Change in medial frontal cerebral metabolite concentrations following bariatric surgery.

Obesity is associated with adverse effects on brain health, including an increased risk of neurodegenerative diseases. Changes in cerebral metabolism may underlie or precede structural and functional brain changes. While bariatric surgery is known to be effective in inducing weight loss and improving obesity-related medical comorbidities, few studies have examined whether it may be able to improve brain metabolism. In the present study, we examined changes in cerebral metabolite concentrations in participants with obesity who underwent bariatric surgery. Thirty-five patients with obesity (body mass index ≥ 35 kg/m2 ) were recruited from a bariatric surgery candidate nutrition class. They completed single voxel proton magnetic resonance spectroscopy at baseline (presurgery) and within 1 year postsurgery. Spectra were obtained from a large medial frontal brain region using a PRESS sequence on a 3-T Siemens Verio scanner. The acquisition parameters were TR = 3000 ms and TE = 37 ms. Tissue-corrected metabolite concentrations were determined using Osprey. Paired t-tests were used to examine within-subject change in metabolite concentrations, and correlations were used to relate these changes to other health-related outcomes, including weight loss and glycated hemoglobin (HbA1c ), a measure of blood sugar levels. Bariatric surgery was associated with a reduction in cerebral choline-containing compounds (Cho; t [34] = - 3.79, p < 0.001, d = -0.64) and myo-inositol (mI; t [34] = - 2.81, p < 0.01, d = -0.47) concentrations. There were no significant changes in N-acetyl-aspartate, creatine, or glutamate and glutamine concentrations. Reductions in Cho were associated with greater weight loss (r = 0.40, p < 0.05), and reductions in mI were associated with greater reductions in HbA1c (r = 0.44, p < 0.05). In conclusion, participants who underwent bariatric surgery exhibited reductions in cerebral Cho and mI concentrations, which were associated with improvements in weight loss and glycemic control. Given that elevated levels of Cho and mI have been implicated in neuroinflammation, reduction in these metabolites after bariatric surgery may reflect amelioration of obesity-related neuroinflammatory processes. As such, our results provide evidence that bariatric surgery may improve brain health and metabolism in individuals with obesity.

Validity of the NIH toolbox cognitive battery in a healthy oldest-old 85+ sample.

OBJECTIVE: To evaluate the construct validity of the NIH Toolbox Cognitive Battery (NIH TB-CB) in the healthy oldest-old (85+ years old). METHOD: Our sample from the McKnight Brain Aging Registry consists of 179 individuals, 85 to 99 years of age, screened for memory, neurological, and psychiatric disorders. Using previous research methods on a sample of 85 + y/o adults, we conducted confirmatory factor analyses on models of NIH TB-CB and same domain standard neuropsychological measures. We hypothesized the five-factor model (Reading, Vocabulary, Memory, Working Memory, and Executive/Speed) would have the best fit, consistent with younger populations. We assessed confirmatory and discriminant validity. We also evaluated demographic and computer use predictors of NIH TB-CB composite scores. RESULTS: Findings suggest the six-factor model (Vocabulary, Reading, Memory, Working Memory, Executive, and Speed) had a better fit than alternative models. NIH TB-CB tests had good convergent and discriminant validity, though tests in the executive functioning domain had high inter-correlations with other cognitive domains. Computer use was strongly associated with higher NIH TB-CB overall and fluid cognition composite scores. CONCLUSION: The NIH TB-CB is a valid assessment for the oldest-old samples, with relatively weak validity in the domain of executive functioning. Computer use's impact on composite scores could be due to the executive demands of learning to use a tablet. Strong relationships of executive function with other cognitive domains could be due to cognitive dedifferentiation. Overall, the NIH TB-CB could be useful for testing cognition in the oldest-old and the impact of aging on cognition in older populations.

Functional Neural Correlates of a Useful Field of View (UFOV)-Based fMRI Task in Older Adults.

Declines in processing speed performance occur in aging and are a critical marker of functional independence in older adults. Studies suggest that Useful Field of View (UFOV) training may ameliorate cognitive decline. Despite its efficacy, little is known about the neural correlates of this task. Within the current study, 233 healthy older adults completed a UFOV-based task while undergoing functional magnetic resonance imaging (fMRI). During the "stimulus" portion of this task, participants must identify a target in the center of the screen and the location of a target in the periphery, among distractors. During the "probe" portion, participants must decide if the object in the center and the location of the target in the periphery were identical to the "stimulus" screen. Widespread bilateral whole-brain activation was observed when activation patterns of the "probe" contrast were subtracted from the "stimulus" contrast. Conversely, the subtraction of "stimulus" from "probe" was associated with discrete activation patterns consisting of 13 clusters. Additionally, when evaluating the variance associated with task accuracy, specific subregions were identified that may be critical for task performance. Our data elucidate the functional neural correlates of a UFOV-based task, a task used in both cognitive training paradigms and assessment of function.

Effects of Prefrontal Transcranial Direct Current Stimulation on Retention of Performance Gains on an Obstacle Negotiation Task in Older Adults.

OBJECTIVES: Complex walking in older adults can be improved with task practice and might be further enhanced by pairing transcranial direct current stimulation (tDCS) to the dorsolateral prefrontal cortex. We tested the hypothesis that a single session of practice of a complex obstacle negotiation task paired with active tDCS in older adults would produce greater within-session improvements in walking performance and retention of gains, compared to sham tDCS and no tDCS conditions. MATERIALS AND METHODS: A total of 50 older adults (mean age = 74.46 years ± 6.49) with self-reported walking difficulty were randomized to receive either active tDCS (active-tDCS group) or sham tDCS (sham-tDCS group) bilaterally to the dorsolateral prefrontal cortex or no tDCS (no-tDCS group). Each group performed ten practice trials of an obstacle negotiation task at their fastest safe speed. Retention of gains in walking performance was assessed with three trials conducted one week later. Within-session effects of practice and between-session retention effects on obstacle negotiation speed were examined. RESULTS: At the practice session, all three groups exhibited significant within-session gains in walking speed (p ≤ 0.005). However, the gains were significantly greater in the sham-tDCS group than in the active-tDCS and no-tDCS groups (p ≤ 0.03) and were comparable between the active-tDCS and no-tDCS groups (p = 0.89). At one-week follow-up, the active-tDCS group exhibited significant between-session retention of gains and continued "offline" improvement in walking speed (p = 0.005). The active-tDCS group showed significantly greater retention of gains than the no-tDCS (p = 0.02) but not the sham-tDCS group (p = 0.24). CONCLUSIONS: Pairing prefrontal active tDCS with a single session of obstacle negotiation practice may enhance one-week retention of gains in walking performance compared to no tDCS. However, the evidence is insufficient to suggest a benefit of active tDCS over sham tDCS for enhancing the gains in walking performance. Additional studies with a multisession intervention design and larger sample size are needed to further investigate these findings. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT03122236.

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.

Neuroenhancement of surgeons during robotic suturing.

BACKGROUND: The initial phases of robotic surgical skills acquisition are associated with poor technical performance, such as low knot-tensile strength (KTS). Transcranial direct-current stimulation (tDCS) can improve force and accuracy in motor tasks but research in surgery is limited to open and laparoscopic tasks in students. More recently, robotic surgery has gained traction and is now the most common approach for certain procedures (e.g. prostatectomy). Early-phase robotic suturing performance is dependent on prefrontal cortex (PFC) activation, and this study aimed to determine whether performance can be improved with prefrontal tDCS. METHODS: Fifteen surgical residents were randomized to either active then sham tDCS or sham then active tDCS, in two counterbalanced sessions in a double-blind crossover study. Within each session, participants performed a robotic suturing task repeated in three blocks: pre-, intra- and post-tDCS. During the intra-tDCS block, participants were randomized to either active tDCS (2 mA for 15 min) to the PFC or sham tDCS. Primary outcome measures of technical quality included KTS and error scores. RESULTS: Significantly faster completion times were observed longitudinally, regardless of active (p < 0.001) or sham stimulation (p < 0.001). KTS was greater following active compared to sham stimulation (median: active = 44.35 N vs. sham = 27.12 N, p < 0.001). A significant reduction in error scores from "pre-" to "post-" (p = 0.029) were only observed in the active group. CONCLUSION: tDCS could reduce error and enhance KTS during robotic suturing and warrants further exploration as an adjunct to robotic surgical training.

Does transcranial direct current stimulation enhance cognitive performance in Parkinson's disease mild cognitive impairment? An event-related potentials and neuropsychological assessment study.

BACKGROUND: Parkinson's disease-mild cognitive impairment (PD-MCI) is garnering attention as a key interventional period for cognitive impairment. Currently, there are no approved treatments for PD-MCI and encouraging results of transcranial direct current stimulation (tDCS) combined with other interventions have been proposed, though the efficacy and neural mechanisms of tDCS alone have not been studied in PD-MCI yet. OBJECTIVES: The present double-blind, randomized, sham-controlled study assessed the effects of tDCS over the dorsolateral prefrontal cortex on cognitive functions via neuropsychological and electrophysiological evaluations in individuals with PD-MCI for the first time. METHOD: Twenty-six individuals with PD-MCI were administered 10 sessions of active (n = 13) or sham (n = 13) prefrontal tDCS twice a day, for 5 days. Changes were tested through a comprehensive neuropsychological battery and event-related potential recordings, which were performed before, immediately, and 1 month after the administrations. RESULTS: Neuropsychological assessment showed an improvement in delayed recall and executive functions in the active group. N1 amplitudes in response to targets in the oddball test-likely indexing attention and discriminability and NoGo N2 amplitudes in the continuous performance test-likely indexing cognitive control and conflict monitoring increased in the active group. Active stimulation elicited higher benefits 1 month after the administrations. CONCLUSION: The present findings substantiate the efficacy of tDCS on cognitive control and episodic memory, along with the neural underpinnings of cognitive control, highlighting its potential for therapeutic utility in PD-MCI. TRIAL REGISTRATION: NCT 04,171,804. Date of registration: 21/11/2019.

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.

The neurobiology of wellness: 1H-MRS correlates of agency, flexibility and neuroaffective reserves in healthy young adults.

Proton magnetic resonance spectroscopy (1H-MRS) is a noninvasive imaging technique that measures the concentration of metabolites in defined areas of the human brain in vivo. The underlying structure of natural metabolism-emotion relationships is unknown. Further, there is a wide range of between-person differences in metabolite concentration in healthy individuals, but the significance of this variation for understanding emotion in healthy humans is unclear. Here we investigated the relationship of two emotional constructs, agency and flexibility, with the metabolites glutamate and glutamine (Glx), N-acetylaspartate (tNAA), choline (Cho), creatine (tCr), and myo-inositol (Ins) in the right dorsal anterior cingulate cortex (dACC) in medically and psychiatrically healthy volunteers (N = 20, 9 female; mean age = 22.8 years, SD = 3.40). The dACC was selected because this region is an integrative hub involved in multiple brain networks of emotion, cognition and behavior. Emotional traits were assessed using the Multidimensional Personality Questionnaire Brief Form (MPQ-BF), an empirically derived self-report instrument with an orthogonal factor structure. Phenotypes evaluated were positive and negative agency (MPQ-BF Social Potency, Aggression), emotional and behavioral flexibility (MPQ-BF Absorption, Control-reversed), and positive and negative affect (MPQ-BF Social Closeness; Stress Reaction, Alienation). The resting concentration of tNAA in the dACC was robustly positively correlated with Absorption (r = +0.56, unadjusted p = .005), moderately positively correlated with Social Potency (r = +0.42, unadjusted p = .03), and robustly negatively correlated with Aggression (r = -0.59, unadjusted p = .003). Absorption and Aggression accounted for substantial variance in tNAA (R2 = 0.31, 0.35; combined R2 = 0.50), and survived correction for multiple comparisons (Holm-Bonferroni adjusted p = .032, 0.021, respectively). dACC Glx and Cho had modest relationships with behavioral flexibility and social affiliation that did not survive this multiple correction, providing effect sizes for future work. Principal Component Analysis (PCA) revealed a three-factor orthogonal solution indicating specific relationships between: 1) Glx and behavioral engagement; 2) Cho and affiliative bonding; and 3) tNAA and a novel dimension that we term neuroaffective reserves. Our results inform the neurobiology of agency and flexibility and lay the groundwork for understanding mechanisms of natural emotion using 1H-MRS.

Associations of alcohol use, HIV infection, and age with brain white matter microstructure.

Heavy drinking and HIV infection are independently associated with damage to the brain's white matter. The purpose of the current study was to investigate whether current alcohol consumption, HIV infection, and associated characteristics were associated with indices of white matter microstructural integrity in people living with HIV (PLWH) and seronegative individuals. PLWH and controls were categorized as non-drinkers, moderate drinkers, or heavy drinkers. White matter fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) were assessed using diffusion tensor imaging (DTI). Voxelwise analyses using tract-based spatial statistics were followed by confirmatory region-of-interest (ROI) analyses. Data from 108 participants (62 PLWH, 46 controls) were suitable for analysis. Average age (± standard deviation) was 45.2 ± 11.1 years, and the sample was 42% female. The majority of PLWH were on antiretroviral therapy (94%) and were virally suppressed (69%). PLWH and controls did not differ on substance use. Heavier alcohol intake was significantly associated with lower FA and higher RD in widespread areas. Heavy drinking was significantly associated with higher AD in a small region. The main effect of HIV was not significant, but a significant HIV-age interaction was observed. Follow-up ROI analyses confirmed the main effect of drinking group and HIV-age interaction. In conclusion, results are consistent with a dose-dependent association of alcohol use with lower white matter microstructural coherence. Concordance between FA and RD findings suggests dysmyelination as a mechanism. Findings underscore the need to address unhealthy alcohol use in HIV-positive and seronegative individuals, the consequences of which may be exacerbated by aging.

Reduced Working Memory is Associated with Heavier Alcohol Consumption History, Role Impairment and Executive Function Difficulties.

Both HIV status and heavy alcohol use have been associated with reduced cognitive function, particularly in the domains of working memory and executive function. It is unclear what aspects of working memory and executive function are associated with HIV status and heavy alcohol use and whether performance on these measures are associated with functional impairment. We examined the relationship between HIV, history of heavy alcohol consumption, and HIV/alcohol interaction on speeded tests of frontal inhibitory abilities, a working memory task related to mental manipulation of letters and numbers, cognitive flexibility, and measures of functional impairment. Study participants included 284 individuals (151 HIV +) recruited from two different studies focusing on HIV associated brain dysfunction, one specific to the effects of alcohol, the other specific to the effects of aging. HIV status was not independently associated with working memory and executive function measures. Higher level of alcohol consumption was associated with reduced performance on Letter Number Sequencing. Poorer Letter Number Sequencing performance was associated with role impairment (an inability to do certain kinds of work, housework, or schoolwork) and executive function difficulties. Future studies should examine causal associations and interventions targeting working memory abilities.

RESUMEN: Tanto el estado del VIH como el consumo excesivo de alcohol se han asociado con una función cognitiva reducida, particularmente en los dominios de la memoria de trabajo y la función ejecutiva. No está claro qué aspectos de la memoria de trabajo y la función ejecutiva están asociados con el estado del VIH y el consumo excesivo de alcohol y si el desempeño en estas medidas está asociado con un deterioro funcional. Examinamos la relación entre el VIH, el historial de consumo excesivo de alcohol y la interacción VIH / alcohol, en pruebas aceleradas de capacidades inhibitorias frontales, tareas de memoria de trabajo relacionadas con la manipulación mental de letras y números, flexibilidad cognitiva y medidas de deterioro funcional. Los participantes del estudio incluyeron 284 personas (151 VIH +) reclutadas de dos estudios diferentes que se centran en la disfunción cerebral asociada al VIH, uno específico de los efectos del alcohol y el otro específico de los efectos del envejecimiento. El estado del VIH no se asoció de forma independiente con las medidas de memoria de trabajo y función ejecutiva. Un mayor nivel de consumo de alcohol se asoció con un rendimiento reducido en la secuenciación de números de letras. Un desempeño deficiente en la secuenciación de números de letras se asoció con un deterioro de los roles (una incapacidad para realizar ciertos tipos de trabajo, tareas domésticas o escolares) y dificultades en las funciones ejecutivas. Los estudios futuros deben examinar las asociaciones causales y las intervenciones dirigidas a las capacidades de la memoria de trabajo.

Pain and the Montreal Cognitive Assessment (MoCA) in Aging.

OBJECTIVE: The present study aimed to determine whether specific cognitive domains part of the Montreal Cognitive Assessment (MoCA) are significantly lower in community-dwelling older adults with chronic pain compared with older adults without pain and whether these domains would be associated with self-reported pain, disability, and somatosensory function. DESIGN: Secondary data analysis, cross-sectional. SETTING: University of Florida. SUBJECTS: Individuals over 60 years old enrolled in the Neuromodulatory Examination of Pain and mobility Across the Lifespan (NEPAL) study were included if they completed the MoCA and other study measures (n = 62). Most participants reported pain on most days during the past three months (63%). METHODS: Subjects underwent a health assessment (HAS) and a quantitative sensory testing (QST) session. Health/medical history, cognitive function and self-reported pain measures were administered during the HAS. Mechanical and thermal detection, and thermal pain thresholds were assessed during the QST session. RESULTS: Older adults with chronic pain had lower MoCA scores compared with controls on domains of executive function, attention, memory, and language (P < 0.05). The attention and language domains survived adjustments for age, sex, education, depression, and pain duration (P < 0.05). Attention was significantly associated with all pain characteristics including pain intensity and disability, while executive function was associated with mechanical detection (P < 0.05). CONCLUSION: Our results support previous findings that individuals with chronic pain tend to show poorer cognitive functioning compared with pain-free controls in domains of attention and executive function. Our findings also extend these findings to community-dwelling older adults, who are already most vulnerable to age-related cognitive declines.

Combining Frontal Transcranial Direct Current Stimulation With Walking Rehabilitation to Enhance Mobility and Executive Function: A Pilot Clinical Trial.

OBJECTIVES: This pilot study assessed whether frontal lobe transcranial direct current stimulation (tDCS) combined with complex walking rehabilitation is feasible, safe, and shows preliminary efficacy for improving walking and executive function. MATERIALS AND METHODS: Participants were randomized to one of the following 18-session interventions: active tDCS and rehabilitation with complex walking tasks (Active/Complex); sham tDCS and rehabilitation with complex walking tasks (Sham/Complex); or sham tDCS and rehabilitation with typical walking (Sham/Typical). Active tDCS was delivered over F3 (cathode) and F4 (anode) scalp locations for 20 min at 2 mA intensity. Outcome measures included tests of walking function, executive function, and prefrontal activity measured by functional near infrared spectroscopy. RESULTS: Ninety percent of participants completed the intervention protocol successfully. tDCS side effects of tingling or burning sensations were low (average rating less than two out of 10). All groups demonstrated gains in walking performance based on within-group effect sizes (d ≥ 0.50) for one or more assessments. The Sham/Typical group showed the greatest gains for walking based on between-group effect sizes. For executive function, the Active/Complex group showed the greatest gains based on moderate to large between-group effect sizes (d = 0.52-1.11). Functional near-infrared spectroscopy (fNIRS) findings suggest improved prefrontal cortical activity during walking. CONCLUSIONS: Eighteen sessions of walking rehabilitation combined with tDCS is a feasible and safe intervention for older adults. Preliminary effects size data indicate a potential improvement in executive function by adding frontal tDCS to walking rehabilitation. This study justifies future larger clinical trials to better understand the benefits of combining tDCS with walking rehabilitation.

The association of white matter free water with cognition in older adults.

BACKGROUND: Extracellular free water within cerebral white matter tissue has been shown to increase with age and pathology, yet the cognitive consequences of free water in typical aging prior to the development of neurodegenerative disease remains unclear. Understanding the contribution of free water to cognitive function in older adults may provide important insight into the neural mechanisms of the cognitive aging process. METHODS: A diffusion-weighted MRI measure of extracellular free water as well as a commonly used diffusion MRI metric (fractional anisotropy) along nine bilateral white matter pathways were examined for their relationship with cognitive function assessed by the NIH Toolbox Cognitive Battery in 47 older adults (mean age â€‹= â€‹74.4 years, SD â€‹= â€‹5.4 years, range â€‹= â€‹65-85 years). Probabilistic tractography at the 99th percentile level of probability (Tracts Constrained by Underlying Anatomy; TRACULA) was utilized to produce the pathways on which microstructural characteristics were overlaid and examined for their contribution to cognitive function independent of age, education, and gender. RESULTS: When examining the 99th percentile probability core white matter pathway derived from TRACULA, poorer fluid cognitive ability was related to higher mean free water values across the angular and cingulum bundles of the cingulate gyrus, as well as the corticospinal tract and the superior longitudinal fasciculus. There was no relationship between cognition and mean FA or free water-adjusted FA across the 99th percentile core white matter pathway. Crystallized cognitive ability was not associated with any of the diffusion measures. When examining cognitive domains comprising the NIH Toolbox Fluid Cognition index relationships with these white matter pathways, mean free water demonstrated strong hemispheric and functional specificity for cognitive performance, whereas mean FA was not related to age or cognition across the 99th percentile pathway. CONCLUSIONS: Extracellular free water within white matter appears to increase with normal aging, and higher values are associated with significantly lower fluid but not crystallized cognitive functions. When using TRACULA to estimate the core of a white matter pathway, a higher degree of free water appears to be highly specific to the pathways associated with memory, working memory, and speeded decision-making performance, whereas no such relationship existed with FA. These data suggest that free water may play an important role in the cognitive aging process, and may serve as a stronger and more specific indicator of early cognitive decline than traditional diffusion MRI measures, such as FA.

Methodology for tDCS integration with fMRI.

Understanding and reducing variability of response to transcranial direct current stimulation (tDCS) requires measuring what factors predetermine sensitivity to tDCS and tracking individual response to tDCS. Human trials, animal models, and computational models suggest structural traits and functional states of neural systems are the major sources of this variance. There are 118 published tDCS studies (up to October 1, 2018) that used fMRI as a proxy measure of neural activation to answer mechanistic, predictive, and localization questions about how brain activity is modulated by tDCS. FMRI can potentially contribute as: a measure of cognitive state-level variance in baseline brain activation before tDCS; inform the design of stimulation montages that aim to target functional networks during specific tasks; and act as an outcome measure of functional response to tDCS. In this systematic review, we explore methodological parameter space of tDCS integration with fMRI spanning: (a) fMRI timing relative to tDCS (pre, post, concurrent); (b) study design (parallel, crossover); (c) control condition (sham, active control); (d) number of tDCS sessions; (e) number of follow up scans; (f) stimulation dose and combination with task; (g) functional imaging sequence (BOLD, ASL, resting); and (h) additional behavioral (cognitive, clinical) or quantitative (neurophysiological, biomarker) measurements. Existing tDCS-fMRI literature shows little replication across these permutations; few studies used comparable study designs. Here, we use a representative sample study with both task and resting state fMRI before and after tDCS in a crossover design to discuss methodological confounds. We further outline how computational models of current flow should be combined with imaging data to understand sources of variability. Through the representative sample study, we demonstrate how modeling and imaging methodology can be integrated for individualized analysis. Finally, we discuss the importance of conducting tDCS-fMRI with stimulation equipment certified as safe to use inside the MR scanner, and of correcting for image artifacts caused by tDCS. tDCS-fMRI can address important questions on the functional mechanisms of tDCS action (e.g., target engagement) and has the potential to support enhancement of behavioral interventions, provided studies are designed rationally.

Inherent physiological artifacts in EEG during tDCS.

Online imaging and neuromodulation is invalid if stimulation distorts measurements beyond the point of accurate measurement. In theory, combining transcranial Direct Current Stimulation (tDCS) with electroencephalography (EEG) is compelling, as both use non-invasive electrodes and image-guided dose can be informed by the reciprocity principle. To distinguish real changes in EEG from stimulation artifacts, prior studies applied conventional signal processing techniques (e.g. high-pass filtering, ICA). Here, we address the assumptions underlying the suitability of these approaches. We distinguish physiological artifacts - defined as artifacts resulting from interactions between the stimulation induced voltage and the body and so inherent regardless of tDCS or EEG hardware performance - from methodology-related artifacts - arising from non-ideal experimental conditions or non-ideal stimulation and recording equipment performance. Critically, we identify inherent physiological artifacts which are present in all online EEG-tDCS: 1) cardiac distortion and 2) ocular motor distortion. In conjunction, non-inherent physiological artifacts which can be minimized in most experimental conditions include: 1) motion and 2) myogenic distortion. Artifact dynamics were analyzed for varying stimulation parameters (montage, polarity, current) and stimulation hardware. Together with concurrent physiological monitoring (ECG, respiration, ocular, EMG, head motion), and current flow modeling, each physiological artifact was explained by biological source-specific body impedance changes, leading to incremental changes in scalp DC voltage that are significantly larger than real neural signals. Because these artifacts modulate the DC voltage and scale with applied current, they are dose specific such that their contamination cannot be accounted for by conventional experimental controls (e.g. differing stimulation montage or current as a control). Moreover, because the EEG artifacts introduced by physiologic processes during tDCS are high dimensional (as indicated by Generalized Singular Value Decomposition- GSVD), non-stationary, and overlap highly with neurogenic frequencies, these artifacts cannot be easily removed with conventional signal processing techniques. Spatial filtering techniques (GSVD) suggest that the removal of physiological artifacts would significantly degrade signal integrity. Physiological artifacts, as defined here, would emerge only during tDCS, thus processing techniques typically applied to EEG in the absence of tDCS would not be suitable for artifact removal during tDCS. All concurrent EEG-tDCS must account for physiological artifacts that are a) present regardless of equipment used, and b) broadband and confound a broad range of experiments (e.g. oscillatory activity and event related potentials). Removal of these artifacts requires the recognition of their non-stationary, physiology-specific dynamics, and individualized nature. We present a broad taxonomy of artifacts (non/stimulation related), and suggest possible approaches and challenges to denoising online EEG-tDCS stimulation artifacts.

Heavy Alcohol Use and Age Effects on HIV-Associated Neurocognitive Function.

BACKGROUND: There is growing concern about the health impact of heavy alcohol use in people infected with human immunodeficiency virus (HIV+). Mixed findings of past studies regarding the cognitive impact of alcohol use in HIV+ adults have been mixed, with inconsistent evidence that alcohol consumption exacerbates HIV-associated brain dysfunction. This study examined contributions of current heavy drinking, lifetime alcohol use disorder (AUD), and age to cognitive deficits in HIV+ adults, and relative to other HIV-associated clinical factors. METHODS: Cognitive performance of HIV+ adults (n = 104) was assessed, and comparisons were made between heavy current to nonheavy drinkers (NIAAA criteria), lifetime AUD versus no-AUD, and older (>50 years) versus younger participants. Hierarchical regression analyses were conducted to examine the association between cognitive performance and current heavy drinking, lifetime AUD, and older age, while also correcting for HIV clinical factors and history of other substance use. RESULTS: Individuals reporting current heavy drinking and meeting criteria for lifetime AUD demonstrated the greatest degree of deficits across multiple cognitive domains. Deficits were greatest among HIV+ adults with lifetime AUD, and older age was also associated with weaker cognitive performance. Lifetime AUD and older age independently exhibited stronger associations with cognitive performance than HIV clinical factors (e.g., viral load, current CD4, and nadir CD4) or past opiate and cocaine use. CONCLUSIONS: Current heavy drinking and lifetime AUD adversely affect cognitive function in HIV+ adults. Greatest deficits existed when there was a history of AUD and continued current heavy drinking, indicating that past AUD continues to have an adverse impact and should not be ignored. That alcohol use was more strongly associated with cognitive performance than HIV clinical factors underscore clinical importance of targeting reduction in heavy alcohol consumption in HIV+ adults.

Effect of transcranial direct current stimulation on decision making and cognitive flexibility in gambling disorder.

Decision making and cognitive flexibility are two components of cognitive control that play a critical role in the emergence, persistence, and relapse of gambling disorder. Transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) has been reported to enhance decision making and cognitive flexibility in healthy volunteers and individuals with addictive disorders. In this triple-blind randomized sham-controlled parallel study, we aimed to determine whether tDCS over DLPFC would modulate decision making and cognitive flexibility in individuals with gambling disorder. Twenty participants with gambling disorder were administered Iowa Gambling Task (IGT) and Wisconsin Card Sorting Test (WCST). Subsequently, participants were administered three every other day sessions of active right anodal /left cathodal tDCS (20 min, 2 mA) or sham stimulation over bilateral DLPFC. WCST and IGT were readministered following the last session. Baseline clinical severity, depression, impulsivity levels, and cognitive performance were similar between groups. TDCS over the DLPFC resulted in more advantageous decision making (F1,16 = 8.128, p = 0.01, ɳp2 =0.33) and better cognitive flexibility (F1,16 =8.782, p = 0.009, ɳp2 = 0.35), representing large effect sizes. The results suggest for the first time that tDCS enhanced decision making and cognitive flexibility in gambling disorder. Therefore, tDCS may be a promising neuromodulation-based therapeutic approach in gambling disorder.Trial registration: Clinicaltrials.gov NCT03477799.

Cerebral Metabolites on the Descending Limb of Acute Alcohol: A Preliminary 1H MRS Study.

AIMS: Chronic alcohol use is associated with cerebral metabolite abnormalities, yet alcohol's acute effects on neurometabolism are not well understood. This preliminary study investigated cerebral metabolite changes in vivo on the descending limb of blood alcohol in healthy moderate drinkers. METHODS: In a pre/post design, participants (N = 13) completed magnetic resonance imaging (MRI) scans prior to and approximately 5 hours after consuming a moderate dose of alcohol (0.60 grams alcohol per kilogram of body weight). Magnetic resonance spectroscopy (1H MRS) was used to quantify cerebral metabolites related to glutamatergic transmission (Glx) and neuroimmune activity (Cho, GSH, myo-inositol) in the thalamus and frontal white matter. RESULTS: Breath alcohol concentration (BrAC) peaked at 0.070±0.008% (mean ± standard deviation) and averaged 0.025±0.011% directly prior to the descending limb scan. In the thalamus, Glx/Cr and Cho/Cr were significantly elevated on the descending limb scan relative to baseline. BrAC area under the curve, an index of alcohol exposure during the session, was significantly, positively associated with levels of Glx/Cr, Cho/Cr and GSH/Cr in the thalamus. GSH/Cr on the descending limb was inversely correlated with subjective alcohol sedation. CONCLUSIONS: This study offers preliminary evidence of alcohol-related increases in Glx/Cr, Cho/Cr and GSH/Cr on the descending limb of blood alcohol concentration. Findings add novel information to previous research on neurometabolic changes at peak blood alcohol in healthy individuals and during withdrawal in individuals with alcohol use disorder.

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.