revealed left DLPFC surface area that significantly predicted the probability of being in the higher performing group (P = 0.017). The left DLPFC BOLD signal and surface area were not significantly associated and did not significantly interact to predict group membership (P values>.05). Importantly, this suggests BOLD signal and surface area may independently contribute to working memory performance in healthy older adults.

Structural Neural Correlates of Double Decision Performance in Older Adults.

Speed of processing is a cognitive domain that encompasses the speed at which an individual can perceive a given stimulus, interpret the information, and produce a correct response. Speed of processing has been shown to decline more rapidly than other cognitive domains in an aging population, suggesting that this domain is particularly vulnerable to cognitive aging (Chee et al., 2009). However, given the heterogeneity of neuropsychological measures used to assess the domains underpinning speed of processing, a diffuse pattern of brain regions has been implicated. The current study aims to investigate the structural neural correlates of speed of processing by assessing cortical volume and speed of processing scores on the POSIT Double Decision task within a healthy older adult population (N = 186; mean age = 71.70 ± 5.32 years). T1-weighted structural images were collected via a 3T Siemens scanner. The current study shows that less cortical thickness in right temporal, posterior frontal, parietal and occipital lobe structures were significantly associated with poorer Double Decision scores. Notably, these include the lateral orbitofrontal gyrus, precentral gyrus, superior, transverse, and inferior temporal gyrus, temporal pole, insula, parahippocampal gyrus, fusiform gyrus, lingual gyrus, superior and inferior parietal gyrus and lateral occipital gyrus. Such findings suggest that speed of processing performance is associated with a wide array of cortical regions that provide unique contributions to performance on the Double Decision task.

Machine learning and individual variability in electric field characteristics predict tDCS treatment response.

BACKGROUND: Transcranial direct current stimulation (tDCS) is widely investigated as a therapeutic tool to enhance cognitive function in older adults with and without neurodegenerative disease. Prior research demonstrates that electric current delivery to the brain can vary significantly across individuals. Quantification of this variability could enable person-specific optimization of tDCS outcomes. This pilot study used machine learning and MRI-derived electric field models to predict working memory improvements as a proof of concept for precision cognitive intervention. METHODS: Fourteen healthy older adults received 20 minutes of 2 mA tDCS stimulation (F3/F4) during a two-week cognitive training intervention. Participants performed an N-back working memory task pre-/post-intervention. MRI-derived current models were passed through a linear Support Vector Machine (SVM) learning algorithm to characterize crucial tDCS current components (intensity and direction) that induced working memory improvements in tDCS responders versus non-responders. MAIN RESULTS: SVM models of tDCS current components had 86% overall accuracy in classifying treatment responders vs. non-responders, with current intensity producing the best overall model differentiating changes in working memory performance. Median current intensity and direction in brain regions near the electrodes were positively related to intervention responses (r=0.811,p<0.001 and r=0.774,p=0.001). CONCLUSIONS: This study provides the first evidence that pattern recognition analyses of MRI-derived tDCS current models can provide individual prognostic classification of tDCS treatment response with 86% accuracy. Individual differences in current intensity and direction play important roles in determining treatment response to tDCS. These findings provide important insights into mechanisms of tDCS response as well as proof of concept for future precision dosing models of tDCS intervention.

Efficacy of Noninvasive Brain Stimulation (tDCS or TMS) Paired with Language Therapy in the Treatment of Primary Progressive Aphasia: An Exploratory Meta-Analysis.

Noninvasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS), paired with behavioral language therapy, have demonstrated the capacity to enhance language abilities in primary progressive aphasia (PPA), a debilitating degenerative neurological syndrome that leads to declines in communication abilities. The aim of this meta-analysis is to systematically evaluate the efficacy of tDCS and TMS in improving language outcomes in PPA, explore the magnitude of effects between stimulation modalities, and examine potential moderators that may influence treatment effects. Standard mean differences for change in performance from baseline to post-stimulation on language-related tasks were evaluated. Six tDCS studies and two repetitive TMS studies met inclusion criteria and provided 22 effects in the analysis. Random effect models revealed a significant, heterogeneous, and moderate effect size for tDCS and TMS in the enhancement of language outcomes. Findings demonstrate that naming ability significantly improves due to brain stimulation, an effect found to be largely driven by tDCS. Future randomized controlled trials are needed to determine long-term effectiveness of noninvasive brain stimulation techniques on language abilities, further delineate the efficacy of tDCS and TMS, and identify optimal parameters to enable the greatest gains for persons with PPA.

Modeling transcranial electrical stimulation in the aging brain.

BACKGROUND: Varying treatment outcomes in transcranial electrical stimulation (tES) recipients may depend on the amount of current reaching the brain. Brain atrophy associated with normal aging may affect tES current delivery to the brain. Computational models have been employed to compute predicted tES current inside the brain. This study is the largest study that uses computational models to investigate tES field distribution in healthy older adults. METHODS: Individualized head models from 587 healthy older adults (mean = 73.9years, 51-95 years) were constructed to create field maps. Two electrode montages (F3-F4, M1-SO) with 2 mA input current were modeled using ROAST with modified codes. A customized template of healthy older adults, the UFAB-587, was created from the same dataset and used to warp individual brains into the same space. Warped models were analyzed to determine the relationship between computed field measures, brain atrophy and age. MAIN RESULTS: Computed field measures were inversely correlated with brain atrophy (R2 = 0.0829, p = 1.14e-12). Field pattern showed negative correlation with age in brain sub-regions including part of DLPFC and precentral gyrus. Mediation analysis revealed that the negative correlation between age and current density is partially mediated by brain-to-CSF ratio. CONCLUSIONS: Computed field measures showed decreasing amount of tES current reaching the brain with increasing atrophy. Therefore, adjusting current dose by modifying tES stimulation parameters in older adults based on degree of atrophy may be necessary to achieve desired stimulation benefits. Results from this study may inform future tES application in healthy older adults.

Effects of in-Scanner Bilateral Frontal tDCS on Functional Connectivity of the Working Memory Network in Older Adults.

Working memory is an executive memory process essential for everyday decision-making and problem solving that declines with advanced age. Transcranial direct current stimulation (tDCS) is a non-invasive form of brain stimulation that has demonstrated potential for improving working memory performance in older adults. However, the neural mechanisms underlying effects of tDCS on working memory are not well understood. This mechanistic study investigated the acute and after-effects of bilateral frontal (F3/F4) tDCS at 2 mA for 12-min on functional connectivity of the working memory network in older adults. We hypothesized active tDCS over sham would increase frontal connectivity during working memory performance. The study used a double-blind within-subject 2 session crossover design. Participants performed an functional magnetic resonance imaging (fMRI) N-Back working memory task before, during, and after active or sham stimulation. Functional connectivity of the working memory network was assessed within and between stimulation conditions (FDR < 0.05). Active tDCS produced a significant increase in functional connectivity between left ventrolateral prefrontal cortex (VLPFC) and left dorsolateral PFC (DLPFC) during stimulation, but not after stimulation. Connectivity did not significantly increase with sham stimulation. In addition, our data demonstrated both state-dependent and time-dependent effects of tDCS working memory network connectivity in older adults. tDCS during working memory performance produces a selective change in functional connectivity of the working memory network in older adults. These data provide important mechanistic insight into the effects of tDCS on brain connectivity in older adults, as well as key methodological considerations for tDCS-working memory studies.

Associations between subclinical depressive symptoms and reduced brain volume in middle-aged to older adults.

OBJECTIVES: The associations between subclinical depressive symptoms, as well specific symptom subscales, on brain structure in aging are not completely elucidated. This study investigated the extent to which depressive symptoms were related to brain volumes in fronto-limbic structures in a sample of middle-aged to older adults. METHOD: Eighty participants underwent structural neuroimaging and completed the Beck Depression Inventory, 2nd Edition (BDI-II), which comprises separate affective, cognitive, and somatic subscales. Gray matter volumes were extracted from the caudal and rostral anterior cingulate, posterior cingulate, hippocampus, and amygdala. Hierarchical regression models examined the relationship between brain volumes and (i) total depressive symptoms and (ii) BDI-II subscales were conducted. RESULTS: After adjusting for total intracranial volume, race, and age, higher total depressive symptoms were associated with smaller hippocampal volume (p = 0.005). For the symptom subscales, after controlling for the abovementioned covariates and the influence of the other symptom subscales, more somatic symptoms were related to smaller posterior cingulate (p = 0.025) and hippocampal (p < 0.001) volumes. In contrast, the affective and cognitive subscales were not associated with brain volumes in any regions of interest. CONCLUSION: Our data showed that greater symptomatology was associated with smaller volume in limbic brain regions. These findings provide evidence for preclinical biological markers of major depression and specifically advance knowledge of the relationship between subclinical depressive symptoms and brain volume. Importantly, we observed variations by specific depressive symptom subscales, suggesting a symptom-differential relationship between subclinical depression and brain volume alterations in middle-aged and older individuals.

Methods to monitor accurate and consistent electrode placements in conventional transcranial electrical stimulation.

BACKGROUND: Inaccurate electrode placement and electrode drift during a transcranial electrical stimulation (tES) session have been shown to alter predicted field distributions in the brain and thus may contribute to a large variation in tES study outcomes. Currently, there is no objective and independent measure to quantify electrode placement accuracy/drift in tES clinical studies. OBJECTIVE/HYPOTHESIS: We proposed and tested novel methods to quantify accurate and consistent electrode placements in tES using models generated from a 3D scanner. METHODS: Accurate electrode placements were quantified as Discrepancy in eight tES participants by comparing landmark distances of physical electrode locations F3/F4 to their model counterparts. Distances in models were computed using curve and linear based methods. Variability of landmark locations in a single subject was computed for multiple stimulation sessions to determine consistent electrode placements across four experimenters. MAIN RESULTS: We obtained an average of 0.4 cm in Discrepancy, which was within the placement accuracy/drift threshold (1 cm) for conventional tES electrodes (∼35 cm2) to achieve reliable tES sessions suggested in the literature. Averaged Variability was 5.2%, with F4 electrode location as the least consistent placement. CONCLUSIONS: These methods provide objective feedback for experimenters on their performance in placing tES electrodes. Applications of these methods can be used to monitor electrode locations in tES studies of a larger cohort using F3/F4 montage and other conventional electrode arrangements. Future studies may include co-registering the landmark locations with imaging-derived head models to quantify the effects of electrode accuracy/drift on predicted field distributions in the brain.

Effects of Transcranial Direct Current Stimulation Paired With Cognitive Training on Functional Connectivity of the Working Memory Network in Older Adults.

BACKGROUND: Working memory, a fundamental short-term cognitive process, is known to decline with advanced age even in healthy older adults. Normal age-related declines in working memory can cause loss of independence and decreased quality of life. Cognitive training has shown some potential at enhancing certain cognitive processes, although, enhancements are variable. Transcranial direct current stimulation (tDCS), a form of non-invasive brain stimulation, has shown promise at enhancing working memory abilities, and may further the benefits from cognitive training interventions. However, the neural mechanisms underlying tDCS brain-based enhancements remain unknown. OBJECTIVE/HYPOTHESIS: Assess the effects of a 2-week intervention of active-tDCS vs. sham paired with cognitive training on functional connectivity of the working memory network during an N-Back working memory task. METHODS: Healthy older adults (N = 28; mean age = 74 ± 7.3) completed 10-sessions of cognitive training paired with active or sham-tDCS. Functional connectivity was evaluated at baseline and post-intervention during an N-Back task (2-Back vs. 0-Back). RESULTS: Active-tDCS vs. sham demonstrated a significant increase in connectivity between the left dorsolateral prefrontal cortex and right inferior parietal lobule at post-intervention during 2-Back. Target accuracy on 2-Back was significantly improved for active vs. sham at post-intervention. CONCLUSION: These results suggest pairing tDCS with cognitive training enhances functional connectivity and working memory performance in older adults, and thus may hold promise as a method for remediating age-related cognitive decline. Future studies evaluating optimal dose and long-term effects of tDCS on brain function will help to maximize potential clinical impacts of tDCS paired with cognitive training in older adults. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT02137122.

Non-invasive Brain Stimulation: Probing Intracortical Circuits and Improving Cognition in the Aging Brain.

The impact of cognitive aging on brain function and structure is complex, and the relationship between aging-related structural changes and cognitive function are not fully understood. Physiological and pathological changes to the aging brain are highly variable, making it difficult to estimate a cognitive trajectory with which to monitor the conversion to cognitive decline. Beyond the information on the structural and functional consequences of cognitive aging gained from brain imaging and neuropsychological studies, non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) can enable stimulation of the human brain in vivo, offering useful insights into the functional integrity of intracortical circuits using electrophysiology and neuromodulation. TMS measurements can be used to identify and monitor changes in cortical reactivity, the integrity of inhibitory and excitatory intracortical circuits, the mechanisms of long-term potentiation (LTP)/depression-like plasticity and central cholinergic function. Repetitive TMS and tDCS can be used to modulate neuronal excitability and enhance cortical function, and thus offer a potential means to slow or reverse cognitive decline. This review will summarize and critically appraise relevant literature regarding the use of TMS and tDCS to probe cortical areas affected by the aging brain, and as potential therapeutic tools to improve cognitive function in the aging population. Challenges arising from intra-individual differences, limited reproducibility, and methodological differences will be discussed.

The effects of medication use in transcranial direct current stimulation: A brief review.

BACKGROUND: There has been increased interest in the potential use of transcranial direct current stimulation (tDCS) as treatment for multiple conditions including depression, pain, and cognitive impairment. However, few studies account for the possible influence of comorbid medications when conducting tDCS research. OBJECTIVE/HYPOTHESIS: This literature review was conducted to examine what is currently known about the impact of medications on tDCS, provide recommendations for future research practices, and highlight areas where more research is needed. METHODS: Key terms were searched in PubMed and Web of Science to identify studies that examine the impact of medication on tDCS effects in adults. Relevant papers' reference lists were also reviewed for thoroughness. Studies examined the effects of medication on 1 mA tDCS delivered to M1 (motor) and orbit/supraorbital (SO) area. All studies measured the effects of tDCS via MEP TMS paradigm. RESULTS: Results of the literature review suggest multiple classes of medications, including sodium and calcium channel blockers, and medications that influence various neurotransmitter systems (GABA, dopamine, serotonin, etc.) may all impact tDCS effects on tissue excitability. CONCLUSIONS: Research to date suggests multiple classes of medications may impact tDCS effects. These results highlight the importance of documenting medication use in research subjects and carefully considering what types of medications should be allowed into tDCS trials. Many questions still remain regarding the exact mechanisms of action for tDCS and how various parameters (medication dosages, tDCS stimulation intensity, etc.) may further impact the effects of medications on tDCS.

Cognitive Aging and the Hippocampus in Older Adults.

The hippocampus is one of the most well studied structures in the human brain. While age-related decline in hippocampal volume is well documented, most of our knowledge about hippocampal structure-function relationships was discovered in the context of neurological and neurodegenerative diseases. The relationship between cognitive aging and hippocampal structure in the absence of disease remains relatively understudied. Furthermore, the few studies that have investigated the role of the hippocampus in cognitive aging have produced contradictory results. To address these issues, we assessed 93 older adults from the general community (mean age = 71.9 ± 9.3 years) on the Montreal Cognitive Assessment (MoCA), a brief cognitive screening measure for dementia, and the NIH Toolbox-Cognitive Battery (NIHTB-CB), a computerized neurocognitive battery. High-resolution structural magnetic resonance imaging (MRI) was used to estimate hippocampal volume. Lower MoCA Total (p = 0.01) and NIHTB-CB Fluid Cognition (p < 0.001) scores were associated with decreased hippocampal volume, even while controlling for sex and years of education. Decreased hippocampal volume was significantly associated with decline in multiple NIHTB-CB subdomains, including episodic memory, working memory, processing speed and executive function. This study provides important insight into the multifaceted role of the hippocampus in cognitive aging.

Frontal Structural Neural Correlates of Working Memory Performance in Older Adults.

Working memory is an executive memory process that allows transitional information to be held and manipulated temporarily in memory stores before being forgotten or encoded into long-term memory. Working memory is necessary for everyday decision-making and problem solving, making it a fundamental process in the daily lives of older adults. Working memory relies heavily on frontal lobe structures and is known to decline with age. The current study aimed to determine the neural correlates of decreased working memory performance in the frontal lobes by comparing cortical thickness and cortical surface area from two demographically matched groups of healthy older adults, free from cognitive impairment, with high versus low N-Back working memory performance (N = 56; average age = 70.29 ± 10.64). High-resolution structural T1-weighted images (1 mm isotropic voxels) were obtained on a 3T Philips MRI scanner. When compared to high performers, low performers exhibited significantly decreased cortical surface area in three frontal lobe regions lateralized to the right hemisphere: medial orbital frontal gyrus, inferior frontal gyrus, and superior frontal gyrus (FDR p < 0.05). There were no significant differences in cortical thickness between groups, a proxy for neurodegenerative tissue loss. Our results suggest that decreases in cortical surface area (a proxy for brain structural integrity) in right frontal regions may underlie age-related decline of working memory function.